Protocol for a randomized controlled trial exploring the brain mechanism and therapeutic effect of electroacupuncture on cognitive function and sleep quality in chronic insomnia.

BACKGROUND: Insomnia is a prevalent sleep disorder that affects up to 15% of the population worldwide and is the second most common mental health issue. There is increasing interest in the effects of long-term insomnia on cognitive function. Electroacupuncture can effectively improve cognitive function and sleep quality, yet the underlying brain network mechanisms remain unclear. This study aims to explore the network regulatory mechanisms associated with enhanced cognitive function and sleep quality, providing theoretical support for the use of electroacupuncture in the clinical treatment of chronic insomnia. METHODS: This study is divided into two parts. Sixteen individuals with chronic insomnia and 16 healthy controls of similar age and gender will be recruited in Study 1 to examine the brain network topology of individuals with chronic insomnia. Study 2 will be a randomized controlled trial with 120 chronic insomnia patients divided into three groups: Group A (electroacupuncture plus placebo drug), Group B (drug plus placebo electroacupuncture), and Group C (placebo electroacupuncture plus placebo drug). Participants will be exposed to 24 treatments over an 8-week period (3 times per week) and monitored for 12 additional weeks. The primary outcome measure will be changes in brainwave data from before to after the treatment. In addition, the Wisconsin Card Sorting Test and the Pittsburgh Sleep Quality Index will be utilized as secondary outcomes to measure from before to after treatment and during the follow-up. A correlation analysis will be conducted to explore links among modifications in brainwave patterns, Wisconsin Card Sorting Test scores, and Pittsburgh Sleep Quality Index scores. Additionally, any adverse events will be strictly monitored. DISCUSSION: Electroacupuncture may represent an alternative treatment for chronic insomnia, and this trial is expected to reveal the brain mechanism by which electroacupuncture improves cognitive function and sleep quality in chronic insomnia patients. TRIAL REGISTRATION: ChiCTR2200060150 (Chinese Clinical Trial Registry, http://www.chictr.org.cn , registered on 20 May 2022).

Toward a panoramic perspective of the association between environmental factors and cardiovascular disease: An environment-wide association study from National Health and Nutrition Examination Survey 1999-2014.

OBJECTIVES: An environment-wide association study (EWAS) may be useful to comprehensively test and validate associations between environmental factors and cardiovascular disease (CVD) in an unbiased manner. APPROACH AND RESULTS: Data from National Health and Nutrition Examination Survey (1999-2014) were randomly 50:50 spilt into training set and testing set. CVD was ascertained by a self-reported diagnosis of myocardial infarction, coronary heart disease or stroke. We performed multiple linear regression analyses associating 203 environmental factors and 132 clinical phenotypes with CVD in training set (false discovery rate < 5%) and significant factors were validated in the testing set (P < 0.05). Random forest (RF) model was used for multicollinearity elimination and variable importance ranking. Discriminative power of factors for CVD was calculated by area under the receiver operating characteristic (AUROC). Overall, 43,568 participants with 4084 (9.4%) CVD were included. After adjusting for age, sex, race, body mass index, blood pressure and socio-economic level, we identified 5 environmental variables and 19 clinical phenotypes associated with CVD in training and testing dataset. Top five factors in RF importance ranking were: waist, glucose, uric acid, and red cell distribution width and glycated hemoglobin. AUROC of the RF model was 0.816 (top 5 factors) and 0.819 (full model). Sensitivity analyses reveal no specific moderators of the associations. CONCLUSION: Our systematic evaluation provides new knowledge on the complex array of environmental correlates of CVD. These identified correlates may serve as a complementary approach to CVD risk assessment. Our findings need to be probed in further observational and interventional studies.

Polysaccharide from Fuzi protects against Ox­LDL­induced calcification of human vascular smooth muscle cells by increasing autophagic activity.

Polysaccharide from Fuzi (FPS) is a water­soluble polysaccharide isolated from the traditional Chinese herbal medicine Fuzi. It has been demonstrated to protect hepatocytes against ischemia­reperfusion injury through its potent antioxidant effects, and to attenuate starvation­induced cytotoxicity in H9c2 cells by increasing autophagic activity. In the present study, Alizarin Red S staining was used to detect mineral deposition and reverse transcription­quantitative polymerase chain reaction was used to detect the core binding factor α1 and smooth muscle 22α mRNA expression. To analyze autophagic activity, western blotting was used to detect microtubule­associated protein 1A/1B light chain 3 and nucleoporin P62 expression. In addition, green fluorescent protein­LC3 dots­per­cell was observed by fluorescence microscopy. It was demonstrated that oxidized low­density lipoprotein (Ox­LDL) could increase the calcification of human vascular smooth muscle cells (VSMCs) in a concentration­dependent manner, and that FPS treatment had a significant protective effect against Ox­LDL­induced calcification of human VSMCs. Furthermore, FPS treatment alleviated the Ox­LDL­induced downregulation of autophagic activity, and the protective effect of FPS on Ox­LDL­induced calcification was attenuated by the autophagy inhibitor 3­methyladenine. In conclusion, the present study demonstrated for the first time to the best of the authors' knowledge that FPS can protect against Ox­LDL­induced vascular calcification in human VSMCs, and that this likely occurs via the activation of autophagy. This supports the hypothesis that autophagy may be an endogenous protective mechanism counteracting vascular calcification, and that FPS may be used as a potential therapeutic for vascular calcification.

Comparison of acarbose and metformin therapy in newly diagnosed type 2 diabetic patients with overweight and/or obesity.

OBJECTIVE: To compare the efficacy of acarbose and metformin in overweight and/or obese patients with newly diagnosed type 2 diabetes mellitus (T2DM). METHODS: A total of 108 drug-naïve patients with newly diagnosed T2DM, whose hemoglobin A1c (HbA1c) was between 7% and 10% and body mass index was greater than 24 kg/m(2), were enrolled in the First People's Hospital and Municipal Central Hospital of Xiangtan City, Xiangtan, China, from 1 February 2010 to 1 August 2011. Patients were randomly assigned to acarbose (100 mg three times a day) and metformin (1.5 g/day) groups for a predictive follow-up period of 24 weeks. Plasma glucose, insulin, and glucagons at 0, 0.5, and 2 hours after a standardized meal, and HbA1c were measured at baseline and 24 weeks. RESULTS: Baseline characteristics of the acarbose and metformin groups were similar. Glucose control improved significantly in both groups at 24 weeks. The percentage of patients achieving HbA1C <6.5% was comparable for acarbose and metformin therapy at 24 weeks. Body weight reduction from baseline to 24 weeks was 3.3 kg in the acarbose group and 2.7 kg in the metformin group, whereas the change in HbA1c and body weight was similar in both groups. The early-phase insulin secretion index improved only in the acarbose group at 24 weeks. After 24 weeks of therapy, fasting glucagon and 0.5 hour postprandial glucagon levels decreased markedly in the acarbose group compared to the metformin group. CONCLUSIONS: Twenty-four weeks of therapy with acarbose and metformin induced similar reductions in HbA1c and body weight, but acarbose showed superior efficacy in improving islet α-cell function compared with metformin in overweight/obese patients with newly diagnosed T2DM. However, more large-sample, multicenter, randomized controlled trials are needed to evaluate the efficacy, safety, cost-effectiveness, and glycemic variability of the two drugs.

Polysaccharide from Fuzi likely protects against starvation-induced cytotoxicity in H9c2 cells by increasing autophagy through activation of the AMPK/mTOR pathway.

There is increasing evidence that starvation induces autophagy, which may be protective during starvation, in an AMPK-dependent manner. Polysaccharides from Fuzi (FPS) reportedly have protective effects on nutrition-limited livers. The present study was designed to determine whether FPS protected H9c2 cells against starvation-induced cytotoxicity using an AMPK/mTOR-dependent mechanism. H9c2 cells were incubated in serum and glucose starvation media for 12 hours to establish a cell injury model. 3-Methyladenine (3MA, an autophagy inhibitor) was used to identify the exact role of autophagy in starvation. Cells were incubated with different FPS concentrations, and the cell injury levels, autophagy activity and AMPK/mTOR phosphorylation were measured. Adenine 9-ß-D-arabinofuranoside (Ara-A, an AMPK inhibitor) and 5-amino-4-imidazole-carboxamide riboside (AICAR, an AMPK activator) were used to identify whether the AMPK/mTOR pathway was involved in FPS-mediated cardioprotection. We demonstrated that starvation decreased cell viability in a time-dependent manner, and 3MA-induced autophagy inhibition aggravated the reduced cell viability. FPS treatment attenuated the cell viability decrement and the starvation-induced decline in the mitochondrial membrane potential (MMP), and autophagy; also, the AMPK/mTOR pathways were activated during treatment. Ara-A treatment abolished the protective effect of FPS, while AICAR treatment had a similar effect to FPS. We conclude that autophagy attenuates starvation-induced cardiomyocyte death, and FPS increases autophagy activity to protect against starvation-induced cytotoxicity in H9c2 cells, likely through AMPK/mTOR pathway activation.

Jiaweisinisan facilitates neurogenesis in the hippocampus after stress damage.

The traditional Chinese medicine Jiaweisinisan has antidepressant effects, and can inhibit hypothalamus-pituitary-adrenal gland axis hyperactivity in stress-induced depression. In this study, rat hippocampal neural precursor cells were cultured in serum-free medium in vitro and a stress damage model was established with 120 µM corticosterone. Cells were treated with 10% (v/v) Jiaweisinisan drug-containing serum and the corticosterone antagonist RU38486. Results of the 3-(4,5-dimethylthiazol-2-yl)-3,5-di-phenytetrazoliumromide assay showed that both Jiaweisinisan drug-containing serum and RU38486 promoted the proliferation of neural precursor cells after corticosterone exposure. Immunofluorescence detection showed that after Jiaweisinisan drug-containing serum and RU38486 treatment, the 5-bromo-2-deoxyuridine/terminal deoxynucleotidyl transferase dUTP nick end labeling ratio in hippocampal neural precursor cells significantly increased, and the apoptotic rates of glial cells reduced, and neuron-like cell differentiation from neural precursor cells significantly increased. Our experimental findings indicate that Jiaweisinisan promotes hippocampal neurogenesis after stress damage.