Transcriptome profiling of fast/glycolytic and slow/oxidative muscle fibers in aging and obesity.

Aging and obesity pose significant threats to public health and are major contributors to muscle atrophy. The trends in muscle fiber types under these conditions and the transcriptional differences between different muscle fiber types remain unclear. Here, we demonstrate distinct responses of fast/glycolytic fibers and slow/oxidative fibers to aging and obesity. We found that in muscles dominated by oxidative fibers, the proportion of oxidative fibers remains unchanged during aging and obesity. However, in muscles dominated by glycolytic fibers, despite the low content of oxidative fibers, a significant decrease in proportion of oxidative fibers was observed. Consistently, our study uncovered that during aging and obesity, fast/glycolytic fibers specifically increased the expression of genes associated with muscle atrophy and inflammation, including Dkk3, Ccl8, Cxcl10, Cxcl13, Fbxo32, Depp1, and Chac1, while slow/oxidative fibers exhibit elevated expression of antioxidant protein Nqo-1 and downregulation of Tfrc. Additionally, we noted substantial differences in the expression of calcium-related signaling pathways between fast/glycolytic fibers and slow/oxidative fibers in response to aging and obesity. Treatment with a calcium channel inhibitor thapsigargin significantly increased the abundance of oxidative fibers. Our study provides additional evidence to support the transcriptomic differences in muscle fiber types under pathophysiological conditions, thereby establishing a theoretical basis for modulating muscle fiber types in disease treatment.

Clinical impact of sarcopenia for overweight or obese patients with colorectal cancer.

BACKGROUND: Sarcopenia, overweight and obesity are all dynamic changes in body composition, which may have a negative effect on the prognosis for patients with colorectal cancer. The aim of this study was to investigate the predictive role of sarcopenia on overweight or obese patients with colorectal cancer. METHODS: We conducted an observative study on the population of overweight or obese patients with colorectal cancer who underwent curative surgeries in two centers between 2015 and 2021. They were grouped by the presence of sarcopenia. Propensity score match analysis was used to balance the baseline of clinicopathologic characteristics of the two groups. Then, the postoperative outcomes between the two groups were compared. Independent risk factors were evaluated for complications using univariate and multivariate analysis. RESULTS: Of 827 patients enrolled, 126 patients were matched for analysis. Patients with sarcopenia had a higher incidence of total complication and medical complications, a higher rate of laparoscopic surgery performed and higher hospitalization costs. Old age (≥65 years, P = 0.012), ASA grade (III, P = 0.008) and sarcopenia (P = 0.036) were independent risk factors for total complications. ASA grade (III, P = 0.002) and sarcopenia (P = 0.017) were independent risk factors for medical complications. CONCLUSIONS: Sarcopenia was prevalent among overweight or obese patients with colorectal cancer and was associated with negative postoperative outcomes. Early recognition of changes in body composition could help surgeons be well prepared for surgical treatment for overweight or obese patients.

Establishment and validation of novel nomograms to predict muscle quality in colorectal cancer patients.

OBJECTIVES: The skeletal muscle mass index and skeletal muscle radiodensity have promise as specific diagnostic indicators for muscle quality. However, the difficulties in measuring low skeletal muscle mass index and low skeletal muscle radiodensity limit their use in routine clinical practice, impeding early screening and diagnosis. The objective of this study is to develop a nomogram that incorporates preoperative factors for predicting low skeletal muscle mass index and low skeletal muscle radiodensity. METHODS: A total of 1692 colorectal cancer patients between 2015 and 2021 were included. The patients were randomly divided into a training cohort (n = 1353) and a validation cohort (n = 339). Nomogram models were calibrated using the area under the curve, calibration curves, and the Hosmer-Lemeshow test to assess their predictive ability. Finally, a decision curve was applied to assess the clinical usefulness. RESULTS: In a prediction model for low skeletal muscle mass index, age, body mass index, and grip strength were incorporated as variables. For low skeletal muscle radiodensity, age, sex, body mass index, serum hemoglobin level, and grip strength were included as predictors. In the training cohort, the area under the curve value for low skeletal muscle mass index was 0.750 (95% CI, 0.726-0.773), whereas for low skeletal muscle radiodensity, it was 0.763 (95% CI, 0.739-0.785). The Hosmer-Lemeshow test confirmed that both models fit well in both cohorts. Decision curve analysis was applied to assess the clinical usefulness of the model. CONCLUSIONS: The incorporation of preoperative factors into the nomogram-based prediction model represents a significant advancement in the muscle quality assessment. Its implementation has the potential to early screen patients at risk of low skeletal muscle mass index and low skeletal muscle radiodensity.

A novel insight into the key gene signature associated with the immune landscape in the progression of sarcopenia.

Sarcopenia is an age-related skeletal muscle disorder that causes falls, disability and death in the elderly, but its exact mechanism remains unknown. In this study, we merged three GEO datasets into the expression profiles of 118 samples and screened 22 differentially expressed genes (DEGs) as candidate genes. Pathway analysis demonstrated that the functional enrichment of DEGs is mainly in the cellular response to insulin stimulus, PPAR signaling pathway and other metabolism-related pathways. Then, we identified six key genes by machine learning, which were confirmed to be closely associated with sarcopenia by bioinformatics analysis. It was experimentally verified that SCD1 exhibits the most substantial alterations in the progression of sarcopenia with disturbed lipid metabolism and myosteatosis. In addition, the immune microenvironment of sarcopenia was found to be affected by these key genes, with Th17 cells down-regulated and NK cells up-regulated. Sarcopenic patients consequently presented a more significant systemic inflammatory state with higher CAR (p = 0.028) and PAR (p = 0.018). For the first time, we identified key genes in sarcopenia with high-throughput data and demonstrated that key genes can regulate the progression of sarcopenia by affecting the immune microenvironment. Among them, SCD1 may influence lipid metabolism and myosteatosis process. Screening of key genes and analyzing of immune microenvironment provide a more accurate target for treating sarcopenia.

Comparison of laparoscopic and open radical gastrectomy for gastric cancer patients with GLIM-defined malnutrition.

PURPOSE: Malnutrition is common in the patients with gastric cancer. Radical gastrectomy remained the primary strategy of curable treatment for gastric cancer. This study is performed to explore the effect of laparoscopic radical gastrectomy on clinical outcomes in gastric cancer patients with malnutrition. METHODS: Gastric cancer patients with GLIM-defined malnutrition between 2014 and 2019 at our center were enrolled. The patients were divided into two groups according to the different type of surgery. Propensity score match analysis was used to balance the clinicopathologic characteristics of two groups. Postoperative outcomes and survival were compared. Multivariate analysis was used to independent risk factors of complication, overall survival (OS), and disease-free survival (DFS). RESULTS: Compared with patients underwent open radical gastrectomy, patients who underwent laparoscopic radical gastrectomy had lower rate of total, surgical and severe complications. They also had shorter postoperative hospital stay with better OS and DFS. Hypoalbuminemia (P = 0.003) was the independent risk factor of complications. Old age (≥75, P = 0.035) and TNM stage (III: P < 0.001, II: P = 0.015) were the independent risk factors of OS. Combined resection (P = 0.003) and TNM stage (III: P < 0.001, II: P = 0.001) posed independent risk factors of lacking DFS. Laparoscopic surgery proved to be the independent protective factor of complications (P = 0.014), OS (P < 0.001) and DFS (P < 0.001). CONCLUSION: Laparoscopic radical gastrectomy was relative safe and showed favorable outcomes in malnourished gastric cancer patients.

Coexistence of GLIM-defined malnutrition and sarcopenia have negative effect on the clinical outcomes in the elderly gastric cancer patients after radical gastrectomy.

Background: Malnutrition and sarcopenia are common in elderly gastric cancer patients, which are also interrelated and affect each other. We aimed to determine the characteristics of coexistence of malnutrition and sarcopenia in the elderly gastric cancer patients and investigate the predictive roles of malnutrition and sarcopenia on clinical outcomes. Methods: Between 2014 and 2019, a total of 742 elderly gastric cancer patients were enrolled. Malnutrition and sarcopenia were diagnosed according to the most recent diagnostic criteria. Patients were divided into four groups according to presence of these two symptoms. Clinical characteristics, short- and long-term outcomes were compared among four groups. The independent risk factors for complications and survival were evaluated using univariate and multivariate analyses. Results: Of all patients, 34.8% were diagnosed with malnutrition and 34.0% were diagnosed with sarcopenia. Patients with both malnutrition and sarcopenia had the highest rate of total (P < 0.001), surgical (P = 0.003), and medical complications (P = 0.025), and the highest postoperative hospital stays (P < 0.001) and hospitalization costs (P < 0.001). They also had the worst overall survival (P < 0.0001) and disease-free survival (P < 0.0001). Sarcopenia and Charlson Comorbidity Index (≥2) were independent risk factors for total complications. Hypoalbuminemia and malnutrition were non-tumor-related independent risk factors for overall survival and disease-free survival. Conclusions: Malnutrition and sarcopenia had superimposed negative effects on elderly gastric cancer patients. Preoperative geriatric evaluation including screening for malnutrition and sarcopenia are recommended for all elderly gastric cancer patients for accurate treatment strategy.

Prognostic significance of postoperative loss of skeletal muscle mass in patients underwent coronary artery bypass grafting.

Background: Increasing life expectancy of coronary artery bypass grafting (CABG) remains to be the major concern of cardiac surgeons. However, few studies have investigated the effect of postoperative skeletal muscle index (SMI) loss on prognosis. This study aims to evaluate the prognostic role of postoperative SMI loss ≥ 5% after CABG, in order to develop a novel nomogram to predict overall survival (OS). Methods: Patients underwent CABG via midline sternotomy from December 2015 to March 2021 were recruited in this study. Preoperative and postoperative 3 months chest computed tomography (CT) images were compared to assess changes in SMI at T12 level. Based on this, patients were classified into the presence or absence of SMI loss ≥ 5%. The association between postoperative SMI loss ≥ 5% and OS was then analyzed by the Kaplan-Meier curves and Cox model. A novel nomogram incorporating independent clinical prognostic variables was also developed. Results: The study enrolled 506 patients receiving CABG, of whom 98 patients experienced T12 SMI loss ≥ 5% and had a significantly worse OS (P < 0.0001). Multivariate regression analysis showed that T12 SMI per cent change (%T12 SMI-change) was an independent prognostic factor for OS (HR = 0.809, 95% CI = 0.749-0.874). The nomogram incorporating %T12 SMI-change with other variables was accurate for predicting OS. Besides, we also found that postoperative oral nutritional supplement (ONS) can rescue T12 SMI loss. Conclusion: Postoperative SMI loss can predict survival outcome after CABG. The nomogram incorporating changes in SMI provides a superior performance than existing systems.

Prognostic value of myosteatosis and sarcopenia for elderly patients with colorectal cancer: A large-scale double-center study.

BACKGROUND: Myosteatosis and sarcopenia are forms of muscle depletion that impair the normal physiological function of elderly patients, resulting in a worse prognosis. This study aimed to evaluate the prognostic value of sarcopenia and myosteatosis on postoperative outcomes in elderly patients with colorectal cancer. METHODS: From February 2015 to March 2021, a total of 921 elderly patients who underwent curative surgeries for colorectal cancer at 2 centers were enrolled and grouped by the presence of either myosteatosis or sarcopenia. Clinicopathological characteristics and postoperative outcomes were compared between the 2 groups. The independent risk factors for complications and overall survival were evaluated. RESULTS: Patients with myosteatosis had higher incidences of total and surgical complications, longer surgical duration, lower numbers of lymph nodes harvested, and longer postoperative hospital stays. Patients with sarcopenia had higher incidences of total complications, medical complications, and shorter surgical durations. Both conditions had adverse effects on overall survival and disease-free survival. Overweight status (P = .004), hypoalbuminemia (P < .001), myosteatosis, (P = .029) and sarcopenia (P = .017) were independent risk factors for total complications. Hypoalbuminemia (P = .035), myosteatosis (P = .003), sarcopenia (P = .027), and tumor-nodes-metastasis stage (≥Ⅲ; P < .001) were independent negative prognostic factors for overall survival. CONCLUSION: Myosteatosis and sarcopenia have different characteristics and are associated with poor prognoses in elderly patients with colorectal cancer. Myosteatosis occurs more frequently. Early diagnosis and intervention for myosteatosis should be included in preoperative management, which may improve prognosis in elderly patients.

Multicomponent TiO2/Ag/Cu7S4@Se Heterostructures Constructed by an Interface Engineering Strategy for Promoting the Electrocatalytic Nitrogen Reduction Reaction Performance.

The electrocatalytic nitrogen reduction reaction (ECNRR) is a sustainable and environmentally friendly method for NH3 synthesis under environmental conditions relative to the Haber-Bosch process; however, its low selectivity (Faradaic efficiency (FE)) and low NH3 yield impede the progress. Herein, benefiting from the application of the interface engineering strategy, a multicomponent TiO2/Ag/Cu7S4@Se-CC heterogeneous electrocatalyst with a unique structure was successfully fabricated, generating a unique sandwich structure by using a Ag layer as an electric bridge intercalated between TiO2 and Cu7S4, in which the optimized catalyst can accelerate the electron transfer efficiency. Moreover, through the electronic structure adjustment, an electron-deficient region was constructed, which can inhibit the H2 adsorption but enhance the N2 adsorption, thereby improving the selectivity and the catalytic activity. Significantly, the FE and NH3 yield of TiO2/Ag/Cu7S4@Se-CC reached 51.05 ± 0.16% and 39.16 ± 2.31 µg h-1 cm-2, in which the FE is among the highest non-precious metal-based NRR electrocatalysts in alkaline electrolytes reported. This study provides insight into the rational design and construction of NRR electrocatalysts for electrocatalytic applications.

Effect of GLIM-defined malnutrition on postoperative clinical outcomes in patients with colorectal cancer.

BACKGROUND: Malnutrition is common in colorectal cancer patients. Malnutrition is recognized as a risk factor for adverse postoperative outcomes, yet there are no consistent diagnostic criteria for it. Thus, the Global Leadership Initiative on Malnutrition published new universal criteria. We aimed to investigate the prevalence of malnutrition with the application of Global Leadership Initiative on Malnutrition criteria, and explore the correlations between Global Leadership Initiative on Malnutrition-defined malnutrition and postoperative clinical outcomes in colorectal cancer patients. METHODS: We included a cohort of 918 patients who underwent radical resection surgery for colorectal cancer from July 2014 to October 2019. Malnutrition was diagnosed based on the Global Leadership Initiative on Malnutrition criteria. The associations between nutritional status and postoperative clinical outcomes were analyzed by the Kaplan-Meier method, logistic and Cox regression analyses. RESULTS: Among the included patients, 23.6% were diagnosed as malnutrition based on Global Leadership Initiative on Malnutrition criteria. Global Leadership Initiative on Malnutrition-defined malnutrition was associated with total postoperative complications [odds ratio: 1.497 (1.042-2.152), P = 0.029]. Further, Global Leadership Initiative on Malnutrition-diagnosed malnutrition was an independent risk factor for overall survival [hazard ratio: 1.647 (1.048-2.587), P = 0.030] and disease-free survival [hazard ratio: 1.690 (1.169-2.441), P = 0.005]. CONCLUSIONS: The Global Leadership Initiative on Malnutrition criteria is effective to assess malnutrition. Preoperative malnutrition is associated with postoperative complications, overall survival and disease-free survival in colorectal cancer patients after radical resection surgery.