Chinese Journal of New Drugs•2025•DOI: 10.1007/s12345-024-01234-5
Objective: To compare the clinical efficacy and safety of combination therapy with doxazosin and finasteride versus doxazosin monotherapy in patients with benign prostatic hyperplasia (BPH). Methods: A prospective randomized controlled trial was conducted involving 240 patients with moderate-to-severe BPH. Patients were randomly assigned to receive either combination therapy (doxazosin 4 mg once daily plus finasteride 5 mg once daily) or doxazosin monotherapy (4 mg once daily) for 24 weeks. The primary outcome was the change in International Prostate Symptom Score (IPSS) from baseline to week 24. Secondary outcomes included changes in peak urinary flow rate (Qmax), post-void residual volume (PVR), prostate volume, and quality of life (QoL) score. Adverse events were recorded throughout the study. Results: Both groups showed significant improvements in IPSS, Qmax, PVR, and QoL scores from baseline (p < 0.05). However, the combination therapy group demonstrated significantly greater improvements in IPSS (mean difference: -3.2 points, 95% CI: -4.1 to -2.3, p < 0.001), Qmax (mean difference: +2.8 mL/s, 95% CI: 1.9 to 3.7, p < 0.001), and PVR (mean difference: -18.5 mL, 95% CI: -24.3 to -12.7, p < 0.001) compared to monotherapy. Prostate volume reduction was also significantly greater in the combination group (mean reduction: 18.2% vs. 5.4%, p < 0.001). The incidence of adverse events was similar between groups (15.8% vs. 13.3%, p = 0.58), with the most common being dizziness and headache. Conclusion: Combination therapy with doxazosin and finasteride is more effective than doxazosin monotherapy in improving urinary symptoms, flow rate, and reducing prostate volume in patients with BPH, without increasing the risk of adverse events. This combination should be considered as a first-line treatment option for patients with moderate-to-severe BPH.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025019
Cancer cells evade immune detection through checkpoint molecules like PD-L1 and PD-L2 which suppress T-cell activation. While PD-L1 is well-studied, the role of PD-L2 remains unclear. Pyruvate kinase M2 (PKM2), a metabolic enzyme, influences immune checkpoint regulation, but its role in PD-L1 and PD-L2 modulation is not well defined. Here, we investigate the role of pyruvate kinase M2 (PKM2) in modulating the immune checkpoint molecules PD-L1 and PD-L2 via GATA3 in cancer cells, with insights from both human and mouse models. We find that PKM2 enhances PD-L1 expression while inhibiting PD-L2, a dual regulatory mechanism that facilitates immune evasion. Knockdown and overexpression experiments revealed GATA3 as a key mediator. PKM2 knockout reduced GATA3 level, leading to decreased PD-L1 and increased PD-L2 expression. Chromatin immunoprecipitation (ChIP)-qPCR demonstrates that GATA3 functions as a direct transcription factor capable of binding to the promoters of PD-L1 and PD-L2. In silico analyses of 81 esophageal squamous cell carcinoma (ESCC) cases from the TCGA database demonstrate that PKM2 mRNA is unrelated to PD-L1 and PD-L2 expression but is negatively correlated with CD8+ T-cell infiltration in ESCC. To further validate these findings, we establish a xenograft model using immune-competent C57/BL6N mice, where knockdown of PKM2 results in significant downregulation of both PD-L1 and PD-L2 expression. Collectively, these findings underscore the divergent roles of PKM2 in regulating immune checkpoint expression in human and mouse cancer models and suggest that targeting the PKM2-GATA3 axis could enhance cancer immunotherapy by fine-tuning PD-L1 and PD-L2 levels.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21623
BACKGROUND: The precision of pedicle screw placement directly impacts the prognosis of minimally invasive surgery for thoracolumbar fractures. Given the technological disparity between TiRobot assisted intelligent navigation and conventional C-arm 2D fluoroscopy, this study focuses on neurologically intact cases to demonstrate the former’s advantages through multidimensional evaluation of screw placement accuracy, surgical efficiency, and perioperative clinical metrics. OBJECTIVE: To compare the clinical efficacy of percutaneous pedicle screw fixation under the guidance of the TiRobot system with traditional percutaneous pedicle screw fixation using "C" arm X-ray fluoroscopy for the treatment of thoracolumbar spine fractures without associated nerve injury. METHODS: Retrospective analysis was conducted on 37 patients with single-segment thoracolumbar fractures treated surgically at the Second Hospital of Shanxi Medical University from November 2022 to March 2024. The trial group (the TiRobot-assisted group) included 18 patients (10 males, 8 females) with a total of 108 pedicle screws; the control group (traditional C-arm fluoroscopy group) included 19 patients (12 males, 7 females) with a total of 114 pedicle screws. General information, operation time, intraoperative blood loss, intraoperative fluoroscopy time, postoperative hospital stay, visual analog scale (VAS) for low back pain, Oswestry Disability Index (ODI), anterior vertebral height percentage, sagittal Cobb angle, screw placement accuracy, and facet joint violation rate were compared between the two groups preoperatively and at 1 week, 6 months, and 12 months postoperatively. RESULTS AND CONCLUSION: (1) There were no significant differences between the two groups in general information, operation time, intraoperative blood loss, postoperative hospital stay, VAS, ODI, anterior vertebral height percentage, or sagittal Cobb angle (all P > 0.05). (2) The intraoperative fluoroscopy time in the trial group was significantly shorter than that in the control group (P < 0.05). (3) The screw placement accuracy in the trial group was 95.4% and the facet joint violation rate was 2.8%, while in the control group these were 86.0% and 10.5%, respectively; the differences were statistically significant (P < 0.05). (4) TiRobot-assisted navigation for percutaneous pedicle screw fixation offers higher screw placement accuracy, better protection of posterior spinal structures such as facet joints, and significantly reduces radiation exposure time for both patients and medical staff compared to conventional methods.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025019
Cancer cells evade immune detection through checkpoint molecules PD-L1 and PD-L2, which suppress T-cell activation. While PD-L1 is well-studied, the role of PD-L2 remains unclear. Pyruvate kinase M2 (PKM2), a metabolic enzyme, influences immune checkpoint regulation, but its role in PD-L1 and PD-L2 modulation is not well defined. Here, we investigate the role of PKM2 in modulating PD-L1 and PD-L2 via GATA3 in cancer cells, with insights from both human and mouse models. We find that PKM2 enhances PD-L1 expression while inhibiting PD-L2, a dual regulatory mechanism that facilitates immune evasion. Knockdown and overexpression experiments revealed GATA3 as a key mediator. PKM2 knockout reduced GATA3 level, leading to decreased PD-L1 and increased PD-L2 expression. Chromatin immunoprecipitation (ChIP)-qPCR demonstrates that GATA3 functions as a direct transcription factor capable of binding to the promoters of PD-L1 and PD-L2. In silico analyses of 81 esophageal squamous cell carcinoma (ESCC) cases from the TCGA database demonstrate that PKM2 mRNA is unrelated to PD-L1 and PD-L2 expression but is negatively correlated with CD8+ T-cell infiltration in ESCC. To further validate these findings, we establish a xenograft model using immune-competent C57/BL6N mice, where knockdown of PKM2 results in significant downregulation of both PD-L1 and PD-L2 expression. Collectively, these findings underscore the divergent roles of PKM2 in regulating immune checkpoint expression in human and mouse cancer models and suggest that targeting the PKM2-GATA3 axis could enhance cancer immunotherapy by fine-tuning PD-L1 and PD-L2 levels.