The success of immunotherapy was overshadowed by its low response rate, and the hot or cold tumor microenvironment was reported to be responsible for it. However, due to the lack of an appropriate method, it is still a huge challenge for researchers to understand the molecular differences between hot and cold tumor microenvironments. Further research is needed to gain deeper insight into the molecular characteristics of the hot/cold tumor microenvironment. A large-scale clinical cohort and single-cell RNA-seq technology were used to identify the molecular characteristics of inflamed or noninflamed tumors. With single-cell RNA sequencing technology, we provided a novel method to dissect the tumor microenvironment into a hot/cold tumor microenvironment to help us understand the molecular differences between hot and cold tumor microenvironments. Compared with cold tumors, hot tumors highly expressed B cell-related genes, such as MS4A1 and CXCR5, neurogenesis-related miRNA such as MIR650, and immune molecule-related lncRNA such as MIR155HG and LINC00426. In cold tumors, the expression of genes related to multiple biological processes, such as the neural system, was significantly upregulated, and methylome analysis indicated that the promoter methylation level of genes related to neurogenesis was significantly reduced. Finally, we investigated the pan-cancer prognostic value of the cold/hot microenvironment and performed pharmacogenomic analysis to predict potential drugs that may have the potential to convert the cold microenvironment into a hot microenvironment. Our study reveals the multiomics characteristics of cold/hot microenvironments. These molecular characteristics may contribute to the understanding of immune exclusion and the development of microenvironment-targeted therapy.
Background: Peritoneal metastasis (PM) is an advanced stage of intra-abdominal malignancy with a very poor prognosis. In recent years, hyperthermic intraperitoneal chemotherapy (HIPEC) combined with cytoreductive surgery (CRS) has been utilized as an active treatment in the prevention and treatment of PM, with encouraging results. However, compared with CRS alone, the results of the CRS plus HIPEC strategy in the treatment of patients with intra-abdominal malignancies are still controversial. This study sought to determine the impact of HIPEC + CRS on patient survival and adverse events (AEs) by reviewing randomized controlled trials (RCTs) for all types of intra-abdominal malignancies.Methods: A PubMed, Embase, Cochrane Library, Web of Science and Clinical Trials.gov search extracted all RCTs until 12 October 2022, examining the CRS + HIPEC vs. CRS alone strategies in the treatment of various types of intra-abdominal malignancies. The outcomes included overall survival (OS), disease-free survival (DFS), relapse-free survival (RFS), progression-free survival (PFS) and AEs. The dichotomous data were pooled and reported as odds ratios (ORs) with 95% confidence intervals (CIs). The survival outcome data were pooled using hazard ratios (HRs) and corresponding 95% CIs. The Cochrane Collaboration’s Risk of Bias Tool was used to assess the risk of bias in the included studies.Results: A total of 12 RCTs were included in this meta-analysis, including 873 patients in the CRS + HIPEC group and 878 patients in the CRS alone group. The studies included 3 (617 patients) on colorectal cancer, 4 (416 patients) on gastric cancer, and 5 (718 patients) on ovarian cancer. Our analysis showed no difference in OS between the CRS + HIPEC and CRS alone groups (HR: 0.79, 95% CI 0.62–1.01). Subgroup analysis showed that CRS + HIPEC improved the OS of gastric cancer patients (HR: 0.49, 95% CI 0.32–0.76) compared with CRS alone. However, CRS + HIPEC did not significantly improve the OS of colorectal cancer (HR: 1.06, 95% CI 0.81–1.38) and ovarian cancer (HR: 0.82, 95% CI 0.62–1.07) patients. In addition, there was no significant difference in DFS/RFS (HR: 0.78, 95% CI 0.57–1.07) or PFS (HR: 1.03, 95% CI 0.77–1.38) between the two groups. Compared with CRS alone, CRS with HIPEC had greater nephrotoxicity (OR: 0.45, 95% CI 0.21–0.98), while other AEs did not differ significantly between the two groups.Conclusion: Our results suggest that CRS + HIPEC may improve OS in gastric cancer patients compared with CRS alone, but we did not observe a benefit for DFS/RFS. For patients with ovarian and colorectal cancers, our results suggest that HIPEC + CRS does not appear to improve survival outcomes. In addition, CRS + HIPEC has higher nephrotoxicity than CRS alone. More evidence from RCTs is needed to evaluate whether the use of CRS + HIPEC is an appropriate option.
Purpose This investigation aimed to compare the medical efficacy of the knotted and knotless suture-bridge procedures in rotator cuff repair. Methods The Pubmed, Embase, and Cochrane Library datasets were searched for all available publications comparing the medical results of arthroscopic rotator cuff repairs utilizing knotted or knotless suture-bridge procedures. Two researchers utilized Newcastle-Ottawa Scale and Cochrane risk-of-bias tool to evaluate the included studies. Employing Revman 5.3 software, meta-analysis was conducted following the PRISMA reporting guideline. Results Eleven investigations with 1083 patients were considered suitable for the final meta-analysis. 522 individuals were assigned to the knotted group, whereas 561 were assigned to the knotless group. No statistical difference was found between the knotted and knotless groups, regarding VAS score (WMD, 0.17; 95% CI, − 0.10 to 0.44; P = 0.21); Constant score (WMD, -1.50; 95% CI, − 3.52 to 0.52; P = 0.14); American Shoulder and Elbow Surgeons Shoulder (WMD, -2.02; 95% CI, − 4.53 to 0.49; P = 0.11); University of California Los Angeles score (WMD, -0.13; 95% CI, − 0.89 to 0.63; P = 0.73); ROM of flexion (WMD, 1.57; 95% CI, − 2.11 to 5.60; P = 0.37), abduction (WMD, 1.08; 95% CI, − 4.53 to 6.70; P = 0.71) and external rotation (WMD, 1.90; 95% CI, − 1.36 to 5.16; P = 0.25); re-tear rate (OR, 0.74; 95% CI, 0.50 to 1.08; P = 0.12), and medical complications (OR, 0.90; 95% CI, 0.37 to 2.20; P = 0.82). Conclusion For arthroscopic rotator cuff repairs, there were no statistical differences in medical results among knotted and knotless suture-bridge procedures. Overall, both techniques showed excellent clinical outcomes and could be safely utilized to treat rotator cuff injuries.
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