Background Several studies have reported that the systemic immune-inflammation index (SII) is associated with the prognosis of patients with urologic cancers (UCs). The aim of this study was to systematically evaluate the prognostic value of SII in UC patients. Methods We searched public databases for relevant published studies on the prognostic value of SII in UC patients. Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted and pooled to assess the relationships between SII and overall survival (OS), progression-free survival (PFS), cancer-specific survival (CSS), overall response rate (ORR) and disease control rate (DCR). Results A total of 14 studies with 3074 patients were included. From the pooled results, we found that high SII was associated with worse overall survival (OS) in patients with UC (HR 2.58, 95% CI 1.59–4.21). Patients with high SII values also had poorer PFS (HR 1.92, 95% CI 1.29–2.88) and CSS (HR 2.58, 95% CI 1.36–4.91) as well as lower ORRs (HR 0.40, 95% CI 0.22–0.71) than patients with low SII values. In addition, the subgroup analysis of OS and PFS showed that the prognosis of patients with high SII was worse than that of patients with low SII. Conclusions SII might be a promising noninvasive predictor in patients with UC. However, more samples and multicenter studies are needed to confirm the effectiveness of SII in predicting the prognosis of patients with UC.

The present meta-analysis revealed that metal stents have significantly lower rate of reintervention and cholangitis than plastic stents. But plastic stents have an obvious superiority over metal stents in terms of the incidence of preoperative pancreatitis. More RCTs are required to support this conclusion and provide more detailed information about the complications and treatment. Meanwhile, a uniform standard for the PBD is required in patients with malignant distal biliary obstruction.

Background: Circular RNAs (circRNAs) are a special class of noncoding RNAs that are involved in gene regulation and compete with mRNA for miRNA binding sites. The roles of circRNAs in cancer, especially breast cancer (BC), are poorly understood. Materials and Methods: The expression levels of circRNA 0001073 (circ-1073) in BC cells (BCCs) and tissues and peritumoural tissues were detected by real-time quantitative reverse transcription-polymerase chain reaction. Kaplan-Meier analysis and receiver operating characteristic curves were used to evaluate relapse-free survival (RFS) and the diagnostic value of circ-1073 for BC, respectively. The biological functions of circ-1073 were determined by cell counting kit-8 assays, colony formation assays, flow cytometry, wound-healing assays, transwell assays, and xenograft model studies. RNA immunoprecipitation assays were conducted to identify the connection between circ-1073 and human antigen R (HuR). Results: Low circ-1073 expression was discovered in BCCs and BC tissues compared with normal mammary epithelial cells and peritumoural tissues, respectively. Circ-1073 downregulation was significantly associated with an unfavourable prognosis, including a shorter RFS, in BC patients. Circ-1073 is a valuable diagnostic biomarker for BC. Circ-1073 overexpression significantly inhibited BCC proliferation and induced apoptosis by increasing Cleaved Caspase-3/9 levels. Moreover, circ-1073 upregulation significantly suppressed cell mobility and epithelial-mesenchymal transition. Notably, xenograft tumour growth was inhibited by the intratumoural injection of nanoparticles containing the circ-1073 plasmid or by circ-1073 overexpression, and this inhibition was accompanied by HuR upregulation. Conclusion: Circ-1073 functions as a tumour suppressor in BC, suggesting its potential as a novel therapeutic target in BC.

The impairment of immunity characterized by T cell exhaustion is the main cause of death in patients with sepsis after the acute phase. Although PD-1 blockade is highly touted as a promising treatment for improving prognosis, the role of PD-1 plays in sepsis and particularly its different roles in different periods are still very limited. A recent study revealed LAG3 can resist the therapeutic effect of PD-1 blockade in tumor, which inspired us to understand their role in sepsis. We enrolled 26 patients with acute sepsis from 422 candidates using strict inclusion criteria. Follow-up analysis revealed that the expression levels of PD-1 were rapidly increased in the early stage of sepsis but did not change significantly as infection continued ( P < 0.05). However, the expression of LAG3 was contrary to that of PD-1. Compared with LAG3 or PD-1 single-positive T cells, T cells coexpressing LAG3 and PD-1 were significantly exhausted ( P < 0.05). The proportion of coexpressing T cells was negatively correlated with the total number of lymphocytes ( r = −0.653, P = 0.0003) and positively correlated with the SOFA score ( r = 0.712, P < 0.0001). In addition, the higher the proportion of coexpressing T cells was, the longer the hospital stay and the higher the mortality. These results showed that LAG3 and PD-1 had a potential synergistic effect in regulating the gradual exhaustion of T cells in sepsis, which seriously affected the clinical prognosis of patients. Therefore, LAG3 and PD-1 double-positive T cells are an important indicator for immunity detection and prognostic evaluation. In the future, precision therapy may pay more attention to the different expression patterns of these two molecules.

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Background: Since T cell exclusion contributes to tumor immune evasion and immunotherapy resistance, how to improve T cell infiltration into solid tumors becomes an urgent challenge. Methods: We employed deep learning to profile the tumor immune microenvironment (TIME) in triple negative breast cancer (TNBC) samples from TCGA datasets and noticed that fibroblast growth factor receptor (FGFR) signaling pathways were enriched in the immune-excluded phenotype of TNBC. Erdafitinib, a selective FGFR inhibitor, was then used to investigate the effect of FGFR blockade on TIME landscape of TNBC syngeneic mouse models by flow cytometry, mass cytometry (CyTOF) and RNA sequencing. Cell Counting Kit-8 (CCK-8) assay and transwell migration assay were carried out to detect the effect of FGFR blockade on cell proliferation and migration, respectively. Cytokine array, western blot, enzyme-linked immunosorbent assay (ELISA) and immunofluorescence (IF) were employed to investigate the potential mechanism by which FGFR inhibition enhanced T cell infiltration. Results: Blocking FGFR pathway by Erdafitinib markedly suppressed tumor growth with increased T cell infiltration in immunocompetent mouse models of TNBC. Mechanistically, FGFR blockade inhibited cancer-associated fibroblasts (CAFs) proliferation, migration and secretion of vascular cell adhesion molecule 1 (VCAM-1) by down-regulating MAPK/ERK pathway in CAFs, thus promoting T cell infiltration by breaking physical and chemical barriers built by CAFs in TIME. Furthermore, we observed that FGFR inhibition combined with immune checkpoint blockade therapy (ICT) greatly improved the therapeutic response of TNBC tumor models. Conclusions: FGFR blockade enhanced ICT response by turning immune “cold” tumor into “hot” tumor, providing remarkable implications of FGFR inhibitors as adjuvant agents for combinatorial immunotherapy.

Background Throughout the world, hepatocellular carcinoma (HCC) remains the primary type of liver cancer. The suicide risk was higher among patients with HCC than the general population. Hence, the purpose of this study was to confirm the suicide rates, standardized mortality ratios (SMRs), and the potential risk factors associated with suicide among HCC patients. Methods HCC patients were collected from the Surveillance, Epidemiology, and End Results (SEER) database during 1975–2016. Suicide rates and SMRs among these patients were calculated, and the general population of the United States (U.S.) during 1975–2016 was used as a reference. Univariable and multivariable Cox regression were taken to find out the underlying risk factors of suicide in HCC patients. Results There were 70 suicides identified among 102,567 individuals with HCC observed for 160,500.88 person years. The suicide rate was 43.61 per 100,000 person-years, and SMR was 2.26 (95% CI: 1.78–2.84). On Cox regression, year of diagnosis (1975–1988 vs . 2003–2016, HR: 3.00, 95% CI: 1.01–8.89, P = 0.047; 1989–2002 vs . 2003–2016, HR: 1.92, 95% CI: 1.10–3.34, P = 0.021), gender (male vs. female, HR: 8.72, 95% CI: 2.73–27.81, P < 0.001), age at diagnosis (63–105 years old vs . 0–55 years old, HR: 2.28, 95% CI: 1.21–4.31, P = 0.011), race (white race vs . American Indian/Alaska Native, Asian/Pacific Islander, HR: 3.02, 95% CI: 1.35–6.76, P = 0.007) were independent risk factors of suicide among HCC patients. Conclusions Diagnosed in the early years (1975–2002), male sex, the older age (63–105 years old), white race, survival months (＜2 months) were significantly associated with suicide among HCC patients. For the sake of preventing suicide behaviors, the government, clinicians, and family members should take adequate measures to decrease the rate of suicide, especially in patients with high-risk factors of suicide.

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