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 However, the existing evidence was not robust enough and the results were out of date.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.

Effect of Huang-Lian Jie-Du Decoction on Glucose and Lipid Metabolism in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Background: Type 2 diabetes mellitus (T2DM) is a heterogeneous disease characterized by persistent hyperglycemia. Huang-Lian Jie-Du decoction (HLJDD) is a traditional Chinese medicine formula which is widely used in treating T2DM in China. A thorough understanding of current body of evidence is needed. Objective: this study aims to summarize the clinical evidence of HLJDD for T2DM to provide an up-to-date and accurate understanding of this issue for research and clinical practice. Methods: Six databases were searched from inception to June 27, 2020 without language and publication status restrictions and randomized controlled trials about HLJDD on T2DM were included. Two evaluators searched and screened citations independently. Risk of bias was assessed by 2019 version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB2). Risk ratio (RR) with 95% confidence interval (CI) was used as an effect measure for dichotomous outcomes and mean difference (MD) with 95% CI was used for continuous outcomes. Subgroup analyses and sensitivity analyses were carried out. Results: Nine studies including 811 participants were included in this study. The overall risk of bias was high risk. Compared with metformin alone, combination treatment of HLJDD and metformin may result in a reduction in HbA1c, FBG, 2hPG, HOMA-IR and an improved lipid metabolism. Evidence comparing HLJDD and metformin or no intervention or placebo was insufficient. The quality of evidence was low. Conclusions: Current evidence about HLJDD on T2DM is still uncertain and more high-quality studies are needed to firmly establish the clinical efficacy and safety of HLJJD.

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.

Effects and safety of herbal medicines among community-dwelling residents during COVID-19 pandemic: A large prospective, randomized controlled trial (RCT).

BACKGROUND: Since the declaration of COVID-19 as a global pandemic by the World Health Organization, countries are struggling with a shortage of medical capacities. It would be essential if the risk for preventable comorbidities, such as the common cold, can be reduced or prevented, so that the scarce medical resources and facilities can be focused on COVID-19. PURPOSE: To evaluate the effects of two herbal medicines (Jinhaoartemisia antipyretic granules and Huoxiangzhengqi oral liquids) in reducing the risk of the common cold in community-dwelling residents in China during the COVID-19 outbreak. STUDY DESIGN: A prospective open-label, parallel-group, cluster-randomized controlled trial (RCT), was conducted in Chengdu, China. METHODS: A total of 22,065 participants from 11 communities were recruited during a period of one month. The trial started on 30 January and participants were followed up till 29 February 2020. Participants were randomly assigned to receive either a five-day herbal medicine therapy plus a reference manual or a reference manual only if they were allocated to the control group. The primary endpoint was the occurrence of patient-reported common cold symptoms. The secondary endpoint was the time in days from the receipt of herbal drugs/reference manual and the occurrence of the common cold symptoms. RESULTS: Use of herbal medicine reduced the risk of the common cold by 89.6% (95% CI, 52.9% to 97.7%) in all community-dwelling residents, and by 94.0% (95% CI, 52.1% to 99.2%) in residents aged between 16 and 59 years old. Sensitivity analyses showed similar results. CONCLUSION: This community-based RCT found that the use of a herbal medicine therapy (Jinhaoartemisia antipyretic granules and Huoxiangzhengqi oral liquids) could significantly reduce the risks of the common cold among community-dwelling residents, suggesting that herbal medicine may be a useful approach for public health intervention to minimize preventable morbidity during COVID-19 outbreak.

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.

Study on the related factors of post-herpetic neuralgia in hospitalized patients with herpes zoster in Sichuan Hospital of Traditional Chinese Medicine based on big data analysis.

Although various factors were reported to be related to post-herpetic neuralgia (PHN), studies based on adequate and comprehensive data were absent. Data was extracted from cases of hospitalized patients with herpes zoster in dermatology department, Sichuan hospital of traditional Chinese medicine range from December, 2011 to February, 2018, and then cleaned to build prediction model with TREENET algorithms. Following evaluated the prediction model by ROC and confusion matrix, variables importance ranking and variables dependency analysis were performed, resulting in the importance ranking of factors for PHN and the dependency between factors and PHN. Based on strict inclusion and exclusion criteria, 1303 (571 PHN and 732 normal controls) cases and 2958 indicators were selected. Model evaluation showed high ROC value (training sample = 0.985, test samples = 0.752) and high accuracy value (70.27%), which indicated that the model was predictive. After variables importance ranking and variables dependency analysis, 62 variables in the model were associated with the occurrence of PHN. Our study identified 62 variables related to PHN and revealed that various variables were the important risk factors for PHN, including age, MCHC, sodium and UA.

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.

[Large- scale prospective clinical study on prophylactic intervention of COVID-19 in community population using Huoxiang Zhengqi Oral Liquid and Jinhao Jiere Granules].

To scientifically evaluate the intervention effect of Chinese medicine preventive administration(combined use of Huo-xiang Zhengqi Oral Liquid and Jinhao Jiere Granules) on community population in the case of coronavirus disease 2019(COVID-19), a large cohort, prospective, randomized, and parallel-controlled clinical study was conducted. Total 22 065 subjects were included and randomly divided into 2 groups. The non-intervention group was given health guidance only, while the traditional Chinese medicine(TCM) intervention group was given two coordinated TCM in addition to health guidance. The medical instructions were as follows. Huoxiang Zhengqi Oral Liquid: oral before meals, 10 mL/time, 2 times/day, a course of 5 days. Jinhao Jiere Granules: dissolve in boiling water and take after meals, 8 g/time, 2 times/day, a course of 5 days, followed up for 14 days, respectively. The study found that with the intake of medication, the incidence rate of TCM intervention group was basically maintained at a low and continuous stable level(0.01%-0.02%), while the non-intervention group showed an overall trend of continuous growth(0.02%-0.18%) from 3 to 14 days. No suspected or confirmed COVID-19 case occurred in either group. There were 2 cases of colds in the TCM intervention group and 26 cases in the non-intervention group. The incidence of colds in the TCM intervention group was significantly lower(P<0.05) than that in the non-intervention group. In the population of 16-60 years old, the incidence rate of non-intervention and intervention groups were 0.01% and 0.25%, respectively. The difference of colds incidence between the two groups was statistically significant(P<0.05). In the population older than 60 years old, they were 0.04% and 0.21%, respectively. The incidence of colds in the non-intervention group was higher than that in the intervention group, but not reaching statistical difference. The protection rate of TCM for the whole population was 91.8%, especially for the population of age 16-60(95.0%). It was suggested that TCM intervention(combined use of Huoxiang Zhengqi Oral Liquid and Jinhao Jiere Granules) could effectively protect community residents against respiratory diseases, such as colds, which was worthy of promotion in the community. In addition, in terms of safety, the incidence of adverse events and adverse reactions in the TCM intervention group was relatively low, which was basically consistent with the drug instructions.

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.

Clinical study for external washing by traditional Chinese medicine in the treatment of multiple infectious wounds of diabetic foot: Study protocol clinical trial (SPIRIT compliant).

BACKGROUND: Diabetic foot (DF) is among the most serious complications of type 2 diabetes. DF infection (DFI) is a key factor in the deterioration and development of DF, so controlling infection plays an important role in the treatment of the disease. Traditional Chinese medicine foot bath has been widely used in China as a complementary and alternative therapy to improve circulation and infection control of DF. However, the existing evidence shows that its efficacy and safety are still insufficient. We report a study protocol about a multicenter, double-blind, randomized, placebo controlled trial which aims to make well-designed clinical trials to evaluate the efficacy and safety of herbal medicine foot bath decoction (FBD) and explore the mechanism of external washing of Chinese herbs in DFI. METHODS: This study is a multicenter, double-blind, randomized, placebo controlled clinical trial in which 60 eligible participants were randomly divided into an experimental group and control group at a 1:2 ratio. Both groups received the same basic treatment for DF disease, the experimental group used FBD and ordinary dressing changes, while half of the patients in the control group received placebo and ordinary dressings, and the other half received placebo and silver ion dressings. Patients in both groups will be evaluated weekly for efficacy during the intervention. The primary efficacy indicators include the types of wound pathogens, interleukin 6 and tumor necrosis factor α. Secondary efficacy indicators included blood glucose, blood lipids, wound area, lower extremity blood vessel diameter, blood flow speed, walking speed, walking distance, and traditional Chinese medicine syndrome scores. We will also conduct a safety evaluation of the drug at the end of the trial. DISCUSSION: This multicenter, double-blind, randomized, placebo clinical trial not only provides data on the efficacy and safety of FBD, but also provides a novel treatment strategy for clinicians and DF patients.

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.

The efficacy and safety of Chinese herbal medicine Shen-Qi Hua-Yu formula in patients with diabetic lower extremity artery disease: Study protocol of a multi-center, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Lower extremity artery disease (LEAD) is greatly harmful to Type 2 Diabetes Mellitus patients. Traditional Chinese Medicine (TCM) is an alternative therapy to delay the development of macrovascular diseases, but the existing evidence of its efficacy, safety and mechanism of action is insufficient. We report a study protocol of a multi-center, randomized, double-blind, placebo-controlled trial that aims to use well-designed clinical trial to evaluate the efficacy and safety of Chinese herbal medicine (CHM) Shen-Qi Hua-Yu formula, and to explore efficacy mechanism of the TCM granules and the biomarkers of TCM syndrome. METHODS: This is a multi-center, double-blind, randomized, and placebo-controlled study that randomized 120 participants into 2 groups. The treatment group will receive TCM granules and conventional medicine, while the control group will receive placebo in addition to conventional medicine. Two groups will receive 12-week treatment and 48-week follow-up, with a total of 13 visits. Primary efficacy outcomes included ankle brachial index. Secondary efficacy outcomes included fasting plasma glucose, blood lipid, hemorheology indexes, advanced glycation end products, the inner diameter, peak systolic velocity, end diastolic velocity and mean average velocity of the anterior tibial artery, posterior tibial artery and dorsalis pedis artery, and TCM syndrome score. The safety and endpoint outcomes will be evaluated in this trial. The study will explain the biological therapeutic mechanism of Shen-Qi Hua-Yu formula for diabetic LEAD, and try to use Isobaric tags for Relative and Absolute Quantitation (iTRAQ) and Western blot to screen biomarkers of characteristic diagnosis and clinical efficiency evaluation of the TCM syndrome. DISCUSSION: This study is a multi-center, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of CHM in patients with diabetic LEAD, and to interpret the therapeutic mechanism of Shen-Qi Hua-Yu formula in treatment of diabetic LEAD through proteomics technology, and to screen biomarkers with characteristics of TCM diagnosis and clinical efficacy evaluation. On the other hand, to our knowledge, this study may be the first trial of CHM formulas to observe cardiovascular outcomes through long-term follow-up for the treatment of diabetic LEAD, which is of great value. TRIAL REGISTRATION: This study is registered on the Chinese Clinical Trial Registry: ChiCTR1900026372.

Effects of qiming granule for diabetic macular edema: A protocol for systematic review and meta-analysis.

BACKGROUND: Diabetic macular edema is a further complication of diabetes. It is an important type of diabetic eye disease and the main cause of blindness of diabetic patients. Qiming granule is a Chinese patent medicine widely used in the treatment of diabetic macular edema. There are some reports about this medicine for macular edema. At present, there is only 1 systematic review on qiming granule in the treatment of diabetic macular edema. However, there are many defects in this article, so it is necessary to re-summarize and evaluate the existing evidence. METHODS AND ANALYSIS: Three English database and 4 Chinese databases other sources will be searched. Two methodological trained researchers will read the title, abstract and full texts, and independently select the qualified literature according to inclusion and exclusion criteria. After assessment of the risk of bias and data extraction, we will conduct meta-analyses for outcomes including central macular thickness, optimum corrected vision, overall effect rates, and adverse effects. The heterogeneity of data will be investigated by Cochrane χ and I tests. We build 3 hypotheses for subgroup analysis according to the guidance for a credible subgroup effect: Disease status at baseline, duration of intervention, type of concomitant medication. Sensitivity analysis will be conducted to evaluate the stability of the results. Then publication bias assessment will be conducted by funnel plot analysis and Egger test. Finally, we will use the Grading of Recommendations Assessment, Development and Evaluate system to evaluate the quality of evidence. RESULTS: The results of our research will be published in a peer-reviewed journal. CONCLUSION: In our study, the evidence of qiming granule in the treatment of macular edema was comprehensively summarized and carefully evaluated. It will provide more options for clinical treatment of the disease. PROSPERO REGISTRATION NUMBER: CRD42018108626.

Huangqi Guizhi Wuwu decoction for diabetic peripheral neuropathy: Protocol for a systematic review.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is one of the most common causes of disability in diabetic population, and its pathogenesis is related to a variety of factors. There is currently no effective treatment for such chronic disease. Traditional Chinese medicine has a long clinical history for the prevention and treatment of diabetes and chronic complications, and it also shows certain advantages in the treatment of DPN. Many clinical studies have confirmed that Chinese medicine Huangqi Guizhi Wuwu decoction (HGWD) can reduce the clinical symptoms and improve neuronal function of patients with DPN. So we intend to conduct a systematic review further clarified the effectiveness and safety of HGWD for DPN. METHODS: We will search each database from the built-in until June 2019. 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 HGWD for DPN to assess its efficacy and safety. The 2 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. The clinical efficacy, median sensory nerve conduction velocity, median motor nerve conduction velocity, peroneal sensory nerve conduction velocity, and peroneal motor nerve conduction velocity were evaluated as the main outcomes. Fasting blood glucose, 2 hours postprandial blood glucose, hemorheology, and adverse reactions were secondary outcomes. Finally, meta-analysis was conducted by RevMan software version 5.3. RESULTS: This study will synthesize and provide high-quality evidence based on the data of the currently published HGWD for the treatment of DPN, especially in terms of clinical efficacy, neurological function, blood glucose, hemorheology, and safety. CONCLUSION: This systematic review aims to provide new options for HGWD treatment of DPN in terms of its efficacy and safety. PROSPERO REGISTRATION NUMBER: PROSPERO 2019 CRD42019132031.