Long-term exercise-induced metabolic adaptations occupy a central position in exercise-afforded cardiac benefits. Emerging evidence suggests that branched-chain amino acid (BCAA) catabolic defect contributes to cardiac dysfunction in multiple cardiometabolic diseases. However, the role of BCAA catabolism in exercise-afforded cardiac benefits remains unknown. Here, we show that exercise improves BCAA catabolism and thus reduce cardiac vulnerability to myocardial ischemic injury. Exercise increased circulating BCAA levels in both humans (male adolescent athletes) and mice (following an 8-week swimming intervention). It increased the expression of mitochondrial localized 2C-type serine-threonine protein phosphatase (PP2Cm), a key enzyme in regulating BCAA catabolism, and decreased BCAA accumulation in mouse hearts, indicating an increase in BCAA catabolism. Pharmacological promotion of BCAA catabolism protected the mouse heart against myocardial infarction (MI) induced by permanent ligation of the left descending coronary artery. Although cardiac-specific PP2Cm knockout showed no significant effects on cardiac structural and functional adaptations to exercise, it blunted the cardioprotective effects of exercise against MI. Mechanistically, exercise alleviated BCAA accumulation and subsequently inactivated the mammalian target of rapamycin in MI hearts. These results showed that exercise elevated BCAA catabolism and protected the heart against myocardial ischemic injury, reinforcing the role of exercise in the promotion of cardiac health.

Background: We conducted a systematic review and meta-analysis to summarize the predictive and prognostic ability of the log odds of positive lymph nodes (LODDS) staging system and compare it with pathological N (pN) classification and the ratio-based lymph node system (rN) for the overall survival (OS) of gastric cancer (GC). Methods: Through a systematic review till March 7, 2022, we identified population-based studies that reported the prognostic effects of LODDS in patients with GC. We compare the predictive effectiveness of the LODDS staging system with that of the rN and pN classification systems for the OS of GC. Results: Twelve studies comprising 20,312 patients were included in this systematic review and meta-analysis. The results showed that LODDS1, LODDS2, LODDS3, and LODDS4 in GC patients were correlated with poor OS compared with LODDS0 (LODDS1 vs. LODDS0: HR = 1.62, 95% CI (1.42, 1.85); LODDS2 vs. LODDS0: HR = 2.47, 95% CI (2.02, 3.03); LODDS3 vs. LODDS0: HR = 3.15, 95% CI (2.50, 3.97); LODDS4 vs. LODDS0: HR = 4.55, 95% CI (3.29, 6.29)). Additionally, significant differences in survival were observed among patients with different LODDS classifications (all P-values were < 0.001) with the same rN and pN classifications. Meanwhile, for patients with different pN or rN classifications with the same LODDS classification, prognosis was highly similar. Conclusion: The findings show that LODDS is correlated with the prognosis of GC patients and is superior to the pN and rN classifications for prognostic assessment.

Background: Colorectal cancer (CRC) is the third most prevalent cancer in the world, which remains one of the leading causes of cancer-related deaths. Accurate prognosis prediction of CRC is pivotal to reduce the mortality and disease burden. Lymph node (LN) metastasis is one of the most commonly used criteria to predict prognosis in CRC patients. However, inaccurate surgical dissection and pathological evaluation may lead to inaccurate nodal staging, affecting the effectiveness of pathological N (pN) classification in survival prediction among patients with CRC. In this meta-analysis, we aimed to estimate the prognostic value of the log odds of positive lymph nodes (LODDS) in patients with CRC. Methods: PubMed, Medline, Embase, Web of Science and the Cochrane Library were systematically searched for relevant studies from inception to July 3, 2021. Statistical analyses were performed on Stata statistical software Version 16.0 software. To statistically assess the prognostic effects of LODDS, we extracted the hazard ratio (HR) and 95% confidence interval (CI) of overall survival (OS) and disease-free survival (DFS) from the included studies. Results: Ten eligible articles published in English involving 3523 cases were analyzed in this study. The results showed that LODDS1 and LODDS2 in CRC patients was correlated with poor OS compared with LODDS0 (LODDS1 vs. LODDS0: HR = 1.77, 95% CI (1.38, 2.28); LODDS2 vs. LODDS0: HR = 3.49, 95% CI (2.88, 4.23)). Meanwhile, LODDS1 and LODDS2 in CRC patients was correlated with poor DFS compared with LODDS0 (LODDS1 vs. LODDS0: HR = 1.82, 95% CI (1.23, 2.68); LODDS2 vs. LODDS0: HR =3.30, 95% CI (1.74, 6.27)). Conclusions: The results demonstrated that the LODDS stage was associated with prognosis of CRC patients and could accurately predict the prognosis of patients with CRC.

Background: Gastric cancer (GC) is a common highly recurrent malignant tumor that is associated with poor prognosis. Circulating tumor cells (CTCs) have drawn much attention because of their diagnostic value in diverse cancers, including GC. This study aimed to assess the relevance of CTCs in predicting the clinicopathological parameters and prognostic significance of GC. Methods: We systematically searched PubMed, Medline and Web of Science for relevant studies. Each database was searched from its date of inception through January 22, 2020. The odds ratios (ORs), hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated as effect values using the random-effects model. Results: In total, 52 articles that reported 68 studies comprising 4158 GC patients were included. The pooled results on TNM stage indicated that the III/IV group had a notably higher CTCs positivity rate than the I/II group (OR=2.73, 95% CI (1.95,3.82), I²=65%). The poorly differentiated group had a significantly higher CTCs positivity rate than the well/moderately differentiated group (overall: OR=1.91, 95% CI (0.77,4.71)), as well as the Lauren classification diffuse/hybrid type group and the intestinal group (overall: OR=1.77, 95% CI (0.70,4.44)). The bulk of analysis revealed that CTC positivity detected in GC patients was correlated with worse overall survival (OS) (HR =1.94, 95% CI (1.64,2.30), P≤0.001), progression-free survival (PFS) (HR =2.45, 95% CI (1.65,3.64), P≤0.001), and disease-free survival (DFS) (HR =2.78, 95% CI (1.89,4.10), P≤0.001). Then, we extracted data and analyzed the DCR of chemotherapy in patients with GC, and the pooled analysis demonstrated that the DCR of the CTC positivity was lower than that of the CTC negativity (RR =0.63, 95% CI (0.44,0.91))Conclusions: In conclusion, our study demonstrated that the CTCs positivity was correlated with the poor OS, PFS and DFS in GC patients and provided a scientific foundation for gastric cancer staging.

Background: Esophageal carcinoma (EC) is the seventh-most prevalent tumor in the world, which is still one of the primary causes of tumor-related death. Identifying noteworthy biomarkers for EC is particularly significant in guiding effective treatment. Recently, circulating tumor cells (CTCs) in peripheral blood (PB) were intensively discussed as prognostic markers in patients with EC. However, an ongoing controversy still exists regarding the prognostic significance of CTCs determined by the CellSearch system in EC sufferers. This meta-analysis was designed to approach this topic. Methods: We systematically conducted searches using PubMed, Medline, Web of Science and the Cochrane Library for relevant studies, which were published through February 20, 2020. Using the random-effects model, our study was performed in Review Manager software, with odds ratios (ORs), risk ratios (RRs), hazard ratios (HRs) and 95% confidence intervals (CIs) as the effect values. Results: Totally 7 articles were finally included in this study. For clinicopathological characteristics, the pooled results on TNM stage indicated that the III/IV group had higher rate of CTCs compared with the I/II group (OR=1.36, 95% CI: 0.68-2.71, I²=0%). Incidence of CTCs was higher in patients with T3/T4 stage (OR=2.92, 95% CI: 1.31-6.51, I²=0%) and distant metastasis group (OR=5.18, 95% CI: 2.38-11.25, I²=0%) compared to patients with T1/T2 stage or non-metastatic group. The pooled analysis revealed that CTC positivity detected in EC patients was correlated with poor overall survival (OS) (HR=2.83, 95% CI:1.99-4.03, I²=0%) and relapse-free survival (RFS) (HR=4.71, 95% CI:2.73-8.13, I²=0%). When pooling the estimated RR, a poor therapeutic response to chemoradiotherapy was discovered in patients with CTC positivity (RR=1.99, 95% CI:1.73-2.29, I²=60%). Conclusions: In summary, our meta-analysis demonstrated that CTCs positivity determined by the CellSearch system are correlated with the prognosis of EC patients and might indicate a poor therapeutic response to chemotherapy in EC patients.