Chinese herbal medicine and active ingredients for diabetic cardiomyopathy: molecular mechanisms regulating endoplasmic reticulum stress.

Background: Diabetic cardiomyopathy (DCM) is one of the serious microvascular complications of diabetes mellitus. It is often associated with clinical manifestations such as arrhythmias and heart failure, and significantly reduces the quality of life and years of survival of patients. Endoplasmic reticulum stress (ERS) is the removal of unfolded and misfolded proteins and is an important mechanism for the maintenance of cellular homeostasis. ERS plays an important role in the pathogenesis of DCM by causing cardiomyocyte apoptosis, insulin resistance, calcium imbalance, myocardial hypertrophy and fibrosis. Targeting ERS is a new direction in the treatment of DCM. A large number of studies have shown that Chinese herbal medicine and active ingredients can significantly improve the clinical outcome of DCM patients through intervention in ERS and effects on myocardial structure and function, which has become one of the hot research directions. Purpose: The aim of this review is to elucidate and summarize the roles and mechanisms of Chinese herbal medicine and active ingredients that have the potential to modulate endoplasmic reticulum stress, thereby contributing to better management of DCM. Methods: Databases such as PubMed, Web of Science, China National Knowledge Internet, and Wanfang Data Knowledge Service Platform were used to search, analyze, and collect literature, in order to review the mechanisms by which phytochemicals inhibit the progression of DCM by targeting the ERS and its key signaling pathways. Keywords used included "diabetic cardiomyopathy" and "endoplasmic reticulum stress." Results: This review found that Chinese herbs and their active ingredients can regulate ERS through IRE1, ATF6, and PERK pathways to reduce cardiomyocyte apoptosis, ameliorate myocardial fibrosis, and attenuate myocardial hypertrophy for the treatment of DCM. Conclusion: A comprehensive source of information on potential ERS inhibitors is provided in this review. The analysis of the literature suggests that Chinese herbal medicine and its active ingredients can be used as potential drug candidates for the treatment of DCM. In short, we cannot ignore the role of traditional Chinese medicine in regulating ERS and treating DCM, and look forward to more research and new drugs to come.

Virtual Standardized Patients Versus Traditional Academic Training for Improving Clinical Competence Among Traditional Chinese Medicine Students: Prospective Randomized Controlled Trial.

BACKGROUND: The practical training course of internal medicine of traditional Chinese medicine (PTC-IMTCM) is primarily based on traditional case teaching, which can be stressful for teachers. The use of virtual standardized patient (VSP) applications could be an alternative; however, there is limited evidence regarding their feasibility and effectiveness. OBJECTIVE: This study aimed to build a VSP-TCM application according to the characteristics of PTC-IMTCM and the needs of students and to compare its efficacy with that of traditional teaching in improving TCM clinical competence among students. METHODS: A prequestionnaire investigation was conducted before the course, and a VSP-TCM system was developed based on the results of the questionnaire. A randomized controlled trial was then conducted between February 26, 2020, and August 20, 2021. A total of 84 medical students were included and were divided into 2 groups: an observation group, trained with VSP-TCM (n=42, 50%), and a control group, trained with traditional academic training (n=42, 50%). Formative and summative assessments were conducted to evaluate teaching effectiveness. After completing the course, the students were administered a questionnaire to self-assess their satisfaction with the course. A questionnaire was also administered to 15 teachers to uncover their perspectives on VSP-TCM. RESULTS: All participants completed the study. In the formative assessment, the VSP-TCM group performed better in medical interviewing ability (mean 7.19, SD 0.63, vs mean 6.83, SD 0.81; P=.04), clinical judgment (mean 6.48, SD 0.98, vs mean 5.86, SD 1.04; P=.006), and comprehensive ability (mean 6.71, SD 0.59, vs mean 6.40, SD 0.58; P=.02) than the control group. Similarly, in the summative evaluation, the VSP-TCM group performed better in the online systematic knowledge test (OSKT; mean 86.62, SD 2.71, vs mean 85.38, SD 2.62; P=.046), application of TCM technology (mean 87.86, SD 3.04, vs mean 86.19, SD 3.08; P=.02), TCM syndrome differentiation and therapeutic regimen (mean 90.93, SD 2.42, vs mean 89.60, SD 2.86; P=.03), and communication skills (mean 90.67, SD 4.52, vs mean 88.24, SD 4.56; P=.02) than the control group. There was no significant difference in medical writing between both groups (mean 75.07, SD 3.61, vs mean 75.71, SD 2.86; P=.37). The postcourse feedback questionnaire indicated that VSP-TCM can better enhance students' TCM thinking ability (n=39, 93%, vs n=37, 88%; P=.002), medical history collection (n=38, 90%, vs n=30, 72; P=.001), syndrome differentiation and treatment and critical thinking (n=38, 90%, vs n=37, 88%; P=.046), comprehensive clinical application ability (n=40, 95%, vs n=36, 86%; P=.009), interpersonal communication skills (n=36, 86%, vs n=28, 67%; P=.01), and autonomous learning ability (n=37, 88%, vs n=28, 67%; P=.01) than traditional academic training. Similarly, the teachers held a positive perspective on VSP-TCM. CONCLUSIONS: VSP-TCM enhances students' TCM clinical competence and dialectical thinking and improves their ability to work autonomously. Moreover, the VSP-TCM system is feasible, practical, and cost-effective and thus merits further promotion in TCM education.

Student standardized patients versus occupational standardized patients for improving clinical competency among TCM medical students: a 3-year prospective randomized study.

BACKGROUND: Standardized patient (SP) simulations are well-recognized patterns for practicing clinical skills and interactions. Our previous study showed that a simulation program using occupational SP for Traditional Chinese Medicine (OSP-TCMs) was efficient, however, a high cost and time-intensive nature have limited its use. TCM postgraduates trained as student SPs (SSP-TCMs) present a potentially cost-effective alternative. The purpose of this study was to examine and determine whether SSP simulation offered more benefits over didactic training alone for improving clinical competency among TCM medical students, and conduct a multifaceted analysis comparing SSP-TCMs and OSP-TCMs. METHODS: This was a prospective, single-blinded, randomized controlled trial. Fourth-year TCM undergraduates were recruited as trainees from the Clinical Medical School, Chengdu University of TCM. Data were collected from September 2018 to December 2020. Trainees were randomly divided into the three following groups: traditional method training group, OSP-TCM training group, and SSP-TCM training group (1:1:1). At the end of a 10-week curriculum, trainees received a two-station examination comprising a systematic online knowledge test and an offline clinical performance examination. Post-training and post-exam questionnaires were administered to collect feedback from these trainees. RESULTS: Students assigned to the SSP-TCM training and OSP-TCM training groups received favorable marks for the "systematic knowledge test" and "TCM clinical skills" (2018, Pa=0.018, Pb=0.042; 2019, Pa=0.01, Pb=0.033; 2020, Pa=0.035, Pb=0.039) compared to the TM trainees. Additionally, trainees in the intervention groups demonstrated a positive post-training edge in scores of "medical records" (2018, Pa=0.042, Pb=0.034; 2019, Pa=0.032, Pb=0.042; 2020, Pa=0.026, Pb=0.03) and "TCM syndrome differentiation and therapeutic regimen" (2018, Pb=0.032; 2019, Pa=0.037, Pb=0.024; 2020, Pa=0.036, Pb=0.043). For the simulation encounter assessment given by SP-TCMs, OSP-TCM trainees and SSP-TCM trainees scored higher than TM trainees (2018, Pa=0.038, Pb=0.037; 2019, Pa=0.024, Pb=0.022; 2020, Pa=0.019, Pb=0.021). For the feedback questionnaires, the students in TM group provided less positive feedback for training efficacy and test performance compared to those in the SSP-TCM and OSP-TCM groups. The trainees responded that the training effect of clinical simulations was similar between the SSP-TCM and OSP-TCM groups. SSP-TCMs were more responsive to unexpected emergencies (Pa=0.022, Pb>0.05) and more likely to encourage questioning (Pa=0.029, Pb>0.05) but tended to provide implied hints (Pc=0.015) and utilize medical jargon (Pc=0.007) as compared to OSP-TCMs. CONCLUSION: Simulation training for SSP-TCMs and OSP-TCMs showed great benefits for enhancing clinical competency. SSP-TCM simulation was feasible, practical, and cost-effective, and may serve as an alternative method to OSP-TCM simulation.

The efficacy and safety of Chinese herbal medicine as an add-on therapy for type 2 diabetes mellitus patients with carotid atherosclerosis: An updated meta-analysis of 27 randomized controlled trials.

Background: Type 2 diabetes mellitus (T2DM) is a clinical metabolic syndrome characterized by persistent hyperglycemia. Patients with T2DM are more likely to have carotid atherosclerosis (CAS), which can lead to dizziness, amaurosis or even stroke. Chinese herbal medicine (CHM) has shown possible efficacy and safety in treating T2DM patients with CAS. However, the existing evidence was not robust enough and the results were out of date. Objective: This meta-analysis aimed to summarize the current evidence and systematically evaluate the effects of CHM on carotid plaque, glucose and lipid metabolism and vascular endothelial parameters in T2DM patients with CAS, providing a reference for subsequent research and clinical practice. Methods: This study was registered in PROSPERO as CRD42022346274. Both Chinese and English databases were searched from their inceptions to 16 July 2022. All retrieved studies were screened according to inclusion and exclusion criteria. Randomized controlled trials (RCTs) using oral CHM to treat T2DM patients with CAS were included. The literature quality was assessed using the risk of bias assessment tool in the Cochrane Handbook. Data extraction was conducted on the selected studies. Review Manager 5.4 and Stata 16.0 were used for meta-analysis. Sources of heterogeneity were explored by meta-regression or subgroup analysis. Funnel plot and Egger's test were used to assess publication bias and the evidence quality was assessed by Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results: 27 eligible studies, involving 2638 patients, were included in this study. Compared with western medicine (WM) alone, the addition of CHM was significantly better in improving carotid intima-media thickness (CIMT) [mean difference (MD) = -0.11mm, 95% confidence interval (CI): -0.15 to -0.07, p < 0.01], carotid plaque Crouse score [MD = -1.21, 95%CI: -1.35 to -1.07, p < 0.01], total cholesterol (TC) [MD = -0.34 mmol/L, 95%CI: -0.54 to -0.14, p < 0.01], triglyceride (TG) [MD = -0.26 mmol/L, 95%CI: -0.37 to -0.15, p < 0.01], low-density lipoprotein cholesterol (LDL-C) [MD = -0.36 mmol/L, 95%CI: -0.47 to -0.25, p < 0.01], high-density lipoprotein cholesterol (HDL-C) [MD = 0.22 mmol/L, 95%CI: 0.13 to 0.30, p < 0.01], glycated hemoglobin (HbA1c) [MD = -0.36%, 95%CI: -0.51 to -0.21, p < 0.01], fasting blood glucose (FBG) [MD = -0.33 mmol/L, 95%CI: -0.50 to -0.16, p < 0.01], 2-h postprandial glucose (2hPG) [MD = -0.52 mmol/L, 95%CI: -0.95 to -0.09, p < 0.01], homeostasis model assessment of insulin resistance (HOMA-IR) [standardized mean difference (SMD) = -0.88, 95%CI: -1.36 to -0.41, p < 0.01] and homeostasis model assessment of beta-cell function (HOMA-ß) [MD = 0.80, 95%CI: 0.51 to 1.09, p < 0.01]. Due to the small number of included studies, it is unclear whether CHM has an improving effect on nitric oxide (NO), endothelin-1 (ET-1), peak systolic velocity (PSV) and resistance index (RI). No serious adverse events were observed. Conclusion: Based on this meta-analysis, we found that in the treatment of T2DM patients with CAS, combined with CHM may have more advantages than WM alone, which can further reduce CIMT and carotid plaque Crouse score, regulate glucose and lipid metabolism, improve insulin resistance and enhance islet ß-cell function. Meanwhile, CHM is relatively safe. However, limited by the quality and heterogeneity of included studies, the efficacy and safety of CHM remain uncertain. More high-quality studies are still needed to provide more reliable evidence for the clinical application of CHM. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022346274.

Preliminary Study of the Distinctive Mechanism of Shenqi Compound in Treating Rats with Type 2 Diabetes Mellitus by Comparing with Metformin.

BACKGROUND: In China, traditional Chinese medicine (TCM) has been used to treat type 2 diabetes mellitus (T2DM) for centuries. METHODS: To investigate how the TCM ShenQi (SQC) formulation differs from metformin, four rat groups, including control, model, T2DM rats treated using SQC (SQC group), and T2DM rats treated using metformin (Met group), were constructed. The differentially expressed genes (DEGs) between SQC and metformin groups were screened, and the co-expression modules of the DEGs were constructed based on the weighted correlation network analysis (WGCNA) method. The correlation between modules and metabolic pathways was also calculated. The potential gene targets of SQC were obtained via the TCM systems pharmacology analysis. RESULTS: A total of 962 DEGs between SQC and Met groups were screened, and these DEGs were significantly enriched in various functions, such as sensory perception of the chemical stimulus, NADH dehydrogenase (ubiquinone) activity, and positive regulation of the fatty acid metabolic process. In addition, seven co-expression modules were constructed after the redundancy-reduced process. Four of these modules involved specific activated or inhibited metabolic pathways. Moreover, 334 effective ingredients of SQC herbs were collected, and four genes (RNASE1 (ribonuclease A family member 1, pancreatic), ADRB1 (adrenoceptor beta 1), PPIF (peptidylprolyl isomerase F), and ALDH1B1 (aldehyde dehydrogenase 1 family member B1)) were identified as potential targets of SQC. CONCLUSION: Comparing SQC with metformin to treat T2DM rats revealed several potential gene targets. These genes provide clues for elucidating the therapeutic mechanisms of SQC.

Chinese herbal medicine Shenqi compound for early intervention in patients at high cardiovascular risk of type 2 diabetes mellitus: the protocol of a multicenter, randomized, double-blind, placebo-controlled trial.

Introduction: Reducing multiple cardiovascular risk factors is a key link and a challenging clinical problem to reduce the risk of cardiovascular complications and death in patients with diabetes. Currently, there is a lack of clinical studies on patients with diabetes combined with multiple risk factors. Traditional Chinese medicine is believed to have therapeutic effects that contribute to the comprehensive control of multiple cardiovascular factors. This study aims to provide evidence for the efficacy and safety of Shenqi compound (SQC) for early intervention in diabetic patients at high cardiovascular risk. Methods and analysis: This study is a multicenter, randomized, double-blind, placebo-controlled trial. A total of 120 diabetic patients with high cardiovascular risk were enrolled in five research centers. After a 2-week run-in period, the intervention group received basic treatment and SQC granules, and the control group received basic treatment and placebo granules for a total of 24 weeks, with a 24-week follow-up. The endpoint outcomes are major adverse cardiovascular events and renal-related and peripheral vascular disease events. The primary efficacy outcome is carotid intima-media thickness, and the secondary efficacy outcomes are carotid shear stress, indicators of glucose and lipid metabolism, pancreatic islets function, hemorheology, traditional Chinese medicine syndrome score, and quality of life scale. Safety indicators and adverse events were used to assess the safety of SQC. Discussion: This study comprehensively evaluated the efficacy and safety of SQC for early intervention in diabetic patients at high cardiovascular risk from the aspects of overall metabolic level, structure, and function of blood vessels, quality of life, and long-term follow-up of endpoint events, providing evidence-based evidence for the short-term efficacy and long-term benefits of early treatment to reduce the risk of diabetic cardiovascular complications.Trial Registration: This trial is registered in the Chinese Clinical Trial Registry on March 9, 2023, https://www.chictr.org.cn/showproj.html?proj=192803 (No. ChiCTR2300069219).

Efficacy, safety and therapeutic mechanism of Shen-Qi Xiao-Tan formula in the treatment of peripheral atherosclerosis in patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled trial protocol.

BACKGROUND: Peripheral atherosclerosis is a common macrovascular complication of diabetes, but the treatment is limited. Chinese herbal medicine is the complementary and alternative therapy to delay the progression of atherosclerosis and reduce blood glucose and lipids. Shen-Qi Xiao-Tan (SQXT) formula is one of the prescriptions commonly used to treat diabetic peripheral atherosclerosis, but there is still a lack of high-quality evidence-based evidence. METHODS: This is a randomized, double-blind, placebo-controlled add-on trial that is expected to enroll 114 diabetic patients with peripheral atherosclerosis. After a 2-week run-in period, participants will been randomly assigned in a 1:1 ratio and receive 12 weeks of usual treatment and SQXT formula (treatment group) or usual treatment and placebo (control group). The primary outcome is the change in carotid intima-media thickness from baseline to endpoint. The secondary outcomes are the structure and function of peripheral arteries, blood glucose and lipids, traditional Chinese medicine syndrome score, and quality of life, and safety and endpoint events are evaluated. To explore the therapeutic mechanism through oxidative stress, inflammation, and advanced glycation end products, and lipidomics will be used to screen for biomarkers for diagnosis and efficacy evaluation. DISCUSSION: The objective of this trial is to evaluate the efficacy, safety and therapeutic mechanism of SQXT formula in the treatment of diabetic peripheral atherosclerosis. It will obtain high-quality evidence-based evidence and promote the treatment of diabetic macroangiopathy and the research and development of new drugs. TRIAL REGISTRATION: This trial is registered on Chinese Clinical Trials.gov with number ChiCTR2100047189 on 10 Jun 2021, and has been approved by the Ethical Review Committee of Hospital of Chengdu University of Traditional Chinese Medicine with number 2020KL-080.

The Mitigatory Effect of Shen-Qi Compound on the Diabetic Thoracic Aortic Complications through Inhibiting the Inflammatory Microenvironment by miR-223-3p/RBP-J/IRF8 Axis.

Background: Disruption of the vascular immunological inflammatory microenvironment is linked to metabolic memory impairment. Even though it has been proven that the Shen-Qi compound (SQC) can efficiently halt metabolic memory and preserve vascular endothelial cells, extensive studies need to be done to investigate if it can also change the vascular immune-inflammatory microenvironment by regulating the immune system. This will help figure out the role of stopping metabolic memory. Methods: After 4 weeks on a high-fat diet (HFD), GK rats were used to create a model for diabetic thoracic aortic problems. The effect and mechanisms of SQC on diabetic thoracic aortic complications were assessed by hematoxylin-eosin (H&E) staining, enzyme-linked immunosorbent assay (ELISA), biochemical analysis, terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL), reverse transcription, real-time polymerase chain reaction (RT-qPCR), immunofluorescence (IF), western blot, and luciferase reporter assays. Results: SQC treatment ameliorates the HFD-induced pathological symptoms as well as the HFD-induced increased concentrations of fasting blood glucose (FBG), fasting insulin (FINS), total cholesterol (TC), triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C) and decreased concentrations of high-density lipoprotein cholesterol (HDL-C). Besides, SQC counteracted the HFD-induced average fluorescence intensity of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), as well as the concentrations of endothelin-1 (ET-1) and monocyte chemoattractant protein-1 (MCP-1), while rescuing the HFD-induced concentrations of nitric oxide (NO) and nitric oxide synthetase (NOS). Also, SQC decreases apoptosis and oxidative stress in rats with diabetic thoracic aortic complications. In addition, SQC facilitated the polarization of macrophages, stimulated the activation of dendritic cells, and regulated the inflammatory milieu in rats with diabetic thoracic aortic complications. Furthermore, SQC also modulated the miR-223-3p/RBP-J/IRF8 axis in the macrophages of rats with diabetic thoracic aortic complications. Conclusion: SQC ameliorated diabetic thoracic aortic complications through the regulation of apoptosis, oxidative stress, and inflammatory microenvironment mediating by the miR-223-3p/RBP-J/IRF8 axis.

The efficacy and safety of dachaihu decoction in the treatment of type 2 diabetes mellitus: A systematic review and meta-analysis.

Background: Type 2 diabetes mellitus (T2DM) is a clinical metabolic syndrome characterized by persistent hyperglycemia, which is caused by defective insulin secretion and decreased function in regulating glucose metabolism. Dachaihu Decoction (DCHD) is a traditional Chinese medicine formula that has been gradually used in T2DM treatment. A comprehensive analysis on the efficacy and safety of DCHD in T2DM treatment is necessary. Objective: This meta-analysis aimed to systematically assess the clinical efficacy and safety of DCHD in the T2DM treatment and provide a reference for subsequent research and clinical practice. Methods: Both Chinese and English databases were searched from their inceptions to November 2021. All retrieved studies were screened according to inclusion and exclusion criteria and randomized controlled trials about DCHD on T2DM were enrolled. The quality of the literature was assessed using the bias risk assessment tool in the Cochrane Handbook. Data extraction was performed on the selected studies. Review Manager 5.4 and Stata 16.0 were used for meta-analysis. Sources of heterogeneity were also explored by using meta-regression and subgroup analysis. Funnel plot and Egger's test were used to assess publication bias and the evidence quality was assessed by GRADE. Results: 17 eligible studies, involving 1,525 patients, were included in this study. Compared with conventional treatment, combined treatment with DCHD was significantly better in improving HbA1c (MD = -0.90%, 95%CI: -1.20 to -0.60, p < 0.01), FBG (MD = -1.08 mmol/L, 95%CI: -1.28 to -0.87, p < 0.01), 2hPG (MD = -1.25 mmol/L, 95%CI: -1.42 to -1.09, p < 0.01), TC (MD = -0.50 mmol/L, 95%CI: -0.70 to -0.30, p < 0.01), TG (MD = -0.44 mmol/L, 95%CI: -0.61 to -0.26, p < 0.01), LDL-C (MD = -0.58 mmol/L, 95%CI: -0.85 to -0.31, p < 0.01), HOMA-IR (SMD = -2.04, 95%CI: -3.09 to -0.99, p < 0.01), HOMA-ß (SMD = 2.48, 95%CI: 2.20 to 2.76, p < 0.01) and BMI (MD = -1.52 kg/m2, 95%CI: -2.55 to -0.49, p < 0.01). When DCHD used alone, it had a similar efficacy to conventional treatment in HbA1c (MD = -0.04%, 95%CI: -0.17 to 0.09, p = 0.57) and FBG (MD = 0.13 mmol/L, 95%CI: -0.09 to 0.36, p = 0.24). It can also reduce 2hPG, even if not as effective as conventional treatment (MD = 0.54 mmol/L, 95%CI: 0.19 to 0.89, p < 0.01). Due to the small number of included studies, it is unclear whether DCHD used alone has an improving effect on lipid metabolism, BMI, HOMA-IR and HOMA-ß. Analysis of adverse events showed DCHD was relatively safe. No obvious publication bias was detected by Funnel plot and Egger's test. Conclusion: Based on this meta-analysis, we found that the combination with DCHD in the T2DM treatment has more advantages than conventional treatment alone, which can further regulate the glucose and lipid metabolism, reduce insulin resistance, improve islet function and lower BMI. DCHD alone also plays a certain role in regulating glucose. Meanwhile, DCHD is relatively safe. However, limited by the quality and quantity of included studies, the efficacy and safety of DCHD remain uncertain. More high-quality studies are still needed to provide more reliable evidence for the clinical application of DCHD. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021296718, identifier CRD42021296718.

The therapeutic effect of Taijiquan combined with acupoint pressing on the treatment of anxiety insomnia in college students: A study protocol for a randomized controlled trial.

Introduction: Sleep health is an important part of health and has become a common concern of society. For anxiety insomnia, the commonly used clinical therapies have limitations. Alternative and complementary therapy is gradually rising and showing remarkable effect in clinical practice. This is the first study to evaluate the therapeutic effect of Taijiquan combined with acupoint pressing in the treatment of anxiety insomnia in college students and to compare the difference in intervention before and after sleep, to choose the best treatment time. Methods and analysis: This is a multicenter, single-blind, randomized controlled trial. A total of 126 eligible subjects who have passed the psychological evaluation and met inclusion criteria by completing a psychometric scale will be randomly divided into treatment group A (treat before sleep), treatment group B (treat after sleep) and control group C (waiting list group) in a ratio of 1:1:1. All the three groups will receive regular psychological counseling during the trial, and the treatment groups will practice 24-style Taijiquan and do meridian acupuncture at Baihui (DU20), Shenting (DU24), Yintang (EX-HN3), Shenmen (HT7) and Sanyinjiao (SP6). This RCT includes a 2-week baseline period, a 12-week intervention period, and a 12-week follow-up period. The main results will be measured by changes in the Pittsburgh sleep quality index (PSQI) and Hamilton anxiety scale (HAMA). The secondary results will be measured by the generalized anxiety scale (GAD-7) and insomnia severity index (ISI). The safety of the intervention will be evaluated at each assessment. The statistical analysis of data will be carried out by SPSSV.26.0 software. Discussion: We expect this trial to explore the effectiveness of Taijiquan combined with acupoint pressing in the treatment of anxiety insomnia in college students and choose the best treatment time by comparison. Clinical trial registration: [www.ClinicalTrials.gov], identifier [ChiCTR2200057003].

Exploration of SQC Formula Effect on Type 2 Diabetes Mellitus by Whole Transcriptome Profile in Rats.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease that has turned out to be a pandemic all over the world. In China, some traditional Chinese herbal formulas have enjoyed a high reputation in T2DM treatment for centuries. METHODS: In this study, ShenQi compound (SQC) is proposed, a formula that has been performed on T2DM clinical therapeutics in China for many years. The efficacy of SQC in a diabetic rat model by measuring food and water intake and examining islet microcirculatory index involves islets microvessel quantity and density, islets size, pancreatic microvascular wall thickness is evaluated. Meanwhile, gene microarray experiments were performed to explore the molecular mechanism of SQC treatment. In addition, a western medicine, metformin, was employed as a comparison. RESULTS: The results indicated that SQC could effectively improve polydipsia, polyphagia and weight loss caused by diabetes as well as pancreatic tissue damage and vascular injury for T2DM. Meanwhile, the gene microarray experiments indicated that SQC may improve the T2DM by affecting the biological functions related to detection of chemical stimulus involved in sensory perception of smell, G-protein coupled receptor signaling pathway, cytoplasmic translation. In addition, SQC presented curative effect by the regulated function associated with translation, while metformin presented curative effect by the regulated function associated coagulation. CONCLUSION: SQC is an effective therapeutic drug on T2DM, and presents curative effect by regulated function associated with translation.

Add-on effect of Qiming granule, a Chinese patent medicine, in treating diabetic macular edema: A systematic review and meta-analysis.

This study aims to evaluate the efficacy and safety of Qiming granule (QG) on diabetic macular edema (DME). PubMed, Embase, the Cochrane Library, CNKI, Wanfang, qvip and China Biology Medicine Disc were searched. Randomized controlled trials (RCTs) about participants with a diagnosis of DME were included. Risk of bias assessment was conducted by Cochrane risk-of-bias tool for RCT. Random-effects model was implemented to pool results. Among 16 included studies, QG combined with conventional treatment was administered 13.5 g daily for a period ranging from 2 to 6 months. Results showed combination therapy was more effective than conventional treatment alone in central macular thickness (weighted mean difference (WMD) = -29.43, 95% confidence interval (CI) (-39.56 to -19.29), p = .0001), optimum corrected vision (pooled standardized mean difference (SMD) = -0.962, 95%CI (-1.35 to -0.57), p = .0001) and overall effective rate (RR = 1.25, 95%CI = [1.13 to 1.35], p < .0001). Only three studies reported adverse effects. The quality of evidence is low. Due to a lack of placebo control, the net efficacy of QG is still uncertain. More high-quality RCTs are needed to confirm the efficacy and safety of QG in DME.

The efficacy of 5-element therapy for senile diabetes with depression: A protocol for a systematic review and meta-analysis.

BACKGROUND: Senile diabetes with depression is a common and frequently-occurring disease, and it is also a difficult and hot point in domestic and international research. However, the efficiency of combination hypoglycemic agents and antidepressants in the treatment of senile diabetes with depression is poor, and new intervention methods are urgently needed. Research shows the 5-element therapy, as a Chinese traditional non-drug intervention, has definite curative effect on the prevention and treatment of various physical and mental diseases. The purpose of this systematic review and meta-analysis is to evaluate the efficacy of 5-element therapy on senile diabetes with depression. METHODS: The electronic databases including Pubmed, Embase, Cochrane Library, Web of science, Chinese National Knowledge Infrastructure, Wanfang Database, Sino Med,China Biomedical Literature Database will be searched. The time limit for retrieving studies is from establishment to October 2020 for each database. Randomized controlled clinical trials related to 5-element therapy intervention on senile diabetes with depression will be included. Stata V.13.0 and Review manager 5.3 software will be implemented for data synthesis, sensitivity analysis, subgroup analysis, and the assessment of bias risk. We will use the grading of recommendations assessment, development, and evaluation system to assess the quality of evidence. RESULTS: This study will provide a quantitative and standardized evaluation for the efficacy of 5-element therapy on senile diabetes with depression. CONCLUSION: This systematic review and meta-analysis will provide the high-quality evidence to assess whether the 5-element therapy has a positive treatment effect for senile diabetes with depression. REGISTRATION NUMBER: INPLASY2020100081.

Qingfei Paidu decoction for treating COVID-19: A protocol for a meta-analysis and systematic review of randomized controlled trials.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is one of the infectious diseases that have seriously threatened global public health since its outbreak in 2019. Due to the complicated Pathogenesis, high infectivity and high fatality rate of COVID-19, there is currently no effective treatment for such epidemic disease. Traditional Chinese medicine has a long clinical history for the prevention and treatment of this kind of acute infectious disease. Qingfei Paidu Decoction (QFPD) is widely used in treating COVID-19 in China. However, there is still a lack of comprehensive and systematic evidence on the effectiveness and safety of Qingfei Paidu Decoction. METHODS: We will search each database from the built-in until May 2020. The English literature mainly searches Cochrane Library, PubMed, EMBASE, and Web of Science, while the Chinese literature comes from CNKI, CBM, VIP, and Wangfang database. Simultaneously we will retrieval clinical registration tests and grey literatures. This study only screen the clinical randomized controlled trials (RCTs) about QFPD for COVID-19 to assess its efficacy and safety. The two researchers worked independently on literature selection, data extraction, and quality assessment. The dichotomous data is represented by relative risk (RR), and the continuous is expressed by mean difference (MD) or standard mean difference (SMD), eventually the data is synthesized using a fixed effect model (FEM) or a random effect model (REM) depending on whether or not heterogeneity exists. Total clinical effective rate, improvement rate of lung CT, adverse events were evaluated as the main outcomes. Effective rate of clinical symptoms, treatment time were secondary outcomes. Finally, meta-analysis was conducted by RevMan software version 5.3. RESULTS: The results of our research will be published in a peer-reviewed journal. CONCLUSION: This systematic review aims to provide new evidence of QFPD for COVID-19 in terms of its efficacy and safety. PROSPERO REGISTRATION NUMBER: CRD42020200894.

Efficacy and safety of Chinese herbal medicine on blood glucose fluctuations in patients with type 2 diabetes mellitus: A protocol of systematic review and meta-analysis.

BACKGROUND: As one of the major chronic diseases that seriously threaten human health, type 2 diabetes mellitus (T2DM) has become a global public health problem. Blood glucose fluctuation is a risk factor independent of hyperglycemia. At present, the measures to treat blood glucose fluctuations in patients with T2DM are insufficient in effectiveness and safety. Medical practice and clinical studies have proved that Chinese herbal medicine has obvious advantages in reducing blood glucose fluctuations. In this systematic review, we will assess the efficacy and safety of Chinese herbal medicine in the treatment of blood glucose fluctuations in patients with T2DM. METHODS: We will search related literature of PubMed, Embase, Cochrane Library, Web of Science, China Biology Medicine Database, China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang Database, and will manually search grey documents such as literature such as conference articles and references articles. Eligible randomized controlled trials will be screened based on inclusion criteria, and data extraction, risk of bias assessment, publication bias assessment, subgroup analysis, and quality assessment will be performed. Review Manager version 5.3 software and stata version 13 software will be used for data analysis. Each process is independently conducted by 2 researchers, and if there is any objection, it will be submitted to the third researcher for resolution. RESULTS: This study will provide evidence for the efficacy and safety of Chinese herbal medicine in the treatment of blood glucose fluctuations in patients with T2DM. Outcome measures include mean amplitude of glycemic excursions, 24 hours mean blood glucose, standard deviations of blood glucose, mean of daily differences, coefficient of variation, glucose time in range, fasting blood glucose, 2 hours postprandial blood glucose, glycated hemoglobin, HOMA-ß, HOMA-IR, quality of life questionnaire, traditional Chinese medicine syndrome score, and adverse event.

Effect of music intervention on mental health in patients with diabetes mellitus: protocol for a systematic review and meta-analysis of randomizsed controlled trials.

INTRODUCTION: About 463 million adults aged 20-79 have diabetes globally. Mental disorders often exist in patients with diabetes as comorbidities, which can lead to aggravation of the diseases, increased difficulties in treatment, as well as elevated mortality rates. Music intervention has been applied in the treatment of comorbidities for 12 years now, but there are still no recommendations due to the lack of evidence. Thus, a meta-analysis is necessary to evaluate the effect of music intervention in treating mental disorders of patients with diabetes. METHODS AND ANALYSIS: We will search the following nine online electronic databases from their inception until March 2020: PubMed, Web of Science, Embase, EBSCO, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang Database, Chinese Scientific Journal Database (VIP) and Chinese Biomedical and Medical Database. We also plan to search other relevant resources, including grey literature and the reference lists of relevant publications. Only randomised controlled trials of music intervention to treat depression or anxiety in patients with diabetes will be involved. The primary outcomes include the depression score and anxiety score measured on certain scales, and the secondary outcome is safety. Data extraction will be independently implemented by two researchers. The risk of bias will be evaluated through the Cochrane Collaboration's Risk of Bias tool. Eventually, all the data will be analysed via the Review Manager V.5.3 software. ETHICS AND DISSEMINATION: This meta-analysis will provide information about applying music intervention to treat depression or anxiety in patients with diabetes. No ethical approval is required because this meta-analysis is based on published data. The results of this systematic review will be published in a peer-reviewed journal.PROSPERO registration numberCRD42019146439.

Effect of Shenqi compound on inflammatory markers and glycemic measures among diabetes mellitus: A protocol for systematic review and meta-analysis.

BACKGROUND: Diabetes is a chronic disease characterized by chronic hyperglycemia, absolute or relative deficiency of insulin secretion, and chronic inflammation. Shenqi compound (SC) is a traditional Chinese medicine formula widely used in the treatment of diabetes and diabetic complications. Although many randomized clinical trials have proved that SC can benefit a lot from diabetes and its complications, the systematic evaluation of the effect of SC on diabetic blood glucose control and inflammatory markers has not yet appeared. The purpose of this study is to provide evidence that the therapeutic effect of SC on diabetes and its multiple system complications is related to its control of blood glucose and inflammatory mediators. METHODS: Three English database and 4 Chinese medical databases will be searched from its inception to May 2020. Then 2 methodological trained researchers will screen the qualified articles by reading the title, abstract, and full texts according to an established inclusion and exclusion criteria. The assessment of risk of bias will be conducted by using the Cochrane collaboration's tool. We will conduct meta-analyses for fasting blood glucose, postprandial blood glucose, glycated hemoglobin, tumor necrosis factor, C-reactive protein or high-sensitivity C-reactive protein, and other outcomes. The heterogeneity of data will be evaluated by Cochrane X and I tests. Subgroup analysis will also be carried out. We will conduct sensitivity analysis to evaluate the stability of the results, funnel plot analysis, and Egger test to evaluate the publication bias, and assessment for the quality of evidence by the grading of recommendations assessment, development, and evaluate system. RESULTS: The results of our research will be published in a peer-reviewed journal. CONCLUSION: In this study, we will systematically evaluate the influences of SC on glycemic measures and inflammatory markers of diabetes mellitus. Our research is supposed to provide evidence-based support for clinical practice. REGISTRATION NUMBER: INPLASY202040179.

Network Pharmacology-Based Identification of the Mechanisms of Shen-Qi Compound Formula in Treating Diabetes Mellitus.

AIM: The purpose of this research is to identify the mechanisms of Shen-Qi compound formula (SQC), a traditional Chinese medicine (TCM), for treating diabetes mellitus (DM) using system pharmacology. METHODS: The active components and therapeutic targets were identified, and these targets were analyzed using gene ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and protein-protein interaction (PPI) analysis. Finally, an integrated pathway was constructed to show the mechanisms of SQC. RESULTS: A total of 282 active components and 195 targets were identified through a database search. The component-target network was constructed, and the key components were screened out according to their degree. Through the GO, PPI, and KEGG analyses, the mechanism network of SQC treating DM was constructed. CONCLUSIONS: This study shows that the mechanisms of SQC treating DM are related to various pathways and targets. This study provides a good foundation and basis for further in-depth verification and clinical application.

Baihu Jia Renshen Decoction for type 2 diabetic mellitus: A protocol for systematic review and meta-analysis.

BACKGROUND: Diabetes mellitus (DM) is one of the main health problems that perplex people all over the world. The prevalence of DM is still increasing in spite of the great efforts have been made to control DM in recent years. Type 2 diabetes mellitus (T2DM) is the most common type of diabetes, accounting for about 90% of all DM cases. Traditional Chinese medicine has been used on treatment of DM and diabetic complications in China for many years. Baihu Jia Renshen Decoction (BJRD) is one of the oldest classic prescriptions of traditional Chinese medicine that applied in the field of diabetes' treatment. BJRD is proved to be effective after years of clinical practice and basic research. The application of BJRD improves the overall clinical efficacy of T2DM. Therefore, a systematic review is necessary to provide available evidence for BJRD in therapy of T2DM. METHODS: Different studies from various databases will be involved in this study. Only randomized controlled trials of T2DM patients diagnosed with World Health Organization 1999 diagnostic criteria will be included. We will search the literature in the databases from China Conference Paper Database, manual searching. Electronic database includes PubMed, Embase, Cochrane Library, Web of Science, CNKI (China National Knowledge Internet), WanFang, VIP (Chongqing VIP), and CBM (China Biomedical Literature CDROM Database). The primary outcomes include 2 hour plasma glucose, fasting plasma glucose, hemoglobin A1c, homeostasis model assessment of insulin resistance, and fasting plasma insulin. The secondary outcomes include clinical efficacy and adverse events. Data will be extracted by 2 researchers independently, risk of bias of the meta-analysis will be evaluated based on the Cochrane Handbook for Systematic Reviews of Interventions. All data analysis will be conducted by data statistics software Review Manager V.5.3. and Stata V.12.0. RESULTS: This study will synthesize and provide high-quality evidence based on the data of the currently published BJRD for the treatment of T2DM, in terms of 2 hour plasma glucose, fasting plasma glucose, hemoglobin A1c, homeostasis model assessment of insulin resistance and fasting plasma insulin, clinical efficacy, and safety. CONCLUSION: This systematic review aims to evaluate the benefits and harms of BJRD for the treatment of T2DM reported in randomized controlled trials, and provide more options for clinicians and patients to treat T2DM. REGISTRATION NUMBER: INPLASY202040006.

Efficacy and safety of shenqi compound for the treatment of diabetic macroangiopathy: A protocol for systematic review and meta-analysis.

BACKGROUND: Diabetic macroangiopathy is a further complication of diabetes mellitus and is the leading cause of death for diabetic patients. Shenqi compound (SC) is a traditional Chinese medicine formula widely used in the treatment of diabetes and diabetic macroangiopathy. At present, there is only 1 systematic review on SC in the treatment of diabetes. However, no meta-analysis has evaluated the efficacy and safety of SC on diabetic macroangiopathy. METHODS AND ANALYSIS: Three English database and four Chinese medical databases will be searched from its inception to February 2020. Then 2 methodological trained researchers will screen the qualified articles by reading the title, abstract, and full texts according to an established inclusion and exclusion criteria. The assessment of risk of bias will be conducted by using the Cochrane collaboration's tool. We will conduct meta-analyses for fasting blood glucose (FBG), postprandial blood glucose (PBG), glycated hemoglobin (HbA1c), and other outcomes. The heterogeneity of data will be evaluated by Cochrane χ and I tests. We establish 3 hypotheses before the subgroup analysis actually starts: disease status at baseline, duration of intervention, type of concomitant medication. We will conduct sensitivity analysis to evaluate the stability of the results, funnel plot analysis, and Egger test to evaluate the publication bias, and assessment for the quality of evidence by the Grading of Recommendations Assessment, Development, and Evaluate system (GRADE). RESULTS: The results will be published at a peer-reviewed journal. CONCLUSION: In this study, we will systematically evaluate the evidence of SC in the treatment of diabetic macroangiopathy. Our research is supposed to provide evidence-based support for clinical practice.