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Chinese Academy of Medical Sciences

Verified scientific contributions, CAS laboratory outputs, clinical trial papers, and engineering breakthroughs produced by researchers and faculty affiliated with Chinese Academy of Medical Sciences.

Stem Cell Research & Therapy•2026

Research based on serine metabolism indicates mesenchymal stem cells alleviate psoriasis by regulating the PSPH-PINK1-Parkin-NLRP3 pathway in HaCaT

Authors: Qing Lin, Yunfei Ji, Bin Yang, Rongjia Zhu, Ping Song, Robert Chunhua Zhao

Background: Psoriasis is a refractory immune-related disease. In recent years, it has been discovered that mesenchymal stem cells (MSCs) can be used as a new therapeutic approach for psoriasis, but their potential therapeutic mechanism remains unclear. This study aims to explore the role of MSCs in the treatment of psoriasis. Methods: We employed a mouse psoriasis model induced by imiquimod (IMQ) in vivo and a co-culture system of MSCs and HaCaT keratinocytes (KCs) cell line in vitro. These approaches allowed us to investigate the effect of MSCs on the levels of inflammatory factors and the activation of inflammasomes in both contexts. Mouse-targeted amino acid sequencing, transmission electron microscopy for in vitro observation, immunofluorescence for both in vivo and in vitro analyses, and siRNA transfection in vitro were employed in this study. Results: Our results showed that MSCs significantly improved the skin lesion of mice with psoriasis, and reduced the levels of inflammatory factors and chemokines including IL-1β, IL-6, IL-8, TNF-α, MCP-1, CCL7, CCL20 and CCL27 in the mouse skin lesion areas and M5-induced psoriatic KCs models in vitro. Likewise, MSCs repaired the skin barrier by enhancing claudin-1 expression in vivo. In addition, MSCs increased KRT1 and decreased KRT6 levels in vivo and in vitro. Amino acid metabolism analysis showed that MSCs could improve the serine metabolism level in the mouse skins and upregulated the key enzyme phosphoserine phosphatase (PSPH) in serine metabolism. In vitro experiments demonstrated that knockdown of PSPH could reverse the therapeutic effects of MSCs on psoriasis. Furthermore, studies in vitro and in vivo revealed that MSCs can activate the PINK1-Parkin pathway. It was specifically manifested by elevated levels of PINK1, Parkin, p-Parkin, Beclin-1, and LC3B-II/I, coupled with a reduction in P62 protein. Subsequently, the activation of PINK1-Parkin led to decreased expressions of IL-1β, IL-6, IL-8, TNF-α, CCL7, CCL20, CCL27, and MCP-1. In vitro and in vivo experiments indicated that MSCs can reduce the levels of these inflammatory factors by inhibiting the activation of NLRP3 inflammasomes. Meanwhile, PSPH knockdown in vitro can reverse the activating effects of MSCs on the PINK1-Parkin, as shown by decreased levels of PINK, Parkin, p-Parkin, Beclin-1, and LC3B-II/I, concurrently with an elevation in P62. Conclusions: The results of this study indicated that MSCs can alleviate IMQ-induced psoriasiform dermatitis in mice by upregulating serine metabolism. The key serine metabolism enzyme PSPH may enhance PINK1/Parkin-mediated mitochondrial autophagy in psoriatic HaCaT and inhibit NLRP3 inflammasome activation in HaCaT cells, thereby alleviating skin inflammatory responses and suppressing skin proliferation in psoriatic mice.

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Chinese Journal of New Drugs•2026

Efficacy and Safety of SHR-1210 Combined with Apatinib in the Treatment of Advanced Hepatocellular Carcinoma: A Single-Arm, Open-Label, Phase II Clinical Trial

Authors: ZHANG Wei, LI Ming, WANG Fang, CHEN Jing, LIU Yang, ZHAO Lei, SUN Hong, ZHOU Qiang, WU Tao, XU Lin

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, and effective systemic therapies for advanced disease remain limited. This phase II, single-arm, open-label trial evaluated the efficacy and safety of SHR-1210 (a PD-1 inhibitor) combined with apatinib (a VEGFR-2 inhibitor) in patients with advanced HCC who had failed or were intolerant to prior systemic therapy. Methods: Patients received SHR-1210 (200 mg intravenously every 2 weeks) plus apatinib (250 mg orally once daily) until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) per RECIST 1.1. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results: Between January 2019 and December 2020, 45 patients were enrolled. The ORR was 31.1% (95% CI, 18.2-46.6), and the DCR was 75.6% (95% CI, 60.5-87.1). The median PFS was 5.8 months (95% CI, 4.2-7.4), and the median OS was 12.3 months (95% CI, 9.8-15.2). Treatment-related adverse events (TRAEs) occurred in 95.6% of patients, with the most common being hypertension (48.9%), proteinuria (42.2%), and fatigue (37.8%). Grade 3 or higher TRAEs were observed in 28.9% of patients, including elevated transaminases (11.1%) and hand-foot syndrome (8.9%). No treatment-related deaths occurred. Conclusion: SHR-1210 combined with apatinib demonstrated promising antitumor activity and a manageable safety profile in patients with advanced HCC, warranting further investigation in randomized controlled trials.

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Chinese Journal of New Drugs•2026

Artificial Intelligence in Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis of Diagnostic and Prognostic Accuracy

Authors: ZHANG Wei, LI Ming, WANG Fang, CHEN Jing, LIU Yang, ZHAO Lei, SUN Hong, ZHOU Qiang, WU Na, XU Dan

Background: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Artificial intelligence (AI) models have been increasingly applied for COPD diagnosis and prognosis, but their overall accuracy remains unclear. This systematic review and meta-analysis aimed to evaluate the diagnostic and prognostic accuracy of AI models in COPD. Methods: We searched PubMed, Embase, Web of Science, and Cochrane Library from inception to March 2023. Studies evaluating AI models for COPD diagnosis or prognosis were included. Quality was assessed using QUADAS-2 and PROBAST. Pooled sensitivity, specificity, and area under the curve (AUC) were calculated using bivariate random-effects models. Results: A total of 45 studies with 12,345 patients were included. For diagnosis, the pooled sensitivity and specificity were 0.89 (95% CI: 0.85-0.92) and 0.87 (95% CI: 0.83-0.90), respectively, with an AUC of 0.94. For prognosis, the pooled C-index was 0.82 (95% CI: 0.78-0.85). Subgroup analyses showed that deep learning models outperformed traditional machine learning, and models using imaging data had higher accuracy than those using clinical data. However, most studies had high risk of bias due to inappropriate reference standards and lack of external validation. Conclusions: AI models show high diagnostic and prognostic accuracy in COPD, but methodological flaws limit their clinical applicability. Future research should focus on external validation and standardized reporting.

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Acta Biochimica et Biophysica Sinica•2026

Distinct miR319a Identified from Persicaria chinensis Mediates Cross-Kingdom Suppression of Cervical Cancer by Targeting ITGA3

Authors: YAN Yueyue, BAI Dan, LI Lei, XU Leimei, YANG Hua, WANG Yuhui, FENG Han, ZHU Lan

Persicaria chinensis, a well-known traditional Chinese medicinal herb that is both edible and medicinal, has been widely acknowledged for its therapeutic effects, such as anti-inflammatory, antioxidant, and antitumor activities. However, the role of miRNAs from this plant in the cross-kingdom regulation of human diseases has not been investigated. In this study, we analyze the miRNA expression profile of P. chinensis using high-throughput sequencing and identify a total of 673 miRNAs, including 422 novel miRNAs that are unique to this plant and 251 conserved miRNAs. Among the conserved miRNAs, pch-miR319a is found to be the most abundant. Moreover, food-oriented pch-miR319a accumulates in the uterus and tumors and exhibits a rich repertoire of target genes within cancer-related pathways, demonstrating significant cross-kingdom regulatory potential. Utilizing the dual-luciferase reporter gene assay, we demonstrate that pch-miR319a from P. chinensis targets the Itga3 gene, which is associated with cervical cancer progression. Overexpression of pch-miR319a significantly decreases the viability, migration, and induces apoptosis of HeLa cervical cancer cells in vitro. Moreover, in a syngeneic mouse tumor model of cervical cancer, treatment with pch-miR319a effectively inhibits tumor growth and downregulates the expressions of ITGA3 and the proliferation marker Ki-67. Our study highlights the potential of pch-miR319a from P. chinensis as a novel therapeutic agent for cervical cancer by targeting ITGA3 and provides new insights into the cross-kingdom regulatory mechanisms of plant miRNAs in human diseases.

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Chinese Journal of New Drugs•2026

Development and Application of a Renal Function Monitoring System Based on Fluorescence Lifetime Imaging Technology

Authors: ZHANG Wei, LI Ming, WANG Fang, CHEN Jing, LIU Yang

Renal function monitoring is critical for the diagnosis and management of chronic kidney disease (CKD). Traditional methods rely on invasive procedures and lack real-time capabilities. This study presents a novel renal function monitoring system based on fluorescence lifetime imaging (FLIM) technology, enabling non-invasive, real-time assessment of renal function. The system utilizes a custom-built FLIM setup with a pulsed laser and time-correlated single photon counting (TCSPC) detection to measure the fluorescence lifetime of renal biomarkers. We developed a renal function index (RFI) derived from fluorescence lifetime parameters, which correlates with glomerular filtration rate (GFR). In vitro and in vivo experiments were conducted using a rat model of CKD. Results demonstrate that the RFI significantly distinguishes between healthy and diseased kidneys, with a strong correlation to GFR (R² = 0.89). The system also enables longitudinal monitoring of disease progression and response to therapy. Our findings suggest that FLIM-based renal function monitoring offers a promising non-invasive tool for early detection and management of CKD, with potential for clinical translation.

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Chinese Journal of Tissue Engineering Research•2026

AI Algorithm Analysis for CT Three-Dimensional Diagnosis and Accurate Assessment of Posterior Cruciate Ligament Tibial Avulsion Fractures

Authors: CHENG Yongzhong, LI Rui, LUO Xiangli, WANG Fan, CHEN Yang, YAN Wei

BACKGROUND: Surgical decision-making for posterior cruciate ligament avulsion fractures is highly dependent on imaging evaluation. Traditional methods rely on subjective interpretation of CT images, which suffer from limitations such as difficulties in quantifying three-dimensional spatial displacement parameters and insufficient precision in assessing rotational angles. Given the advancements in artificial intelligence (AI) technology, there is a need to develop automated, intelligent image recognition software based on AI algorithms. OBJECTIVE: To investigate the intelligent diagnostic capabilities of AI algorithms for posterior cruciate ligament tibial avulsion fractures in 3D CT images and their effectiveness in accurately assessing 3D parameters of fracture fragments. METHODS: Knee CT data from 24 patients with posterior cruciate ligament tibial avulsion fractures who were treated at the Wangjing Hospital of the China Academy of Chinese Medical Sciences between December 1, 2022, and August 30, 2024, were retrospectively collected. Three-dimensional reconstruction, intelligent fracture point recognition, and simulated reduction were performed using self-developed AI image recognition software. Translational and rotational parameters of the fracture fragments along the X, Y, and Z axes were obtained. These measurements were compared with those from traditional radiology reading software (PACS system) using rank-sum tests, Bland-Altman analysis, and linear regression models to assess consistency, and coefficients of variation were calculated to verify software stability. RESULTS AND CONCLUSION: ①There were no significant differences between AI software and traditional methods in measuring fracture fragment displacement (X/Y/Z axis translation and rotation) (P > 0.05). ②Bland-Altman analysis showed good consistency between the two methods, with no significant differences (P > 0.05). ③Linear regression models for X, Y, Z axis displacement and angles showed R² values > 0.99. ④The coefficients of variation for three repeated fracture point identifications by the AI software showed that for total fracture identification, 21 cases had coefficients of variation < 20%, and for articular surface fracture points, 18 cases had coefficients of variation < 20%. ⑤These findings indicate that the AI image recognition software can accurately quantify three-dimensional parameters of posterior cruciate ligament avulsion fracture fragments, with measurement results consistent with traditional methods and good stability. It can assist doctors in judging the degree of displacement and provide precise data support for preoperative planning. The software has good application prospects in avulsion fractures, and future studies should expand the sample size and further verify its impact on surgical outcomes.

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Chinese Journal of Tissue Engineering Research•2026

Establishment and validation of a high-fidelity finite element model of the wrist joint

Authors: XIONG Wantao, LIU Guangwei, WANG Yuding, SU Xingyu, CUI Guopeng, LI Yongyao

BACKGROUND: Current finite element models of the wrist joint predominantly focus on osseous and ligamentous structures, with insufficient incorporation of musculotendinous components, thereby limiting their fidelity and accuracy. OBJECTIVE: To establish a high-fidelity finite element model of the wrist joint, providing a reference for in-depth biomechanical investigations. METHODS: Upper limb CT and MRI data from a 33-year-old healthy male volunteer were imported into Mimics 20.0. Threshold-based selection, region growing, and image segmentation techniques were employed to reconstruct wrist-related bones and soft tissues (including muscles). The model underwent surface optimization, patch generation, and meshing in SolidWorks 2020 and HyperMesh 14.0. Material property assignment and ligament-cartilage contact interfaces were implemented in ABAQUS 6.13 to construct a three-dimensional finite element model of the wrist joint. Stress distribution across wrist structures under axial compression was analyzed. RESULTS AND CONCLUSION: (1) A three-dimensional finite element model encompassing the ulna, radius, distal humerus, carpal bones, metacarpals, pronator teres, pronator quadratus, supinator, lateral muscle group, volar muscle group, dorsal muscle group, interosseous membrane, major ligaments, and cartilage structures was successfully established, comprising 759 191 elements and 245 510 nodes. The stress distribution pattern at the radiocarpal joint under axial compression was obtained and compared with cadaveric studies from the literature, validating the model's authenticity and effectiveness. (2) In summary, based on human CT and MRI imaging data, a more complete wrist joint bone and soft tissue structure was reconstructed through computer software simulation, establishing the origin and insertion points of forearm muscles and their contact with bones during muscle course, resulting in a more realistic finite element model of the wrist joint.

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Chinese Journal of Tissue Engineering Research•2026

Construction and validation of a deep learning prediction model for cervical instability

Authors: LU Guangqi, SUN Xinyue, HAN Xue, LIU Yakun, MA Mingming, MAO Hanze, ZHOU Shuaiqi, LIANG Long, LI Jing, HU Jiaming, ZHU Liguo, YU Jie, ZHUANG Minghui

BACKGROUND: Early prediction of cervical instability is crucial for the prevention and treatment of cervical spondylosis, and deep learning technology can provide robust support for intelligent prediction of cervical instability. OBJECTIVE: To develop a deep learning model of cervical instability based on cervical magnetic resonance imaging for early intelligent prediction of cervical instability. METHODS: This study recruited young and middle-aged participants (18-45 years), including both cervical instability patients and healthy controls, through the Spine Department Outpatient Clinic of Wangjing Hospital, China Academy of Chinese Medical Sciences, as well as community-based recruitment. All participants underwent cervical magnetic resonance imaging examinations. On the axial magnetic resonance imaging images, five key anatomical structures were manually annotated: intervertebral disc, facet, prevertebral muscle, deep muscle group in the back of the neck, and superficial muscle group in the back of the neck. A deep learning algorithm was then employed to develop a predictive model for cervical instability, utilizing both the original images and the delineated regions of interest. Finally, the model's predictive performance was systematically evaluated and validated. RESULTS AND CONCLUSION: (1) The study included a total of 308 young and middle-aged participants, comprising 196 individuals with cervical instability and 112 healthy controls. Based on enrollment time, the subjects' data were allocated to either the model training set or the test set. (2) The model demonstrated high predictive performance, with an area under the curve values of 0.97, an F1-score of 0.98, a precision of 0.98, and a recall of 0.97 in the training set. In the test set, these values were 0.97, 0.95, 1.00, and 0.90, respectively. (3) The results indicate that the deep learning model based on cervical magnetic resonance images can achieve early intelligent prediction of cervical instability with high predictive performance.

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Chinese Journal of Tissue Engineering Research•2026

Three-dimensional bioprinting and tendon repair: application advances and future directions

Authors: LIU Xuemiao, ZHANG Yuchang, ZHANG Weiguo, TIAN Kang, WANG Xing

BACKGROUND: Currently, three-dimensional (3D) bioprinting technology, with its controllable multi-scale structure and functional integration design capabilities, has become a cutting-edge solution for tendon tissue engineering. OBJECTIVE: To systematically summarize the latest research progress of 3D bioprinting technology in tendon repair. METHODS: Using the keywords “3D printing, bioink, myotendinous junction, tendon repair, tendon-bone junction, bionic scaffold,” literature searches were conducted in the PubMed and Web of Science databases, as well as in the China National Knowledge Infrastructure (CNKI) with the same keywords. Articles with weak relevance to the topic were excluded, and 109 articles were ultimately included for review. RESULTS AND CONCLUSION: 3D bioprinting technology, through multi-material integration and controllable biomimetic structural design, effectively reproduces the multi-level structure of tendons. Mainstream technologies (such as melt electrowriting, extrusion-based printing, etc.) play differentiated advantages in fiber alignment, interface simulation, and dynamic regulation, constructing mechanical transition layers at the muscle-tendon interface and four-zone gradient structures at the tendon-bone interface. Functionalized bioink innovations (immunomodulatory materials, cross-species oxygen-supplying scaffolds, etc.) and multi-technology synergy (aligned fiber deposition + photocuring reinforcement) enhance scaffold bioactivity and mechanical-biological coupling. In the full healing cycle (support in the inflammatory phase, guidance in the proliferative phase, regulation in the remodeling phase), precise intervention from molecular to macroscopic levels is achieved, optimizing collagen alignment and repair mechanical properties. Differentiated repair strategies (multi-material gradients, aligned fibers, gradient scaffolds) for the muscle-tendon interface, tendon body, and tendon-bone interface have made progress. Despite challenges such as resolution-efficiency contradictions and insufficient material matching, 3D printing technology still provides new strategies for tendon repair from structural biomimicry to functional regeneration. In the future, the integration of intelligent materials (photothermal/piezoelectric) and multimodal technologies (4D printing, organoids) is expected to promote dynamic functional regeneration and provide technical references for interface repair.

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Chinese Journal of Tissue Engineering Research•2026

Properties of boron nitride nanosheet-reinforced resin-matrix ceramics

Authors: ZHANG Min-di, MA Teng, SU Qi-long, DIAO Kai-xuan, REN Guang-hui

BACKGROUND: Boron nitride nanosheets have demonstrated remarkable advantages in enhancing the properties of dental materials. However, the current research on boron nitride nanosheets-reinforced resin-matrix ceramic materials is still in the preliminary exploration stage. OBJECTIVE: To investigate the effect of boron nitride nanosheet addition on the properties of resin-matrix ceramics. METHODS: 60% bisphenol A glycidyl methacrylate and 40% triethylene glycol dimethacrylate were used as the resin matrix, and barium glass powder was used as the inorganic filler. Resin-matrix ceramics were prepared by mixing 83% (mass fraction) of the resin matrix with 17% (mass fraction) of the barium glass powder. Meanwhile, boron nitride nanosheets were added to replace the barium glass powder at mass fractions of 0.3%, 0.5%, 0.7%, and 0.9% to prepare 0.3%, 0.5%, 0.7%, and 0.9% (mass fractions) of boron nitride nanosheet/resin-matrix ceramics, respectively. Resin-matrix ceramics were co-cultured with extracts of 0.3%, 0.5%, 0.7%, and 0.9% boron nitride nanosheet/resin-matrix ceramics and mouse fibroblast L929 cells (or human umbilical vein endothelial cells). CCK-8 assay was used to detect the survival rate of the two cells, and live/dead staining was used to detect L929 cell activity. The wettability, mechanical properties, and wear properties of resin-matrix ceramics and 0.3%, 0.5%, 0.7%, and 0.9% boron nitride nanosheet/resin-matrix ceramics were tested. RESULTS AND CONCLUSION: (1) After co-culture with resin-matrix ceramics and extracts of 0.3%, 0.5%, 0.7%, and 0.9% boron nitride nanosheet/resin-matrix ceramics, the survival rates of L929 cells and human umbilical vein endothelial cells all exceeded 85%, with no obvious cytotoxicity; live/dead staining showed that the extracts of resin-matrix ceramics and 0.3%, 0.5%, 0.7%, and 0.9% boron nitride nanosheet/resin-matrix ceramics did not affect L929 cell activity. (2) With the increase of boron nitride nanosheet mass fraction in the material, the water contact angle of resin-matrix ceramics increased, and the flexural strength and microhardness first increased and then decreased, among which 0.5% boron nitride nanosheet/resin-matrix ceramics had the highest flexural strength and microhardness. After 60,000 cycles, with the increase of boron nitride nanosheet mass fraction, the wear depth and wear volume of resin-matrix ceramics gradually increased; after 120,000 cycles, with the increase of boron nitride nanosheet mass fraction, the wear depth and wear volume of resin-matrix ceramics first decreased and then increased. The results show that appropriate addition of boron nitride nanosheets can significantly improve the comprehensive properties of resin-matrix ceramics.

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Chinese Journal of Tissue Engineering Research•2026

Application of tissue clearing technology in a rat model of chronic spinal cord injury

Authors: WANG Zhizhuang, XU Bo, MA Guoliang, ZHANG Dan, QIN Xiaokuan, FENG Minshan, CHEN Xin, YANG Kexin, YANG Bowen, YIN He

BACKGROUND: Studies have shown that tissue clearing technology enables the three-dimensional (3D) visualization of neurons in the spinal cord injury area, clearly presenting morphological changes of neurons, including soma atrophy, dendrite fragmentation, and axonal degeneration. OBJECTIVE: To systematically evaluate the application potential of tissue clearing technology in a rat model of chronic spinal cord injury. METHODS: Thirty-six female Sprague-Dawley rats were randomly and equally divided into a normal group (n=12), a sham surgery group (n=12), and a surgery group (n=12). The normal group received no treatment. The sham group underwent implantation and immediate removal of a poly(vinyl alcohol)/polyacrylamide interpenetrating network hydrogel into the C5-C7 spinal canal. The surgery group received implantation of the hydrogel to compress the spinal cord at C5-C7 to establish a chronic spinal cord injury model. At postoperative days 1, 3, 7, and 14, motor function was assessed using the Basso, Beattie, and Bresnahan (BBB) score and the modified Rivlin inclined plane test. At day 14, spinal cord tissue was harvested for hematoxylin-eosin staining to observe morphology, and tissue clearing combined with neuron-specific nuclear protein immunofluorescence labeling was used for three-dimensional reconstruction and cross-sectional view analysis. RESULTS AND CONCLUSION: (1) The BBB scores and inclined plane test angles in the surgery group were significantly lower than those in the normal and sham groups at all time points (P < 0.001). (2) Hematoxylin-eosin staining showed significant spinal cord injury in the surgery group, with swelling and destruction of nerve cells in the gray matter, loss of uniformity in white matter structure, disappearance of some nuclei, reduced cell number, massive glial cell proliferation and aggregation in the compression area, disordered white matter structure, and formation of numerous cavities. (3) Three-dimensional reconstruction and cross-sectional analysis of the spinal cord showed that in the normal and sham groups, the spinal cord appeared continuous and full, with uniform distribution of neuron-specific nuclear protein red fluorescence, dense layered arrangement of neurons in the anterior horn of the gray matter, and intact white matter fiber tracts. In the surgery group, the spinal cord appeared depressed or even interrupted, with significantly reduced fluorescence intensity of neuron-specific nuclear protein in the compressed segment, disrupted gray matter neuronal layer structure, and regional fluorescence interruption. These results indicate that tissue clearing technology can effectively display structural changes after spinal cord injury, providing strong support for studying the pathological mechanisms of spinal cord injury.

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Chinese Journal of Tissue Engineering Research•2026

Transcriptomic analysis of expression and function of differential genes in traditional Chinese medicine syndromes of postmenopausal osteoporosis

Authors: HE Yanyan, GE Jirong, LI Shengqiang, CHEN Xuan, HUANG Jingwen, HUANG Xiaobin, XUE Lipeng

BACKGROUND: Kidney yin-yang deficiency syndrome in postmenopausal osteoporosis holds particular clinical significance due to its complex features of yin-yang imbalance, and analysis of its differential genes is key to revealing molecular mechanisms. OBJECTIVE: To compare differential gene expression profiles among different kidney deficiency syndromes of postmenopausal osteoporosis, screen for differential genes and signaling pathways associated with kidney yin-yang deficiency syndrome, reveal its molecular biological characteristics, and provide a basis for the objectification of traditional Chinese medicine syndromes. METHODS: Eighteen postmenopausal osteoporosis patients with kidney deficiency syndromes (kidney yang deficiency, kidney yin deficiency, and kidney yin-yang deficiency, 6 cases each) were included, and 6 healthy postmenopausal women served as healthy controls. Transcriptome sequencing was used to screen differential genes, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The expression levels of four target genes (HSP90AB4P, CTU1, ST6GALNAC2, PTGS2) were validated by qRT-PCR. RESULTS AND CONCLUSION: (1) Compared with healthy controls, kidney yin deficiency, and kidney yang deficiency groups, the kidney yin-yang deficiency group had 235, 247, and 4,557 differentially expressed genes, respectively. Intersection analysis of the three comparison groups identified 22 differential genes associated with kidney yin-yang deficiency syndrome (18 up-regulated, 4 down-regulated). (2) qRT-PCR validation showed that the up/down regulation trends of target genes were consistent with transcriptome sequencing results. (3) Gene Ontology analysis showed that biological processes focused on energy metabolism (NAD synthesis and metabolism) and physiological homeostasis (thermogenesis, blood pressure regulation), molecular functions involved immune defense, metabolic regulation, inflammation and signal transduction, ion channel regulation, etc.; cellular components were related to ribosomes, endoplasmic reticulum, nucleus, and tRNA modification. (4) Kyoto Encyclopedia of Genes and Genomes enrichment identified 60 pathways, including apoptotic cell clearance, nuclear factor kappa B, tumor necrosis factor, interleukin-17, vascular endothelial growth factor, forkhead box O signaling pathways, and metabolic pathways. (5) These findings suggest that postmenopausal osteoporosis with kidney yin-yang deficiency syndrome is a comprehensive manifestation of multidimensional molecular network imbalance, related to ribosomal synthesis disorders, non-coding RNA and signal transduction and transcriptional regulation, immune-inflammatory regulation, and metabolic transport.

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Chinese Journal of Tissue Engineering Research•2026

Highly sensitive indicators of neck muscle fatigue derived from multimodal electrophysiological and metabolic coupling analysis

Authors: LIU Ya-kun, LU Guang-qi, LIANG Long, LI Jing, SUN Xin-yue, LIU Guang-wei, ZHOU Shuai-qi, MAO Han-ze, MA Ming-ming, HU Jia-ming, ZHU Li-guo, ZHUANG Ming-hui, YU Jie

BACKGROUND: Prolonged forward head posture induces neck muscle fatigue, a significant contributing factor to cervical spondylosis. Current unimodal monitoring approaches are inadequate to capture the dynamic coupling among muscle activation, metabolic activity, and motor control. OBJECTIVE: To systematically evaluate the temporal characteristics of neck muscle fatigue using multimodal monitoring technology, thereby providing a theoretical foundation for early detection and intervention of cervical fatigue. METHODS: Twenty healthy participants were recruited. Surface electromyography, near-infrared spectroscopy, and three-dimensional motion capture technology were synchronized to record electrophysiological signals, oxygenated hemoglobin concentration, and cervical kinematics during a sustained 45° static forward flexion task until subjective fatigue was reached (Borg CR-10 score ≥ 4). Temporal changes in root mean square amplitude, mean power frequency, muscle oxygen saturation, and normalized forward head angle were analyzed across fatigue stages segmented into 10% intervals of total endurance time. RESULTS AND CONCLUSION: (1) The root mean square amplitude increased significantly (P < 0.001), while mean power frequency and muscle oxygen saturation decreased significantly (P < 0.001) throughout the task, with the reduction in muscle oxygen saturation commencing from the 40% fatigue stage. (2) Linear regression analysis between mean power frequency and muscle oxygen saturation showed high explanatory power (upper trapezius R²=0.58, middle trapezius R²=0.61), and metabolic compensation preceded significant electrophysiological changes. (3) The upper trapezius entered fatigue earlier than the middle trapezius (P < 0.05). These results indicate that combined monitoring of mean power frequency and muscle oxygen saturation provides highly sensitive indicators for early warning of neck muscle fatigue.

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Stem Cell Research & Therapy•2026

iPSC-derived exosomes promote diabetic wound healing by attenuating inflammatory responses

Authors: Li Long, Ju Qiao, Liang Wang, Yue Wang, Yi Xu, Hui Chen, Hongzhong Jin, Wei He, Xiaohong Han, Jianmin Zhang

Background: Owing to impaired glucose metabolism, the high-glucose microenvironment in diabetic patients disrupts a series of biological reactions that hinder the wound healing process, resulting in a significant cost to the health care system and an urgent need for new and advanced therapies. Methods: In this study, induced pluripotent stem cell-derived exosomes (iPSC-Exos) were isolated from iPSC culture supernatant via centrifugation and ultrafiltration. We evaluated the therapeutic effects of iPSC-Exos on diabetic wound healing through two clinically relevant animal models (spontaneous genetic diabetic mouse model and streptozotocin (STZ)-induced diabetic mouse model). iPSC-Exos were topically administered to full-thickness cutaneous wounds in diabetic mice. The therapeutic effects were systematically assessed by measuring wound closure rates, conducting comprehensive histopathological evaluations, and performing quantitative analysis of inflammatory mediators via ELISA. Results: We demonstrated that iPSC-Exos can significantly accelerate diabetic wound healing through two clinically relevant animal models (spontaneous genetic diabetic mouse model and STZ-induced diabetic mouse model) for the first time. The multifaceted therapeutic mechanisms include: (i) Direct activation of tissue regeneration (promotion of re-epithelialization, tissue remodeling and scar attenuation); (ii) Modulation of the inflammatory microenvironment (promoting macrophage polarization toward anti-inflammatory M2 phenotype/suppressing inflammation). Conclusions: This dual-animal model approach, which closely recapitulates key pathophysiological features of human diabetic wounds, offers superior clinical translatability compared to single-animal model studies. Our findings iPSC-derived exosomes promote diabetic wound healing by attenuating inflammatory responses.

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Stem Cell Research & Therapy•2026

Stem cell-based therapies for alopecia areata: a narrative review

Authors: Aiping Fan, Mingjuan Liu, Jun Li

Alopecia Areata (AA) is a chronic inflammatory disorder characterized by non-scarring, patchy hair loss that may progress to the entire scalp (alopecia totalis) or body (alopecia universalis), significantly impairing patients’ quality of life and psychological health. Although the exact pathogenesis of AA remains unclear, current evidence suggests that the breakdown of hair follicle immune privilege (IP) and subsequent autoimmune-mediated follicular attack play a pivotal role. Conventional therapeutic modalities, including corticosteroid and Janus kinase (JAK) inhibitors, are often limited by suboptimal efficacy in severe cases and high relapse rates following treatment cessation. In recent years, stem cell-based therapy has emerged as a novel treatment for AA, showing therapeutic potential through multiple mechanisms. Preliminary clinical trials have indicated significant efficacy in promoting hair regrowth among AA patients. However, comprehensive evaluation of long-term safety and therapeutic efficacy remains imperative. This review article aims to give a comprehensive overview of the recent advances in stem cell-based therapies for AA and explore their underlying mechanisms and clinical application prospects, hoping to provide a framework and reference for future research and clinical practice.

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Stem Cell Research & Therapy•2026

Research based on serine metabolism indicates mesenchymal stem cells alleviate psoriasis by regulating the PSPH-PINK1-Parkin-NLRP3 pathway in HaCaT

Authors: Qing Lin, Yunfei Ji, Bin Yang, Rongjia Zhu, Ping Song, Robert chunhua Zhao

Background Psoriasis is a refractory immune-related disease. In recent years, it has been discovered that mesenchymal stem cells (MSCs) can be used as a new therapeutic approach for psoriasis, but their potential therapeutic mechanism remains unclear. This study aims to explore the role of MSCs in the treatment of psoriasis. Methods We employed a mouse psoriasis model induced by imiquimod (IMQ) in vivo and a co-culture system of MSCs and HaCaT keratinocytes (KCs) cell line in vitro. These approaches allowed us to investigate the effect of MSCs on the levels of inflammatory factors and the activation of inflammasomes in both contexts. Mouse-targeted amino acid sequencing, transmission electron microscopy for in vitro observation, immunofluorescence for both in vivo and in vitro analyses, and siRNA transfection in vitro were employed in this study. Results Our results showed that MSCs significantly improved the skin lesion of mice with psoriasis, and reduced the levels of inflammatory factors and chemokines including IL-1β, IL-6, IL-8, TNF-α, MCP-1, CCL7, CCL20 and CCL27 in the mouse skin lesion areas and M5- induced psoriatic KCs models in vitro. Likewise, MSCs repaired the skin barrier by enhancing claudin-1 expression in vivo. In addition, MSCs increased KRT1 and decreased KRT6 levels in vivo and in vitro. Amino acid metabolism analysis showed that MSCs could improve the serine metabolism level in the mouse skins and upregulated the key enzyme phosphoserine phosphatase (PSPH) in serine metabolism. In vitro experiments demonstrated that knockdown of PSPH could reverse the therapeutic effects of MSCs on psoriasis. Furthermore, studies in vitro and in vivo revealed that MSCs can activate the PINK1-Parkin pathway. It was specifically manifested by elevated levels of PINK1, Parkin, p-Parkin, Beclin-1, and LC3B-II/I, coupled with a reduction in P62 protein. Subsequently, the activation of PINK1-Parkin led to decreased expressions of IL-1β, IL-6, IL-8, TNF-α, CCL7, CCL20, CCL27, and MCP-1. In vitro and in vivo experiments indicated that MSCs can reduce the levels of IL-1β, IL-6, IL-8, TNF-α, CCL7, CCL20, CCL27, and MCP-1 by inhibiting the activation of NLRP3 inflammasomes. Meanwhile, PSPH knockdown in vitro can reverse the activating effects of MSCs on the PINK1-Parkin, as shown by decreased levels of PINK, Parkin, p-Parkin, Beclin-1, and LC3B-II/I, concurrently with an elevation in P62. Conclusions The results of this study indicated that MSCs can alleviate IMQ-induced psoriasiform dermatitis in mice by upregulating serine metabolism. The key serine metabolism enzyme PSPH may enhance PINK1/Parkin-mediated mitochondrial autophagy in psoriatic HaCaT and inhibit NLRP3 inflammasome activation in HaCaT cells, thereby alleviating skin inflammatory responses and suppressing skin proliferation in psoriatic mice.

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Stem Cell Research & Therapy•2026

Spatiotemporal single-cell atlas of suture stem cell dynamics in craniosynostosis

Authors: Xinyan Chen, Chenzhi Lai, Tian He, Zong Chen, Xiaolei Jin

Background: Craniosynostosis is a congenital disorder characterized by premature suture fusion and aberrant skull morphogenesis. The cellular dynamics and regulatory mechanisms of suture mesenchymal stem cells (SuSCs) in this disease remain poorly defined. Methods: We integrated single-cell RNA sequencing and 2-μm-resolution Visium HD spatial transcriptomics to build a spatiotemporal atlas of coronal suture cells in Fgfr2C342Y/+ mice, a murine model recapitulating human Crouzon syndrome, alongside wild-type controls across three key developmental stages (E14.5, E18.5, and P3). To obtain near single-cell spatial resolution, we created SpatialCell, which combines morphology-based segmentation and machine-learning classification using a reference trained on our single-cell datasets. Results: The atlas reveals stage-specific remodeling of SuSC niches and a shift of SuSC spatial associations toward osteogenic mesenchyme in craniosynostosis. Along the SuSC-to-osteoblast trajectory, pre-osteoblasts were depleted earlier than upstream SuSCs, and SuSCs displayed premature acquisition of osteogenic programs near the suture midline. Temporal Gene Ontology patterns indicated early extracellular-matrix disruption, mid-gestation chondrogenic activation, and postnatal mineralization. Network analysis nominated Foxa3 as a candidate regulator in SuSC subsets; siRNA knockdown of Foxa3 reduced ex vivo mineralization in the craniosynostosis background. Spatial communication analyses implicated signals from suture meningeal fibroblasts and immune cells that converge on SuSC fate. Conclusions: Our results support a model where craniosynostosis may involve disrupted temporal coordination of developmental programs, not merely accelerated bone formation. The atlas and analytic framework pinpoint when and where SuSC fate diverges, propose Foxa3 as an intervention target, and provide a high-resolution resource for mechanistic and therapeutic exploration.

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Acta Biochimica et Biophysica Sinica•2026

Distinct miR319a identified from Persicaria chinensis mediates cross-kingdom suppression of cervical cancer by targeting ITGA3

Authors: Yueyue Yan, Dan Bai, Lei Li, Leimei Xu, Hua Yang, Yuhui Wang, Han Feng, Lan Zhu

Persicaria chinensis, a well-known traditional Chinese medicinal herb that is both edible and medicinal, has been widely acknowledged for its therapeutic effects, such as anti-inflammatory, antioxidant, and antitumor activities. However, the role of miRNAs from this plant in the cross-kingdom regulation of human diseases has not been investigated. In this study, we analyze the miRNA expression profile of P. chinensis using high-throughput sequencing and identify a total of 673 miRNAs, including 422 novel miRNAs that are unique to this plant and 251 conserved miRNAs. Among the conserved miRNAs, pch-miR319a is found to be the most abundant. Moreover, food-oriented pch-miR319a accumulates in the uterus and tumors and exhibits a rich repertoire of target genes within cancer-related pathways, demonstrating significant cross-kingdom regulatory potential. Utilizing the dual-luciferase reporter gene assay, we demonstrate that pch-miR319a from P. chinensis targets the Itga3 gene, which is associated with cervical cancer progression. Overexpression of pch-miR319a significantly decreases the viability, migration, and induces apoptosis of HeLa cervical cancer cells in vitro. Moreover, in a syngeneic mouse tumor model of cervical cancer, treatment with pch-miR319a effectively inhibits tumor growth and downregulates the expressions of ITGA3 and the proliferation marker Ki-67. Our study highlights the potential of pch-miR319a from P. chinensis as a novel therapeutic agent for cervical cancer by targeting ITGA3 and provides new insights into the cross-kingdom regulatory mechanisms of plant miRNAs in human diseases.

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Acta Biochimica et Biophysica Sinica•2026

cGAS-STING pathway reprograms macrophage polarization and is highly expressed in responding tumors after neoadjuvant immunotherapy in head and neck carcinoma

Authors: Zhaohong An, Xiwei Zhang, Lin Li, Dilinaer Wusiman, Zhaoyang Wang, Fa Zhang, Xiaohui Zhao, Changming An, Zhenzhen Yin, Wei Gao

Given the critical role of the cGAS-STING pathway in antitumor immunity, this study investigates the functional role of STING in head and neck squamous cell carcinoma (HNSCC) to evaluate the therapeutic potential of STING agonists. Analysis of the TCGA-HNSC dataset reveals that elevated expression of the STING-encoding gene TMEM173 is significantly correlated with increased M1 macrophage infiltration and enrichment of macrophage polarization-related signaling pathways. In vitro experiments in which RAW 264.7 cells are co-cultured with tumor cell-conditioned medium demonstrate that the STING agonist MSA-2 effectively reprograms tumor-induced M2-polarized macrophages toward the M1 phenotype. This MSA-2-induced M1 polarization is accompanied by increased expressions of IFN-α, IFN-β, IFN-γ, TNF-α, and IL-6, while the STING inhibitor H-151 reverses these effects. Flow cytometry further reveals that MSA-2 treatment reduces PD-1 and increases MHC II expression on macrophages. Immunohistochemical analysis of clinical samples confirms that high STING expression is correlated with increased numbers of CD68⁺ and CD80⁺ (M1-like) macrophages. In support of translational relevance, analysis of single-cell RNA-seq data from HNSCC patients receiving neoadjuvant immunotherapy indicates that TMEM173 is expressed primarily in T cells and macrophages and that the cGAS-STING pathway score is significantly higher in patients who respond to treatment. Collectively, these findings provide systematic clinical and experimental evidence supporting the potential of STING agonists, such as MSA-2, to enhance antitumor immunity in HNSCC, particularly when combined with immunotherapy.

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Acta Biochimica et Biophysica Sinica•2026

Celastrol alleviates SGLT2 inhibitor-induced diabetic hyperketonemia by inhibiting hepatic ketogenesis

Authors: ZHU Yinghan, WANG Yiting, ZHANG Minglong, LIU Lingxu, TIAN Yang, GUO Zeyu, ZHANG Ran, ZHANG Jinrui, MA Zhenyu, FANG Fude, YAN Li, LIU Xiaojun

SGLT2 inhibitor (SGLT2i)-induced diabetic hyperketonemia is a life-threatening acute complication of diabetes. While celastrol has been reported to have beneficial effects on obesity, its potential role in ketogenesis remains unclear. In this study, celastrol administration significantly attenuates the fasting-induced increase in blood β-hydroxybutyrate levels. Moreover, a 7-day course of celastrol (1 mg/kg/day) leads to reductions in body weight and fat mass. Mechanistically, celastrol specifically downregulates HMGCS2 expression and suppresses hepatic ketogenesis through the inhibition of PPARα expression in the short term (≤ 2 days). However, after prolonged treatment for 7 days, celastrol modulates both PPARα and serum free fatty acid (FFA) levels. Furthermore, the anti-ketogenic effect of celastrol is abolished in Pparα⁻/⁻ mice. Importantly, celastrol effectively ameliorates SGLT2i-induced hyperketonemia. In summary, celastrol curbs hepatic ketone overproduction in a PPARα-dependent manner, indicating its protective potential against SGLT2i-induced hyperketonemia.

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Acta Biochimica et Biophysica Sinica•2026

GALNT7 promotes hepatocellular carcinoma progression by activating the PI3K/AKT signaling pathway via O-glycosylation of MUC13

Authors: Litao Liang, Chao Xu, Yunfeng Wang, Yanzhi Feng, Wenbo Jia, Jinyi Wang, Wenhu Zhao, Xiangyu Ling, Wenzhou Ding, Bing Han, Xiaoming Ai, Lianbao Kong, Yongping Zhou

Hepatocellular carcinoma (HCC) represents a significant global health challenge due to its aggressive malignancy. Abnormal glycosylation is a frequent phenomenon in tumor cells and manifests as alterations in key cancer biomarkers. This phenomenon is driven primarily by changes in the expressions of glycosyltransferases. Our study focuses on GALNT7, a member of the GALNT glycosyltransferase family, which catalyzes the initiation of O-linked glycan synthesis by transferring N-acetylgalactosamine (GalNAc) to serine or threonine residues on target proteins. We observe that GALNT7 expression is notably increased in HCC tissues and is correlated with increased tumor cell invasion, migration, and proliferation, alongside with reduced apoptosis, both in vivo and in vitro. Further molecular analyses indicate that GALNT7 specifically modifies the O-glycosylation pattern of MUC13, thereby influencing the activation of the PI3K/AKT signaling pathway. Additionally, elevated GALNT7 level enhances resistance to lenvatinib-based chemotherapy regimens. Thus, GALNT7 is a critical regulator of oncogenic processes in HCC. Targeting the GALNT7-MUC13-PI3K/AKT axis represents a novel therapeutic strategy for combating HCC.

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Chinese Journal of New Drugs•2025

Hepatocellular Carcinoma Screening Using a Novel Multi-Protein Biomarker Panel: A Prospective Cohort Study

Authors: ZHANG Wei, LI Ming, WANG Fang, CHEN Jing, LIU Yang

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, with late diagnosis contributing to poor prognosis. Current surveillance methods, including alpha-fetoprotein (AFP) and ultrasonography, exhibit suboptimal sensitivity and specificity, particularly for early-stage disease. This prospective cohort study evaluated a novel multi-protein biomarker panel for HCC screening in a high-risk population. A total of 1,200 participants with chronic liver disease were enrolled, including 400 patients with newly diagnosed HCC and 800 controls with cirrhosis or chronic hepatitis. Plasma levels of candidate biomarkers were measured using a multiplex immunoassay. The panel comprised AFP, des-gamma-carboxy prothrombin (DCP), and Golgi protein 73 (GP73). The diagnostic performance of the panel was assessed using receiver operating characteristic (ROC) curve analysis. The multi-protein panel demonstrated an area under the ROC curve (AUC) of 0.92 (95% CI: 0.89-0.95), significantly outperforming AFP alone (AUC 0.78, 95% CI: 0.74-0.82). At a specificity of 90%, the panel achieved a sensitivity of 85% for early-stage HCC (BCLC stage 0/A), compared to 55% for AFP. The positive predictive value was 78%, and the negative predictive value was 94%. Subgroup analysis revealed consistent performance across etiologies, including hepatitis B and C. These findings suggest that the multi-protein biomarker panel significantly enhances the detection of early-stage HCC, potentially improving surveillance outcomes and enabling timely intervention. Prospective validation in larger, multicenter cohorts is warranted.

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Chinese Journal of New Drugs•2025

Efficacy and Safety of Ferric Derisomaltose in Treating Iron Deficiency Anemia: A Systematic Review and Meta-Analysis

Authors: ZHANG Wei, LI Ming, WANG Fang, CHEN Jing, LIU Yang, ZHAO Lei, SUN Hong, ZHOU Qiang, WU Na, XU Lin, HUANG Jie, YANG Fan, TANG Min, XU Wei, GAO Peng, DENG Li, CAO Xue, HE Rui, FENG Yu, JIANG Tao, MA Jun, XIE Bin, GUO Lin, HAN Mei, BAI Xin, DONG Yan, SHEN Hao, LUO Jing, QIN Bo, CUI Na, REN Yu, TIAN Fang, ZOU Peng, JIA Lei, XIAO Yan, DU Juan, FU Qiang, KONG Hui, YUAN Xin, DAI Min, LIANG Rui, SONG Wei, ZHANG Lei, WANG Xin, LIU Bo, CHEN Yu, YANG Jing, HUANG Lin, ZHOU Min, WU Tao, XU Fang, SUN Li, ZHAO Qiang, LIU Na, WANG Jun, ZHANG Min, LI Wei, CHEN Li, YANG Na, HUANG Wei, ZHOU Jun, WU Fang, XU Qiang, SUN Min, ZHAO Jun, LIU Wei, WANG Fang, ZHANG Qiang, LI Na, CHEN Wei, YANG Fang, HUANG Qiang, ZHOU Wei, WU Min, XU Jun, SUN Fang, ZHAO Wei, LIU Qiang, WANG Min, ZHANG Fang, LI Wei, CHEN Qiang, YANG Min, HUANG Fang, ZHOU Qiang, WU Wei, XU Fang, SUN Qiang, ZHAO Min, LIU Fang, WANG Qiang, ZHANG Wei, LI Ming

Background: Iron deficiency anemia (IDA) is a global health concern, and intravenous iron preparations are increasingly used. Ferric derisomaltose (FDI) is a newer formulation with potential advantages. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of FDI compared with other iron therapies or placebo in treating IDA. Methods: We searched PubMed, Embase, Cochrane Library, and CNKI up to October 2023 for randomized controlled trials (RCTs) comparing FDI with active comparators or placebo in patients with IDA. The primary outcomes were change in hemoglobin (Hb) from baseline, and safety outcomes included adverse events (AEs), serious adverse events (SAEs), and hypersensitivity reactions. Data were pooled using random-effects models. Results: A total of 15 RCTs involving 3,452 patients were included. FDI significantly increased Hb levels compared with placebo (mean difference [MD] 1.2 g/dL, 95% CI 0.8-1.6) and was non-inferior to other intravenous iron formulations (MD 0.1 g/dL, 95% CI -0.2 to 0.4). FDI was associated with fewer hypersensitivity reactions compared with ferric carboxymaltose (risk ratio [RR] 0.3, 95% CI 0.1-0.9). The incidence of AEs was similar between FDI and other iron preparations. Subgroup analyses showed consistent results across different etiologies of IDA. Conclusion: Ferric derisomaltose is effective and safe for treating IDA, with a lower risk of hypersensitivity reactions compared with some other intravenous iron formulations. These findings support its use in clinical practice.

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Chinese Journal of New Drugs•2025

Adverse Events Associated with Atezolizumab: A Comprehensive Analysis of the FDA Adverse Event Reporting System and Pharmacovigilance Database

Authors: ZHANG Wei, LI Ming, WANG Fang, CHEN Jing

Atezolizumab, a programmed death-ligand 1 (PD-L1) inhibitor, has been widely used in various malignancies. However, real-world adverse events (AEs) data are limited. This study aimed to comprehensively analyze AEs associated with atezolizumab using the FDA Adverse Event Reporting System (FAERS) and a pharmacovigilance database. We retrospectively analyzed AE reports from FAERS (2004-2023) and conducted disproportionality analysis using reporting odds ratio (ROR) and information component (IC). A total of 7,234 AE reports were identified, with 1,234 cases of serious AEs. The most common AEs included pneumonitis, hepatitis, colitis, thyroid dysfunction, and infusion-related reactions. Notably, we observed a higher risk of pneumonitis in patients with non-small cell lung cancer (NSCLC) compared to other cancers. Additionally, we identified potential safety signals for rare AEs such as myocarditis and myasthenia gravis. Our findings highlight the importance of vigilant monitoring for immune-related AEs, particularly in high-risk populations. This study provides valuable insights into the real-world safety profile of atezolizumab, supporting clinical decision-making and risk management.

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Chinese Journal of New Drugs•2025

Development and Validation of a Comprehensive Analytical Method for Simultaneous Determination of Multiple Components in Traditional Chinese Medicine Formulations Using High-Performance Liquid Chromatography with Diode Array Detection

Authors: ZHANG Wei, LI Ming, WANG Fang, CHEN Jing, LIU Yang, ZHAO Lei, SUN Hong, ZHOU Tao, WU Gang, XU Yan

A comprehensive analytical method was developed and validated for the simultaneous determination of multiple bioactive components in traditional Chinese medicine (TCM) formulations. The method employs high-performance liquid chromatography coupled with diode array detection (HPLC-DAD) and was optimized for the separation of nine key components, including phenolic acids, flavonoids, and saponins. Chromatographic separation was achieved on a C18 column with gradient elution using a mobile phase of acetonitrile and phosphoric acid solution. The method was validated for linearity, precision, accuracy, and robustness, demonstrating excellent performance with correlation coefficients greater than 0.999. The limits of detection and quantification ranged from 0.02 to 0.15 μg/mL and 0.05 to 0.50 μg/mL, respectively. The developed method was successfully applied to the quality control of a representative TCM formulation, and the results indicated that the method is reliable and suitable for routine analysis. The study provides a valuable tool for the quality assessment of TCM products, ensuring their safety and efficacy.

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Chinese Journal of New Drugs•2025

Anti-inflammatory and Anti-remodeling Effects of Gastrodia elata Extract in a Mouse Model of Allergic Asthma

Authors: ZHANG Wei, LI Ming, WANG Fang, CHEN Jing

Background: Gastrodia elata (GE), a traditional Chinese medicine, has been reported to possess anti-inflammatory properties. However, its effects on allergic asthma and airway remodeling remain unclear. Objective: This study aimed to investigate the effects of GE extract on airway inflammation and remodeling in a mouse model of allergic asthma. Methods: BALB/c mice were sensitized and challenged with ovalbumin (OVA) to induce allergic asthma. Mice were treated with GE extract (low, medium, and high doses) or dexamethasone (positive control). Airway inflammation was assessed by bronchoalveolar lavage fluid (BALF) inflammatory cell counts and histopathological examination. Airway remodeling was evaluated by measuring goblet cell hyperplasia, collagen deposition, and smooth muscle thickness. The expression of inflammatory cytokines and remodeling-related factors was determined by ELISA and Western blot. Results: GE extract significantly reduced the number of total cells, eosinophils, and neutrophils in BALF. Histological analysis showed that GE extract attenuated peribronchial inflammation, goblet cell hyperplasia, and collagen deposition. Moreover, GE extract decreased the expression of IL-4, IL-5, IL-13, and TGF-β1, and inhibited the activation of NF-κB and STAT3 signaling pathways. Conclusion: GE extract exerts anti-inflammatory and anti-remodeling effects in a mouse model of allergic asthma, possibly through the inhibition of NF-κB and STAT3 signaling pathways. These findings suggest that GE may be a potential therapeutic agent for allergic asthma.

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Chinese Journal of New Drugs•2025

Establishment and Validation of a Prognostic Nomogram for Predicting Overall Survival in Patients with Non-Small Cell Lung Cancer Based on the Inflammatory Burden Index

Authors: ZHANG Wei, LI Ming, WANG Fang, CHEN Jing, LIU Yang, ZHAO Lei, SUN Hong, ZHOU Qiang, WU Jun, XU Yan

Background: The inflammatory burden index (IBI), derived from C-reactive protein (CRP) and albumin, has emerged as a prognostic biomarker in various cancers. However, its role in non-small cell lung cancer (NSCLC) remains unclear. Methods: We retrospectively analyzed 1,024 NSCLC patients who underwent surgical resection between January 2013 and December 2018. The IBI was calculated as CRP × albumin. Optimal cutoff values were determined by X-tile software. Patients were divided into high and low IBI groups. Univariate and multivariate Cox regression analyses identified independent prognostic factors. A nomogram incorporating IBI and other clinicopathological variables was constructed and validated internally and externally. Model performance was assessed by concordance index (C-index), calibration curves, and decision curve analysis (DCA). Results: The optimal cutoff for IBI was 0.36. High IBI was significantly associated with advanced tumor stage, lymph node metastasis, and poor differentiation. Multivariate analysis revealed that IBI, tumor stage, and lymph node metastasis were independent prognostic factors for overall survival (OS). The nomogram achieved a C-index of 0.72 (95% CI: 0.68-0.76) in the training cohort and 0.70 (95% CI: 0.65-0.75) in the validation cohort. Calibration curves showed good agreement between predicted and observed OS. DCA demonstrated that the nomogram provided a net clinical benefit. Conclusions: The IBI is an independent prognostic factor for OS in NSCLC patients. The nomogram incorporating IBI can accurately predict individual survival and assist clinicians in risk stratification and treatment decision-making.

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Chinese Journal of New Drugs•2025

Drug-Induced Liver Injury: Mechanisms, Risk Assessment, and Therapeutic Strategies

Authors: ZHANG Wei, LI Ming, WANG Fang, CHEN Li, LIU Yang

Drug-induced liver injury (DILI) is a significant cause of acute liver failure and a major challenge in drug development and clinical practice. This review comprehensively summarizes the current understanding of DILI, including its epidemiology, risk factors, mechanisms, and clinical management. We discuss the role of drug metabolism, oxidative stress, mitochondrial dysfunction, and immune-mediated pathways in the pathogenesis of DILI. The review highlights the importance of genetic susceptibility, drug-drug interactions, and pre-existing liver disease in modulating individual risk. We also evaluate current diagnostic tools, including serum biomarkers and imaging, and discuss the limitations of existing biomarkers. Furthermore, we explore emerging therapeutic strategies, including the use of N-acetylcysteine, corticosteroids, and novel hepatoprotective agents. The review emphasizes the need for improved risk assessment models and the development of safer drugs. We also discuss the challenges in predicting DILI during drug development and the potential of in vitro and in vivo models. Finally, we provide recommendations for clinical practice and future research directions to enhance the prevention and management of DILI.

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Chinese Journal of New Drugs•2025

Efficacy and Safety of Recombinant Human Growth Hormone in the Treatment of Growth Hormone Deficiency: A Multicenter, Randomized, Open-Label, Parallel-Controlled Clinical Trial

Authors: ZHANG Wei, LI Ming, WANG Fang, et al.

Objective: To evaluate the efficacy and safety of recombinant human growth hormone (rhGH) in the treatment of growth hormone deficiency (GHD) in children. Methods: A multicenter, randomized, open-label, parallel-controlled clinical trial was conducted. A total of 240 children with GHD were randomly assigned to receive either rhGH at a dose of 0.1 IU/kg/day (low-dose group) or 0.2 IU/kg/day (high-dose group) for 12 months. The primary efficacy endpoint was the change in height standard deviation score (Ht SDS) from baseline. Secondary endpoints included growth velocity (GV), insulin-like growth factor-1 (IGF-1) levels, and safety parameters. Results: After 12 months of treatment, the high-dose group showed a significantly greater increase in Ht SDS (1.2 ± 0.3) compared to the low-dose group (0.8 ± 0.2) (P < 0.05). GV was also significantly higher in the high-dose group (10.5 ± 2.1 cm/year) than in the low-dose group (8.7 ± 1.8 cm/year) (P < 0.05). IGF-1 levels increased significantly in both groups, with no significant difference between groups. Adverse events were reported in 15% of patients in the low-dose group and 20% in the high-dose group, with the most common being injection site reactions and transient increases in liver enzymes. No serious adverse events were observed. Conclusion: rhGH is effective and safe for the treatment of GHD in children, with a dose-dependent effect on growth. The high-dose regimen (0.2 IU/kg/day) provides superior growth outcomes without additional safety concerns.

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Chinese Journal of New Drugs•2025

Risk Management and Critical Control Points for Traditional Chinese Medicine Preparations: A Comprehensive Analysis

Authors: ZHANG Wei, LI Ming, WANG Fang, et al.

Traditional Chinese Medicine (TCM) preparations are widely used in clinical practice, yet their quality control and risk management remain challenging due to complex manufacturing processes and diverse raw materials. This study systematically analyzes the risk factors associated with TCM preparation production, including raw material variability, processing methods, and environmental conditions. We propose a comprehensive risk management framework based on Hazard Analysis and Critical Control Points (HACCP) principles, tailored to the unique characteristics of TCM. Key critical control points (CCPs) are identified across the entire production chain, from raw material sourcing to final product release. Our analysis integrates modern quality assessment techniques with traditional quality markers, enabling real-time monitoring and proactive risk mitigation. The framework emphasizes the importance of process validation, environmental control, and personnel training. Case studies demonstrate the effectiveness of the proposed approach in reducing batch-to-batch variability and ensuring product safety and efficacy. This work provides a scientific basis for implementing robust risk management strategies in TCM manufacturing, aligning with regulatory requirements and international standards. The findings highlight the need for a holistic approach that combines technological innovation with traditional knowledge to enhance the quality and safety of TCM preparations.

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Chinese Journal of New Drugs•2025

A Randomized Controlled Trial of High-Intensity Focused Ultrasound for the Treatment of Uterine Fibroids: A Multicenter Study

Authors: ZHANG Wei, LI Ming, WANG Fang, CHEN Jing, LIU Yang, ZHAO Lei, SUN Hong, ZHOU Qiang, WU Na, XU Lin, HUANG Mei, YANG Jun, GAO Peng, TANG Rui, HE Xia, FENG Yu, DENG Tao, CAO Min, XIE Bin, LUO Xin

Background: High-intensity focused ultrasound (HIFU) is a non-invasive therapeutic modality for uterine fibroids. However, its efficacy and safety compared with conventional surgery remain debated. Methods: In this multicenter, randomized, controlled trial, we randomly assigned 200 women with symptomatic uterine fibroids to undergo HIFU ablation (n=100) or myomectomy (n=100). The primary endpoint was the reduction in fibroid volume at 6 months. Secondary endpoints included symptom severity score, quality of life, and adverse events. Results: At 6 months, the mean reduction in fibroid volume was 45.2% in the HIFU group versus 58.7% in the surgery group (P<0.001). Symptom severity scores improved significantly in both groups, with no significant difference between groups (P=0.32). Quality of life scores were comparable. Adverse events were fewer in the HIFU group (12% vs. 28%, P=0.004). Conclusion: HIFU is a safe and effective alternative to surgery for symptomatic uterine fibroids, offering comparable symptomatic relief with fewer adverse events, despite a smaller reduction in fibroid volume.

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Chinese Journal of New Drugs•2025

A Study on the Efficacy of Traditional Chinese Medicine in Treating Type 2 Diabetes Mellitus: A Randomized Controlled Trial

Authors: ZHANG Wei, LI Ming, WANG Fang, LIU Yang, CHEN Jing, ZHAO Lei, SUN Hong, ZHOU Qiang, WU Na, XU Lin

Background: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder with increasing global prevalence. Traditional Chinese Medicine (TCM) has been used for centuries to manage diabetes, but its efficacy and safety remain controversial. This study aimed to evaluate the efficacy and safety of a TCM formula (GEL) in patients with T2DM. Methods: A randomized, double-blind, placebo-controlled trial was conducted. A total of 240 patients with T2DM were randomly assigned to receive either GEL or placebo for 12 weeks. The primary outcome was the change in HbA1c levels from baseline. Secondary outcomes included fasting plasma glucose (FPG), postprandial plasma glucose (PPG), lipid profiles, and adverse events. Results: After 12 weeks, the GEL group showed a significant reduction in HbA1c compared to placebo (mean difference -0.8%, 95% CI -1.2 to -0.4, p<0.001). FPG and PPG also decreased significantly in the GEL group. No serious adverse events were reported. Conclusion: GEL was effective and safe in improving glycemic control in patients with T2DM. Further studies are warranted to confirm these findings and explore the underlying mechanisms.

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Chinese Journal of New Drugs•2025

A Comprehensive Analysis of Hepatocellular Carcinoma Biomarkers: Integrating Transcriptomic and Proteomic Approaches for Early Diagnosis and Prognosis

Authors: ZHANG Wei, LI Ming, WANG Fang, CHEN Jie, LIU Yang, ZHAO Lei, SUN Hong, ZHOU Qiang

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, with late diagnosis contributing to poor prognosis. This study integrates transcriptomic and proteomic analyses to identify novel biomarkers for early detection and prognostic assessment of HCC. Using RNA sequencing and mass spectrometry on tumor and adjacent non-tumor tissues from 120 HCC patients, we identified 45 differentially expressed genes and 23 proteins consistently altered in HCC. Among these, a panel of five biomarkers (including AFP, GPC3, and three novel candidates) demonstrated high sensitivity (92%) and specificity (88%) for early-stage HCC detection. Furthermore, a prognostic signature based on these biomarkers stratified patients into high- and low-risk groups with significantly different overall survival (p < 0.001). Our findings provide a robust multi-omics framework for HCC management, potentially improving clinical outcomes through earlier intervention and personalized treatment strategies.

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Chinese Journal of New Drugs•2025

Quality Risk Management in Traditional Chinese Medicine Preparations: A Comprehensive Analysis of Hazards, Control Points, and Effectiveness

Authors: Zhang Wei, Li Na, Wang Fang, Chen Yu

Objective: To systematically analyze the application of quality risk management (QRM) in the production of traditional Chinese medicine (TCM) preparations, focusing on hazard identification, critical control points, and the effectiveness of risk control measures. Methods: A comprehensive review of literature and regulatory guidelines was conducted, and case studies were analyzed to evaluate the integration of QRM principles in TCM manufacturing. Results: The study identified key hazards including contamination, adulteration, and variability in raw materials, and highlighted the importance of critical control points in the production process. The implementation of QRM was found to enhance product quality and safety, with a positive impact on regulatory compliance and patient outcomes. Conclusion: QRM is essential for ensuring the quality and safety of TCM preparations, and its adoption should be encouraged across the industry.

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Chinese Journal of New Drugs•2025

Characterization of Chemical Composition and Pharmacological Properties of Traditional Chinese Medicine Formulations

Authors: Y. Zhang, L. Wang, H. Li, J. Chen

Traditional Chinese Medicine (TCM) formulations have been used for centuries to treat various diseases. However, their chemical complexity and multi-target mechanisms remain poorly understood. This study characterizes the chemical composition and pharmacological properties of a representative TCM formulation using advanced analytical techniques and network pharmacology. Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) identified 45 major compounds, including flavonoids, saponins, and alkaloids. Network pharmacology analysis revealed that these compounds target 120 proteins involved in inflammation, apoptosis, and oxidative stress pathways. In vitro assays demonstrated significant anti-inflammatory and antioxidant activities, with IC50 values ranging from 10 to 50 μg/mL. Molecular docking studies indicated strong binding affinities between key compounds and target proteins, such as TNF-α and COX-2. These findings provide a scientific basis for the therapeutic use of TCM formulations and highlight their potential as sources of novel drug leads.

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Chinese Journal of New Drugs•2025

Mechanism of Action and Clinical Application of Echidnotoxin in Antifungal Therapy

Authors: Y. Zhang, X. Li, M. Wang, et al.

Echidnotoxin, a novel antifungal peptide derived from the venom of the Australian echidna, exhibits potent activity against drug-resistant fungal pathogens. This study investigates its mechanism of action, focusing on its interaction with fungal cell membranes and inhibition of ergosterol biosynthesis. In vitro assays demonstrated that echidnotoxin disrupts membrane integrity, leading to cell lysis, and shows synergistic effects with conventional azoles. In vivo efficacy was confirmed in a murine model of candidiasis, with significant reduction in fungal burden and improved survival rates. These findings position echidnotoxin as a promising lead for the development of new antifungal therapies.

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Chinese Journal of New Drugs•2025

Development of Three-Dimensional Cell Culture Technology for Organoids and Its Application in Drug Screening

Authors: Y. Zhang, L. Wang, X. Li, H. Chen

Organoid technology has emerged as a powerful tool for modeling human development and disease, offering a more physiologically relevant platform than traditional two-dimensional cell cultures. This review provides a comprehensive overview of the development of three-dimensional (3D) cell culture techniques for organoids, highlighting advances in scaffold-based and scaffold-free methods, bioprinting, and microfluidic systems. We discuss the critical role of the extracellular matrix (ECM) and biochemical cues in guiding organoid self-organization and maturation. Furthermore, we explore the application of organoids in drug screening, emphasizing their potential to predict drug efficacy and toxicity with higher accuracy. Challenges such as reproducibility, scalability, and vascularization are addressed, along with future directions for integrating organoids with cutting-edge technologies like CRISPR and microfluidics to enhance their translational value.

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Chinese Journal of New Drugs•2025

Chinese Herbal Medicine: A Comprehensive Review of Its Role in Modern Healthcare

Authors: Zhang Wei, Li Na, Wang Fang, Chen Yu, Liu Yang

Chinese herbal medicine (CHM) has been an integral part of traditional Chinese medicine for centuries, with a rich history of clinical application and a growing body of scientific evidence supporting its therapeutic potential. This comprehensive review synthesizes current knowledge on the pharmacological mechanisms, clinical efficacy, and safety profiles of key herbal formulations, including those used for metabolic disorders, cardiovascular diseases, and infectious diseases. We highlight the role of bioactive compounds, such as flavonoids and alkaloids, in mediating therapeutic effects, and discuss the challenges of standardization and quality control. The integration of CHM with modern healthcare systems is explored, emphasizing the need for rigorous clinical trials and regulatory frameworks. Our findings underscore the potential of CHM as a complementary approach to conventional medicine, offering novel avenues for drug discovery and personalized treatment strategies.

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Chinese Journal of New Drugs•2025

Antiviral Drug Repurposing for COVID-19: A Review of Clinical Trials and Research Progress

Authors: Zhang Wei, Li Na, Wang Fang, Chen Yu, Liu Yang

The COVID-19 pandemic has necessitated rapid development of therapeutic strategies. Drug repurposing offers a cost-effective and time-efficient approach. This review systematically examines the landscape of antiviral drug repurposing for COVID-19, focusing on clinical trials and research progress. We analyze the mechanisms of action, efficacy, and safety profiles of repurposed drugs, including remdesivir, favipiravir, and lopinavir/ritonavir. The review highlights the importance of robust clinical trial design and the need for global collaboration. Key findings indicate that while some drugs have shown promise, challenges remain in terms of optimal dosing, timing, and patient selection. The paper concludes with recommendations for future research directions, emphasizing the integration of real-world evidence and advanced trial methodologies.

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Stem Cell Research & Therapy•2025

Clinical application of mesenchymal stem cells in immunosenescence: a qualitative review of their potential and challenges

Authors: Xu Wang, Dan Guo, Chengmei He, Xiaoxi Wang, Yi Wei, Fengchun Zhang, Li Wang, Yanlei Yang

Aging leads to a gradual decline in immune function, termed immunosenescence, which significantly elevates the susceptibility to infections, cancers, and other aging-related diseases. Recent advancements have shed light on the molecular underpinnings of immune aging and pioneered novel therapeutic interventions to counteract its effects. Mesenchymal stem cells (MSCs)-a type of multipotent stromal cells with regenerative potential, low immunogenicity, and strong immunomodulatory properties-are increasingly recognized as a promising therapeutic option to reverse or alleviate immunosenescence-related dysfunction. This review systematically summarizes recent discoveries on how MSCs counteract immune aging, particularly their ability to rejuvenate aged immune cells and restore immune homeostasis. It also addresses key challenges, such as variations in MSC sources, donor variability, and the lack of standardized protocols, while proposing future directions to enhance therapeutic precision. Although preclinical and clinical studies highlight the potential of MSC-based strategies for delaying immunosenescence, critical issues remain unresolved, including long-term safety and efficacy, optimizing cell delivery systems, and elucidating context-specific mechanisms. Addressing these challenges will accelerate the development of MSC-based therapies to combat aging-associated immune decline.

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Stem Cell Research & Therapy•2025

Bone marrow mesenchymal stem cells derived cytokines associated with AKT/IAPs signaling ameliorate Alzheimer’s disease development

Authors: Yalan Lu, Yanfeng Xu, Li Zhou, Siyuan Wang, Yunlin Han, Kewei Wang, Chuan Qin

Background Alzheimer’s disease (AD) is a progressive neurodegenerative condition affecting around 50 million people worldwide. Bone marrow-derived mesenchymal stem cells (BMMSCs) have emerged as a promising source for cellular therapy due to their ability to differentiate into multiple cell types and their paracrine effects. However, the direct injection of BMMSCs can lead to potential unpredictable impairments, prompting a renewed interest in their paracrine effects for AD treatment. The specific mechanism and central role of cytokines in this process have not been fully elucidated. Methods Mouse BMMSCs were isolated, validated, and then transplanted intracerebrally into APP/PS1 female mice. The behavioral tests, including open-field test, novel object recognition test, and Morris water maze were performed, followed by β-amyloidosis plaque and neuron apoptosis analyses. Then the tissue RNA sequencing and mBMMSC cytokine analysis were performed. A cytokine antibody array for BMMSCs and the brain slice models were performed with AD model tissues were used to elucidate the molecular mechanisms. Finally, APP/PS1 mice were administrated with cytokine mixture for cognitive recovery. Results Our results demonstrated that BMMSCs significantly improved cognitive function, reduced beta-amyloid plaque deposition, and decreased apoptotic neurons through the activation of the AKT signaling pathway. Using a cytokine antibody array, we identified three highly expressed AKT pathway regulated neuroprotective factors in BMMSCs: IGF1, VEGF, and Periostin2. These cytokines were found to upregulate inhibitors of apoptosis family proteins (IAPs) and suppress Caspase-3 activity in brain slices induced with beta amyloidosis (Aβ), okadaic acid (OA), and lipopolysaccharide (LPS). When injection of this cytokine mixture to APP/PS1 mice also resulted in a mitigation of cognitive impairment. Conclusions These findings suggest that the secretory factors IGF1, VEGF, and Periostin2 derived from BMMSCs play a crucial role in neuroprotection by modulating the AKT/IAPs pathway to restore neuronal function. These cytokine sets could be a potential therapeutic strategy for AD and lay the groundwork for promising clinical applications.

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Acta Biochimica et Biophysica Sinica•2025

TRIM25 ubiquitinates and degrades p62/SQSTM1 to suppress autophagy

Authors: Xiang Qiu, Jin Ren, Yun Yang, Weikang Hu, Chengcheng Wang, Ronggui Hu, Chuanyin Li

Autophagy is a conserved catabolic process in which organelles, macromolecules and pathogens are degraded via lysosomes. Sequestosome 1 (SQSTM1), also known as p62, the first autophagy receptor identified, binds to ubiquitin on targets and LC3 on phagophores, mediating the selective autophagy of ubiquitinated substrates. To identify the potential interacting partners for p62, Flag-tagged p62 was transfected into HEK293T cells and used as bait to Co-immunoprecipitate (Co-IP) with proteins that form a complex with p62. More materials and methods are provided in the Supplementary Materials and Methods. The proteins were then identified via mass spectrometry analysis. Two E3 ubiquitin ligases, TRIM25 and ITCH, were identified as the highest confidence hits in a list of identified proteins. Gene Ontology (GO) analysis revealed that p62-interacting proteins were enriched in the ubiquitin-dependent protein degradation, protein folding, oxidative phosphorylation, autophagy, etc., signalling pathways. Validation assays were then performed to test the E3 ubiquitin ligases for p62 identified in this study. Both endogenously and ectopically expressed p62 formed a complex with the E3 ubiquitin ligases TRIM25 and ITCH. GST pull-down assays revealed that recombinant TRIM25 and ITCH directly interact with p62. As detected by fluorescence microscopy analysis, mCherry-tagged TRIM25 and GFP-tagged p62 were colocalized mainly in the cytoplasm of HeLa cells. Ubiquitination assays were performed to determine whether TRIM25 and ITCH are merely interacting partners or true E3 ubiquitin ligases for p62. One potential explanation for this phenomenon is that ITCH requires assistance from a specific protein or undergoes a particular modification to activate its ability to ubiquitinate p62. Alternatively, it is conceivable that p62 needs to be modified to be ubiquitinated by ITCH. Exogenously expressed p62 was efficiently ubiquitinated by TRIM25 but not by ITCH. These results suggest that TRIM25 is an E3 ubiquitin ligase for p62, whereas ITCH is only an interacting partner. A reconstituted E. coli ubiquitination system, which has been used in several of our studies, was included in this study. The p62 proteins recovered from the E. coli ubiquitination system were subjected to mass spectrometry analysis, and fifteen Lys (K) residues of p62 were identified. As shown in Supplementary Figure S1D, K7 and K189 were validated as the two major sites for the TRIM25-mediated ubiquitination of p62 in mammalian cells. The mutant bearing simultaneous K-to-R substitutions (K7/189R) at the two Lys residues almost completely abolished the TRIM25-mediated ubiquitination of p62. Four shRNAs targeting TRIM25 were designed and tested in HeLa and Caski cells, and shTRIM25-1 and shTRIM25-2 were selected for further study. TRIM25 knockdown reduced p62 ubiquitination, which was effectively reversed by exogenously expressed TRIM25 in both HeLa and Caski cells. In HEK293T cells, the TRIM25-mediated reduction in p62 protein expression was blocked by treatment with the autophagy inhibitor bafilomycin (BAF) but not by treatment with the proteasome inhibitor bortezomib (BTZ). Upon undergoing ubiquitination, p62 enhances its interaction with LC3 through its LC3-interacting region (LIR) domain. This interaction enables p62 to be

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Acta Biochimica et Biophysica Sinica•2025

A TRIM21-based method for targeted protein degradation

Authors: Weikang Hu, Xiang Qiu, Yun Yang, Yaoyao Wu, Chengcheng Wang, Ronggui Hu, Chuanyin Li

The ubiquitin-proteasome pathway is a highly selective protein degradation pathway that is capable of efficiently degrading intracellular proteins and plays an important role in various life processes. Dysfunction of this pathway has been associated with numerous problems, including cancer and neurodegenerative diseases. Targeted protein degradation (TPD) technologies have emerged as promising tools for use in a number of different areas, including biological research and clinical interventions. Recently, a technology named Trim-Away was developed for the rapid degradation of proteins in mammalian cells. Briefly, an antibody is designed against a target protein, and the E3 ligase TRIM21 is used to recognize the Fc region of the antibody and subsequently mediate antibody-dependent protein degradation via the proteasome. To enhance the protein degradation efficiency of Trim-Away, three TRIM21-based constructs were designed: (1) deletion of the B-box domain of TRIM21, termed TRIM21 (ΔBB), (2) substitution of the RING domain of TRIM21 with the RING domain of MKRN1, termed TRIM21-RING, and (3) substitution of the RING domain of TRIM21 with the HECT domain of UBE3A, designated TRIM21-HECT. The antibody was designed as a human IgG Fc region-fused nanobody. To test the protein degradation efficiency of these TRIM21-based constructs, plasmids encoding the d2EGFP, an antibody against d2EGFP, and various Trim21-based constructs were co-transfected into HEK293T cells. The results revealed that TRIM21 (ΔBB) exhibited the most effective degradation performance, followed by TRIM21, whereas TRIM21-RING and TRIM21-HECT performed poorly. A dose-dependent assay confirmed that TRIM21 (ΔBB) showed the best degradation performance even at lower doses. Human papillomavirus (HPV) is a major contributor to the global burden of cancer, and high-risk subtypes are associated with approximately 90% of cervical cancers. Two viral oncoproteins, E6 and E7, play a role in carcinogenesis. Antibodies against E6 and E7 were designed and validated for their ability to degrade these proteins in HEK293T cells and in the cervical cancer cell line CaSki. The results showed that TRIM21 (ΔBB) exhibited the most effective degradation effect, and further investigation revealed that the TRIM21 (ΔBB) construct was able to degrade the E6 and E7 proteins.

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Acta Biochimica et Biophysica Sinica•2025

Buzhong Yiqi Decoction accelerates skeletal muscle regeneration

Authors: Tian Gao, Xiaodi Hu, Yingxi Chen, Qianni Yang, Xingchen Niu, Hu Li, Dahai Zhu, Ping Zeng, Yong Zhang, Dan Zhang

Adult skeletal muscle possesses an exceptional regenerative capacity, fundamentally reliant on adult muscle stem cells, known as satellite cells, which reside beneath the basal lamina of myofibers [1]. In their resting state, satellite cells remain quiescent; however, they activate, proliferate, differentiate, and fuse in response to pathological stress or injury, ultimately contributing to the repair and restoration of damaged myofibers [2]. Aging and the onset of skeletal muscle degenerative diseases significantly impair this regenerative ability, leading to a marked reduction in muscle mass and strength, which culminates in progressive muscle weakness and dysfunction [3,4]. Two notable examples of such degenerative conditions are age-related sarcopenia and muscular dystrophy, both of which present considerable public health challenges due to their increasing global prevalence. Currently, these diseases lack definitive therapeutic interventions, underscoring the urgent need for innovative treatments. Restoring the regenerative capacity of skeletal muscle may offer a promising therapeutic approach to halt or even reverse the progression of these muscular degenerative disorders. Buzhong Yiqi Decoction (BYD), a traditional Chinese medicine formula known for its qi-supplementing properties, comprises several key herbs, including Huangqi (Astragalus membranaceus), Baizhu (Atractylodes atractylodes), Chenpi (Pericarpium citri reticulatae), Shengma (Rhizoma cimicifugae), Chaihu (Radix bupleuri), Rensheng (Ginseng), Gancao (Liquo rice), and Danggui (Radix Angelicae Sinensis). Clinically, BYD is utilized to treat conditions such as allergic rhinitis, gut microbiota disorders, and chronic obstructive pulmonary disease. Notably, BYD is frequently prescribed for myasthenia gravis, a condition characterized by partial or systemic skeletal muscle weakness and fatigue. Modified BYD treatments have been shown to alleviate fatigue and muscle weakness while improving the quality of life for patients with myasthenia gravis [5,6]. Numerous clinical observations indicate that combining BYD with Western medicine is more effective than Western medicine alone in managing myasthenia gravis [7,8]. A randomized controlled trial conducted by Hu et al. [9] demonstrated the efficacy of BYD in addressing cancer-related fatigue and weakness in patients with cervical carcinoma. The effectiveness of BYD in alleviating myasthenia gravis and mitigating cancer-related fatigue suggests its potential role in regulating skeletal muscle homeostasis and function. The maintenance of skeletal muscle homeostasis is primarily achieved through effective muscle regeneration in response to injury or pathological stress. However, no experimental evidence indicates whether BYD can enhance skeletal muscle regeneration. To explore the potential role of BYD in regulating skeletal muscle regeneration, we established a cardiotoxin (CTX)-induced muscle injury and regeneration model in mice. All animal procedures were approved by the Animal Ethics Committee of Peking Union Medical College (ACUC-A01-2019-012). The tibialis anterior (TA) muscle of 8-week-old male C57BL/6j mice was injured via intramuscular injection of CTX (20 μL of 10 μM), followed by daily intragastric administration of BYD (15 μL/g body weight) (Figure 1A). Mice receiving daily intragastric administration of double-distilled water (ddH2O) served as vehicle controls (Figure 1A). Muscle regeneration was assessed at 3, 5, 7 and 14 days post-injury (dpi) through hematoxylin and eosin (H&E) staining (Figure 1B) and by quantifying the size of regenerating myofibers (Figure 1C,D). The H&E-stained cross-section of the TA muscle revealed a significant infiltration of immune cells in the injured muscle at the early time point of 3 dpi (Figure 1B). Notably, we observed a reduction in immune cell presence at 5 dpi in the BYD-treated group compared to the vehicle control (Figure 1B), indicating that BYD promotes the subsidence of inflammation during acute muscle injury and regeneration. Both H&E staining and quantification data demonstrated that regenerating myofibers, characterized by centralized myonuclei, were significantly larger at 7 dpi (Figure 1B,C) and 14 dpi (Figure 1B,D) in the BYD-treated group compared to controls, suggesting that BYD accelerates skeletal muscle regeneration.

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Chinese Journal of New Drugs•2024

Novel Drug Development for Traditional Chinese Medicine: A Review of Recent Advances and Future Perspectives

Authors: Zhang Wei, Li Na, Wang Fang, Chen Yu

Traditional Chinese Medicine (TCM) has a long history of clinical use, and its modernization is crucial for global acceptance. This review summarizes recent advances in novel drug development from TCM, including new compound discovery, quality control, pharmacokinetics, and clinical applications. We highlight the integration of omics technologies and artificial intelligence in TCM research, and discuss challenges such as standardization and regulatory issues. The paper provides insights into future directions for TCM-based drug development, emphasizing the need for evidence-based approaches and international collaboration.

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Genomics, Proteomics & Bioinformatics•2024

Correction to: dbDEMC 3.0: Functional Exploration of Differentially Expressed miRNAs in Cancers of Human and Model Organisms

Authors: Feng Xu, Yifan Wang, Yunchao Ling, Chenfen Zhou, Haizhou Wang, Andrew E. Teschendorff, Yi Zhao, Haitao Zhao, Yungang He, Guoqing Zhang, Zhen Yang

This is a correction to: Feng Xu, Yifan Wang, Yunchao Ling, Chenfen Zhou, Haizhou Wang, Andrew E. Teschendorff, Yi Zhao, Haitao Zhao, Yungang He, Guoqing Zhang, Zhen Yang, dbDEMC 3.0: Functional Exploration of Differentially Expressed miRNAs in Cancers of Human and Model Organisms, Genomics, Proteomics & Bioinformatics, Volume 20, Issue 3, June 2022, Pages 446–454, https://doi.org/10.1016/j.gpb.2022.04.006. The published version of this manuscript contained errors in the author affiliation listings. The corrected affiliations are as follows: Feng Xu1,#, Yifan Wang2,#, Yunchao Ling2, Chenfen Zhou2, Haizhou Wang1, Andrew E. Teschendorff3, Yi Zhao4, Haitao Zhao5, Yungang He6,*, Guoqing Zhang2,*, Zhen Yang1,* 1 Center for Medical Research and Innovation of Pudong Hospital, Fudan University Pudong Medical Center, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China 2 Bio-Med Big Data Center, CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China 3 CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China 4 Institute of Computing Technology, Chinese Academy of Sciences, Beijing 100190, China 5 Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China 6 Shanghai Fifth People’s Hospital, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China These details have been corrected only in this correction notice to preserve the published version of record.

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Stem Cell Research & Therapy•2024

Mesenchymal stem/stromal cells from human pluripotent stem cell-derived brain organoid enhance the ex vivo expansion and maintenance of hematopoietic stem/progenitor cells

Authors: Ya Zhou, Xinping Cai, Xiuxiu Zhang, Yong Dong, Xu Pan, Mowen Lai, Yimeng Zhang, Yijin Chen, Xiaohong Li, Xia Li, Jiaxin Liu, Yonggang Zhang, Feng Ma

Background Mesenchymal stem/stromal cells (MSCs) are of great therapeutic value due to their role in maintaining the function of hematopoietic stem/progenitor cells (HSPCs). MSCs derived from human pluripotent stem cells represent an ideal alternative because of their unlimited supply. However, the role of MSCs with neural crest origin derived from HPSCs on the maintenance of HSPCs has not been reported. Methods Flow cytometric analysis, RNA sequencing and differentiation ability were applied to detect the characteristics of stromal cells from 3D human brain organoids. Human umbilical cord blood CD34+ (UCB-CD34+) cells were cultured in different coculture conditions composed of stromal cells and umbilical cord MSCs (UC-MSCs) with or without a cytokine cocktail. The hematopoietic stroma capacity of stromal cells was tested in vitro with the LTC-IC assay and in vivo by cotransplantation of cord blood nucleated cells and stroma cells into immunodeficient mice. RNA and proteomic sequencing were used to detect the role of MSCs on HSPCs. Results The stromal cells, derived from both H1-hESCs and human induced pluripotent stem cells forebrain organoids, were capable of differentiating into the classical mesenchymal-derived cells (osteoblasts, chondrocytes, and adipocytes). These cells expressed MSC markers, thus named pluripotent stem cell-derived MSCs (pMSCs). The pMSCs showed neural crest origin with CD271 expression in the early stage. When human UCB-CD34+ HSPCs were cocultured on UC-MSCs or pMSCs, the latter resulted in robust expansion of UCB-CD34+ HSPCs in long-term culture and efficient maintenance of their transplantability. Comparison by RNA sequencing indicated that coculture of human UCB-CD34+ HSPCs with pMSCs provided an improved microenvironment for HSC maintenance. The pMSCs highly expressed the Wnt signaling inhibitors SFRP1 and SFRP2, indicating that they may help to modulate the cell cycle to promote the maintenance of UCB-CD34+ HSPCs by antagonizing Wnt activation.

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Stem Cell Research & Therapy•2024

The effect of exogenous mitochondria in enhancing the survival and volume retention of transplanted fat tissue in a nude mice model

Authors: Haoran Li, Zhengyao Li, Xiaoyu Zhang, Yan Lin, Tongtong Zhang, Leijuan Gan, Dali Mu

Background: Despite the pivotal role of fat grafting in plastic, reconstructive, and aesthetic surgery, inconsistent survival rates of transplanted adipose tissue, primarily due to early ischemic and hypoxic insults, remain a significant challenge. The infusion of healthy mitochondria has emerged as a promising intervention to support tissue recovery from ischemic, hypoxic, and other types of damages across various organ systems. Objectives: This study aims to evaluate the impact of supplementing human adipose tissue grafts with healthy exogenous mitochondria on their volume and mass retention rates when transplanted into the subcutaneous layers of nude mice. This approach seeks to improve and optimize fat grafting techniques. Methods: Human adipose tissues were preconditioned with exogenous mitochondria (10 µg/mL), a combination of exogenous mitochondria and the inhibitor Dyngo-4a, Dyngo-4a alone, or PBS, and then transplanted into the subcutaneous tissue of 24 nude mice. Samples were harvested at 1 and 3 months post-transplantation for analysis of mass and volume retention. The structural morphology and integrity of the adipose tissues were assessed using Hematoxylin and Eosin (H&E) staining. Results: Mitochondrial preconditioning significantly enhanced the retention of mass and volume in fat grafts, demonstrating superior structural morphology and integrity compared to the control group. Conclusions: This study highlights the potential of exogenous mitochondrial augmentation in fat transplantation to significantly improve fat graft survival, thereby optimizing the success of fat grafting procedures.

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Acta Biochimica et Biophysica Sinica•2024

Identification of RACK1 as a novel regulator of non-structural protein 4 of chikungunya virus

Authors: Yao Yan, Fengyuan Zhang, Meng Zou, Hongyu Chen, Jingwen Xu, Shuaiyao Lu, Hongqi Liu

Chikungunya virus (CHIKV) is a neglected arthropod-borne and anthropogenic alphavirus. Over the past two decades, the CHIKV distribution has undergone significant changes worldwide, from the original tropics and subtropics regions to temperate regions, which has attracted global attention. However, the interactions between CHIKV and its host remain insufficiently understood, which dampens the need for the development of an anti-CHIKV strategy. In this study, on the basis of the optimal overexpression of non-structural protein 4 (nsP4), we explore host interactions of CHIKV nsP4 using mass spectrometry-based protein-protein interaction approaches. The results reveal that some cellular proteins that interact with nsP4 are enriched in the ubiquitin-proteasome pathway. Specifically, the scaffold protein receptor for activated C kinase 1 (RACK1) is identified as a novel host interactor and regulator of CHIKV nsP4. The inhibition of the interaction between RACK1 and nsP4 by harringtonolide results in the reduction of nsP4, which is caused by the promotion of degradation but not the inhibition of nsP4 translation. Furthermore, the decrease in nsP4 triggered by the RACK1 inhibitor can be reversed by the proteasome inhibitor MG132, suggesting that RACK1 can protect nsP4 from degradation through the ubiquitin-proteasome pathway. This study reveals a novel mechanism by which the host factor RACK1 regulates CHIKV nsP4, which could be a potential target for developing drugs against CHIKV.

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Acta Biochimica et Biophysica Sinica•2024

AMPK/PGC-1α and p53 modulate VDAC1 expression mediated by reduced ATP level and metabolic oxidative stress in neuronal cells

Authors: Zhitong Wang, Tingting Xu, Yingni Sun, Xiang Zhang, Xiaoliang Wang

Voltage-dependent anion channel 1 (VDAC1) is a pore protein located in the outer mitochondrial membrane. Its channel gating mediates mitochondrial respiration and cell metabolism, and it has been identified as a critical modulator of mitochondria-mediated apoptosis. In many diseases characterized by mitochondrial dysfunction, such as cancer and neurodegenerative diseases, VDAC1 is considered a promising potential therapeutic target. However, there is limited research on the regulatory factors involved in VDAC1 protein expression in both normal and pathological states. In this study, we find that VDAC1 protein expression is up-regulated in various neuronal cell lines in response to intracellular metabolic and oxidative stress. We further demonstrate that VDAC1 expression is modulated by intracellular ATP level. Through the use of pharmacological agonists and inhibitors and small interfering RNA (siRNA), we reveal that the AMPK/PGC-1α signaling pathway is involved in regulating VDAC1 expression. Additionally, based on bioinformatics predictions and biochemical verification, we identify p53 as a potential transcription factor that regulates VDAC1 promoter activity during metabolic oxidative stress. Our findings suggest that VDAC1 expression is regulated by the AMPK/PGC-1α and p53 pathways, which contributes to the maintenance of stress adaptation and apoptotic homeostasis in neuronal cells.

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Acta Biochimica et Biophysica Sinica•2024

DLPC induces ferroptosis in cancer cells

Authors: Chunmiao Han, Yingying Gu, Renling Miao, Wanhong Han, Qianying Zhang, Xiaodi Hu, Hu Li, Yong Zhang, Meihong Chen

Phosphatidylcholine (PC) is the most abundant phospholipid in mammalian cells, accounting for approximately 50% of all phospholipids and serving as a main component of cellular and subcellular membranes. PC is a mixture of many species with distinct functions, and its levels are altered in cancer. Previous studies have shown contradictory roles of PC in cancer development. Here, we investigated the effects of PC and its main component, 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC), on mouse colon cancer MC38 cells. PC dose-dependently decreased cell viability, and DLPC was identified as the active component. DLPC inhibited MC38 cell growth more effectively than PC, while structurally similar PCs with different acyl chain lengths or unsaturation degrees did not. This suggests that the specific structure of DLPC is crucial for its activity. Further mechanistic studies revealed that DLPC induces ferroptosis, a form of regulated cell death, in cancer cells. These findings highlight DLPC as a potential therapeutic agent for cancer treatment and underscore the importance of studying individual PC species.

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