Rapamycin, a specific inhibitor for mTOR complex 1, is an FDA-approved immunosuppressant for organ transplant. Recent developments have raised the prospect of using rapamycin to treat cancer or diabetes and to delay aging. It is therefore important to assess how rapamycin treatment affects glucose homeostasis. Here, we show that the same rapamycin treatment reported to extend mouse life span significantly impaired glucose homeostasis of aged mice. Moreover, rapamycin treatment of lean C57B/L6 mice reduced glucose-stimulated insulin secretion in vivo and ex vivo as well as the insulin content and beta cell mass of pancreatic islets. Confounding the diminished capacity for insulin release, rapamycin decreased insulin sensitivity. The multitude of rapamycin effects thus all lead to glucose intolerance. As our findings reveal that chronic rapamycin treatment could be diabetogenic, monitoring glucose homeostasis is crucial when using rapamycin as a therapeutic as well as experimental reagent.

Aging of the skin is associated with skin thinning, atrophy, dryness, wrinkling, and delayed wound healing. These undesirable aging effects are exacerbated by declining estrogen levels in postmenopausal women. With the rise in interest in long-term postmenopausal skin management, studies on the restorative benefits that estrogen may have on aged skin have expanded. Systemic estrogen replacement therapy (ERT) has been shown to improve some aspects of skin. Estrogen restores skin thickness by increasing collagen synthesis while limiting excessive collagen degradation. Wrinkling is improved following estrogen treatment since estrogen enhances the morphology and synthesis of elastic fibers, collagen type III, and hyaluronic acids. Dryness is also alleviated through increased water-holding capacity, increased sebum production, and improved barrier function of the skin. Furthermore, estrogen modulates local inflammation, granulation, re-epithelialization, and possibly wound contraction, which collectively accelerates wound healing at the expense of forming lower quality scars. Despite its promises, long-term ERT has been associated with harmful systemic effects. In the search for safe and effective alternatives with more focused effects on the skin, topical estrogens, phytoestrogens, and tissue-specific drugs called selective estrogen receptor modulators (SERMs) have been explored. We discuss the promises and challenges of utilizing topical estrogens, SERMs, and phytoestrogens in postmenopausal skin management.

Background Diabetic peripheral neuropathy (DPN) is the most common chronic complication of diabetes mellitus that has a considerable impact on quality of life, but there are few effective therapeutic strategies. The aim of this trial is to determine the efficacy and safety of manual acupuncture (MA) versus sham acupuncture (SA) for DPN. Methods/design This is a study protocol for a randomized, placebo-controlled clinical trial. A total of 118 patients with DPN will be recruited and randomly assigned in a 1:1 ratio to either the MA group or SA group. All patients will receive 24 sessions over 12 weeks. Participants will complete the trial by visiting the research center at month 6 for a follow-up assessment. The primary outcome is peroneal motor nerve conduction velocity (peroneal MNCV) at week 12 compared with baseline. Secondary outcomes include peroneal motor nerve action potential amplitude (peroneal MNAP) and latent period (peroneal MNLP), sural sensory nerve conduction velocity (sural SNCV), action potential amplitude (sural SNAP) and latent period (sural SNLP), fasting plasma glucose (FPG), 2-h postprandial blood glucose (2hPG), glycated hemoglobin (HbAlc) at week 12 compared with baseline, Michigan Neuropathy Screening Instrument (MNSI) score and Diabetes Specific Quality of Life scale (DSQL) at week 12 and month 6 compared with baseline. Safety will be assessed during the whole trial. Masking effectiveness will be assessed by patients. Discussion This trial may provide high-quality evidence for evaluating the efficacy and safety of MA treatment for DPN compared with SA treatment. Results of this study will be published in peer-reviewed journals. Trial registration Chinese Clinical Trials Registry ChiCTR1800020444. First registered on 29 December 2018, retrospectively registered, http://www.chictr.org.cn/showproj.aspx?Proj=31063.

Background Diabetic peripheral neuropathy (DPN) is the most common chronic complication of diabetes mellitus that has a considerable impact on quality of life, but there are few effective therapeutic strategies. The aim of this trial is to determine the efficacy and safety of manual acupuncture (MA) versus sham acupuncture (SA) for DPN. Methods/design: This is a study protocol for a randomized, two-arm, single centre, clinical trial. A total of 118 patients with DPN will be recruited and randomly assigned to the MA group or the SA group in a 1:1 ratio. All patients will receive 24 sessions over 12weeks. Participants will complete the trial by visiting the research centre at month 6 for a follow-up assessment. The primary outcome is the peroneal motor nerve conduction velocity (peroneal MNCV) at week 12 compared with baseline. Secondary outcomes include the peroneal motor nerve action potential amplitude (peroneal MNAP) and latent period(peroneal MNLP), the sural sensory nerve conduction velocity (sural SNCV), action potential amplitude (sural SNAP) and latent period (sural SNLP), fasting plasma glucose(FPG), 2-hour postprandial blood glucose (2hPG), glycated hemoglobin (HbAlc) at week 12 compared with baseline, the Michigan Neuropathy Screening Instrument (MNSI) score and Diabetes Specific Quality of Life scale(DSQL) at week 12 and month 6 compared with baseline. Safety is assessed during the whole trial. Masking effectiveness is assessed by patients. Discussion This trial may provide high-quality evidence for evaluating the efficacy and safety of MA treatment for DPN compared with SA treatment. The results of this study will be published in peer-reviewed journals. Trial registration: Chinese Clinical Trials Registry, ID: ChiCTR1800020444. First registered on 29 December 2018 - Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?Proj =31063

Background: Diabetic peripheral neuropathy (DPN) is the most common chronic complication of diabetes mellitus that has a considerable impact on quality of life, but there are few effective therapeutic strategies. The aim of this trial is to determine the efficacy and safety of manual acupuncture (MA) versus sham acupuncture (SA) for DPN.Methods/Design: This is a study protocol for a randomized, placebo-controlled clinical trial. A total of 118 patients with DPN will be recruited and randomly assigned in a 1:1 ratio to either MA group or SA group. All patients will receive 24 sessions over 12 weeks. Participants will complete the trial by visiting the research center at month 6 for a follow-up assessment. The primary outcome is peroneal motor nerve conduction velocity (peroneal MNCV) at week 12 compared with baseline. Secondary outcomes include peroneal motor nerve action potential amplitude (peroneal MNAP) and latent period (peroneal MNLP), sural sensory nerve conduction velocity (sural SNCV), action potential amplitude (sural SNAP) and latent period (sural SNLP), fasting plasma glucose (FPG), 2-hour postprandial blood glucose (2hPG), glycated hemoglobin (HbAlc) at week 12 compared with baseline, Michigan Neuropathy Screening Instrument (MNSI) score and Diabetes Specific Quality of Life scale (DSQL) at week 12 and month 6 compared with baseline. Safety will be assessed during the whole trial. Masking effectiveness will be assessed by patients.Discussion: This trial may provide high-quality evidence for evaluating the efficacy and safety of MA treatment for DPN compared with SA treatment. Results of this study will be published in peer-reviewed journals.Trial registration: Chinese Clinical Trials Registry, ID: ChiCTR1800020444. First registered on 29 December 2018 - Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?Proj =31063

Background: Diabetic peripheral neuropathy (DPN) is the most common chronic complication of diabetes mellitus that has a considerable impact on quality of life, but there are few effective therapeutic strategies. The aim of this trial is to determine the efficacy and safety of manual acupuncture (MA) versus sham acupuncture (SA) for DPN.Methods/Design: This is a study protocol for a randomized, placebo-controlled clinical trial. A total of 118 patients with DPN will be recruited and randomly assigned in a 1:1 ratio to either MA group or SA group. All patients will receive 24 sessions over 12 weeks. Participants will complete the trial by visiting the research center at month 6 for a follow-up assessment. The primary outcome is peroneal motor nerve conduction velocity (peroneal MNCV) at week 12 compared with baseline. Secondary outcomes include peroneal motor nerve action potential amplitude (peroneal MNAP) and latent period (peroneal MNLP), sural sensory nerve conduction velocity (sural SNCV), action potential amplitude (sural SNAP) and latent period (sural SNLP), fasting plasma glucose (FPG), 2-hour postprandial blood glucose (2hPG), glycated hemoglobin (HbAlc) at week 12 compared with baseline, Michigan Neuropathy Screening Instrument (MNSI) score and Diabetes Specific Quality of Life scale (DSQL) at week 12 and month 6 compared with baseline. Safety will be assessed during the whole trial. Masking effectiveness will be assessed by patients.Discussion: This trial may provide high-quality evidence for evaluating the efficacy and safety of MA treatment for DPN compared with SA treatment. Results of this study will be published in peer-reviewed journals.Trial registration: Chinese Clinical Trials Registry, ID: ChiCTR1800020444. First registered on 29 December 2018 - Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?Proj =31063