Dun, Yaoshan

ABSTRACT Background The optimal exercise regimen for alleviating sarcopenia remains uncertain. This study aimed to investigate the efficacy of high‐intensity interval training (HIIT) over moderate‐intensity continuous training (MICT) in ameliorating sarcopenia. Methods We conducted a randomized crossover trial to evaluate plasma proteomic reactions to acute HIIT (four 4‐min high‐intensity intervals at 70% maximal capacity alternating with 4 min at 30%) versus MICT (constant 50% maximal capacity) in inactive adults. We explored the relationship between a HIIT‐specific protein relative to MICT, identified via comparative proteomic analysis, eukaryotic translation elongation factor 1 epsilon 1 (EEF1E1) and sarcopenia in a paired case–control study of elderly individuals (aged over 65). Young (3 months old) and aged (20 months old) mice were randomized to sedentary, HIIT and MICT groups (five sessions/week for 4 weeks; n = 8 for each group). Measurements included skeletal muscle index, hand grip strength, expression of atrophic markers Atrogin1 and MuRF1 and differentiation markers MyoD, myogenin and MyHC‐II via western blotting. We examined the impact of EEF1E1 siRNA and recombinant protein on D‐galactose‐induced myoblast senescence, measuring senescence‐associated β‐galactosidase and markers like p21 and p53. Results The crossover trial, including 10 sedentary adults (32 years old, IQR 31–32) demonstrated significant alterations in the abundance of 21 plasma proteins after HIIT compared with MICT. In the paired case–control study of 84 older adults (84 years old, IQR 69–81; 52% female), EEF1E1 was significantly increased in those with sarcopenia compared to those without (14.68 [95%CI, 2.02–27.34] pg/mL, p = 0.03) and was associated with skeletal muscle index ( R 2 = 0.51, p < 0.001) and hand grip strength ( R 2 = 0.54, p < 0.001). In the preclinical study, aged mice exhibited higher EEF1E1 mRNA and protein levels in skeletal muscle compared to young mice, accompanied by a lower muscle mass and strength, increased cellular senescence and protein degradation markers and reduced muscle differentiation efficiency (all p < 0.05). HIIT reduced EEF1E1 expression and mitigated age‐related muscle decline and atrophy in aged mice more effectively than MICT. Notably, EEF1E1 downregulation via siRNA significantly counteracted D‐galactose‐induced myoblast senescence as evidenced by reduced markers of muscle protein degradation and improved muscle differentiation efficiency (all p < 0.05). Conversely, treatments that increased EEF1E1 levels accelerated the senescence process ( p < 0.05). Further exploration indicated that the decrease in EEF1E1 was associated with increased SIRT1 level and enhanced autophagy. Conclusions This study highlights the potential of HIIT as a promising approach to prevent and treat sarcopenia while also highlighting EEF1E1 as a potential intervention target.

Background: The role of minute ventilation/carbon dioxide production ( / CO2) slope, a ventilation efficiency marker, in predicting short-term and long-term health outcomes for patients with nonsmall-cell lung cancer (NSCLC) undergoing lung resection has not been well investigated. Material and Methods: This prospective cohort study consecutively enrolled NSCLC patients who underwent a presurgical cardiopulmonary exercise test from November 2014 to December 2019. The association of / CO2 slope with relapse-free survival (RFS), overall survival (OS), and perioperative mortality was evaluated using the Cox proportional hazards and logistic models. Covariates were adjusted using propensity score overlap weighting. The optimal cut-off point of the E/ CO2 slope was estimated using the receiver operating characteristics curve. Internal validation was completed through bootstrap resampling. Results: A cohort of 895 patients [median age (interquartile range), 59 (13) years; 62.5% male] was followed for a median of 40 (range, 1–85) months. Throughout the study, there were 247 relapses or deaths and 156 perioperative complications. The incidence rates per 1000 person-years for relapses or deaths were 108.8 and 79.6 among patients with high and low E/ CO2 slopes, respectively [weighted incidence rate difference per 1000 person-years, 29.21 (95% CI, 7.30–51.12)]. A E/ CO2 slope of greater than or equal to 31 was associated with shorter RFS [hazard ratio for relapse or death, 1.38 (95% CI, 1.02–1.88), P=0.04] and poorer OS [hazard ratio for death, 1.69 (1.15–2.48), P=0.02] compared to a lower / CO2 slope. A high E/ CO2 slope increased the risk of perioperative morbidity compared with a low E/ CO2 slope [odds ratio, 2.32 (1.54–3.49), P<0.001]. Conclusions: In patients with operable NSCLC, a high E/ CO2 slope was significantly associated with elevated risks of poorer RFS, OS, and perioperative morbidity.

Introduction Insulin resistance (IR) plays a key role in the pathogenesis and clinical course of patients with multiple metabolic diseases and diabetes. This study aimed to explore the effect of trimetazidine (TMZ) on skeletal muscle IR in mice fed a high-fat diet (HFD) and explore the possible underlying mechanism. Research design and methods In vivo, a HFD mouse IR model was adopted and TMZ and exercise were used to intervene. Postintervention the following were determined: blood levels of glucose and insulin, homeostasis model assessment of IR index, expression of skeletal muscle insulin signaling-related proteins phosphorylated insulin receptor substrate 1 (p-IRS1/IRS1) and phosphorylated protein kinase B (p-AKT/AKT), nuclear factor erythroid 2 related factor 2 (Nrf2) signaling pathway, and oxidative stress. In vitro, a palmitate-treated C2C12 myotube IR model was constructed. Cellular glucose uptake, p-IRS1/IRS1, and p-AKT/AKT were determined, and reactive oxygen species (ROS) production was analyzed based on treatments with specific small interfering RNA of Nrf2 with or without TMZ. Western blot was used to obtain the protein expression level and ROS production by functional analysis kits. Results In vivo, TMZ and exercise decreased the blood glucose and insulin levels and homeostasis model assessment of IR index, increased skeletal muscle insulin signaling-related protein ratios of p-IRS1/IRS1 and p-AKT/AKT, and both interventions activated Nrf2 signaling and reduced oxidative stress production in HFD mice. In vitro, TMZ reduced the oxidative stress reaction, increased the ratios of p-AKT/AKT and p-IRS1/IRS1, and attenuated the insulin stimulation of PA-induced glucose uptake. However, in the absence of Nrf2, TMZ failed to resist the effects of IR. Conclusions This study showed that TMZ, like exercise, brought about marked improvements to HFD-induced skeletal muscle IR through TMZ, a common pathway with exercise in the form of Nrf2, regulating oxidative stress. We provide new evidence to support the use of TMZ for diabetes treatment.

Abstract Background the Xiangya Hospital circuit training (X-CircuiT), was developed to reverse pre-frailty in Chinese older adults and determine potential mechanisms through which pre-frailty is reversed. Methods this randomised controlled trial was performed at Xiangya Hospital, Changsha, China from September 2020 to May 2021. Forty-eight pre-frail older adults were enrolled. Participants were randomly assigned (1:1) to X-CircuiT (46 min/session, three supervised sessions/week for 3 months at a community health centre) or control (1-time advice on physical activity without supervised exercise). The primary outcome was the proportion of participants with pre-frailty after 3-month intervention. The secondary outcomes included absolute risk reduction (ARR), number needed to treat (NNT), and the changes in senior fitness, body composition and clinical measures. Results among 48 participants (mean age, 72 years; women [65%]), 22 participants in the X-CircuiT (92%) and 21 participants in the control (88%) completed the study. After 3 months, the proportion of pre-frailty was significantly lower in the X-CircuiT group than the control (14% versus 95%, P &lt; 0.001). The ARR and NNT were 82% [95% CI, 65–99] and 1 [1–2], respectively. X-CircuiT was associated with significant improvements in senior fitness indicators and body composition. No significant difference in blood chemistry, carotid ultrasound and echocardiography parameters was found between groups. No significant interaction was detected between sex, BMI, baseline peak oxygen consumption and study groups. Conclusion this study demonstrates that X-CircuiT could significantly reverse pre-frailty in Chinese older adults. The underlying mechanisms may involve X-CircuiT-induced improvements in body composition and senior fitness. The trial is registered at Chictr.org.cn. Number: ChiCTR2100048125.

Objectives To observe the weight change in Chinese youth during a 4-month COVID-19 lockdown, and the association between weight change and mental health, physical activity and sedentary time changes, and dietary habits. Design A retrospective observational study. Settings Two universities located in Zhejiang and Hunan provinces, China. Participants This study enrolled 12 889 college students whose body weight was measured before the lockdown (1 December 2019–20 January 2020) at the two universities, and reported their weight measured at home or community after the end of the lockdown (1–23 May 2020) via an online follow-up questionnaire. Primary and secondary outcome measures The primary outcome was the weight change in Chinese youth during a 4-month lockdown resulting from the COVID-19 pandemic. The secondary outcomes were the relationships of weight change to COVID-19-related stress, depression, anxiety, physical activity and sedentary time changes, and dietary habits. Results Participants’ ages ranged from 17 to 27 years ( M =19, SD=1) with 80.2% identified as female. The average absolute and relative changes in body weight were 2.6 (95% CI 2.0 to 3.2)) kg and 4.2% (95% CI 4.0% to 4.3%) for men, and 2.1 (1.9 to 2.4) kg and 4.2% (95% CI 3.9% to 4.4%) for women. An increase in overweight and obese individuals according to Asian cut-off points as a demographic percentage by 4.5% and 2.7% and 4.8% and 3.4% in men and women, respectively ( P <0.001), was observed. Weight gain was significantly associated with increased sedentary time and an increase in COVID-19-related stress and depression score. Conclusion The present study’s results suggest that the risk of weight gain in Chinese youth during the lockdown increased and that strategies to decrease sedentary time and improve mental health may be warranted to mitigate weight gain during and after the COVID-19 pandemic.

Background The COVID-19 pandemic has led to a spike in deleterious mental health. This dual-center retrospective cross-sectional study assessed the prevalence of depression in young adults during this pandemic and explored its association with various physical fitness measures. Methods This study enrolled 12,889 (80% female) young adults (mean age 20 ± 1) who performed a National Student Physical Fitness battery from December 1st, 2019, to January 20th, 2020, and completed a questionnaire including Beck’s Depression Inventory in May 2020. Independent associations between prior physical fitness and depression during the pandemic were assessed using multivariable linear and binary logistic regressions accordingly, covariates including age, dwelling location, economic level, smoking, alcohol, living status, weight change, and exercise volume during the pandemic. Sex- and baseline stress-stratified analyses were performed. Results Of the study population 13.9% of men and 15.0% of women sampled qualified for a diagnosis of depression. After multivariable adjustment, anaerobic (mean change 95% CI −3.3 [−4.8 to 1.8]) aerobic (−1.5 [−2.64 to −0.5]), explosive (−1.64 [−2.7 to −0.6]) and muscular (−1.7 [−3.0 to −0.5]) fitness were independently and inversely associated with depression for the overall population. These remained consistent after sex- and baseline stress-stratification. In binary logistic regression, the combined participants with moderate, high or excellent fitness also showed a much lower risk compared to those least fit in anaerobic (odd ratio (OR) 95% CI 0.68 [0.55–0.82]), aerobic (0.80 [0.68–0.91]), explosive (0.72 [0.61–0.82]), and muscular (0.66 [0.57–0.75]) fitness. Conclusions These findings suggest that prior physical fitness may be inversely associated with depression in young adults during a pandemic.

Abstract Background: The coronavirus disease-2019 (COVID-19) has resulted in nationwide lockdowns, cessation of school and work, and social distancing. Reducing the negative impacts, such as weight-gain, has garnered global attention.Methods: In this dual-center retrospective observational study of 12,889 students (aged 18-20), who performed a national student physical fitness battery between December 1, 2019, to January 20, 2020, and completed a follow-up online questionnaire beginning on May 1, 2020, and ending on May 23, 2020, and examined the associations between weight-gain and COVID-19 induced stress, depression and self-reported physical activity, dietary habits and sedentary time. Results: Participants gained an average of 2.6 kg (95% CI: 2.0 to 3.2 kg) for males and 2.1 kg (1.9 to 2.4 kg) for females. An increase in overweight and obese individuals according to Asian cut-off points as a demographic percentage by 4.5% and 2.7% and 4.8% and 3.4% in males and females respectively (P<0.001). Weight change was associated with sedentary time, COVID-19 induced stress, and depression score. Conclusion: These findings suggest that limiting sedentary time during lockdowns and strategies aimed t improve lifestyle habits and psychological health may be warranted to mitigate weight-gain during the pandemic.Registration: Registered with ChiCTR, registration no.: ChiCTR2000033514