Prognostic role of different PD-L1 expression patterns and tumor-infiltrating lymphocytes in high-grade serous ovarian cancer: a systematic review and meta-analysis.

Background: The prognostic value of programmed cell death ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs) in high-grade serous ovarian cancer (HGSOC) remains a controversial topic in the research field. To comprehensively assess the importance of PD-L1 and TILs in this particular subtype of ovarian cancer, we performed a meta-analysis. Methods: We conducted a comprehensive search of PubMed, Embase, Scopus, Web of Science, and Cochrane Library databases up to December 25, 2022. The association between PD-L1, TILs, and survival outcomes was evaluated using the combined hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs). Results: This meta-analysis comprised 11 trials involving a total of 1746 cases. The results revealed no significant association between PD-L1 expression in tumor cells (TCs) and overall survival (OS, HR = 0.76, 95% CI: 0.52-1.09, p = 0.136) or progression-free survival (PFS, HR = 0.71, 95% CI: 0.4 -1.24, p = 0.230). Nevertheless, a correlation was observed between PD-L1 expression in immune cells (ICs) and OS (HR = 0.73, 95% CI: 0.55-0.97, p = 0.031). Furthermore, the presence of CD8+ and PD-1+ TILs was found to significantly enhance OS (HR = 0.70, 95% CI = 0.55-0.87, p = 0.002; HR = 0.57, 95% CI = 0.40-0.80, p = 0.001, respectively) and PFS (HR = 0.62, 95% CI = 0.41-0.92, p = 0.019; HR = 0.52, 95% CI = 0.35-0.78, p = 0.002, respectively), whereas the presence of CD3+ and CD4+ TILs was positively associated with OS (HR = 0.50, 95% CI = 0.29-0.87, p = 0.014; HR = 0.55, 95% CI = 0.34-0.91, p = 0.020, respectively). Conclusion: This study indicates a positive correlation between ICs-derived PD-L1 and survival, while no significant correlation was observed between TCs-derived PD-L1 and prognosis. These results highlight the importance of studying PD-L1 expression in ICs as a prognostic predictor. In addition, the presence of TILs was found to significantly improve patient survival, suggesting that TILs may be a valuable prognostic biomarker. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022366411.

Direct and indirect effects of pathogenic bacteria on the integrity of intestinal barrier.

Bacterial translocation is a pathological process involving migration of pathogenic bacteria across the intestinal barrier to enter the systemic circulation and gain access to distant organs. This phenomenon has been linked to a diverse range of diseases including inflammatory bowel disease, pancreatitis, and cancer. The intestinal barrier is an innate structure that maintains intestinal homeostasis. Pathogenic infections and dysbiosis can disrupt the integrity of the intestinal barrier, increasing its permeability, and thereby facilitating pathogen translocation. As translocation represents an essential step in pathogenesis, a clear understanding of how barrier integrity is disrupted and how this disruption facilitates bacterial translocation could identify new routes to effective prophylaxis and therapy. In this comprehensive review, we provide an in-depth analysis of bacterial translocation and intestinal barrier function. We discuss currently understood mechanisms of bacterial-enterocyte interactions, with a focus on tight junctions and endocytosis. We also discuss the emerging concept of bidirectional communication between the intestinal microbiota and other body systems. The intestinal tract has established 'axes' with various organs. Among our regulatory systems, the nervous, immune, and endocrine systems have been shown to play pivotal roles in barrier regulation. A mechanistic understanding of intestinal barrier regulation is crucial for the development of personalized management strategies for patients with bacterial translocation-related disorders. Advancing our knowledge of barrier regulation will pave the way for future research in this field and novel clinical intervention strategies.

LASP1 Induces Epithelial-Mesenchymal Transition in Lung Cancer through the TGF-ß1/Smad/Snail Pathway.

Background: LIM and SH3 domain protein 1 (LASP1), highly expressed in a variety of tumors, is considered as a novel tumor metastasis biomarker. However, it is unknown which signaling pathway works and how the signal transduces into cell nucleus to drive tumor progression by LASP1. The aim of this study is to explore the essential role of LASP1 in TGF-ß1-induced epithelial-mesenchymal transition (EMT) in lung cancer cells. Methods: The gene and protein levels of LASP-1 were successfully silenced or overexpressed by LASP-1 shRNA lentivirus or pcDNA in TGF-ß1-treated lung cancer cell lines, respectively. Then, the cells were developed EMT by TGF-ß1. The cell abilities of invasion, migration, and proliferation were measured using Transwell invasion assay, wound healing assay, and MTT assay, respectively. Western blotting was used to observe the protein levels of EMT-associated molecules, including N-cadherin, vimentin, and E-cadherin, and the key molecules in the TGF-ß1/Smad/Snail signaling pathway, including pSmad2 and Smad2, pSmad3 and Smad3, and Smad7 in cell lysates, as well as Snail1, pSmad2, and pSmad3 in the nucleus. Results: TGF-ß1 induced higher LASP1 expression. LASP1 silence and overexpression blunted or promoted cell invasion, migration, and proliferation upon TGF-ß1 stimulation. LASP1 also regulated the expression of vimentin, N-cadherin, and E-cadherin in TGF-ß1-treated cells. Activity of key Smad proteins (pSmad2 and pSmad3) and protein level of Smad7 were markedly regulated through LASP1. Furthermore, LASP1 affected the nuclear localizations of pSmad2, pSmad3, and Snail1. Conclusion: This study reveals that LASP1 regulates the TGF-ß1/Smad/Snail signaling pathway and EMT markers and features, involving in key signal molecules and their nuclear levels. Therefore, LASP1 might be a drug target in lung cancer.

A comparative study of thoracoscopic sympathectomy for the treatment of hand sweating.

BACKGROUND: To compare postoperative satisfaction, compensatory hyperhidrosis, and the quality of life between thoracoscopic T3 and T4 sympathectomy for the treatment of hand sweating. METHODS: From December 2010 to October 2014, 192 consecutive patients with hand sweating underwent a thoracoscopic bilateral sympathectomy with different planes (T3/T4). The patients were randomly divided into two groups, the T3 and the T4 groups, for those who underwent thoracoscopic T3 and T4 sympathectomy, respectively. All patients underwent double-lumen intubation during the thoracoscopic bilateral sympathectomy. The patients were followed up with by telephone for postoperative evaluation on the safety and effectiveness of the procedure, and the two groups (T3 versus T4) were compared to each other for any potential differences. RESULTS: All of the patients' sweating symptoms improved after the procedure. The incidence of compensatory hyperhidrosis and palm dryness in the T4 group was lower than that in the T3 group (P<0.05). The satisfaction rate and the rate of improvement in sweating and the incidence of palm moisture in the T4 group were higher than those in the T3 group (P<0.05). CONCLUSIONS: Thoracoscopic T3 and T4 sympathectomy are safe and effective methods for the treatment of hand sweating. Lowering the sympathetic chain resection plane can increase patients' satisfaction and enhance improvements in sweating. It can also reduce the incidence of long-term compensatory hyperhidrosis and palm dryness, but it also increases the incidence of palm moisture.