Previous studieshave reported the prognostic value of neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), and systemic immune-inflammation index (SII). However, the prognostic performance of these indices in patients with testicular lymphoma has not yet been studied. This study was to systematically evaluate the role of NLR, PLR, LMR, and SII in predicting survival for patients with testicular diffuse large B-cell lymphoma.Methods: In this study, 28 patients with testicular diffuse large B-cell lymphoma were enrolled. We performed univariate and multivariate analyses to assess associations of indices incorporating blood cell counts with progression-free survival (PFS) and overall survival (OS). Results:The results of univariate analysis revealed that International Prognostic Index (IPI) score (p = 0.010, p = 0.034, respectively), NLR (p = 0.003, p = 0.025, respectively), and LMR (p = 0.004, p = 0.010, respectively) were significantly associated with PFS and OS. Lactic dehydrogenase (LDH) (p = 0.017), absolute neutrophil counts (p = 0.018), absolute monocyte counts (p = 0.001), and SII (p = 0.005) were significantly associated with the risk of disease progression, while ECOG performance status (p = 0.016) was shown to be related to the risk of death. In the multivariate analysis, NLR (HR 9.069, p = 0.001) and absolute monocyte counts (HR 37.076, p = 0.001) were shown to be independently associated with risk for disease progression, while LMR (HR 0.077, p = 0.028), and ECOG performance status (HR 20.013, p = 0.026) were proved to be independent predictors of OS. Conclusions:In conclusion, high absolute monocyte counts, high NLR and low LMR may indicate unfavorable prognosis in testicular diffuse large B-cell lymphoma patients. Since indices incorporating blood cell counts are low cost parameters, they may provide additional prognostic value beyond standard clinicopathological parameters. However, further studies are needed to confirm our findings.

Introduction Numerous therapeutic agents specifically targeting the mesenchymal-epithelial transition (MET) oncogene are being developed. Objective The aim of the current review was to systematically identify and analyze clinical trials that have evaluated MET inhibitors in various cancer types and to provide an overview of their clinical outcomes. Methods An electronic literature search was carried out in the PubMed and Embase databases to identify published clinical trials related to MET inhibitors. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement was followed for the systematic appraisal of the literature. Data related to clinical outcomes, including progression-free survival, overall survival, objective response rate, and overall tumor response, were extracted. Results In total, 49 publications were included. Among these, 51.02% were phase II studies, 14.28% were randomized controlled trials, three were phase III studies, two were prospective observational studies, and the remainder were either phase I or Ib studies. The majority (44.89%) of articles reported the clinical outcomes of MET inhibitors, including small molecules, monoclonal antibodies, and other agents, in patients with non-small-cell lung cancer (NSCLC) harboring MET alterations. MET amplification, overexpression, and MET exon 14 skipping mutations were the major MET alteration types reported across the included studies. Clinical responses/outcomes varied considerably. Conclusion This systematic literature review provides an overview of the literature available in Embase and PubMed regarding MET-targeted therapies. MET-selective tyrosine kinase inhibitors (TKIs) (capmatinib, tepotinib, and savolitinib) may become a new standard of care in NSCLC, specifically with MET exon 14 skipping mutations. A combination of MET TKIs with epidermal growth factor receptor (EGFR) TKIs (osimertinib + savolitinib, tepotinib + gefitinib) may be a potential solution for MET-driven EGFR TKI resistance. Further, MET alteration (MET amplification/overexpression) may be an actionable target in gastric cancer and papillary renal cell carcinoma.

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Objective To evaluate the association of hepatic steatosis index (HSI) in the first trimester and the risk of gestational diabetes mellitus (GDM) as well as large for gestational age (LGA) infant in Chinese women. Methods A total of 1082 pregnant women were included in this study. Maternal basic laboratory data, including ALT, AST, FBG, insulin, TG, and HDL-C, were tested during 6–12 weeks of gestation and anthropometric characteristics were monitored during gestation. A 75-g oral glucose tolerance test (OGTT) was conducted at 24–28 weeks of gestation. HSI, nonalcoholic fatty liver disease (NAFLD) liver fat score, triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) and triglyceride-glucose (TyG) index were calculated. Odds ratio with 95% confidence interval for subsequent risk of GDM and LGA by HSI quartiles were assessed by binary logistic regression model. The predictive ability of HSI for GDM and LGA was evaluated by the receiver operating characteristic (ROC) curve analysis and was compared with other indices. Results The incidence of GDM and LGA were 22.09% (239/1082) and 10.53% (87/826). HSI was higher in GDM group than in NGT group (median, interquartile range: 30.67, 27.20–35.10 vs 27.98, 25.70–30.82, P <0.001). Incidence of GDM was gradually increased with increasing HSI values. Women in the highest HSI quartile had significantly higher risk of LGA delivery than those in the lowest HSI quartile ( P <0.05). The area under the ROC curves of HSI for GDM and LGA were higher than other indices, reaching 0.646 (95%CI: 0.605–0.686) and 0.600 (95%CI: 0.541–0.660), respectively. Conclusion Higher HSI was independently associated with higher risk of GDM and LGA in Chinese women. HSI in the first trimester can predict the risk of GDM and LGA.

The endometrium plays a critical role in embryo implantation and pregnancy, and a thin uterus is recognized as a key factor in embryo implantation failure. Umbilical cord mesenchymal stem cells (UC-MSCs) have attracted interest for the repair of intrauterine adhesions. The current study investigated the repair of thin endometrium in rats using the UC-MSCs and the mechanisms involved. Rats were injected with 95% ethanol to establish a model of thin endometrium. The rats were randomly divided into normal, sham, model, and UC-MSCs groups. Endometrial morphological alterations were observed by hematoxylin–eosin staining and Masson staining, and functional restoration was assessed by testing embryo implantation. The interaction between UC-MSCs and rat endometrial stromal cells (ESCs) was evaluated using a transwell 3D model and immunocytochemistry. Microarray mRNA and miRNA platforms were used for miRNA-mRNA expression profiling. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses were performed to identify the biological processes, molecular functions, cellular components, and pathways of endometrial injury and UC-MSCs transplantation repair and real-time quantitative reverse transcription PCR (qRT-PCR) was performed to further identify the expression changes of key molecules in the pathways. Endometrium thickness, number of glands, and the embryo implantation numbers were improved, and the degree of fibrosis was significantly alleviated by UC-MSCs treatment in the rat model of thin endometrium. In vitro cell experiments showed that UC-MSCs migrated to injured ESCs and enhanced their proliferation. miRNA microarray chip results showed that expression of 45 miRNAs was downregulated in the injured endometrium and upregulated after UC-MSCs transplantation. Likewise, expression of 39 miRNAs was upregulated in the injured endometrium and downregulated after UC-MSCs transplantation. The miRNA-mRNA interactions showed the changes in the miRNA and mRNA network during the processes of endometrial injury and repair. GO and KEGG analyses showed that the process of endometrial injury was mainly attributed to the decomposition of the extracellular matrix (ECM), protein degradation and absorption, and accompanying inflammation. The process of UC-MSCs transplantation and repair were accompanied by the reconstruction of the ECM, regulation of chemokines and inflammation, and cell proliferation and apoptosis. The key molecules involved in ECM-receptor interaction pathways were further verified by qRT-PCR. Itga1 and Thbs expression decreased in the model group and increased by UC-MSCs transplantation, while Laminin and Collagen expression increased in both the model group and MSCs group, with greater expression observed in the latter. This study showed that UC-MSCs transplantation could promote recovery of thin endometrial morphology and function. Furthermore, it revealed the expression changes of miRNA and mRNA after endometrial injury and UC-MSCs transplantation repair processed, and signaling pathways that may be involved in endometrial injury and repair.