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.

Sleep duration and the risk of new-onset arthritis in middle-aged and older adult population: results from prospective cohort study in China.

Background: The pain and sleep disorders caused by arthritis are health issues that have been re-emphasized with the aging population. However, the majority of research on arthritis and sleep disorders has focused on cases that have already been diagnosed with arthritis. This research aims to explore the correlation between sleep duration and new-onset arthritis in middle-aged and older adult individuals. Methods: Utilizing data from the China Health and Retirement Longitudinal Study from baseline (2011) to the Wave 3 follow-up (2018), we conducted a 7-year longitudinal investigation targeting populations with valid sleep questionnaire records and without arthritis. Sleep duration was assessed from nighttime sleep and daytime nap records. The new-onset of arthritis was determined based on self-reported diagnosis. We employed different logistic regression models to consider the potential impact of sleep duration on arthritis and conducted mediation analyses to assess the involvement of BMI in the association between sleep duration and the new-onset risk of arthritis. Results: Out of the 6,597 individuals analyzed in the cohort, 586 (8.9%) were diagnosed with new-onset arthritis. Median sleep duration was notably shorter in the new-onset arthritis group (6.63 vs. 6.41 h, p < 0.05). There was a notable negative correlation found between new-onset risk of arthritis and sleep duration, with each Interquartile Range (IQR) increment in sleep leading to a 16% risk reduction (OR: 0.864; 95% CI: 0.784-0.954). Stratified analyses revealed BMI as a potential modifier in the sleep-arthritis relationship (P for interaction = 0.05). Mediation analyses further showed that about 3.5% of the association was mediated by BMI. Additionally, the inclusion of sleep duration improved the arthritis predictive power of our model, with an IDI of 0.105 (0.0203, 0.1898) and an NRI of 0.0013 (0.0004, 0.0022) after adding sleep duration to the basic model. Conclusion: In the middle-aged and older adult demographic of China, increased sleep duration is associated with a decreased new-onset risk of arthritis, with BMI potentially playing a role in mediating this connection.

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.

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.

[Effect of Hemoglobin on Efficacy of CAR-T Therapy in Patients with Multiple Myeloma].

OBJECTIVE: To investigate the effect of hemoglobin (Hb) on the efficacy of chimeric antigen receptor T cell therapy (CAR-T) in patients with multiple myeloma (MM). METHODS: From June 2017 to December 2020, 76 MM patients who received CAR-T therapy in the Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, with complete clinical data and evaluable efficacy, were selected as the research objects. According to the receiver operating characteristic (ROC) curve, the best cut-off value was obtained. The patients were divided into groups on the basis of Hb 105.5 g/L as the cut-off value. The age, sex, serum calcium, ß2-microglobulin, serum creatinine, lactate dehydrogenase (LDH), and the influencing factors of CAR-T treatment efficacy in MM patients were analyzed. RESULTS: Hb was an influencing factor of efficacy. Univariate analysis showed that Hb, LDH, and albumin affected the efficacy of CAR-T therapy. Multivariate analysis showed that Hb ( OR=1.039, 95% CI: 1.002-1.078) and LDH ( OR=1.014, 95% CI: 1.000-1.027) were the influencing factors for the efficacy of CAR-T therapy. CONCLUSION: The efficacy of CAR-T therapy in MM patients with low Hb is poor, and Hb is a factor affecting the efficacy of CAR-T therapy.

Curative efficiency and adverse events of alternative therapy and medicine for functional constipation in adults: A protocol for systematic review and meta-analysis.

BACKGROUND: The efficacy of alternative therapies and medications for functional constipation (FC) in adults is well established, however, the efficacy and safety of different alternative therapies and medications for FC in adults is not fully clarified. Due to there are many different alternative therapies and medications available for the treatment of febrile FC in adults, the selection of appropriate alternative therapies and medications has become an urgent issue. The purpose of this study was to evaluate the effectiveness and safety of alternative therapy and medicine for FC in adults. METHODS: PubMed, Web of Science, Scopus, Cochrane Library, Embase, China National Knowledge Infrastructure, China Science and Technology Journal Database and Wanfang Data were searched to identify randomized controlled trials which focused on alternative therapy and medicine for FC in adults from December 15, 2020 to July 1, 2021. Subsequently, 2 researchers will be independently responsible for literature screening, data extraction, and assessment of their quality. This study uses The R Programming Language 4.0.2 based on Bayesian framework for NMA. Odds ratios or standardized mean differences will be modeled using Markov chain Monte Carlo methods, both with 95% confidence intervals. RESULTS: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. CONCLUSIONS: The conclusion of this systematic review will provide evidence for selecting an optimal alternative therapy and medicine for patients with FC in adults. 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: INPLASY202210091.

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.

Mechanisms of the Bushen Huoxue formula in the treatment of osteoarthritis based on network pharmacology-molecular targets.

BACKGROUND: Osteoarthritis is a common degenerative disease with a high incidence, high disability rate, and poor prognosis. Clinical studies have shown that Bushen Huoxue formula can relieve joint swelling and pain and improve limb function and joint mobility, but there is a lack of high-quality scientific basis. Using network pharmacology and molecular docking technology to study the mechanism of Bushen Huoxue formula in the treatment of osteoarthritis. METHODS: First, the active ingredients and corresponding target predictions of the formula were obtained through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and the China National Knowledge Infrastructure. Meanwhile, the osteoarthritis disease targets were obtained through the genome annotation database platform (GeneCards) and the DrugBank database, and the target proteins obtained above were standardized using the Uniprot (https://www.uniprot.org) database standardization of names. Then, the Venn diagram was created by taking the intersection of the active ingredient and the target of the disease, and the "active ingredient-target" network was constructed and analyzed using Cytoscape 3.7.2 software. At the same time, the intersecting targets were imported into the Search Tool for the Retrieval of Interaction Gene/Proteins database to build a protein-protein interaction network and to screen the core targets; the intersecting targets were visualized by using the Database for Annotation, Visualization and Integrated Discovery 6.8 database for gene ontology functional analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and construct the "active ingredient-target-pathway" network. Finally, the main active ingredients of the formula for tonifying the kidney and invigorating the blood were validated by molecular docking with the core targets. RESULTS: A total of 194 active ingredients and 365 targets of the Bushen Huoxue formula were collected, 776 targets for osteoarthritis diseases and 96 targets for the intersection of active ingredients and diseases. The Kyoto Encyclopedia of Genes and Genomes enrichment analysis yielded 104 relevant pathways, including tumor necrosis factor signaling pathways, cancer signaling pathways, nucleotide-binding oligomerization domain-like receptor signaling pathways, Toll-like receptors signaling pathways, and osteoclast differentiation, apoptosis, T-cell receptor signaling pathway, and other related pathways. The molecular docking results showed good binding of the main active ingredients to the core targets. CONCLUSION: This study shows that the treatment of osteoarthritis involves multicomponent, multitarget, and multipathway processes. The mechanism of anti-inflammatory, antioxidant, inhibition of cartilage matrix degradation, and reduction of subchondral bone destruction may be an important mechanism for the therapeutic effect.

Underlying Mechanism and Active Ingredients of Tianma Gouteng Acting on Cerebral Infarction as Determined via Network Pharmacology Analysis Combined With Experimental Validation.

Cerebral infarction (CI), a common cerebrovascular disease worldwide, is caused by unknown factors common to many diseases, including hypokalemia, respiratory diseases, and lower extremity venous thrombosis. Tianma Gouteng (TMGT), a traditional Chinese Medicine (TCM) prescription, has been used for the clinical treatment of CI. In this study, high-performance liquid chromatography (HPLC) fingerprint analysis was used to detect and identify major chemical constituents of TMGT. TCMSP and BATMAN-TCM databases were used to screen for active TMGT constituent compounds, while the GeneCards database was used to screen for protein targets associated with CI. Next, GO and KEGG enrichment analysis of these core nodes were performed to determine the identities of key associated biological processes and signal pathways. Meanwhile, a total of six possible gene targets of TMGT, including NFKBIA, PPARG, IL6, IL1B, CXCL8, and HIF1A, were selected for further study using two cellular models of CI. For one model, PC12 cells were treated under oxygen and glucose deprivation (OGD) conditions to generate an OGD cellular model of CI, while for the other model, BV2 cells were stimulated with lipopolysaccharide (LPS) to generate a cellular model of CI-associated inflammation. Ultimately TMGT treatment increased PPARγ expression and downregulated the expression of p-P65, p-IκBα, and HIF-1α in both OGD-induced and LPS-induced cell models of CI. In addition, molecular docking analysis showed that one TMGT chemical constituent, quercetin, may be a bioactive TMGT compound with activity that may be associated with the alleviation of neuronal damage and neuroinflammation triggered by CI. Moreover, additional data obtained in this work revealed that TMGT could inhibit neuroinflammation and protect brain cells from OGD-induced and LPS-induced damage by altering HIF-1α/PPARγ/NF-κB pathway functions. Thus, targeting this pathway through TMGT administration to CI patients may be a strategy for alleviating nerve injury and neuroinflammation triggered by CI.

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.

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.

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.