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Background Diabetic peripheral neuropathy (DPN) is one of the common complications in diabetic patients, and TCM external therapies represented by acupuncture has some advantages in treating DPN, but what combination of TCM external therapies and conventional Western medicine has the best efficacy in treating DPN is still lacking evidence-based medical studies. Objective To evaluate the efficacy and safety of the five commonly used external therapies of TCM combined with conventional Western medicine in treating DPN by Bayesian Network Meta-analysis. Methods The five commonly used external therapies of TCM confirmed by pre-survey were acupuncture, foot bath, acupoint massage, acupoint injection and moxibustion, respectively. The Cochrane Library, Web of Science, PubMed, SinoMed, VIP, Wanfang Data and CNKI were searched by computer from their inception to December 29th, 2020, to screen randomized controlled trials (RCTs) about efficacy and safety of the five commonly used external therapies of TCM combined with conventional Western medicine in treating DPN. RevMan 5.3, Stata 15.0 and ADDIS 1.16.6 software were used for plotting and data analysis. Results A total of 44 RCTs were enrolled, including 3 471 patients with DPN. Bayesian network Meta-analysis showed that the five commonly used external therapies of TCM combined with Western medicine were all superior to conventional Western medicine alone in improving overall efficacy rate, of which acupuncture had the best effect〔OR=0.20, 95%CI (0.11, 0.36) 〕. Except for acupoint massage, the other four commonly used external therapies of TCM combined with conventional Western medicine were all superior to conventional Western medicine alone in improving median nerve motor conduction velocity (MNCV) , with acupoint injection being the most effective〔MD=-4.50, 95%CI (-5.91, -3.11) 〕. The five commonly used external therapies of TCM combined with conventional Western medicine were all superior to conventional Western medicine alone in improving median nerve sensory conduction velocity (SNCV) , in which moxibustion had the best effect〔MD=-9.03, 95%CI (-12.59, -5.47) 〕. Except for acupoint massage, the other four commonly used external therapies of TCM combined with conventional Western medicine were all superior to conventional Western medicine alone, with moxibustion having the best effect〔MD=-6.34, 95%CI (-9.31, -3.30) 〕. Except for acupoint massage, the other four commonly used external therapies of TCM combined with conventional western medicine were all superior to conventional Western medicine alone in improving SNCV of the common peroneal nerve, with acupuncture showing the best efficacy〔MD=-5.70, 95%CI (-8.03, -3.31) 〕. Conclusion Acupuncture combined with conventional Western medicine is recommended preferentially in treating DPN based on available literature evidence, especially in improving overall efficacy rate and SNCV of the common peroneal nerve, but more high-quality studies are still needed for further validation.

Protein synthesis regulation is critical for skeletal muscle hypertrophy, yet other established cellular processes are necessary for growth-related cellular remodeling. Autophagy has a well-acknowledged role in muscle quality control, but evidence for its role in myofiber hypertrophy remains equivocal. Both mammalian target of rapamycin complex I (mTORC1) and bone morphogenetic protein (BMP)-Smad1/5 (Sma and Mad proteins from Caenorhabditis elegans and Drosophila, respectively) signaling are reported regulators of myofiber hypertrophy; however, gaps remain in our understanding of how this regulation is integrated with growth processes and autophagy regulation. Therefore, we investigated the mTORC1 and Smad1/5 regulation of protein synthesis and autophagy flux during serum-stimulated myotube growth. Chronic serum stimulation experiments were performed on day 5 differentiated C2C12 myotubes incubated in differentiation medium [2% horse serum (HS)] or growth medium [5% fetal bovine serum (FBS)] for 48 h. Rapamycin or LDN193189 was dosed for 48 h to inhibit mTORC1 and BMP-Smad1/5 signaling, respectively. Acute serum stimulation was examined in day 7 differentiated myotubes. Protein synthesis was measured by puromycin incorporation. Bafilomycin A1 and immunoblotting for LC3B were used to assess autophagy flux. Chronic serum stimulation increased myotube diameter 22%, total protein 21%, total RNA 100%, and Smad1/5 phosphorylation 404% and suppressed autophagy flux. Rapamycin, but not LDN193189, blocked serum-induced myotube hypertrophy and the increase in total RNA. Acute serum stimulation increased protein synthesis 111%, Smad1/5 phosphorylation 559%, and rpS6 phosphorylation 117% and suppressed autophagy flux. Rapamycin increased autophagy flux during acute serum stimulation. These results provide evidence for mTORC1, but not BMP-Smad1/5, signaling being required for serum-induced myotube hypertrophy and autophagy flux by measuring LC3BII/I expression. Further investigation is warranted to examine the role of autophagy flux in myotube hypertrophy. NEW & NOTEWORTHY: The present study demonstrates that myotube hypertrophy caused by chronic serum stimulation requires mammalian target of rapamycin complex 1 (mTORC1) signaling but not bone morphogenetic protein (BMP)-Smad1/5 signaling. The suppression of autophagy flux was associated with serum-induced myotube hypertrophy and mTORC1 regulation of autophagy flux by measuring LC3BII/I expression. Rapamycin is widely investigated for beneficial effects in aging skeletal muscle and sarcopenia; our results provide evidence that rapamycin can regulate autophagy-related signaling during myotube growth, which could benefit skeletal muscle functional and metabolic health. [ABSTRACT FROM AUTHOR]