Effect of repetitive transcranial magnetic stimulation on patients with severe depression: a study protocol for systematic review and meta-analysis of randomised clinical trials.

INTRODUCTION: Depression is characterised by easy recurrence, high disability and high burden, and antidepressant therapy is the standard treatment. However, its treatment effect on patients with severe depressive disorder has been unsatisfactory. Previous studies have shown that repetitive transcranial magnetic stimulation (rTMS), as a neurotherapy, can effectively mitigate the severity of depressive symptoms. Yet, more evidence is still required for TMS to treat severe depression. This study will be the first systematic review of the efficacy and tolerability of TMS for treating severe depression. We expect it to guide future clinical practice of TMS for the treatment of psychiatric disorders. METHODS AND ANALYSIS: We will search for the randomised controlled trial (RCT) involving rTMS for treating depression in eight electronic databases, including PubMed, Web of Science, EMBASE, the Cochrane Library and Wanfang Database, from publication up to September 2021. We will define Improvement in depressive symptoms, the difference between pretreatment (baseline) and post-treatment as the primary outcomes. The difference between pretreatment and post-treatment changes in resting state fMRI will be regarded as the secondary outcomes. Quality assessment of the included articles will be independently performed according to the Cochrane Risk of Bias tool. ETHICS AND DISSEMINATION: Ethical approval is not essential because there is no need to collect individual patient data. And this study will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: CRD42020211460.

Astragaloside IV protects against diabetic nephropathy via activating eNOS in streptozotocin diabetes-induced rats.

BACKGROUND: Astragaloside IV (AS-IV) was reported to play a role in improving diabetic nephropathy (DN), however, the underlying mechanisms still remain unclear. The aim of the present study is to investigate whether AS-IV ameliorates DN via the regulation of endothelial nitric oxide synthase (eNOS). METHODS: DN model was induced in Sprague-Dawley (SD) male rats by intraperitoneal injection of 65 mg/kg streptozotocin (STZ). Rats in the AS-IV treatment group were orally gavaged with 5 mg/kg/day or 10 mg/kg/day AS-IV for eight consecutive weeks. Body weight, blood glucose, blood urea nitrogen (BUN), Serum creatinine (Scr), proteinuria and Glycosylated hemoglobin (HbA1c) levels were measured. Hematoxylin-Eosin (HE) and Periodic Acid-Schiff (PAS) staining were used to detect the renal pathology. The apoptosis status of glomerular cells was measured by TUNEL assay. The phosphorylation and acetylation of eNOS were detected by western blot. The effects of AS-IV on high-glucose (HG)-induced apoptosis and eNOS activity were also investigated in human renal glomerular endothelial cells (HRGECs) in vitro. RESULTS: Treatment with AS-IV apparently reduced DN symptoms in diabetic rats, as evidenced by reduced BUN, Scr, proteinuria, HbA1c levels and expanding mesangial matrix. AS-IV treatment also promoted the synthesis of nitric oxide (NO) in serum and renal tissues and ameliorated the phosphorylation of eNOS at Ser 1177 with decreased eNOS acetylation. Moreover, HG-induced dysfunction of HRGECs including increased cell permeability and apoptosis, impaired eNOS phosphorylation at Ser 1177, and decreased NO production, were all reversed by AS-IV treatment. CONCLUSIONS: These novel findings suggest that AS-IV ameliorates functional abnormalities of DN through inhibiting acetylation of eNOS and activating its phosphorylation at Ser 1177. AS-IV could be served as a potential therapeutic drug for DN.