Health Qigong Mawangdui Guidance can improve pelvic floor muscle function and quality of life in females with stress urinary incontinence: A randomized controlled trial pilot study.

BACKGROUND: Urinary incontinence (UI) is a great problem of public health, especially for women's quality of life. UI afflicts at least 21.6% of the global population, and more than half of the UI is related to female stress urinary incontinence (SUI). Mawangdui Guidance plays an important role in preventing diseases and maintaining health. METHODS: Sixty female patients with SUI were randomly divided into a control group (n = 30) and an experimental group (n = 30). Patients in both groups were treated with basic rehabilitation therapy under the guidance of rehabilitation therapists who were trained in Mawangdui Guidance, based on the former, the experimental group was taught to exercise Mawangdui Guidance(including selected movements: "Qishi," "Longdeng," "Chishi," and "Yinyao"), while the control group performed Kegel exercise with a procedure of 20 min, six times per week for 6 weeks. The function was mainly evaluated by the 1 h pad-test, incontinence quality of life questionnaire (I-QOL), and international consultation on incontinence questionnaire urinary incontinence short form (ICI-Q-SF). In addition, evaluation of pelvic floor muscle function was also included in our assessment. RESULTS: The leakage of urine in the 1 h pad-test was significantly decreased in both two groups after treatment (P < .05), and the urine leakage in the experimental group was significantly less than that in the control group (P < .05). The muscle strength of type I and II muscle fibers of the pelvic floor, intravaginal pressure, and I-QOL score in both two groups were increased after treatment; moreover, the experimental group was more significant than the control group (P <.05). The fatigue degree of type I and type II muscle fibers of the pelvic floor, and the ICI-Q-SF score in both groups were significantly improved after treatment (P < .05); however, there were no differences between these two groups. The total effective rate of the experimental group was 90.00%, and 76.67% in the control group (P <.05). CONCLUSION: Mawangdui Guidance can effectively improve the function of pelvic floor muscle, improve the ability of urine storage and control, and alleviate the symptoms of female patients with SUI. However, the international research on Mawangdui Guidance is very limited, and more in-depth research is needed.

The therapeutic efficacy of guided therapy for PCI after acute myocardial infarction: A meta-analysis.

OBJECTIVE: To systematically evaluate the effects of lead therapies on percutaneous coronary intervention (PCI) after acute myocardial infarction (AMI). METHODS: A randomized controlled trial (RCT) in the CNKI, Wanfang, VIP, ProQuest, PubMed, Cochrane Library, Scopus, and Web of Science databases was searched until January 2023. Two researchers strictly screened and checked the included literature, extracted relevant data, and used the Cochrane Manual to assess the risk quality of the literature. Using RevMan 5.3 software, Meta-analysis of 4 main outcome measures [cardiac function-related indicators, 6-minute walking distance (6 MWT), quality of life (SF-36), Seattle angina pectoris scale (SAQ)], and 3 secondary outcome measures [adverse event incidence, death incidence, and readmission rate]. RESULTS: 22 studies were finally included with 1754 subjects, but the overall quality of the included studies was not high. The results of the meta-analysis showed that, in the cardiac function-related indicators compared to controls, improved left ventricular ejection fraction (LVEF) index (MD = 1.42, 95%CI [-0.94, 3.79], P < .00001); however, compared with the Baduanjin group, Tai Chi ball + Baduanjin group and control group, there was no significant difference (P > .05); compared with the control group, the guidance therapy group improved the left ventricular end-diastolic volume (LVEDV) index (MD = -4.67, 95%CI [-6.8, -2.71], P < .00001). In comparison, the lead group improved the 6 MWT (MD = 69.44, 95%CI [30.12, 108.76], P < .00001); the SF-36 score (MD = 10.05, 95%CI [8.68, 11.42], P < .00001])and the SAQ score (MD = 6.2, 95%CI [3.97, 8.44], P < .00001). Among the secondary outcome measures, the incidence of adverse events was statistically significant (RR = 0.17, 95%CI [0.1, 0.32], P < .00001); statistically significant (RR = 0.29, 95%CI (0.1, 0.87), P < .00001); readmission (RR = 0.39, 95%CI [0.17, 0.87, 0.89], P < .00001). CONCLUSION: Based on the current study, combining conventional therapy/ exercise or using simple lead therapy after PCI can improve the treatment effect and improve the quality of life.

Covalent Modification of Proteins by Osthole Reactive Metabolites using Proteomic Approaches.

BACKGROUND: Osthole (OST) is a bioactive natural coumarin derived from the plant Cnidium monnieri (L.) Cusson fruit (She Chuang Zi), which has various pharmacological and biological activities. OST contains an α,ß- unsaturated lactone, which is an electrophilic group that tends to be metabolized into reactive metabolites (RMs). Then, RMs are able to covalently modify nucleophilic amino acid (AA) residues of target proteins. However, few researchers considered the contribution of the covalent modification induced by OST or its metabolites. OBJECTIVE: This study aims to investigate the metabolic profile and the metabolites-protein modification of OST. METHODS: The metabolites of OST were qualitatively identified using UHPLC-Q-TOF-MS. The RMs modification patterns and potentially modified AA residues were confirmed by UHPLC-Q-TOF-MS using rat liver microsomes (RLMs) and model AAs. Finally, the modified peptides derived from high-abundance microsomal peptides were separated via nano-LC-Orbitrap-MS, and then RM-modified proteins were identified using a proteome discoverer. RESULTS: In the presence of RLMs, OST could rapidly be metabolized within 1 h and hardly identified at 4 h. We detected 10 OST metabolites, 13 OST metabolites-NAC (N-acetyl cysteine) adducts, 3 NAL (N-acetyl lysine) adducts, and 11 GSH (glutathione) adducts. Furthermore, 16 RM-modified protein targets were identified, many of which are included in the essential biological processes of OST's anti-Alzheimer's disease (AD) and anti-tumor. CONCLUSION: This study provides a novel perspective on the molecular mechanism of OST's pharmacological activities, as well as identifies potential targets for further development and application of OST and other Natural products (NPs).

Systems pharmacology-based mechanism exploration of Acanthopanax senticosusin for Alzheimer's disease using UPLC-Q-TOF-MS, network analysis, and experimental validation.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease, characterized by progressive cognitive dysfunction and memory loss. However, the disease-modifying treatments for AD are still lacking. Traditional Chinese herbs, have shown their potentials as novel treatments for complex diseases, such as AD. PURPOSE: This study was aimed at investigating the mechanism of action (MOA) of Acanthopanax senticosusin (AS) for treatment of AD. METHODS: In this study, we firstly identified the chemical constituents in Acanthopanax senticosusin (AS) utilizing ultra-high performance liquid chromatography coupled with Q-TOF-mass spectrometry (UPLC-Q-TOF-MS), and next built the drug-target network of these compounds. We also performed the systems pharmacology-based analysis to preliminary explore the MOA of AS against AD. Moreover, we applied the network proximity approach to identify the potential anti-AD components in AS. Finally, experimental validations, including animal behavior test, ELISA and TUNEL staining, were conducted to verify our systems pharmacology-based analysis. RESULTS: 60 chemical constituents in AS were identified via the UPLC-Q-TOF-MS approach. The systems pharmacology-based analysis indicated that AS might exert its therapeutic effects on AD via acetylcholinesterase and apoptosis signaling pathway. To explore the material basis of AS against AD, we further identified 15 potential anti-AD components in AS. Consistently, in vivo experiments demonstrated that AS could protect cholinergic nervous system damage and decrease neuronal apoptosis caused by scopolamine. CONCLUSION: Overall, this study applied systems pharmacology approach, UPLC-Q-TOF-MS, network analysis, and experimental validation to decipher the potential molecular mechanism of AS against AD.

Ferulic acid prevents Diosbulbin B-induced liver injury by inhibiting covalent modifications on proteins.

Diosbulbin B (DIOB) has been reported to cause serious liver injury. However, in traditional medicine, DIOB-containing herbs are highly safe in combination with ferulic acid (FA)-containing herbs, suggesting potential neutralizing effect of FA on the toxicity of DIOB. DIOB can be metabolized to generate reactive metabolites (RMs), which can covalently bind to proteins and lead to hepatoxicity. In the present study, the quantitative method was firstly established for investigating the correlation between DIOB RM-protein adducts (DRPAs) and hepatotoxicity. Then, we estimated the detoxication effect of FA in combination with DIOB and revealed the underlying mechanism. Our data indicated that the content of DRPAs positively correlate with the severity of hepatotoxicity. Meanwhile, FA is able to reduce the metabolic rate of DIOB in vitro. Moreover, FA suppressed the production of DRPAs and decreased the serum alanine/aspartate aminotransferase (ALT/AST) levels elevated by DIOB in vivo. Thus, FA can ameliorate DIOB-induced liver injury through reducing the production of DRPAs.

Combination of chemical profiling and network pharmacology analysis to investigate the potential mechanism of Li-Zhong-Xiao-Pi granules in the treatment of gastric precancerous lesions.

Li-Zhong-Xiao-Pi granules (LZXP) are effective for treating gastric precancerous lesions (GPL) in traditional Chinese medicine. However, the active compounds of LZXP and their potential therapeutic mechanism in GPL remained unclarified. The purpose of this study is to investigate the chemical composition and potential targets of LZXP. Based on the accurate masses, ion fragments, and literature data, a total of 128 compounds were identified in the LZXP sample using ultra-performance liquid chromatography and quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) in both positive and negative ion modes, and 28 of these compounds were exactly determined by comparison with authentic reference standards. Meanwhile, 11 typical components were quantified via UPLC during a 24 min period. The linearity, accuracy, stability and recovery of the method were all proven. Through the network pharmacological analysis, six chemicals (quercetin, 4'-hydroxywogonin, sinensetin, 5, 7, 8, 3', 4'-pentamethoxyflavanone, 8-gingerdione and quercetin) were identified as the active ingredients, and five LZXP targets (AKT1, CYP1B1, PTGS2, MMP9 and EGFR) were found to be the crucial molecules in the treatment of GPL. This study provides a systematic and applicable method for the rapid screening and identification of the chemical constituents from LZXP, and an effective understanding the mechanism of LZXP in the treatment of GPL.

Efficacy of ginseng supplements on disease-related fatigue: A systematic review and meta-analysis.

BACKGROUND: Ginseng has been believed to provide energy, physical health, and well-being to patients for hundreds of years. Fatigue is a multidimensional symptom with unknown etiology and varying severity, and lots of patients suffer from fatigue. METHODS: We search for research of ginseng treatment of disease-related fatigue in adult patients in Pubmed, Embase, Medline, and Cochrane library. Two independent reviewers assessed included studies and met to develop consensus on included studies. And we used Review Manager 5.3 software to evaluate the risk of bias. RESULTS: The present meta-analysis included 12 randomized controlled trial containing 1298 patients. In the fixed-effect meta-analysis of 12 randomized controlled trial, ginseng supplements had a statistically significant efficacy on disease-related fatigue reduction (standardized mean difference = 0.33, 95% confidence interval = 0.44-0.22). CONCLUSIONS: The use of ginseng supplements is benefit for patients to reduce disease-related fatigue.

Ultrasound-Assisted Extraction of Anthocyanins from Malus 'Royalty' Fruits: Optimization, Separation, and Antitumor Activity.

Red Malus 'Royalty' fruits are rich in anthocyanins. This study aimed to obtain the optimal parameters for the extraction and separation of anthocyanins from Malus 'Royalty' fruits and to evaluate the inhibitory effect of the enriched anthocyanin fraction on gastric cancer cells. Ultrasonic-assisted extraction was used for the extraction of the anthocyanins of Malus 'Royalty' fruit, and the extraction results showed that the optimum parameters were an extraction temperature of 20 °C, a solid-liquid ratio of 1:6 (g/mL), ethanol and formic acid contents of 70% and 0.4%, respectively, an extraction time of 40 min, and an ultrasonic power of 300 W. The optimum extraction parameters to achieve the highest anthocyanin yield by a single-factor experiment coupled with response surface methodology were identified. The separation results showed that the AB-8 macroporous resin was a better purifying material, with 60% ethanol as an adsorbent, and the adsorption-desorption equilibrium times were 6 h and 1 h, respectively. Cyanidin-3-galactoside was the main body composition separation of anthocyanins by a high-performance liquid chromatography-diode array detector. The antitumor activity results showed that the anthocyanins of Malus 'Royalty' fruits have a significant inhibitory effect on the gastric cancer cell line BGC-803. The in vitro cell viability test of CCK-8 showed that the inhibitory effect on tumor cells was more significant with the increased anthocyanin concentration, with a half maximal inhibitory concentration (IC50) value of 105.5 µg/mL. The cell morphology was observed by an inverted microscope, and it was found that the backbone of BGC-803 treated with a high concentration of anthocyanins was disintegrated and the nucleoplasm was concentrated. The mechanism of apoptosis was analyzed by Western blotting, and the results showed that with increasing anthocyanin concentration in the medium, the expression levels of the proapoptotic proteins Bax and Bak increased, and the expression levels of the antiapoptotic proteins Bcl-2 and Bcl-xL decreased, which coordinated the regulation of cell apoptosis. This research suggests that the enriched anthocyanin fraction from Malus 'Royalty' fruits have potential antitumor and adjuvant therapeutic effects on gastric cancer.

Evolving Roles of Natural Terpenoids From Traditional Chinese Medicine in the Treatment of Osteoporosis.

Osteoporosis (OP) is a systemic metabolic skeletal disease which can lead to reduction in bone mass and increased risk of bone fracture due to the microstructural degradation. Traditional Chinese medicine (TCM) has been applied in the prevention and treatment of osteoporosis for a long time. Terpenoids, a class of natural products that are rich in TCM, have been widely studied for their therapeutic efficacy on bone resorption, osteogenesis, and concomitant inflammation. Terpenoids can be classified in four categories by structures, monoterpenoids, sesquiterpenoids, diterpenoids, and triterpenoids. In this review, we comprehensively summarize all the currently known TCM-derived terpenoids in the treatment of OP. In addition, we discuss the possible mechanistic-of-actions of all four category terpenoids in anti-OP and assess their therapeutic potential for OP treatment.

Efficacy and safety of external therapy of TCM for primary dysmenorrhea: A protocol for systematic review and meta-analysis.

BACKGROUND: Primary dysmenorrhea (PD) is a painful disease that severely affects the daily lives of young women. External therapy using traditional Chinese medicine (TCM) is widely used in the clinical treatment of this disease and has achieved a good effect. There are many kinds of TCM external therapies, but the effectiveness, safety, and advantages of various methods have not been confirmed by high-quality meta-analyses. The purpose of this study was to evaluate the efficacy and safety of representative TCM external therapies in patients with PD. METHODS: Published randomized controlled trials that assessed the efficacy of these interventions in patients with PD were included. We searched the following electronic databases: PubMed, Cochrane Library, Embase, Web of Science, China Science and Technology Journal, China National Knowledge Infrastructure, Wanfang, and Chinese Biomedical Literature Database and other sources. The main outcomes included menstrual pain intensity and the clinical effectiveness rate. The secondary outcomes were the quality of life and safety. The meta-analysis will be performed using the Review Manager version 5.3 software. RESULTS: We will provide more practical results investigating the efficacy of external TCM therapy with high clinical frequency for PD patients in several respects, including the improvement of menstrual pain intensity, quality of life, and safety. CONCLUSION: This review systematically reviews the effectiveness and safety of common TCM external therapies for PD and provides clinicians with the best treatment options. ETHICS AND DISSEMINATION: This systematic review aimed to evaluate the efficacy and safety of external TCM therapy for PD. Since all data included were published, the systematic review did not require ethical approval. REGISTRATION NUMBER: CRD42021297078.

In Silico Identification and Mechanism Exploration of Active Ingredients against Stroke from An-Gong-Niu-Huang-Wan (AGNHW) Formula.

An-Gong-Niu-Huang-Wan (AGNHW) is a well-known formula for treating cerebrovascular diseases, with roles including clearing away heat, detoxification, and wake-up consciousness. In recent years, AGNHW has been commonly used for the treatment of ischemic stroke, but the mechanism by which AGNHW relieves stroke has not been clearly elucidated. In the current study, we developed a multiple systems pharmacology-based framework to identify the potential antistroke ingredients in AGNHW and explore the underlying mechanisms of action (MOA) of AGNHW against stroke from a holistic perspective. Specifically, we performed a network-based method to identify the potential antistroke ingredients in AGNHW by integrating the drug-target network and stroke-associated genes. Furthermore, the oxygen-glucose deprivation/reoxygenation (OGD/R) model was used to validate the anti-inflammatory effects of the key ingredients by determining the levels of inflammatory cytokines, including interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α. The antiapoptotic effects of the key ingredients were also confirmed in vitro. Integrated pathway analysis of AGNHW revealed that it might regulate three biological signaling pathways, including IL-17, TNF, and PI3K-AKT, to play a protective role in stroke. Moreover, 30 key antistroke ingredients in AGNHW were identified via network-based in silico prediction and were confirmed to have known neuroprotective effects. After drug-like property evaluation and pharmacological validation in vitro, scutellarein (SCU) and caprylic acid (CA) were selected for further antistroke investigation. Finally, systems pharmacology-based analysis of CA and SCU indicated that they might exert antistroke effects via the apoptotic signaling pathway and inflammatory response, which was further validated in an in vitro stroke model. Overall, the current study proposes an integrative systems pharmacology approach to identify antistroke ingredients and demonstrate the underlying pharmacological MOA of AGNHW in stroke, which provides an alternative strategy to investigate novel traditional Chinese medicine formulas for complex diseases.

Chinese medicine therapies for neurogenic bladder after spinal cord injury: A protocol for systematic review and network meta-analysis.

BACKGROUND: Neurogenic bladder (NB), a refractory disease, is characterized by voiding dysfunction of bladder and/or urethra, and spinal cord injury (SCI) is a common cause. Chinese medicine therapies have been applied extensively in the treatment of NB, especially in China, and the results are promising but varying. Thus, the aim of this work is to assess the efficacy and safety of various Chinese medicine therapies for NB after SCI. METHODS: A retrieval will be performed in 8 online databases (the Cochrane Library, Web of Science, PubMed, EMBASE Database, China Biological Medicine Database, Chinese Scientific Journals Database, Wan Fang databases, and China National Knowledge Infrastructure) from their inception throughout June 2021. Only randomized controlled trials of testing Chinese medicine therapies for NB after SCI will be enrolled. The outcome indicators measured will be overall response rate, urodynamic tests, clinical assessment, and safety assessments. The methodological quality of this Bayesian-based network meta-analysis will be conducted with the "Risk of Bias" tool. Stata14.0 and WinBUGS 1.4.3 will be used to analyze the data. Furthermore, the assessment of heterogeneity, inconsistency, subgroup, sensitivity, and publication bias will also be taken into consideration with the help of Cochrane Collaboration's tool. RESULTS: The findings of this study will be submitted to a peer-reviewed journal for publication. CONCLUSION: This work will furnish evidence-based recommendations to figure out the optimal Chinese medicine therapy or their combinations for NB induced by SCI, and in turn contribute to further research and public health.

Efficacy and safety of dissimilar acupuncture intervention time-points in treating stroke: a systematic review and network meta-analysis.

BACKGROUND: Impairment of motor function and activities of daily living is very common in post-stroke patients. Acupuncture has been used in stroke for a long time. Although growing evidence supports the beneficial effects of acupuncture, there is still no clear conclusion on the optimal intervention time-point for acupuncture in stroke. Thus, we tried to assess the efficacy and safety of dissimilar acupuncture intervention time-points by network meta-analysis (NMA). METHODS: A retrieval was performed in several databases from beginning to October 2020. We only enrolled randomized controlled trials (RCTs) testing acupuncture for stroke, and the outcome indicators measured were Fugl-Meyer assessment (FMA) score, Barthel Index (BI), and adverse events. RESULTS: Thirty-eight trials involving 3,836 participants were included in this NMA, the vast majority of which had a low or unclear risk of selection bias, detection bias, reporting bias, attrition bias, but had a high risk of performance bias. The results showed as following: (I) acupuncture treatment (Acu) is significantly more effective than non-acupuncture treatment (Non-Acu) with a good safety. (II) In terms of FMA, acupuncture within 48 h post-stroke (Acu I) was superior to acupuncture within 2-15 d post-stroke (Acu II) [standard mean difference (SMD): 7.17; 95% confidence interval (CI), 1.11 to 13.22], acupuncture within 16-30 d post-stroke (Acu III) (SMD: 20.73; 95% CI, 13.68 to 27.78), acupuncture within 1 month to half a year post-stroke (Acu IV) (SMD: 26.95; 95% CI, 14.88 to 39.02). As for BI, Acu I was the optimal time-point, comparing with Acu III (SMD: 15.18; 95% CI, 8.97 to 21.39) and Acu IV (SMD: 22.88; 95% CI, 11.07 to 34.69). (III) Results of ranking indicated that Acu was better than Non-Acu at a similar stage in improving FMA and BI, while Acu I was the optimal intervention time-point, followed by Acu II. CONCLUSIONS: Although the credibility of our conclusions is low, our NMA indicates that acupuncture can be beneficial for stroke survivors with good safety. In terms of improvement in FMA score and BI, the soon use of acupuncture the better the efficacy. The optimal acupuncture intervention time-point for stroke is within 48 h post-stroke, and the significant validity period lasts until 15 days after onset.

Efficacy and safety of acupuncture in treating acute low back pain: a systematic review and bayesian network meta-analysis.

BACKGROUND: Acute low back pain (ALBP) is common and acupuncture therapy is a treatment option. The comparative efficacy and safety of different acupuncture therapies are still unclear. The aim of this network meta-analysis (NMA) was to evaluate and compare the efficacy and safety of different acupuncture therapies for ALBP. METHODS: We performed a systematic search in PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), VIP Database, Wanfang Database, and Chinese Biomedical Database (CBM). The outcome indicators measured were visual analog scale (VAS) score, lumbar range of motion (ROM) score, and adverse events. The risk of bias among included studies was assessed with the Cochrane risk-of-bias tool. WinBUGS 1.4 was used for the NMA. RESULTS: In total, nineteen randomized controlled trials (RCTs) comprising 1,427 participants were included. Results of NMA showed the following: (I) compared with placebo, motion style acupuncture (MSA) (SMD: -2.21; 95% CI, -3.33 to -1.08), manual acupuncture (MA) (SMD: -1.14; 95% CI, -2.01 to -0.27), and electroacupuncture (EA) (SMD: -1.57; 95% CI, -2.98 to -0.15) were found to be more effective for decreasing VAS score; (II) compared with pharmacotherapy, MSA (SMD: -1.00; 95% CI, -1.47 to -0.54) and MA (SMD: -0.60; 95% CI, -1.15 to -0.05) were found to be more effective in reducing ROM score. Results of the surface under the cumulative ranking curve indicated that all acupuncture types were superior to placebo or pharmacotherapy in lowering VAS and ROM score. It was noted that MSA was the most effective treatment. CONCLUSIONS: This study indicated that acupuncture therapy achieved good therapeutic effects in the treatment of ALBP, especially MSA therapy. Nevertheless, due to the low quality of the included trials, the credibility of our conclusions is low. Further well-designed RCTs with high quality and large samples are still needed to evaluate the efficacy and safety of acupuncture therapy for ALBP.

Hepatotoxic evaluation of toosendanin via biomarker quantification and pathway mapping of large-scale chemical proteomics.

Drug-induced liver injury (DILI) is a major side effect, sometimes can't be exactly evaluated by current approaches partly as the covalent modification of drug or its reactive metabolites (RMs) with proteins is a possible reason. In this study, we developed a rapid, sensitive, and specific analytical method to assess the hepatotoxicity induced by drug covalently modified proteins based on the quantification of the modified amino acids using toosendanin (TSN), a hepatotoxic chemical, as an example. TSN RM-protein adducts both in rat liver and blood showed good correlation with the severity of hepatotoxicity. Thus, TSN RM-protein adducts in serum can potentially serve as minimally invasive biomarkers of hepatotoxicity. Meanwhile, large-scale chemical proteomics analysis showed that at least 84 proteins were modified by TSN RMs in rat liver, and the bioinformatics analysis revealed that TSN might induce hepatotoxicity through multi-target protein-protein interaction especially involved in energy metabolism. These findings suggest that our approach may serve as a valuable tool to evaluate DILI and investigate the possible mechanism, especially for complex compounds.

Different acupuncture intervention time-points for improving capacity in motor function and activities of daily living after stroke: A protocol for systematic review and network meta-analysis.

BACKGROUND: The incidence of stroke has been found in an increasing trend worldwide, resulting in significant negative effects and severe impairments to survivors in terms of motor function and activities of daily living. Acupuncture therapy has been widely used in the clinical treatment of stroke for a long time, meanwhile, the efficacy has been confirmed by many studies. However, the optimal intervention time-point of acupuncture in stroke is controversial. Therefore, the purpose of our study is to provide scientific evidence and reasonable suggestions for this issue. METHODS: A computer-based retrieval will be employed in 7 electronic databases: EMBASE Database, PubMed, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang databases, Chinese Scientific Journals Database (VIP) and China Biological Medicine Database (CBM), from the establishment date of each database throughout October 2020. Only randomized controlled trials of acupuncture for stroke will be recruited and language is limited to English or Chinese. The outcomes we focus on include the Fugl-Meyer Assessment score and the Barthel Index. Additionally, safety assessments such as adverse events and drop-out cases may also be taken into consideration. The network meta-analysis will be performed based on the Bayesian framework and literature selection will be conducted by 2 trained reviewers. All data analysis will be calculated by Revman5.3, WinBUGS 1.4.3, Stata13.0, and R software 3.6.1. The Assessment of heterogeneity, inconsistency, subgroup, sensitivity, and publication bias will also be done under the guidelines of Cochrane Collaboration's tool. RESULTS: The results of this study will be submitted to a peer-reviewed journal for publication. CONCLUSION: This network meta-analysis will provide evidence-based references to evaluate the efficacy of different acupuncture intervention time-points during the treatment of stroke. Furthermore, it will help the clinicians to formulate appropriate medical plans and improve clinical efficacy. TRIALS REGISTRATION NUMBER: INPLASY2020120060.

Genome-Wide Regulation of Electroacupuncture and Treadmill Exercise on Diet-Induced Obese Rats.

Acupuncture has been widely used for obesity treatment, but its mechanism is still unclear. To investigate the molecular mechanisms, we applied electroacupuncture (EA) at the Zusanli (ST36) acupoint and treadmill exercise (TE) in a diet-induced obese (DIO) rat model and used RNA sequencing (RNA-seq) to identify molecular consequences. Forty Sprague-Dawley male rats were selected and randomly divided into five groups: control (C), DIO model (M), EA, TE, and EA + TE groups. According to the results, acupuncture reduced body weight and the ratio of retroperitoneal white adipose tissue (retro-WAT) to body weight. Total RNA was extracted from the retro-WAT from five groups for RNA-seq. Differentially expressed genes (DEG) analysis showed that there were obvious differences among the four comparisons of C vs. M, M vs. EA, M vs. TE, and M vs. EA + TE, followed by 1383, 913, 3324, and 2794 DE genes. Gene ontology (GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed to further classify the DEGs. Several GO terms were commonly significantly enriched in both M vs. TE and M vs. EA, such as myofibril and muscle contraction. In addition, some pathways were regulated by EA and TE, such as the peroxisome proliferator activated receptor signaling pathway and calcium signaling pathway. This study is the first to compare and analyze the differences in gene expression profiles in the retro-WAT of rats in different groups, which provide a clue for further investigation into the molecular mechanisms of obesity treatment by EA and TE.

[Effect of electroacupuncture combined with treadmill exercise on body weight and expression of PGC-1α， Irisin and AMPK in skeletal muscle of diet-induced obesity rats].

OBJECTIVE: To investigate the effect of electroacupuncture (EA) plus treadmill exercise on the expression of peroxisome proliferator activated receptor γ coactivator 1α(PGC-1α), Irisin, AMP-activated protein kinase (AMPK) in skeletal muscle of diet-induced obesity (DIO) rats, so as to explore its mechanism underlying body reduction promotion. METHODS: Forty-two male SD rats were divided into normal diet (control, n＝10), high fat diet (model), EA, treadmill exercise and EA plus treadmill exercise (combination) groups (n＝8 in each of the latter 4 groups). The obesity model was established by feeding the rats with high fat diet. EA (2 Hz/15 Hz, 1 mA) was applied to bilateral "Zusanli" (ST36) and "Tianshu" (ST25) for 30 min, 5 times per week for a total of 8 weeks. Rats of the treadmill exercise group were forced to perform exercise on a treadmill (16 m/min) for 30 min, 5 times per week for a total of 8 weeks. Rats in the combination group received the above-mentioned two methods. During the treatment, rats in the control group were fed with normal fodder, rats in other groups were fed with high fat fodder, and their body weight was measured once a week. The expression levels of PGC-1α， fibronectin type Ⅲ domain containing 5 (FNDC5), AMPK mRNA and protein of skeletal muscle were measured by quantitative real-time PCR and Western blot，respectively. RESULTS: After modeling, the body weight was significantly increased (P<0.05), and the expression levels of PGC-1α and FNDC5 mRNA and protein, AMPK mRNA and phosphorylated AMPK (p-AMPK) protein in the skeletal muscle were considerably decreased in the model group relevant to the control group (P<0.05). Following the treatment, the body weight was significantly down-regulated, while the expression levels of PGC-1α and FNDC5 mRNAs and proteins, AMPK mRNA and p-AMPK protein were obviously up-regulated in the EA, treadmill exercise and combination groups relevant to the model group (P<0.05). The therapeutic effect of EA plus treadmill exercise was significantly superior to those of both simple EA and simple treadmill exercise in down-regulating the body weight, as well as in up-regulating the expression of PGC-1α and FNDC5 mRNAs and proteins, AMPK mRNA, and p-AMPK protein (P<0.05). CONCLUSION: Both EA and treadmill exercise can significantly increase the expression of PGC-1α， FNDC5 and p-AMPK in skeletal muscle of DIO rats, suggesting their efficacy in restoring fatty acid oxidation in skeletal muscle cells and improving mitochondrial function, which may contribute to their function in body reduction. The therapeutic effect of EA plus treadmill exercise is better than that of simple EA and simple treadmill exercise.

Integrated Proteomics, Biological Functional Assessments, and Metabolomics Reveal Toosendanin-Induced Hepatic Energy Metabolic Disorders.

Toosendanin (TSN), a compound from Melia toosendan, exhibits severe hepatotoxicity, which restricts its clinical application. However, the mechanism is not clear. Our previous research found that covalent modification of TSN for proteins might be a possible reason using human liver microsomes, and the glycolytic enzymes, triosephosphate isomerase 1 (TPIS) and α-enolase (ENOA), were responsible for the hepatotoxicity. In this study, we tried to prove these findings in cell and animal models by integration of proteomics, metabolomics, and biological methods. Proteomics analysis in rats showed that TPIS and ENOA were covalently modified by TSN reactive metabolites. The biological functional assessments revealed that the modifications inhibited the activity of TPIS and induced the activity of ENOA, in vitro and in vivo, followed by an increase in the level of cellular methylglyoxal, advanced glycation end products, and reactive oxygen species/superoxide, and the induction of mitochondrial dysfunction, which further inhibited oxidative phosphorylation and stimulated glycolysis. Furthermore, metabolomics demonstrated the decrease in the level of metabolites in the tricarboxylic acid cycle, fatty acid ß-oxidation, and amino acid metabolism; i.e., TSN induced hepatocyte energy metabolism disorder. In conclusion, these data suggest novel mechanistic insights into TSN-induced liver injury on the upstream level and provide valuable proteins and energy metabolic targets for diagnosis and therapy in the clinic.

Antioxidant Properties of Phenolic Compounds in Renewable Parts of Crataegus pinnatifida inferred from Seasonal Variations.

In this study, the effect of seasonal variations on Crataegus pinnatifida, changes in antioxidant activity and active components in C. pinnatifida leaves, roots, twigs, and fruits from May to October were investigated. Through correlation analysis of climatic factors and 7 phenolic compounds yield, the phenolic compounds content was positively correlated with temperatures and daytime. The correlation coefficient of temperatures and daytime were 0.912 and 0.829, respectively. 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, 2,2'-azino-bis 3-ethylbenzothiazoline-6-sulphonic acid (ABTS) radical scavenging and reducing power tests were employed to evaluate the antioxidant activity of the C. pinnatifida. C. pinnatifida leaves exhibited significant advantages in terms of higher phenolic contents and excellent antioxidant activities. Principal component analysis (PCA) revealed that 2 main PC characterize the C. pinnatifida phenolic composition (82.1% of all variance). C. pinnatifida leaves in September possessed remarkable antioxidant activity. The results elucidate that C. pinnatifida leaves, as renewable parts, are suitable for application as antioxidant ingredients.