Metabolic impairments associated with type 2 diabetes mellitus and the potential effects of exercise therapy: An exploratory randomized trial based on untargeted metabolomics.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a common condition that is characterized by metabolic impairments. Exercise therapy has proven effective in improving the physiological and psychological states of patients with T2DM; however, the influence of different exercise modalities on metabolic profiles is not fully understood. This study first aimed to investigate the metabolic changes associated with T2DM among patients and then to evaluate the potential physiological effects of different exercise modalities (Tai Chi and brisk walking) on their metabolic profiles. METHODS: This study included 20 T2DM patients and 11 healthy subjects. Patients were randomly allocated to either the Tai Chi or walking group to perform Dijia simplified 24-form Tai Chi or brisk walking (80-100 m/min), with 90 minutes each time, three times per week for 12 weeks, for a total of 36 sessions. The healthy group maintained daily living habits without intervention. Glycemic tests were conducted at the baseline and after 12 weeks. Serum and urine samples were collected for untargeted metabolomic analyses at baseline and 12 weeks to examine the differential metabolic profiles between T2DM and healthy subjects, and the metabolic alterations of T2DM patients before and after exercise therapy. RESULTS: Compared to the healthy group, T2DM patients exhibited metabolic disturbances in carbohydrates (fructose, mannose, galactose, glycolysis/gluconeogenesis), lipids (inositol phosphate), and amino acids (arginine, proline, cysteine, methionine, valine, leucine, and isoleucine) metabolism, including 20 differential metabolites in the serum and six in the urine. After exercise, the glycemic results showed insignificant changes. However, patients who practiced Tai Chi showed significant improvements in their post-treatment metabolic profiles compared to baseline, with nine serum and six urine metabolites, including branch-chained amino acids (BCAAs); while those in the walking group had significantly altered nine serum and four urine metabolites concerning steroid hormone biosynthesis and arachidonic acid metabolism compared to baseline. CONCLUSION: T2DM patients displayed impaired carbohydrate, lipid, and amino acid metabolism, and exercise therapy improved their metabolic health. Different modalities may act through different pathways. Tai Chi may improve disrupted BCAAs metabolism, whereas brisk walking mainly regulates steroid hormone biosynthesis and arachidonic acid metabolism.

Clinical Research Progress of the Post-Stroke Upper Limb Motor Function Improvement via Transcutaneous Auricular Vagus Nerve Stimulation.

Stroke is a disease with high morbidity and disability, and motor impairment is a common sequela of stroke. Transcutaneous auricular vagus nerve stimulation (taVNS) is a type of non-invasive stimulation, which can effectively improve post-stroke motor dysfunction. This review discusses stimulation parameters, intervention timing, and the development of innovative devices for taVNS. We further summarize the application of taVNS in improving post-stroke upper limb motor function to further promote the clinical research and application of taVNS in the rehabilitation of post-stroke upper limb motor dysfunction.

Effects of integrated action and sensory observation therapy based on mirror neuron and embodied cognition theory on upper limb sensorimotor function in chronic stroke: a study protocol for a randomised controlled trial.

INTRODUCTION: This study protocol aims to explore the effectiveness and neural mechanism of the integration of action observation therapy (AOT) and sensory observation therapy (SOT) for post-stroke patients on upper limb sensorimotor function. METHODS AND ANALYSIS: This is a single-centre, single-blind, randomised controlled trial. A total of 69 patients with upper extremity hemiparesis after stroke will be recruited and randomly divided into an AOT group, a combined action observation and somatosensory stimulation therapy (AOT+SST) group, and a combined AOT and SOT (AOT+SOT) group in a 1:1:1 ratio. Each group will receive 30 min of daily treatment, five times weekly for 4 weeks. The primary clinical outcome will be the Fugl-Meyer Assessment for Upper Extremity. Secondary clinical outcomes will include the Box and Blocks Test, modified Barthel Index and sensory assessment. All clinical assessments and resting-state functional MRI and diffusion tensor imaging data will be obtained at pre-intervention (T1), post-intervention (T2) and 8 weeks of follow-up (T3). ETHICS AND DISSEMINATION: The trial was approved by the Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Chinese Traditional Medicine (Grant No. 2020-178). The results will be submitted to a peer-review journal or at a conference. TRIAL REGISTRATION NUMBER: ChiCTR2000040568.

Lifestyle intervention Tai Chi for adult patients with type 2 diabetes mellitus: a PRIO-harms based overview of 17 systematic reviews.

Objective: To systematically summarize current evidence and determine the clinical effectiveness and safety of Tai Chi for type 2 diabetes mellitus (T2DM) in adults by conducting an overview of systematic reviews (SRs). Methods: A systematic search encompassing five electronic databases was conducted until July 30, 2023, to identify relevant systematic reviews (SRs) based on randomized controlled trials (RCTs) concerning Tai Chi for T2DM. The methodological quality of the included SRs was assessed using the A MeaSurement Tool to Assess systematic Reviews (AMSTAR 2) and the Risk of Bias in Systematic Reviews (ROBIS) tool. The Preferred Reporting Items for Overview of Systematic Review (PRIO-harms) checklist was used to promote a more balanced reporting of benefits and harms in this overview. Corrected covered area (CCA) was used to calculate the degree of overlapping primary studies. Primary outcome measures were glycosylated hemoglobin (HbA1c) and fasting blood glucose (FBG), while secondary outcomes encompassed health-related quality measures. The GRADE (Grades of Recommendations, Assessment, Development, and Evaluation) framework was utilized to assess the quality of evidence for the outcome measures. Results: A total of 17 eligible SRs were included in this overview. One SR reported negative conclusions, while the remaining 16 reported positive ones on different outcomes. A total of 4 SRs reported adverse events, either absent or minor. Most of the SRs exhibited critically low quality (15/17) and a high risk of bias (14/17), as indicated by AMSTAR2 and ROBIS, respectively. The CCA was 12.14%, indicating a high degree of primary study overlapping. Evidence from 135 results for 24 outcomes concerning Tai Chi for T2DM was evaluated using the GRADE approach, most of which were rated very low. Conclusion: Tai Chi shows promise as a potentially effective and safe lifestyle intervention for adults with T2DM, particularly in improving HbA1c, FBG, BMI, and overall quality of life (QoL). However, these results should be cautiously interpreted due to methodological flaws observed in the current SRs and the low quality of the SRs based on GRADE. Furthermore, there is a compelling need for additional well-designed, high-quality RCTs and SRs to establish robust and conclusive evidence regarding the efficacy of Tai Chi for managing T2DM in the future. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD 42019140988.

Gamma oscillations and application of 40-Hz audiovisual stimulation to improve brain function.

BACKGROUND: Audiovisual stimulation, such as auditory stimulation, light stimulation, and audiovisual combined stimulation, as a non-invasive stimulation, which can induce gamma oscillation, has received increased attention in recent years, and it has been preliminarily applied in the clinical rehabilitation of brain dysfunctions, such as cognitive, language, motor, mood, and sleep dysfunctions. However, the exact mechanism underlying the therapeutic effect of 40-Hz audiovisual stimulation remains unclear; the clinical applications of 40-Hz audiovisual stimulation in brain dysfunctions rehabilitation still need further research. OBJECTIVE: In order to provide new insights into brain dysfunction rehabilitation, this review begins with a discussion of the mechanism underlying 40-Hz audiovisual stimulation, followed by a brief evaluation of its clinical application in the rehabilitation of brain dysfunctions. RESULTS: Currently, 40-Hz audiovisual stimulation was demonstrated to affect synaptic plasticity and modify the connection status of related brain networks in animal experiments and clinical trials. Although its promising efficacy has been shown in the treatment of cognitive, mood, and sleep impairment, research studies into its application in language and motor dysfunctions are still ongoing. CONCLUSIONS: Although 40-Hz audiovisual stimulation seems to be effective in treating cognitive, mood, and sleep disorders, its role in language and motor dysfunctions has yet to be determined.

Evidence construction of Huangkui capsule against chronic glomerulonephritis: A systematic review and network pharmacology.

BACKGROUND: Chronic glomerulonephritis (CGN) is a relatively common primary glomerular disease. Huangkui capsule (HKC) combined with angiotensin receptor blocker (ARB) for CGN is frequently used in clinical practice, however, there is still lack of high-quality evidence-based evidence and network pharmacology to clarify the therapeutic efficacy and pharmacological mechanisms. PURPOSE: Integrating evidence-based medicine and network pharmacology to explain the therapeutic efficacy and pharmacological mechanisms of ARB combined with HKC for CGN. METHODS: Studies matching the topic were searched from PubMed, Web of Science, Embase database, the Cochrane Library, Chinese National Knowledge Infrastructure, CBM databases, the VIP medicine information system and the Wanfang database and screened according to inclusion and exclusion criteria. The data of the included studies were meta-analyzed by blood urea nitrogen (BUN), serum creatinine (SCR), 24-h urine protein (24hUP) and effective rate (ER). A meta-analysis of the data from the included studies was performed. Then, based on the network pharmacology, the chemical ingredients in HKC and their targets of action, disease targets, common targets and other relevant information were screened, and the key pathways were relevantly annotated based on bioinformatics technology to explore the potential mechanisms of HKC and ARB for CGN. RESULTS: The results showed that SCR index (p < 0.05), 24hUP index (p < 0.001) in the group treated with HKC and ARB were significantly lower than those in the control group. BUN index in the group treated with HKC and VAL were significantly lower than those in the control group (p < 0.001). Effective rate index in the group treated with HKC and ARB was significantly higher than those in the control group (p < 0.001). There was no significant difference in BUN treated with IRB, LOS, and TEL (p = 0.181; p = 0.811; p = 0.067). Based on network pharmacology, the results were as follows: The PPI network indicated that STAT3, AKT1, MAPK1, TP53 and JUN were key target proteins. The results of KEGG analysis suggested that the pharmacological mechanisms were mainly associated with AGE-RAGE signaling pathway in diabetic complications. CONCLUSION: The combination of ARB and HKC can achieve better therapeutic effects in the treatment of CGN, meanwhile, ARB and HKC have a significant improved effectiveness in the treatment of CGN compared with ARB or HKC alone. In addition, HKC and ARB synergistically treated CGN through a multi-pathway network.

Systematic Review of the Efficacy and Safety of Shuxuening Injection in the Treatment of Unstable Angina.

The aim of this study was to systematically review the efficacy and safety of Shuxuening injection combined with conventional Western medicine in the treatment of unstable angina. Randomized controlled trials of Shuxuening injection combined with conventional Western medicine in the treatment of unstable angina were searched by the computer system from PubMed, EMBASE, Cochrane Library, VIP, CNKI, Wanfang Database, and Chinese Biomedical Database since the establishment of the database until June 2020, according to the inclusion and exclusion criteria for the selection of literature, using Rev Man5.3 Meta-analysis Software. The 28 randomized controlled trials were included, with a total of 3,127 patients. Meta-analysis results showed that Shuxuening injection combined with conventional western medicine was effective in improving the clinical efficacy of angina pectoris (RR = 1.23, 95% CI [1.19, 1.27], P<0.00001), improvement of ECG (RR = 1.31, 95% CI [1.23, 1.40], P < 0.00001), reduction of angina pectoris attack frequency (MD = -1.28, 95% CI [-1.88, -0.67], P < 0.0001), duration of angina (MD = -3.36, 95% CI [-3.69, -3.03], P < 0.00001), nitroglycerin dosage (MD = -0.39, 95% CI [-0.65, -0.13], P = 0.003), C-reactive protein (MD = -2.72, 95% CI [-3.41, -2.03], P < 0.00001), BNP (MD = -23.33, 95% CI [-27.87, -18.79], P < 0.00001), lower triglycerides (MD = -0.72, 95% CI [-1.05, -0.38], P < 0.0001), total cholesterol (MD = -1.39, 95% CI [-1.84, -0.94], P < 0.00001), and LDL cholesterol (MD = -1.20, 95% CI [-2.12, -0.29], P = 0.01) which is better than that of control group. The effect on raising HDL cholesterol was comparable between the two groups (MD = 0.49, 95% CI [-0.06, 1.04], P = 0.08) and the incidence of adverse reactions to differences had no statistical significance (RR = 0.99, 95% CI [0.54, 1.81], P = 0.97). The Shuxuening injection combined with conventional Western medicine in the treatment of unstable angina has clear efficacy and a certain degree of safety, so it is recommended for clinical application.

The Modulation of Working-Memory Performance Using Gamma-Electroacupuncture and Theta-Electroacupuncture in Healthy Adults.

Working memory (WM), a central component of general cognition, plays an essential role in human beings' daily lives. WM impairments often occur in psychiatric, neurodegenerative, and neurodevelopmental disorders, mainly presenting as loss of high-load WM. In previous research, electroacupuncture (EA) has been shown to be an effective treatment for cognitive impairments. Frequency parameters are an important factor in therapeutic results, but the optimal frequency parameters of EA have not yet been identified. In this study, we chose theta-EA (θ-EA; 6 Hz) and gamma-EA (γ-EA; 40 Hz), corresponding to the transcranial alternating-current stimulation (tACS) frequency parameters at the Baihui (DU20) and Shenting (DU24) acupoints, in order to compare the effects of different EA frequencies on WM. We evaluated WM performance using visual 1-back, 2-back, and 3-back WM tasks involving digits. Each participant (N = 30) attended three different sessions in accordance with a within-subject crossover design. We performed θ-EA, γ-EA, and sham-EA in a counterbalanced order, conducting the WM task both before and after intervention. The results showed that d-prime (d') under all three stimulation conditions had no significance in the 1-back and 2-back tasks. However, in the 3-back task, there was a significant improvement in d' after intervention compared to d' before intervention under θ-EA (F [1, 29] = 22.64; P < 0.001), while we saw no significant difference in the γ-EA and sham-EA groups. Reaction times for hits (RT-hit) under all three stimulation conditions showed decreasing trends in 1-, 2-, and 3-back tasks but without statistically significant differences. These findings suggest that the application of θ-EA might facilitate high-load WM performance.

Tai Chi for type 2 diabetes mellitus: A protocol for systematic review.

BACKGROUND: Tai Chi is gaining an increasing popularity in rehabilitation management of chronic conditions. Yet no consensus has reached on its efficacy and safety of type 2 diabetes despite that several systematic reviews (SRs) were published on this topic. Therefore, we will conduct an overview to critically evaluate current SRs and implement an updated metaanalysis with recently published randomized controlled trials (RCTs). METHODS: A systematic literature search of relevant RCTs-based SRs will be conducted in electronic databases including Medline, Embase, the Cochrane Library, the Chinese National Knowledge Infrastructure, the Chinese Biomedical Literature Database from their inceptions to search date without language restrictions. Eligible SRs will be methodologically assessed by the assessment of multiple SRs 2 and Risk of Bias in SRs tool and their RCTs included will be extracted for further evidence synthesis. To update current meta-analysis on this topic, a supplementary search will be implemented for related newly emerged RCTs. Cochrane risk of bias assessment tool will be applied for RCTs quality evaluation. The grading of recommendations assessment, development and evaluation will be utilized for evidence quality assessment of outcomes. Study characteristic information on participants, interventions, outcomes, comparisons and conclusions will be described in detail. Review Manager V5.3 will be used for risk of bias assessment and Stata 14.0 for meta-analysis and sensitivity analysis. RESULTS: The study results will be disseminated through a peer-reviewed journal publication or conference presentation. CONCLUSIONS: This study finding will provide an updated evidence of Tai Chi for patients with type 2 diabetes mellitus (T2DM), thus to help inform clinical physicians, T2DM patients and their families to develop better rehabilitation plans and to draw more attention of decision-makers in exercise rehabilitation related policy-making.This study protocol has been applied for registration on PROSPERO platform (https://www.crd.york.ac.uk/PROSPERO/), with an assigned ID: CRD42019140988.

TCM nonpharmacological interventions for chronic obstructive pulmonary disease (COPD): Protocol for a systematic review and network meta-analysis.

BACKGROUND: Traditional Chinese medicine (TCM) nonpharmacological interventions are gaining an increasing popularity for chronic pulmonary obstructive disease (COPD) treatment and rehabilitation, yet their comparative effectiveness and safety remains unclear. Therefore, this study will aim to compare their effectiveness and safety for COPD by implementing a network-meta analysis. METHODS: Electronic databases including MEDLINE via Ovid, and EMBASE via Ovid, the Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Infrastructure (CNKI) and Chinese BioMedical Literature Database (CBM) will be searched for related randomized controlled trials (RCTs) from inceptions to the search date without language restrictions. RCTs that compare TCM nonpharmacological interventions with placebo or conventional treatments will be included. The primary outcome will be lung function measures, dyspnea level and COPD-specified life quality and secondary ones will include functional exercise capacity, and general health-related life quality. Both classical meta-analysis and network meta-analysis will be implemented to investigate direct and indirect evidences on this topic. Continuous data will be expressed as standard mean differences (SMDs) and categorical data as risk ratios (RRs) with 95% confidence intervals. The evidence transitivity and consistency within network will be evaluated with Cochrane Q statistic and net-heat plot. RESULTS: The study results will be disseminated through a peer-reviewed journal publication or conference presentation. CONCLUSIONS: The review findings will provide a ranking evidence of current TCM nonpharmacological interventions and help to inform clinical practitioners, COPD patients, and policy-makers in the decision-making. TRIAL REGISTRATION NUMBER: PROSPERO CRD42019126554.

Effect of electroacupuncture on arginine vasopressin-induced endolymphatic hydrops.

OBJECTIVE: To investigate the influence of electroacupuncture (EA) on experimentally induced endolymphatic hydrops (EH) in guinea pigs, and elucidate the association between the dehydrating effect of EA and changes in stria vascularis ultrastructure and expression of vasopressin type 2 receptor (V2R), cyclic adenosine monophosphate (cAMP), and aquaporin 2 (AQP2) in the endolymphatic sac (ES). METHODS: The EH model was established by intraperitoneal injection of arginine vasopressin (AVP). As a treatment, EA was delivered to Baihui (GV 20) and Tinggong (SI 19) acupoints, once daily for 10 consecutive days. For histomorphological studies, degree of cochlear hydrops was evaluated by hematoxylin-eosin staining, and the ratio of scala media (SM) area to SM + scala vestibuli area was calculated. In mechanical studies, ultrastructural changes in stria vascularis tissue were examined by transmission electron microscopy. In addition, cAMP levels and mRNA expression levels of V2R and AQP2 in the ES were compared among groups. RESULTS: EA treatment significantly reduced cochlear hydrops compared with hydropic guinea pigs (P = 0.015). Furthermore, EA attenuated ultrastructural changes in the stria vascularis tissue following EH, significantly upregulated the expression of V2R (P = 0.016), and attenuated AVP-induced upregulation of both cAMP (P = 0.038) and AQP2 expression (P = 0.017) in the ES. CONCLUSION: Collectively, the results of the present study suggest that the dehydrating effect of EA is associated with improvement of stria vascularis ultrastructure and V2R-cAMP-AQP2 signaling pathway regulation in the ES.

Arginine Vasopressin-Aquaporin-2 Pathway-Mediated Dehydration Effects of Electroacupuncture in Guinea Pig Model of AVP-Induced Eendolymphatic Hydrops.

OBJECTIVE: To investigate the effects of electroacupuncture (EA) on endolymphatic hydrops (EH) and the regulation of arginine vasopressin (AVP)-aquaporin-2 (AQP2) pathway in guinea pigs. METHODS: EH was induced in male guinea pigs by an intraperitoneal injection of AVP. For the treatment, EA was delivered to Baihui (GV 20) and Tinggong (SI 19) acupoints, once per day for 10 consecutive days. In histomorphological studies, cochlear hydrops degree was evaluated by hematoxylin-eosin (HE) staining, and then the ratio of scala media (SM) area to SM + scala vestibuli (SV) area (R value) was calculated. In mechanical studies, a comparison of plasma AVP (p-AVP) concentrations, cyclic adenosine monophosphate (cAMP) levels, vasopressin type 2 receptor (V2R) and AQP2 mRNA expressions in the cochlea were compared among groups. RESULTS: EA significantly reduced cochlear hydrops in guinea pigs (P=0.001). EA significantly attenuated the AVPinduced up-regulation of p-AVP concentrations (P=0.006), cochlear cAMP levels (P=0.003) and AQP2 mRNA expression (P=0.016), and up-regulated the expression of V2R mRNA (P=0.004) in the cochlea. CONCLUSIONS: The dehydrating effect of EA might be associated with its inhibition of AVP-AQP2 pathway activation.

Gambogic acid suppresses inflammation in rheumatoid arthritis rats via PI3K/Akt/mTOR signaling pathway.

Gamboge is the dried resin secreted by the Garcinia maingayi gambogic tree and is a substance that may be used to treat a variety of diseases, exhibits anti­tumor and detoxification effects and prevents bleeding. The primary active constituent is gambogic acid. The present study aimed to investigate the anti­inflammatory effects of gambogic acid in rheumatoid arthritis (RA) rats and to elucidate the mechanisms by which these effects occur. The swelling degree, the clinical arthritic scoring and pain threshold measurements were used to evaluate the effects of gambogic acid on RA. ELISA kits and western blot analysis were used to investigate inflammatory processes and the expression of RA­associated proteins, respectively. The present results demonstrated that gambogic acid significantly inhibited the degree of right foot swelling, increased pain thresholds and reduced clinical arthritic scores of RA rats. Treatment with gambogic acid suppressed the activities of interleukin (IL)­1ß and IL­6, promoted the protein expression of phosphorylated (p)­Akt serine/threonine kinase (Akt), p­mammalian target protein of rapamycin (mTOR) and inhibited hypoxia­inducible factor­1α and vascular endothelial growth factor expression in RA rats. The results of the present study therefore suggest that the anti­inflammatory effects of gambogic acid in RA rats occur via regulation of the phosphoinositide 3­kinase/Akt/mTOR signaling pathway.

Electro-acupuncture treatment for internet addiction: Evidence of normalization of impulse control disorder in adolescents.

OBJECTIVE: To observe the impacts of electro-acupuncture (EA) and psychological intervention (PI) on impulsive behavior among internet addiction (IA) adolescents. METHODS: Thirty-two IA adolescents were allocated to either EA (16 cases) or PI (16 cases) group by a randomized digital table. Subjects in the EA group received EA treatment and subjects in the PI group received cognition and behavior therapy. All adolescents underwent 45-d intervention. Sixteen healthy volunteers were recruited into a control group. Barratt Impulsiveness Scale (BIS-11) scores, Young's Internet Addiction Test (IAT) as well as the ratio of brain N-acetyl aspartate (NAA) to creatine (NAA/Cr) and choline (Cho) to creatine (Cho/Cr) were recorded by magnetic resonance spectroscopy before and after intervention respectively. RESULTS: The IAT scores and BIS-11 total scores in both EA and PI group were remarkably decreased after treatment (P<0.05), while EA group showed more significant decrease in certain BIS-11 sub-factors (P<0.05). Both NAA/Cr and Cho/Cr were significantly improved in EA group after treatment (P<0.05); however, there were no significant changes of NAA/Cr or Cho/Cr in PI group after treatment (P>0.05). CONCLUSIONS: Both EA and PI had significantly positive effect on IA adolescents, especially in the aspects of psychological experiences and behavioral expressions, EA might have an advantage over PI in terms of impulsivity control and brain neuron protection. The mechanism underlying this advantage might be related to the increased NAA and Cho levels in prefrontal and anterior cingulate cortices.

Effective Monitoring of Fluxapyroxad and Its Three Biologically Active Metabolites in Vegetables, Fruits, and Cereals by Optimized QuEChERS Treatment Based on UPLC-MS/MS.

Qualitative analysis and quantification of pesticide residues in foodstuff are essential to our health in daily life, especially regarding their metabolites, which may be more toxic and persistent. Thus, a valid analytical measure for detection of fluxapyroxad and its three metabolites (M700F002 (C-2), M700F008 (C-8), M700F048 (C-48)) in vegetables (cucumber, tomato, and pepper), fruits (grape, apple), and cereals (wheat, rice) was developed by UPLC-MS/MS with negative ion mode. The target compounds were extracted by acetonitrile contain 0.2% formic acid (v/v), and the extractions were cleaned up by octadecylsilane sorbents. The limits of quantitation and quantification were less than 0.14 µg kg-1 and 0.47 µg kg-1 in seven matrices. Furthermore, recoveries at levels of 0.01, 0.05, and 0.1 mg kg-1 ranged from 74.9% to 110.5% with relative standard deviations ≤15.5% (n = 5). The method is validated to be effective and robust for the routine supervising of fluxapyroxad and its metabolites.