Potential effect of acupuncture on mitochondrial biogenesis, energy metabolism and oxidation stress in MCAO rat via PGC-1α/NRF1/TFAM pathway.

PURPOSE: To explore possible mechanism(s) underlying beneficial effects of acupuncture treatment for alleviating focal cerebral infarction-induced neuronal injury, mitochondrial biogenesis, energy metabolism, oxidative stress and dendrite regeneration were evaluated in rats with experimentally induced cerebral ischemia and dendron reperfusion. MATERIALS AND METHODS: Rats were randomly assigned to three groups (sham-operated, operated group without acupuncture, operated group with acupuncture). RT-PCR and Western blotting were used to assess variations of hippocampal cell mitochondrial DNA (mtDNA) copy number and mRNA and protein expression levels associated with key mitochondrial biogenesis proteins, namely peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), nuclear respiration factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM). To evaluate mitochondrial oxidative phosphorylation and respiratory function in ischemic tissues, oxidative phosphorylation protein complex expression levels were assessed via Western blot analysis, mitochondrial membrane potential (MMP) was assessed via confocal microscopy and flow cytometry and adenosine triphosphate (ATP) concentration was assessed using an enzymatic fluorescence-based assay. Immunofluorescence staining was used to evaluate the expression of the neuronal dendron formation marker-Microtubule Associated Protein 2 (MAP2). Additionally, oxidative stress levels were assessed based on superoxide dismutase (SOD) activity, lipid oxidation levels (malondialdehyde, MDA) and glutathione (GSH) levels. Meanwhile, 2,3,5-triphenyltetrazolium chloride (TTC) staining, Nissl staining, transmission electron microscopy observation and neuro behavioral status were used to determine cerebral infarction volume and extent of brain injury. RESULTS: Acupuncture treatment effectively stimulated mRNA-level and protein-level expression associated with PGC-1α, NRF-1 and TFAM and increased levels of electron transport chain complexes I, IV and V, thereby increasing the ATP concentration, maintaining mitochondrial membrane potential, and promoting dendron regeneration levels. Meanwhile, in hippocampal neurons SOD activity and the glutathione/glutathione disulfide (GSH/GSSG) ratio increased and MDA level decreased. CONCLUSION: Acupuncture treatment after ischemic injury promoted mitochondrial biogenesis, as reflected by beneficially increased mitochondrial oxidative phosphorylation complex protein levels and brain tissue energy supply, while preventing oxidative stress injury. These results should guide future explorations to elucidate acupuncture-based mechanisms for alleviating neuronal injury triggered by acute cerebral ischemia.

Exploring the molecular mechanism of Yinao Fujian formula on ischemic stroke based on network pharmacology and experimental verification.

Background: Ischemic stroke (IS) is a leading cause of long-term disability and even mortality, threatening people's lives. Yinao Fujian (YNFJ) formula is a Traditional Chinese Medicine formula that has been widely used to treat patients with IS. However, the molecular mechanism of YNFJ for the treatment of IS is still elusive. Our study aimed to explore the potential protective effect and the underlying mechanisms of YNFJ on IS using a network pharmacology approach coupled with experimental validation. Materials and methods: Effective compounds of YNFJ were collected from BATMAN-TCM and TCMSP databases, while IS targets were obtained from GeneCards, OMIM, TTD and DrugBank databases. The protein-protein interaction (PPI) network was constructed to further screen the hub targets of YNFJ in IS treatment. GO and KEGG enrichment analyses were used to identify the critical biological processes and signaling pathways of YNFJ for IS. Moreover, Nissl staining, HE, TTC staining and Tunel staining were used in the MCAO model to prove the neuroprotective effect of YNFJ. Oxidative damage, inflammatory factor release and related pathways were tested in MCAO rat model and hypoxia-induced BV2 cell model, respectively. Results: We found that YNFJ treatment significantly alleviated MCAO-induced nerve damage and apoptosis. Then, network pharmacology screening combined with literature research revealed IL6, TNF, PTGS2, NFKBIA and NFE2L2 as the critical targets in a PPI network. Moreover, the top 20 signaling pathways and biological processes associated with the protective effects of YNFJ on IS were enriched through GO and KEGG analyses. Further analysis indicated that NF-κB and Nrf2/HO-1 signaling pathways might be highly involved in the protective effects of YNFJ on IS. Finally, in vitro and in vivo experiments confirmed that YNFJ inhibited the release of inflammatory factors (IL-6 and TNF-α) and MDA content, and increased the activity of SOD. In terms of the mechanism, YNFJ inhibited the release of inflammatory factors by suppressing the NF-κB pathway and decreased the expression of iNOS and COX-2 to protect microglia from inflammation damage. In addition, YNFJ initiated the dissociation of Keap-1 and Nrf2, and activated the downstream protein HO-1, NQO1, thus decreasing oxidative stress. Conclusion: Taken together, the findings in our research showed that the protective effects of YNFJ on IS were mainly achieved by regulating the NF-κB and Nrf2/HO-1 signaling pathways to inhibit oxidative stress damage and inflammatory damage of microglia.

Effect of TCM rehabilitation program on activities of daily living in patients with post-stroke limb spasticity: An observational study.

BACKGROUND: Stroke is a neurological disease with many common complications that reduce the activities of daily living and the quality of life of patients. Traditional Chinese medicine (TCM) rehabilitation techniques, scalp acupuncture, and TCM can relieve spasticity symptoms and recovery from physical obstacles is significant. METHODS: Three hundred twenty-one patients with post-stroke limb spasticity were randomly divided into trial and control groups, with 159 and 162 patients in the trial and control groups, respectively. The control group received basic treatment combined with modern rehabilitation techniques, whereas the trial group received basic treatment combined with TCM, Tuina, and scalp acupuncture with kinesiotherapy. The treatment course in both groups was 4 weeks. The Modified Ashworth Scale, magnetic resonance imaging, and Stroke Specific Quality of Life Scale were used to evaluate limb spasticity, activities of daily living, and quality of life, respectively. PASW 18.0 was used for statistical analysis. RESULTS: With a longer treatment period, the improvement in limb spasticity was greater in the trial group than in the control group (P < .05). Similarly, improvements in activities of daily living and quality of life were better in the trial group than in the control group (P < .05). CONCLUSION: The TCM rehabilitation program using Tongjing Tiaoxing combined with scalp acupuncture and kinesiotherapy can effectively treat spasticity symptoms in stroke patients and improve their activities of daily living and quality of life.

Scalp acupuncture alleviates cerebral ischemic stroke-induced motor dysfunction in rats via regulating endoplasmic reticulum stress and ER-phagy.

Cerebral ischemic stroke is a high-risk disease and imposes heavy burdens on patients in china. Acupuncture has been used for thousands of years to treat motor dysfunction, cognitive disorder and language barrier caused by cerebral ischemic stroke. Acupoint lines, vertex middle line and anterior oblique line of vertex temple, are always employed to treat cerebral ischemic stroke. However, the mechanism of the two acupoint lines in relieving cerebral ischemic stroke needs further exploration. In the present study, scalp acupuncture treatment alleviated the motor dysfunction, brain damage, and cell death induced by middle cerebral artery occlusion (MCAO) in rats. Proteomics analysis and ultrastructure observation indicated that endoplasmic reticulum and lysosomes might involve in the mechanism of the scalp acupuncture treatment in suppressing MCAO-triggered neural deficits. Effect of the scalp acupuncture treatment on ER stress was then investigated and found that the activation of ER stress mediators, including PERK, IRE1, and ATF6, was downregulated after the scalp acupuncture treatment. Co-localisation analysis of KDEL and CD63 showed that the engulfment of ER fragments by lysosomes was accelerated by the scalp acupuncture treatment. Moreover, expression of pro-apoptotic protein CHOP, phosphorylated-JNK, cleaved capases-3 and -9 also decreased after the scalp acupuncture. In conclusion, the present study showed that scalp acupuncture of vertex middle line and anterior oblique line of vertex temple may alleviate cerebral ischemic stroke by inhibiting ER stress-accelerated apoptosis.

Acupuncture for shoulder-hand syndrome after stroke: An overview of systematic reviews.

BACKGROUND: To provide evidence, this review evaluated the methodological quality, risk of bias, and reporting quality of SRs/MAs in the treatment of shoulder-hand syndrome after stroke with acupuncture. METHODS: Systematic reviews and Meta analyses (SRs/MAs) of acupuncture for shoulder and hand syndromes after stroke were retrieved from 6 databases from inception to May 1, 2022. Two reviewers independently screened the literature and extracted the data, then used Assessment of Multiple Systematic Reviews-2 (AMSTAR-2), Bias Risk in Systematic Review (ROBIS), and Preferred Report Item for Systematic review and Meta-analysis (PRISMA), Grading of Recommendations, Assessment, Development and Evaluation (GRADE) to assess methodological quality, risk of bias, quality of reporting, and quality of evidence. RESULTS: We included 7 SRs/MAs, of which all SRs/MAs had very low AMSTAR-2 assessment quality and one study had a very low assessment bias risk. According to the PRISMA checklist, Protocol and registration, Synthesis of results, Summary of evidence, Conclusions and Funding were the main reporting limitations. GRADE evaluation showed a total of 37 results, but no high-quality evidence results, 6 results (16.22%) of the evidence quality were moderate, and supported acupuncture combined with exercise rehabilitation and drug therapy was better than exercise joint drug rehabilitation and rehabilitation, we also found that the result of limitations were the main factors that influence the evidence of low quality, followed by imprecision, inconsistency, and publication bias. CONCLUSIONS: Acupuncture is a relatively safe and effective adjuvant therapy for shoulder and hand syndromes after stroke. However, because of the low quality of SRs/MAs evidence supporting these findings, high-quality randomized controlled trials should be conducted, and the quality of relevant SRs should be improved to provide evidence for clinical application.

Abdominal massage: A review of clinical and experimental studies from 1990 to 2021.

OBJECTIVE: To systematically review the current state and holistic application of abdominal massage (AM). DESIGN: A systematic review of qualitative evidence was conducted. All English articles exploring the topic of AM that had been published until the end of June 2021 were retrieved. DATA SOURCES: The PubMed, Cochrane library, and Embase databases were accessed. Some original texts were obtained from Google Scholar. DATA EXTRACTION AND SYNTHESIS: Two authors independently evaluated all search data to identify relevant studies. Disagreements were settled by discussion with a third author. Results were independently extracted into standardized sheets and checked for accuracy. MAIN RESULTS: A total of 107 full-text reports were eligible for inclusion. Adult digestive disorders, pediatric disorders, gynecological disorders, obstetric disorders, metabolic disorders, psychological disorders, the side effects of AM, and animal experiments accounted for 49.53%, 14.02%, 7.48%, 7.48%, 4.67%, 4.67%, 5.61%, and 6.54% of all these papers, respectively, with most reports focusing on clinical studies. CONCLUSION: The variety of diseases treated with AM is gradually increasing, and the treatment programs of AM for many diseases are being gradually optimized. Different forms of AM, especially mechanical AM, have been widely studied; the side effects of AM have also been considered; and the possible mechanisms of AM therapy continue to be discovered. In general, AM is an effective and safe therapy and can be widely used in various diseases, but further studies are necessary to clarify the mechanism of AM for different diseases. In the future, AM could become an even safer, more popular, and more modern therapy.

Ginsenoside Rf inhibits human tau proteotoxicity and causes specific LncRNA, miRNA and mRNA expression changes in Caenorhabditis elegans model of tauopathy.

Under pathological conditions, human tau (htau) hyperphosphorylation promotes formation of proteotoxic intracellular amyloid aggregates that may underlie neurodegenerative diseases known as tauopathies, prompting researchers to develop treatments that inhibit htau aggregation as a promising therapeutic strategy. Ginsenosides, the main active constituents of Panax ginseng C. A. Meyer (ginseng), appear to inhibit tau aggregation and disassociation in tauopathy models, although their active components and molecular mechanisms are unknown. Here, we used a novel Caenorhabditis elegans (C. elegans) tauopathy model to identify ginsenoside monomers which may repress htau proteotoxicity. Our findings indicated that ginsenoside Rf prevented tau aggregation and reversed abnormal tau aggregation-induced phenotypes and alleviated neurodegeneration in worms. Notably, deep RNA-seq analysis of ginsenoside Rf-treated and untreated worms with tauopathy revealed that ginsenoside Rf altered expression levels of 24 up- and 36 down-regulated lncRNA transcripts, 32 up- and 22 down-regulated miRNAs and 65 up- and 30 down-regulated mRNA transcripts. Based on GO and KEGG pathway annotation analyses, identified mRNAs, miRNAs and lncRNAs-associated gene targets were functionally related to neuron-related terms (e.g., neuron development, axon and motor neuron axon guidance) and longevity regulating pathways. Importantly, RT-qRCR results suggested that 6 miRNAs (miR-786, miR-2208b, miR-34, miR-241, miR-247 and miR-4805), 8 lncRNAs (MSTRG.20812.2, MSTRG.22617.2, MSTRG.28210.13, MSTRG.5728.12, MSTRG.29708.1, MSTRG.3342.25, MSTRG.3342.31 and MSTRG.8841.8) and 7 mRNAs (nas-33, math-28, T14B4.19, col-17, rol-6, sqt-1 and irg-4) were potential targets of ginsenoside Rf inhibition of tauopathy. These results partially explain mechanisms underlying ginsenoside Rf-associated alleviation of htau proteotoxicity and will guide future strategies to discover potential therapeutic targets for preventing and alleviating tauopathies.

Tuina combined with physical therapy for spasticity of poststroke: A protocol for systematic review and meta-analysis.

BACKGROUND: Limb spasms are a common complication of stroke. It not only affects the quality of life of stroke survivors, but also brings an economic burden. Tuina combined with physical therapy is widely used in the rehabilitation of poststroke spasticity. However, there is no supporting evidence for its efficacy and safety. This study aimed to evaluate the effectiveness and safety of Tuinas combined with physical therapy in the treatment of spasticity after stroke. METHODS: Literature will be collected from the following databases: China Biology Medicine (CBM), Wanfang Database, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), PubMed, Embase, Cochrane Library, and Web of Science; We will include randomized controlled trials of Tuina combined with physical therapy for poststroke spasticity range from the establishment to May 1, 2021. There were no limitations to the publication time, and the language was limited to Chinese and English. The primary outcome was evaluated using the Modified Ashworth scale, and the secondary outcomes were the simplified Fugl-Meyer Assessment scale, Modified Barthel Index, Functional Independence Measurement (FIM), and Visual Analog Scale. RevMan V.5.4.1 software was used for the meta-analysis. The Cochrane Intervention System Evaluation Manual analyzes the risk of bias, and the recommended grading assessment, development and evaluation are used to assess the quality of evidence. ETHICS AND DISSEMINATION: This study will be based on published systematic review studies, no ethical approval is required and the results of the study will be published in a peer-reviewed scientific journal. SYSTEMATIC REVIEW REGISTRATION: INPLASY2021110064.

Tuina combined with diet and exercise for simple obesity: A protocol for systematic review.

BACKGROUND: The incidence of simple obesity is increasing annually, with the number of obese people in all age groups increasing significantly. Obesity has become an important public health concern. Simple obesity affects not only appearance but also health. Obesity has an increasing impact on individuals, families, and society. Therefore, the treatment of obesity is becoming increasingly important. Prior studies have shown that Tuina combined with diet and exercise is capable of producing improvements in body weight and fasted health markers. In recent years, there are many clinical studies on the intervention of simple obesity by Tuina combined with diet and exercise, however, no study systematically evaluated the clinical efficacy. The purpose of this study is to evaluate its effects of Tuina combined with diet and exercise on people with simple obesity. METHODS: We will search the following electronic databases: PubMed, EMBASE, MEDLINE, Web of science, Cochrane Library, WanFang Data, CBM, CNKI, and VIP from the inception of the coverage of these databases to December 2021. Randomized controlled clinical trials related to Tuina combined with diet and exercise intervention on simple obesity will be included. Cochrane's collaboration tool will be used to assess the quality of the studies. RevMan 5.3 software will be used for the data analysis. RESULTS: This study will provide a standardized evaluation for the efficacy of Tuina combined with diet and exercise for simple obesity. CONCLUSION: The conclusion of this study will provide evidence for the safety and effectiveness of Tuina combined with diet and exercise on weight loss. ETHICS AND DISSEMINATION: Ethical approval is not required for systematic review and meta- analysis. The results of this review will be disseminated in a peer-review journal. PROSPERO REGISTRATION NUMBER: INPLASY202210079.

Electrocupuncture combined rehabilitation therapy for upper limb spasticity after stroke: A protocol for systematic review and meta-analysis.

BACKGROUND: The purpose of this study was to evaluate the effectiveness and safety of electroacupuncture combined with rehabilitation in the treatment of spasticity after stroke. METHODS: To collect relevant literature, we will research following databases: Medicine, PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wan-Fang Database, Chongqing VIP Chinese Science and Technology Periodicals Database and China Biomedical Database; the time is from its creation to May 2021, and the language is limited to Chinese and English. In addition, we will retrieve other literature resources, including the Chinese Clinical Trial Register and conference papers. Two reviewers will independently complete the literature screen and data extraction, and quality assessment of the included studies will be independently completed by two other researchers. The primary outcomes included the Modified Ashworth scale (MAS) and the simplified Fugl-Meyer Assessment scale (SFMA). The Modified Barthel Index (MBI), the China Stroke Scale (CSS), and adverse reactions as secondary outcomes were assessed. RevMan V.5.4.1 software will be used for meta-analysis, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) will be used to assess the quality of evidence. RESULTS: This systematic review will provide a high-quality synthesis to evaluate the efficacy and safety of electroacupuncture combined with rehabilitation therapy in the treatment of upper limb spasticity after stroke, providing a reference for the safe and effective treatment of upper limb spasm after stroke. CONCLUSION: This study provides evidence that electroacupuncture combined with rehabilitation therapy is effective. ETHICS AND DISSEMINATION: The protocol of the systematic review does not require ethical approval because it does not involve humans. This article will be published in peer-reviewed journals and presented at relevant conferences. SYSTEMATIC REVIEW REGISTRATION: INPLASY202160005.

Study on the mechanism of regulating the hypothalamic cortical hormone releasing hormone/corticotropin releasing hormone type I receptor pathway by vibro-annular abdominal massage under the brain-intestine interaction in the treatment of insomnia.

BACKGROUND: Insomnia is a common disease associated with different nervous system stress response and endocrine disorders. It has been reported previously that abdominal vibration and ring massage therapy can significantly improve the symptoms of insomnia patients, enhance the activity of neurons. In addition, functional MRI (resting state brain functional magnetic resonance imaging [Rs_fMRI]) of the resting state brain test has proved that the functional connection between hypothalamus and parahippocampal gyrus could be significantly enhanced after abdominal massage treatment. It has been confirmed that there is possible involvement of brain-gut interaction effect in the treatment of insomnia, but there is a lack of research to elucidate the possible mechanisms of brain-gut interaction in the treatment of insomnia. The purpose of this study is to investigate the relationship between the hypothalamus and intestinal interaction in the treatment of insomnia by abdominal massage. METHODS AND DESIGN: A single blind randomized controlled trial will be conducted. Sixty chronic insomnia volunteers and 30 healthy volunteers will be recruited for this study. Sixty insomnia volunteers will be randomly divided into a drug group and a massage group, and 30 healthy volunteers will be assigned to the healthy group. The manipulation of the treatment group will be mainly carried out through abdominal rubbing and vibration massage, once a day, 30 min/time, 5 days for a course of treatment, and a total of 4 intervention courses will be carried out. Patients in the drug group will be given orally spleen-invigorating bolus, twice a day, 1 pill in the morning and 1 pill in the evening. The course of treatment will be carried for 5 days, and a total of 4 courses of treatment will be administered.The massage group will be compared with the healthy group and the drug group by Pittsburgh Sleep Index scale (PSQI), Hyperarousal scale (HAS), Hamilton Depression scale (HAMD), Fatigue scale-14 (FS-14), and Wechsler Adult Memory scale (WAIS) scales using to observe the sleep quality. Rs-fMRI will be used to observe various BOLD signals in the brain and compare the values of Reho, fALFF, and FC. MRS technology will be used to observe the contents of GABA and 5-HT in the hypothalamus. Additionally, the contents of cortical hormone releasing hormone (CRH), adrenocorticotropic hormone (ACTH), COR, GABA, NE, PGE2, and 5-HT in the serum will be also detected. The serum of each group will be taken for 1H nuclear magnetic resonance (1HNMR) metabolomics study to analyze the various common metabolites, differential metabolites, potential metabolic biomarkers, and metabolic pathways among the 3 groups. Finally, in combination with the brain functional imaging and brain spectrum, the potential mechanism of abdominal vibration and ring massage will be discussed. DISCUSSION: The results of this study will be used to possibly elaborate the various mechanisms of brain and intestine interaction in the treatment of insomnia by employing abdomen ring rubbing.

Tuina plus acupuncture for post-stroke depression: A protocol for systematic review and meta-analysis.

BACKGROUND: Post-stroke depression (PSD) is the most common mental health issue, affecting approximately 33% of stroke survivors. Tuina and acupuncture treatments are often combined to treat PSD; however, there has been no meta-analysis on their synergistic effect. Therefore, we aimed to perform a systematic review and meta-analysis to estimate the effectiveness of Tuina and acupuncture in PSD treatment. METHODS: The following electronic databases will be searched: PubMed, the Cochrane Library, Embase, Web of Science, Medline, CNKI, Chinese Biomedical Literature Database, VIP, and Wan Fang databases. We will consider articles published between database initiation and April 2021. Clinical randomized controlled trials related to Tuina combined with acupuncture for post-stroke depression will be included in the study. Language is limited to Chinese and English. Research selection, data extraction, and research quality assessment were independently completed by 2 researchers. Data were synthesized using a fixed effect model or random effect model, depending on the heterogeneity test. The Hamilton depression rating scale (HDRS) and effective rate were the primary outcomes. The post-stroke depression rating scale (PSDRS), patient health questionnaire-9 (PHQ-9), and the incidence of adverse events will also be assessed as secondary outcomes. RevMan V.5.4 statistical software will be used for meta-analysis. If it is not appropriate for a meta-analysis, a descriptive analysis will be conducted. Data synthesis uses the risk ratio and the standardized or weighted average difference of continuous data to represent the results. RESULTS: This study provides a high-quality synthesis to assess the effectiveness and safety of Tuina for post-stroke depression. CONCLUSION: This systematic review will provide evidence to determine whether Tuina plus acupuncture is an effective and safe intervention for patients with post-stroke depression. ETHICS AND DISSEMINATION: The protocol of the systematic review does not require ethical approval because it does not involve humans. This article will be published in peer-reviewed journals and presented at relevant conferences. SYSTEMATIC REVIEW REGISTRATION: INPLASY202140098.

Non-pharmacological intervention for rehabilitation of post-stroke spasticity: A protocol for systematic review and network meta-analysis.

BACKGROUND: Post-stroke spasticity (PSS) is a major worldwide health problem, and timely and effective rehabilitation is associated with the risk of diabetes development; there are a variety of non-pharmacological interventions applied to the rehabilitation of PSS in these treatments; however, the relative efficacy and safety of different therapies remain uncertain, and we will conduct a systematic review and network meta-analysis to evaluate different non-pharmacological interventions. The relative efficacy and safety of intervention in PSS rehabilitation, thus providing evidence to support the optimization of the PSS rehabilitation program. METHODS: We searched the following databases electronically, including four English literature databases (i.e., PubMed, Medline, Embase, and Cochrane Library) and two Chinese literature databases (i.e., China National Knowledge Infrastructure and VIP). We will also search for randomized controlled trials on non-pharmacological interventions for post-stroke spasticity, and the search time limit is from its establishment to May 2020. Two reviewers working independently will screen the titles, abstracts, and full papers. Data extraction will be completed by two independent authors. The primary outcome was the motor function. The secondary outcome was the assessment of daily living ability. We will use RevMan V.5.3 software to compute the data synthesis carefully when a meta-analysis is allowed. We will conduct Bayesian network meta-analysis using the Markov Chain Monte Carlo random effects model in Aggregate Data Drug Information System version 1.16.8 (Drugis, Groningen, NL). RESULTS: This study provides a high-quality synthesis to assess the effectiveness and safety of non-pharmacological interventions for patients with PSS. CONCLUSION: The results of this study will provide evidence to judge whether non-pharmacological interventions are effective interventions for patients with post-stroke spasticity. ETHICS AND DISSEMINATION: The results of this meta-analysis and meta-regression will be disseminated through publication in a peer-reviewed journal and presented at a relevant conference. The data used in the network meta-analysis did not contain individual patient data. Therefore, ethical approval was not required. INPLASY REGISTRATION NUMBER: INPLASY202140059.

Electroacupuncture for patients with spasticity after stroke: A protocol for systematic review and meta-analysis.

BACKGROUND: The purpose of this paper is to evaluate the effectiveness and safety of electroacupuncture in the treatment of spasticity after stroke. METHODS: We will electronically search PubMed, Medline, Embase, Web of Science, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientific Journal Database, and Wan-Fang Database from the date of creation to November 2020. In addition, we will manually retrieve other resources including the reference lists of identified publications, conference articles, and gray literature. The clinical randomized controlled trials or quasi-randomized controlled trials related to electroacupuncture in the treatment of spasticity after stroke will be included in the study. The language is limited to Chinese and English. Research selection, data extraction, and research quality assessment will be independently completed by 2 researchers. Data were synthesized by using a fixed effect model or random effect model depend on the heterogeneity test. The modified Ashworth scale was the primary outcomes. Simplified Fugl-Meyer assessment scale (FMA), Stroke specific quality of life scale (SS-QOL) and adverse events will also be assessed as secondary outcomes. RevMan V.5.3 statistical software will be used for meta-analysis. If it is not appropriate for a meta- analysis, then a descriptive analysis will be conducted. Data synthesis will use the risk ratio and the standardized or weighted average difference of continuous data to represent the results. RESULTS: This study will provide a high-quality synthesis to assess the effectiveness and safety of electroacupuncture in the treatment of spasticity after stroke. CONCLUSION: This systematic review will provide evidence to judge whether electroacupuncture is an effective and safety intervention for patients with spasticity after stroke. ETHICS AND DISSEMINATION: The protocol of the systematic review does not require ethical approval because it does not involve humans. We will publish this article in peer-reviewed journals and presented at relevant conferences. SYSTEMATIC REVIEW REGISTRATION: CRD42021220300.

Community intervention study of viscera massage in overweight/obese type 2 diabetes high-risk population.

BACKGROUND: Prediabetes is an intermediate metabolic state between normoglycemia and diabetes. Without intervention, prediabetes often progresses to diabetes and prediabetes is associated with increased risk of cardiovascular disease, cancer, renal disease, and dementia. Lifestyle modification play a major role in controlling prediabetes. But lifestyle interventions are often with poor compliance and side effects of drugs are often be dislike by people. As a non-invasive therapy with no side effects, abdominal massage (AM), also called viscera massage in China, has been used to treat prediabetes and obesity-associated diseases. The gut microbiota has been recognized as an important factor in the development of metabolic diseases. Individuals with prediabetes have aberrant intestinal microbiota character. Colonic transport time and stool consistency are strongly associated with gut microbiota. Viscera massage can ease constipation by reducing colonic transport time and promoting intestinal motility. We can infer that viscera massage can modulate composition of gut microbiota affects human metabolism. So, in this trial, we will explore the mechanism of viscera massage on prediabetes from the perspective of intestinal microbiota. METHODS AND DESIGN: Eighty prediabetes individuals will be recruited for this study. Eighty prediabetes individuals will be divided into lifestyle intervention group and viscera massage + lifestyle intervention group by a simple random method. Each group will have 40 individuals. The manipulation of the viscera massage + lifestyle intervention group will be mainly carried out through rubbing the abdomen, kneading abdomen, vibrating abdomen, and pressing the abdomen, 30 minutes per time, once a day, with 2 days off every 5 days. Lifestyle interventions will be performed by combining pushing healthy lifestyle guidance information through Wechat application and giving face-to-face advice together daily. The lifestyle intervention group will receive healthy lifestyle intervention only. All the intervention will be conducted for 4 weeks. Weight, body mass index (BMI), waist circumference, waist-to-hip ratio, and waist-to-height ratio will be measured at the last day of every week. Triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fasting blood-glucose, 2-hour post-meal blood glucose (2hPG) and glycosylated hemoglobin, fasting insulin and insulin resistance index will be tested at the first day and last day of the intervention course. The fecal samples of subjects will be gathered at the first day and last day of the intervention course and will be performed 16S rRNA gene sequencing and metagenomic detection. Finally, the effect and potential mechanism of viscera massage on prediabetes will be discussed in combination with all the results. DISCUSSION: The results of this study will be used to verify the effect of AM on prediabetes and explore the mechanism of AM on prediabetes from the perspective of gut microbiota.

Standardization of rehabilitation program for post-apoplectic limb spasm treated by Tongjing Tiaoxing tuina and scalp acupuncture with physical therapy.

BACKGROUND: Tong Jing Tiao Xing tuina (TJTX) is a Chinese massage method. Excising with scalp acupuncture (ESA) is a treatment combining scalp electroacupuncture with physical therapy (PT), and yinao fujian formula (YNFJ) is a Chinese oral herbal granule medicine. The combination of the 3 methods is called the "Zhishen Tiaoxing" (ZSTX) rehabilitation program, which is used as an alternative of limb spasm after stroke. There is little available evidence demonstrating its safety and efficacy. METHODS: This will be a subject-blind, randomized controlled trial conducted in 3 medical centers. It will strictly follow the Standards for Reporting Interventions in Clinical Trials of Acupuncture, 2010. We will recruit 316 patients with limb spasm after stroke, 200 from the Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, China, 80 from the Second Affiliated Hospital of Heilongjiang University of Chinese medicine, Harbin, China, and 36 from Huashan Hospital of Fudan University, Shanghai, China. A block randomization sequence stratified by centers will be generated using SAS Version 9.2 software (SAS Institute, Cary, NC, USA), which was performed at the Guangdong Provincial Hospital of Chinese Medicine's Key Unit of Methodology in Clinical Research. The treatment group is treated with TJTX (once a day), ESA (once a day), and oral YNFJ (twice a day). The control group will be treated with PT. Two groups of patients will be treated 5 sessions a week for 4 weeks, and there will be 6-month follow-up. The outcome evaluators will be blinded to patient grouping. The primary outcome will be modified Ashworth scales. The secondary outcome indexes will be the simplified Fugl-Meyer assessment scale, surface electromyogram root mean square value, modified Barthel index, stroke-specific quality of life scale, health scale of traditional Chinese medicine, visual analogue scale (VAS), and the Hamilton depression scale. DISCUSSION: The Randomized Controlled Trial (RCT) mainly aim to evaluate the effectiveness and safety of traditional Chinese medicine rehabilitation program, by comparing the treatment of ZSTX with the PT for the treatment of limb spasm after stroke. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR 1900024255. Registered on July 3, 2019.

The Protective Effect of DiDang Tang Against AlCl3-Induced Oxidative Stress and Apoptosis in PC12 Cells Through the Activation of SIRT1-Mediated Akt/Nrf2/HO-1 Pathway.

Aluminum (Al) is considered a pathological factor for various neurological and neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). The neurotoxicity of aluminum can cause oxidative brain damage, trigger apoptosis, and ultimately cause irreversible damage to neurons. DiDang Tang (DDT), a classic formula within traditional Chinese medicine for promoting blood circulation and removing blood stasis and collaterals, is widely used for the treatment of stroke and AD. In this study, models of oxidative stress and apoptosis were established using AlCl3, and the effects of DDT were evaluated. We found that DDT treatment for 48 h significantly increased cell viability and reduced the release of lactate dehydrogenase (LDH) in AlCl3-induced PC12 cells. Moreover, DDT attenuated AlCl3-induced oxidative stress damage by increasing antioxidant activities and apoptosis through mitochondrial apoptotic pathways. Additionally, DDT treatment significantly activated the Sirtuin 1 (SIRT1) -mediated Akt/nuclear factor E2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathways to limit AlCl3-mediated neurotoxicity. Our data indicated that DDT potently inhibited AlCl3-induced oxidative-stress damage and apoptosis in neural cells by activating the SIRT1-mediated Akt/Nrf2/HO-1 pathway, which provides further support for the beneficial effects of DDT on Al-induced neurotoxicity.

Effectiveness of Chinese herbal medicine for patients with primary insomnia: A PRISMA-compliant meta-analysis.

BACKGROUND: Traditional medicine is widely used for patients with primary insomnia, but the studies showed inconsistent results. We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the effectiveness of Chinese herbal medicine (CHM) versus placebo for primary insomnia patients. METHODS: The electronic databases including PubMed, EmBase, Cochrane library, and China National Knowledge Infrastructure were searched to identify the RCTs published from inception till July 2018. The summary weighted mean difference (WMD) with its 95% confidence interval (CI) for Pittsburgh sleep quality index (PSQI), sleep onset latency, total sleep duration, Athens insomnia scale (AIS), and sleep efficiency were calculated using random-effects model. RESULTS: Fifteen RCTs comprising 1500 patients were finally included in the meta-analysis. Overall, patients who received CHM had lower levels of PSQI (WMD: -2.36; 95% CI: -4.02 to -0.70; P = .005), sleep onset latency (WMD: -11.54; 95% CI: -20.55 to -2.54; P = .012), and AIS (WMD: -0.59; 95% CI: -0.97 to -0.22; P = .002) as compared with placebo. Moreover, the summary WMDs of CHM versus placebo were associated with higher total sleep duration (WMD: 0.79; 95% CI: 0.56-1.02; P < .001), and sleep efficiency (WMD: 9.72; 95% CI: 6.49-12.96; P < .001). The treatment effect on PSQI might be affected by publication year, sample size, mean age, percentage male, diagnostic tool, duration of insomnia, treatment duration, and study quality. CONCLUSION: The findings of this meta-analysis indicated that CHM could significantly improve the symptoms of insomnia than placebo for patients with primary insomnia.