The effectiveness of optimal exercise-based strategy for patients with hip fracture: a systematic review and Bayesian network meta-analysis.

The implementation of exercise intervention (EI) presents a promising and economical way for patients with hip fracture. However, the optimal type of EI remains unclear. The objective of this study is to evaluate the efficacy of various EI approaches and identify the optimal intervention for improving the prognosis of patients with hip fracture. A comprehensive search of Medline (via PubMed), Web of Science, Embase, Cochrane Central Register of Controlled Trials, CINAHL, CNKI, Wan Fang, VIP, and CBM was conducted from their earliest records to June 2022. The included randomized controlled trials (RCTs) included at least one type of exercise for patients with hip fracture. The methodological quality of these trials was assessed using the Cochrane Collaboration Risk of Bias Tool. All direct and indirect comparisons were analyzed by Stata 14.0 and OpenBUGS 3.2.3 software. The primary outcome was hip function, and the secondary outcomes were activity of daily living (ADL), walking capacity and balance ability of patients. Based on the ranking probabilities, resistance exercise (RE) was ranked as the most effective among all exercise interventions (surface under cumulative ranking curve values [SUCRA]: 94.8%, [MD]: - 11.07, [Crl]: - 15.07 to - 7.08) in improving the efficacy of patients' hip function, followed by balance exercise (BE) ([SUCRA]:81.1%, [MD]: - 8.79, [Crl]: - 13.41 to - 4.18) and muscle strength exercise ([SUCRA]:57.6%, [MD]: - 5.35, [Crl]: - 9.70 to - 0.95). For the improvement of ADL for patients with hip fracture, BE ([SUCRA]:98.4%, [MD]: - 17.38, [Crl]: - 23.77 to - 11.04) may be the best EI. The findings of this study indicate that RE and BE might be the best approach to improve prognosis for patients with hip fracture. However, further rigorous and meticulously planned RCTs are required to substantiate the conclusions drawn from this study.

Endogenous asymmetric dimethylarginine accumulation precipitates the cardiac and mitochondrial dysfunctions in type 1 diabetic rats.

Myocardial mitochondrial function and biogenesis are suppressed in diabetes, but the mechanisms are unclear. Increasing evidence suggests that asymmetric dimethylarginine (ADMA) is associated with diabetic cardiovascular complications. This study was to determine whether endogenous ADMA accumulation contributes to cardiac and mitochondrial dysfunctions of diabetic rats and elucidate the potential mechanisms. Diabetic rat was induced by single intraperitoneal injection of streptozotocin (50 mg/kg). N-acetylcysteine was given (250 mg/kg/d) by gavage for 12w. Cardiac function was detected by echocardiography. Left ventricle papillary muscles were isolated to examine myocardial contractility. Myocardial ATP and mitochondrial DNA contents were measured to evaluate mitochondrial function and biogenesis. Endogenous ADMA accumulation was augmented resulting in decreased nitric oxide (NO) production and increased oxidative stress, suggesting NO synthase (NOS) uncoupling in the myocardium of T1DM rats compared with control rats. ADMA augmentation was associated with cardiac and mitochondrial dysfunctions along with myocardial uncoupling protein-2 (UCP2) upregulation and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) downregulation in T1DM rats. Exogenous ADMA could directly inhibit myocardial contractility, mitochondrial function and biogenesis in parallel with decreasing NO content and PGC-1α expression while increasing oxidative stress and UCP2 expression in papillary muscles and cardiomyocytes. Treatment with antioxidant N-acetylcysteine, also an inhibitor of NOS uncoupling, either ameliorated ADMA-associated cardiac and mitochondrial dysfunctions or reversed ADMA-induced NO reduction and oxidative stress enhance in vivo and in vitro. These results indicate that myocardial ADMA accumulation precipitates cardiac and mitochondrial dysfunctions in T1DM rats. The underlying mechanism may be related to NOS uncoupling, resulting in NO reduction and oxidative stress increment, ultimate PGC-1α down-regulation and UCP2 up-regulation.

Asymmetrical dimethylarginine induces dysfunction of insulin signal transduction via endoplasmic reticulum stress in the liver of diabetic rats.

AIMS: Endoplasmic reticulum stress (ERS) as an emerging factor is involved in insulin resistance (IR), which is the pathological basis of diabetes mellitus. Accumulation of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase is associated with IR, but the underlying mechanisms have not been elucidated. This study was to reveal the important role of ADMA in IR and determine whether endogenous ADMA accumulation contributes to hepatic IR via ERS in diabetic rats and hepatocytes. MATERIALS AND METHODS: Diabetic rat model was induced by a single intraperitoneal injection of streptozotocin (50 mg/kg). Phosphorylation of insulin receptor substrate 1 (IRS1) and protein kinase B (Akt) was detected to evaluate IR. The protein kinase PKR-like ER kinase (PERK) and eukaryotic initiation factor 2α kinase (eIF2α) phosphorylation, x-box binding protein-1 (XBP-1) splicing, glucose-regulated protein 78 (GRP78) and C/EBP homologues protein (CHOP) expressions were measured to assess ERS. KEY FINDINGS: Endogenous ADMA content was significantly increased and positively correlated with either IR as evidenced by increased IRS1 at serine and reduced Akt phosphorylation or ERS as indicated by upregulations of PERK and eIF2α phosphorylation, XBP-1 splicing, GRP78 and CHOP expressions in the liver of diabetic rats compared with control rats. Exogenous ADMA directly caused IR and ERS in dose- and time-dependent manners in primary mouse hepatocytes. Pretreatment with ERS inhibitor 4-phenylbutyrate or ADMA antagonist L-arginine not only improved ADMA-associated or -induced hepatic IR but also attenuated ADMA-associated or -induced ERS in diabetic rats or hepatocytes. SIGNIFICANCE: These findings indicate that endogenous ADMA accumulation contributes to hepatic IR via ERS in diabetic rats.