Chinese patent medicine as a complementary and alternative therapy for type 2 diabetes mellitus: A scoping review.

OBJECTIVE: This scoping review aims to document Chinese Patent Medicines (CPMs) for Type 2 Diabetes Mellitus, explore whether CPMs can improve patients' health outcomes, and set priorities in addressing research gaps in this area. METHODS: Following the framework of PRISMA-SCr, we proposed the research questions based on PICOS principle, and searched the CPMs for T2DM from three drug lists, followed by a systematic search of the literature in eight databases from their inception to June 22, 2023. Then, we developed the eligibility criteria and systematically reviewed the relevant studies, retained the studies about CPMs for T2DM, extracted the related data, and identified the differences across studies in structured charts. RESULTS: A total of 25 types of CPMs were extracted from the three drug lists. Radix astragali appeared most frequently (19 times) among the herbal medicinal ingredients of CPMs. A total of 449 articles were included in the full-paper analysis ultimately, all of which were about 20 types of CPMs, and there were no related reports on the remaining five CPMs. Except about a quarter (25.39 %, 114/449) using CPMs alone, the remaining studies all involved the combination with oral hypoglycemics for T2DM. Biguanides are the most common drugs used in combination with CPMs (50.14 %, 168/335). Fasting plasma glucose (FPG) is the most frequently reported outcomes in efficacy evaluation (82.41 %, 370/449). CONCLUSION: There are a total of 25 types of CPMs currently available for T2DM patients. However, the volume of related evidence on these CPMs varies. It is necessary to standardize the combined use of CPMs and conventional medicine and select appropriate outcomes in future studies.

Effect of electroacupuncture at the acupoints for Tiaozang Xingshen on cerebral metabolism in the patients with type 2 diabetes mellitus-associated cognitive dysfunction. / "调脏醒神"电针对2åž‹ç³–å°¿ç— ç›¸å ³è®¤çŸ¥åŠŸèƒ½éšœç¢æ‚£è€ è„‘å† ä»£è°¢çš„å½±å“.

OBJECTIVES: To investigate the cerebral metabolism in the patients with type 2 diabetes mellitus-associated cognitive dysfunction (T2DACD) and explore the mechanism of electroacupuncture (EA) at the acupoints for Tiaozang Xingshen (adjusting zangfu function and rescuing the spirit) in treatment of T2DACD, using magnetic resonance spectroscopy. METHODS: Fifteen patients with T2DACD (observation group) and 22 healthy subjects (control group) were enrolled. In the observation group, the patients were treated with EA for Tiaozang Xingshen at Baihui (GV 20) and Shenting (GV 24), and bilateral Feishu (BL 13), Pishu (BL 20), Shenshu (BL 23), Zusanli (ST 36), Sanyinjiao (SP 6), Hegu (LI 4) and Taichong (LR 3). EA was operated with disperse-dense wave, 2 Hz/100 Hz in frequency and 0.1 mA to 1.0 mA in current intensity; 30 min each time, once daily. One course of EA consisted of 5 treatments, at the interval of 2 days and the intervention lasted 8 courses. Before treatment in the control group, before and after treatment in the observation group, the score of Montreal cognitive assessment scale (MoCA), the score of clinical dementia rating (CDR), Flanker paradigm, Stroop paradigm, Nback paradigm, the score of self-rating anxiety scale (SAS), the score of self-rating depression scale (SDS), and the score of Hamilton depression rating scale (HAMD) were evaluated separately; the glycolipid metabolic indexes (fasting plasma glucose [FPG], glycosylated hemoglobin type A1c [HbA1c], total cholesterol [TC], triacylglycerol [TG], high-density lipoprotein cholesterol [HDL-C] and low-density lipoprotein cholesterol [LDL-C]) were determined；with the magnetic resonance spectroscopy technique adopted, the metabolites in the basal ganglia area were detected. The correlation analysis was performed for the metabolite values with MoCA score, CDR score , Flanker paradigm, Stroop paradigm, and Nback paradigm. RESULTS: Before treatment, compared with the control group, in the observation group, MoCA score was lower (P<0.001), CDR score and the levels of FPG and HbA1c were higher (P<0.001); the reaction times of Flanker non-conflict, Flanker conflict, Stroop neutrality, Stroop congruence, Stroop conflict, and 1-back were prolonged (P<0.05, P<0.001), and the accuracy of Flanker conflict, Stroop conflict, and 1-back decreased (P<0.05, P<0.01); the ratio of N-acetyl aspartate (NAA) to creatine (Cr) in the left basal ganglia area was dropped (P<0.001), and that of myo-inositol (MI) to Cr in the right side increased (P<0.05). In the observation group after treatment, compared with the levels before treatment, MoCA score was higher (P<0.001), the scores of CDR, SAS and HAMD were reduced (P<0.01, P<0.05), the reaction times of Flanker conflict and Stroop conflict shortened (P<0.001, P<0.05), and the accuracy of Flanker conflict and 1-back increased (P<0.001, P<0.05); the ratio of NAA to Cr in the left basal ganglia area and that of the gamma-aminobutyric acid (GABA) to Cr in the right increased (P<0.05), that of MI to Cr in the right decreased (P<0.05). Before treatment, in the observation group, the ratio of MI to Cr in the right basal ganglia area was positively correlated with the reaction time of Stroop congruence (r=0.671, P=0.012) and this ratio was positively correlated with the reaction time of Stroop conflict (r=0.576, P=0.039). CONCLUSIONS: Electroacupuncture for "adjusting zangfu function and rescuing the mind" improves the cognitive function of T2DACD patients, which may be related to the regulation of NAA, MI and GABA levels in the basal ganglia.

"Adjust Zang and arouse spirit" electroacupuncture ameliorates cognitive impairment by reducing endoplasmic reticulum stress in db/db mice.

Introduction: Diabetic cognitive impairment (DCI) is a chronic complication of the central nervous system (CNS) caused by diabetes that affects learning and memory capacities over time. Recently, acupuncture has been shown to improve cognitive impairment in streptozotocin-induced diabetic rats. However, the effects of electroacupuncture on DCI and its underlying mechanism have not yet been elucidated in detail. Methods: In this study, we used db/db mice as DCI animal models which showed low cognitive, learning and memory functions. Electroacupuncture significantly ameliorated DCI, which is reflected by better spatial learning and memory function using behavioral tests. The db/db mice with cognitive impairment were randomly divided into a model group (Mod) and an electroacupuncture treatment group (Acup), while db/m mice were used as a normal control group (Con). First, the mice were subjected to behavioural tests using the Morris water maze (MWM), and body weight, blood glucose, insulin, triglycerides (TG) and total cholesterol (TC) were observed; HE, Nissl, and TUNEL staining were used to observe the morphological changes and neuronal apoptosis in the mice hippocampus; Finally, Western blot and rt-PCR were applied to detect the essential proteins and mRNA of ERS and insulin signalling pathway, as well as the expression levels of Tau and Aß. Results: Electroacupuncture significantly ameliorated DCI, which is reflected by better spatial learning and memory function using behavioral tests. Moreover, electroacupuncture attenuated diabetes-induced morphological structure change, neuronal apoptosis in the hippocampus of db/db mice. Our results revealed that electroacupuncture could regulate the expression levels of Tau and Aß by improving hippocampal ERS levels in db/db mice, inhibiting JNK activation, attenuating IRS1 serine phosphorylation, and restoring normal transduction of the insulin signaling pathway. Discussion: In summary, ERS and insulin signaling pathway paly causal roles in DCI development. Electroacupuncture can significantly alleviate the pathogenesis of DCI, improve mice's learning and memory ability, and improve cognitive dysfunction. This study adds to our understanding of the effect of acupuncture on DCI and opens the door to further research on DCI.

Effect of acupuncture on the modulation of functional brain regions in migraine: A meta-analysis of fMRI studies.

Background: Acupuncture, a traditional Chinese medicine therapy, is an effective migraine treatment, especially in improving pain. In recent years, many acupuncture brain imaging studies have found significant changes in brain function following acupuncture treatment of migraine, providing a new perspective to elucidate the mechanism of action of acupuncture. Objective: To analyse and summarize the effects of acupuncture on the modulation of specific patterns of brain region activity changes in migraine patients, thus providing a mechanism for treating migraine by acupuncture. Methods: Chinese and English articles published up to May 2022 were searched in three English databases (PubMed, Embase and Cochrane) and four Chinese databases (China national knowledge infrastructure, CNKI; Chinese Biomedical Literature database, CBM; the Chongqing VIP database, VIP; and the Wanfang database, WF). A neuroimaging meta-analysis on ALFF, ReHo was performed on the included studies using Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) software. Subgroup analyses were used to compare differences in brain regions between acupuncture and other groups. Meta-regression was used to explore the effect of demographic information and migraine alterations on brain imaging outcomes. Linear models were drawn using MATLAB 2018a, and visual graphs for quality evaluation were produced using R and RStudio software. Results: A total of 7 studies comprising 236 patients in the treatment group and 173 in the control group were included in the meta-analysis. The results suggest that acupuncture treatment helps to improve pain symptoms in patients with migraine. The left angular gyrus is hyperactivation, and the left superior frontal gyrus and the right superior frontal gyrus are hypoactivated. The migraine group showed hyperactivation in the corpus callosum compared to healthy controls. Conclusion: Acupuncture can significantly regulate changes in brain regions in migraine patients. However, due to the experimental design of neuroimaging standards are not uniform, the results also have some bias. Therefore, to better understand the potential mechanism of acupuncture on migraine, a large sample, multicenter controlled trial is needed for further study. In addition, the application of machine learning methods in neuroimaging studies could help predict the efficacy of acupuncture and screen migraine patients suitable for acupuncture treatment.

Effect of acupuncture on brain regions modulation of mild cognitive impairment: A meta-analysis of functional magnetic resonance imaging studies.

Background: As a non-pharmacological therapy, acupuncture has significant efficacy in treating Mild Cognitive Impairment (MCI) compared to pharmacological therapies. In recent years, advances in neuroimaging techniques have provided new perspectives to elucidate the central mechanisms of acupuncture for MCI. Many acupuncture brain imaging studies have found significant improvements in brain function after acupuncture treatment of MCI, but the underlying mechanisms of brain regions modulation are unclear. Objective: A meta-analysis of functional magnetic resonance imaging studies of MCI patients treated with acupuncture was conducted to summarize the effects of acupuncture on the modulation of MCI brain regions from a neuroimaging perspective. Methods: Using acupuncture, neuroimaging, magnetic resonance, and Mild Cognitive Impairment as search terms, PubMed, EMBASE, Web of Science, Cochrane Library, Cochrane Database of Systematic Reviews, Cochrane Database of Abstracts of Reviews of Effects (DARE), Google Scholar, China National Knowledge Infrastructure (CNKI), China Biology Medicine disk (CBM disk), Wanfang and Chinese Scientific Journal Database (VIP) for brain imaging studies on acupuncture on MCI published up to April 2022. Voxel-based neuroimaging meta-analysis of fMRI data was performed using voxel-based d Mapping with Permutation of Subject Images (SDM-PSI), allowing for Family-Wise Error Rate (FWER) correction correction for correction multiple comparisons of results. Subgroup analysis was used to compare the differences in brain regions between the acupuncture treatment group and other control groups. Meta-regression was used to explore demographic information and altered cognitive function effects on brain imaging outcomes. Linear models were drawn using MATLAB 2017a, and visual graphs for quality evaluation were produced using R software and RStudio software. Results: A total of seven studies met the inclusion criteria, with 94 patients in the treatment group and 112 patients in the control group. All studies were analyzed using the regional homogeneity (ReHo) method. The experimental design of fMRI included six task state studies and one resting-state study. The meta-analysis showed that MCI patients had enhanced activity in the right insula, left anterior cingulate/paracingulate gyri, right thalamus, right middle frontal gyrus, right median cingulate/paracingulate gyri, and right middle temporal gyrus brain regions after acupuncture treatment. Further analysis of RCT and longitudinal studies showed that Reho values were significantly elevated in two brain regions, the left anterior cingulate/paracingulate gyrus and the right insula, after acupuncture. The MCI group showed stronger activity in the right supramarginal gyrus after acupuncture treatment compared to healthy controls. Meta-regression analysis showed that the right anterior thalamic projection ReHo index was significantly correlated with the MMSE score after acupuncture treatment in all MCI patients. Conclusions: Acupuncture therapy has a modulating effect on the brain regions of MCI patients. However, due to the inadequate experimental design of neuroimaging studies, multi-center neuroimaging studies with large samples are needed better to understand the potential neuroimaging mechanisms of acupuncture for MCI. In addition, machine learning algorithm-based predictive models for evaluating the efficacy of acupuncture for MCI may become a focus of future research. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022287826, identifier: CRD 42022287826.

Multimodal brain imaging effect of "Adjust Zang-fu and Arouse Spirit" electroacupuncture on diabetic cognitive impairment: study protocol of a randomized, sham-controlled pilot trial.

BACKGROUND: Diabetic cognitive impairment (DCI) is a serious chronic complication caused by diabetes. The pathogenesis of DCI is complex, but brain nerve injury and brain nerve cell apoptosis are important pathological changes. Multimodal brain imaging is one of the most important techniques to study the neural mechanism of the brain. For the clinical treatment of DCI, there is no effective targeted Western medicine and a lack of clear drug intervention methods. Therefore, there is an urgent need to find effective complementary and alternative methods and clarify their mechanism. This research seeks to explore the multimodal brain imaging effect of "Adjust Zang-fu and Arouse Spirit" electroacupuncture for DCI. METHODS: This clinical research will be a randomized, sham-controlled pilot trial. Eligible participants will be randomly assigned to the intervention group (n = 60) and the control group (n = 30). The intervention group will be divided into the "Adjust Zang-fu and Arouse Spirit" electroacupuncture group (n = 30) and sham electroacupuncture group (n = 30). All participants will continue to receive routine hypoglycemic therapy. The treatment period is the same in both groups. The primary outcomes include functional magnetic resonance imaging (fMRI), magnetic resonance spectroscopy (MRS), Montreal Cognitive Assessment Scale (MoCA), and Clinical Dementia Rating (CDR). The secondary outcomes include blood glucose and blood lipid tests, Instrumental Activities of Daily Living Scale (IADL), Hachinski Ischemic Scale (HIS), Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS). Outcomes will be assessed at baseline and before and after treatment, and adverse events will be examined. Inter- and intragroup analyses will be performed. DISCUSSION: This randomized controlled study, combined with multimodal brain imaging techniques and a clinical evaluation scale, was designed to explore the mechanism of "Adjust Zang-fu and Arouse Spirit" electroacupuncture in improving the central nervous system in DCI. TRIAL REGISTRATION: Chinese Clinical Trial Registration ChiCTR2000040268 . Registered on 26 November 2020.

Multimodal cerebral imaging study on the effects of "Adjust Zang Dredge Meridian" electroacupuncture on cerebral central sensitization in PDPN patients: a study protocol for a sham-controlled, randomized trial.

BACKGROUND: Painful diabetic peripheral neuropathy (PDPN) has a great impact on an individual's quality of life. The current researchers' previous trial suggested that acupuncture was a promising adjunctive treatment for PDPN. However, the underlying mechanism of action of acupuncture treatment for PDPN is still unclear, especially its effects at the cerebral level. The aim of this trial will be to explore how acupuncture works in treating PDPN by using multimodal cerebral imaging. METHOD AND DESIGN: This will be a randomized controlled trial. A total of 150 participants will be recruited and assigned to one of three groups: the healthy group, the DM without PDPN group and the DM with PDPN group. Participants in the DM without PDPN and the DM with PDPN groups will each be further divided between an electroacupuncture group and a sham electroacupuncture group. Participants will receive six treatment sessions per week for 4 weeks. Multimodal cerebral imaging includes resting-state functional magnetic resonance imaging (rs-fMRI), diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS); this neurophysiological testing will be the primary outcome measure. Subjective pain scales and blood analysis will be a secondary outcome measure and will be used to assess the clinical efficacy of the intervention. Multimodal cerebral imaging will be used to detect cerebral activity changes in each treatment group. The clinical data and fMRI data will be analysed for all the groups. Multiple correlation regression analyses will be used to assess the association between changes in cerebral functional activity and the improvement of clinical outcomes after acupuncture treatment. DISCUSSION: This study is based on the results of the researchers' previous study, and using combined clinical and cerebral function changes, it will help evaluate the effects of acupuncture on PDPN. The investigation of acupuncture's central mechanism of action will further expand the understanding of acupuncture treatment of PDPN. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900024109 . Registered on 26 June 2019.

Study on acupuncture in the treatment of painful diabetic peripheral neuropathy based on rs-fMRI: a protocol for systematic review and meta-analysis.

INTRODUCTION: Studies have shown that acupuncture has significant therapeutic effects on painful diabetic peripheral neuropathy (PDPN) yet the precise mechanism of action underpinning these effects remains controversial. Resting-state functional MRI (rs-fMRI) is an advanced imaging technique that can be used to monitor changes in the activity of the brain, particularly in PDPN. However, the data from several studies remain inconclusive and there is currently no systematic review and meta-analysis for the use of rs-fMRI in PDPN. METHODS AND ANALYSIS: In this study, we will select all eligible studies published on or before 30 June 2021. Four English and four Chinese databases will be searched, specifically, PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, WanFang database, China Science Technology Journal Database (VIP) and China Doctor/Master Dissertations Full-text Database. Only clinical trials and the first cycle of a cross-over trial linked to acupuncture for PDPN will be included in the analysis. The main outcomes include the amplitude of low-frequency fluctuation, regional homogeneity, functional connectivity of the brain, bilateral superficial peroneal nerve sensory nerve conduction velocity, bilateral dorsal current perception threshold values and the degree of subjective pain. The secondary outcomes include biochemical indicators, the degree of depression and anxiety and changes in efficiency. The study selection, data extraction and risk of bias assessment will be performed by two investigators. For statistical analyses, Review Manager V.5.4 software will be used. If necessary, heterogeneity testing, data synthesis, and subgroup analysis will be performed. ETHICS AND DISSEMINATION: Our systematic review and meta-analysis will be based on published literature for data extraction and will not include the use of individual patient data and so no ethical approval required. PROSPERO REGISTRATION NUMBER: CRD42021211644.

Study on acupuncture improving insomnia comorbid with depression and anxiety based on rs-fMRI: A protocol for systematic review and meta-analysis.

BACKGROUND: Long term insomnia and low sleep quality often lead to depression, anxiety and other negative emotions, and often interact with each other. Many studies have confirmed the effectiveness of acupuncture in the treatment of insomnia comorbid with emotional disorders, but its specific mechanism needs to be further explored. Resting-state functional magnetic resonance (rsfMRI) is an important means to study the changes of brain activity. However, the results are inconsistent and lack of systematic evaluation and analysis. METHODS: Nine databases will be searched, including PubMed, EMBASE, EBSCOhost-medline, Web of Science, Cochrane Library, China National Knowledge Infrastructure, VIP Database and Wan-Fang Database, Chinese Biomedical Literature Database from inception to January 2021. And screening clinical registration platform related research, in order to obtain more relevant studies. The outcomes include the change of rs-fMRI, sleep quality, depression, and anxiety. Quality assessment of the included studies will be performed according to the Cochrane Risk of Bias tool. Evidence quality will be assessed by using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. RevMan software (Version 5.3) and stata13.1will be used for statistical analyses. Subgroup analysis will be performed if necessary. If the data is insufficient, qualitative synthesis will be conducted instead of quantitative synthesis. RESULTS: This study will analyze the effect of acupuncture on the brain activity changes, improvement of sleep quality and clinical symptoms of anxiety and depression with insomnia comorbid with emotional disorders. CONCLUSION: This study used meta-analysis method to explore the characteristics of acupuncture on brain activity changes in insomnia comorbid with emotional disorders, so as to provide effective evidence for clarifying its pathogenesis.

Acupuncture for type 2 diabetes mellitus with nonalcoholic fatty liver disease: A protocol for systematic review and meta-analysis.

BACKGROUND: T2DM with NAFLD is a common disorder of glucose and lipid metabolism affecting the quality of life of patients. Due to the limitations and adverse reactions of drug treatment, acupuncture has been proved to be an effective method for the treatment of T2DM with NAFLD. This study aims to evaluate the efficacy and safety of acupuncture in the treatment of NAFLD in T2DM class, and to provide high-quality evidence for acupuncture in the treatment of this disease. METHODS: From establishment of the database to 31 July 2021, We will search the Cochrane Central Register of controlled trials, PubMed, MEDLINE, EMBASE, Web of science. Five Chinese databases, including China National Knowledge Infrastructure (CNKI), WanFang database, VIP, Chinese Biomedical Literature Database (CBM) and the Chinese clinical trial registry. There are no restrictions on language or publication, and they are independently screened and collected by two reviewers. Review Manager 5.3 software will be used for meta analysis. If necessary, heterogeneity testing, data synthesis, and subgroup analysis will be performed. RESULTS: The effectiveness and safety of acupuncture in the treatment of T2DM with NAFLD will be assessed by the outcomes of test's, including: imaging indicators, biomarkers of hepatic steatosis, serological indicators of hepatic fibrosis, improvement of serum NAFLD liver fat score, BMI, blood glucose indexes, blood lipid indexes, insulin level and safety indicators. CONCLUSION: This meta-analysis will further determine the beneficial efficacy and safety of acupuncture for T2DM combined with NAFLD.