Integrating clinical data mining, network analysis and experimental validation reveal the anti-inflammatory mechanism of Huangqin Qingre Chubi Capsule in rheumatoid arthritis treatment.

ETHNOPHARMACOLOGICAL RELEVANCE: Huangqin Qingre Chubi Capsule (HQC) is a Chinese medicinal compound used for the treatment of damp-heat pattern rheumatism, guided by the traditional Chinese medicine syndrome differentiation practice. HQC has been used in the clinical treatment of rheumatic diseases for more than 20 years with remarkable efficacy. HQC has been experimentally shown to exert anti-arthritic effects via the Wnt signaling pathway. AIM OF THE STUDY: This study used clinical data mining, network analysis, and in vitro and in vivo tests to investigate the anti-arthritic and possible anti-inflammatory mechanism of HQC. Specifically, emphasis was placed on the function of the hsa_circ_0091,685/EIF4A3/IL-17 axis in the anti-inflammatory process. MATERIALS AND METHODS: A random walk model was used to evaluate the effects of HQC on clinical immune inflammatory marker function in patients with RA. Network analysis was used to predict the potential target genes and pathways of HQC. Hematoxylin & eosin, safranin O-fast green and toluidine blue staining, immunohistochemistry, and transmission electron microscopy were performed to evaluate the anti-arthritic effects of HQC in rat models. Cell Counting Kit-8 assay, quantitative real-time polymerase chain reaction, western blotting, enzyme-linked immunosorbent assay, and RNA pull-down were used to study the anti-proliferation and anti-inflammatory mechanisms of HQC. RESULTS: Patients with RA who underwent HQC treatment showed a significant reduction in inflammatory response levels, according to retrospective clinical study. Network analysis revealed that HQC potentially targeted genes and pathways related to inflammation, especially IL-6, IL-17, TNF-α, IL-23, and IL-17 signaling pathway. Animal experiments showed that HQC inhibits inflammation through the IL-17 signaling pathway in rat models. Cellular experiments showed that HQC-containing serum inhibited the inflammatory response in patients with RA-FLS or RA by blocking hsa_circ_0091,685 and EIF4A3 expression. CONCLUSION: In RA patients, HQC reduces the inflammatory response. The antiproliferative and anti-inflammatory qualities of HQC are responsible for its therapeutic impact. The suppression of the hsa_circ_0091,685/EIF4A3/IL-17 axis was linked to these favorable outcomes.

Traditional Chinese Medicine is Associated with the Reduction in Endpoint Events in Patients with Gouty Arthritis: Cohort Study and Association Rule Analysis.

Objective: This study aimed to evaluate the effect of traditional Chinese medicine (TCM) on endpoint events in patients with gouty arthritis (GA). Methods and Materials: A total of 2091 hospitalized GA patients were followed up by telephone, and propensity score matching (PSM) was used to reduce potential bias in the study design. Cox proportional risk model and Kaplan-Meier survival curve were utilized to analyze the impact and time effect of factors on the readmission of GA patients. The differences of laboratory indexes before and after treatment between the low and high exposure groups were compared, and the types and frequencies of medicines in all patients were counted. Association rule analysis was performed to investigate the association between TCM and test indexes or endpoint events. Results: After 1:1 PSM, 187 patients were enrolled in the TCM group and 187 patients in the non-TCM group. The incidence of readmission, new tophus, and all-cause death was lower in the TCM group than that in the non-TCM group (P < 0.05). Cox proportional risk regression analysis showed that TCM, NSAIDs and uric acid lowering drug were independent protective factors for GA readmission. The protective effect was enhanced by the prolongation of TCM treatment and the drug combinations. Kaplan-Meier survival curves indicated a significantly lower readmission rate in the high exposure group than in the low exposure group (P < 0.01). Compared with before treatment, NLR, hs-CRP, UA, TC and other laboratory indexes of the low and high exposure groups were improved after treatment (P < 0.01); The improvement of TG and TC in the high exposure group was more significant than the low exposure group (P < 0.01). The analysis of medicines used by all patients identified the top 20 Chinese herbal medicines and the top 2 Chinese patent medicines. The core drugs identified through association rule analysis that can improve test index and reduce the incidence of endpoint events include Yiyiren, Danshen, and HQC, among others. The network diagram of association rule analysis intuitively shows the relationship between core drugs and "improvement of indicators" and "the absence of endpoint events". Conclusion: TCM is associated with a reduced incidence of endpoint events in patients with GA.

Ultrathin 2D As2Se3 Nanosheets for Photothermal-Triggered Cancer Immunotherapy.

Arsenic trioxide (As2O3) has achieved groundbreaking success in the treatment of acute promyelocytic leukemia (APL). However, its toxic side effects seriously limit its therapeutic application in the treatment of solid tumors. To detoxify the severe side effects of arsenic, herein we synthesized innovative 2D ultrathin As2Se3 nanosheets (As2Se3 NSs) with synergistic photothermal-triggered immunotherapy effects. As2Se3 NSs are biocompatible and biodegradable under physiological conditions and can release As(III) and Se(0). Furthermore, selenium increases the immunomodulatory efficacy of arsenic treatments, facilitating reprogramming of the tumor microenvironment by As2Se3 NSs by enhancing the infiltration of natural killer cells and effector tumor-specific CD8+ T cells. The synergistic combination of photothermal therapy and immunotherapy driven by As2Se3 NSs via a simple but effective all-in-one strategy achieved efficient anticancer effects, addressing the key limitations of As2O3 for solid tumor treatment. This work demonstrates not only the great potential of selenium for detoxifying arsenic but also the application of 2D As2Se3 nanosheets for cancer therapy.

[Correlation of traditional Chinese medicine to reduced re-admission risk in ankylosing spondylitis patients with dampness-heat syndrome: a retrospective cohort study].

This study aimed to analyze the impact of traditional Chinese medicine(TCM) on the risk of re-admission for ankylosing spondylitis(AS) patients with dampness-heat syndrome. In this study, a telephone follow-up was conducted on 1 295 AS inpatients, and after screening and exclusions, 1 044 successfully followed-up patients were included. A retrospective cohort study was conducted using propensity score matching(PSM), and a Cox proportional risk model was employed to assess the effect of various factors on the risk of re-admission for AS patients with dampness-heat syndrome. Kaplan-Meier survival curves were used to analyze the effect of TCM intervention time on re-admission. The incidence rate of dampness-heat syndrome in AS patients was found to be 51.3% in this study. After 1∶1 PSM, 385 AS patients with dampness-heat syndrome and 385 AS patients without dampness-heat syndrome were included for analysis. The results indicated that the re-admission rate was higher for patients with dampness-heat syndrome compared with those without dampness-heat syndrome(P<0.05). AS patients with dampness-heat syndrome in the TCM group had a lower admission rate than those in the non-TCM group(P=0.01). The cox proportional risk model demonstrated that TCM was an independent protective factor, as it reduced the risk of re-admission by 35%(HR=0.35, 95%CI[0.26, 0.95], P<0.05). Moreover, the subgroup with high exposure(time to use Chinese medicine >12 months) had a significantly lower risk of re-admission than that with low TCM exposure(time to use Chinese medicine ≤12 months). The re-admission rate for AS patients with dampness-heat syndrome was higher than that without dampness-heat syndrome, and TCM was identified as a protective factor in reducing the risk of re-admission. Furthermore, a longer duration of TCM intervention was associated with a lower risk of re-admission.

Huangqin Qingre Chubi Capsule is Associated with Reduced Risk of Readmission in Patients with Rheumatoid Arthritis: A Real-World Retrospective Cohort Study.

Purpose: The therapeutic effects of Huangqin Qingre Chubi (HQC) in rheumatoid arthritis (RA) have been documented. However, there is a lack of real-world clinical evidence supporting its efficacy. Methods: Patients diagnosed with RA were recruited from the First Affiliated Hospital of the Anhui University of Chinese Medicine. Patient information was obtained from the hospital's database. Propensity score matching (PSM), Kaplan-Meier curve, and Cox proportional hazards model were used to control confounding factors and analyze the factors influencing readmission. Association rule analysis and random walk evaluation models were used to evaluate the correlations among HQC treatment, inflammation indicators, and self-perception of patients (SPP) scale. Results: After PSM, 3423 patients were enrolled, with 1142 in the HQC group and 2281 in the non-HQC group. The readmission risk of the HQC group was significantly lower than that of the non-HQC group. Combined univariate and multivariate analysis results revealed that risk factors for readmission were age >60 years, female sex, hypertension, chronic gastritis, and elevated levels of laboratory indices, including anticyclic citrullinated peptide and complement component 3 (C3) and C4. HQC, disease-modifying antirheumatic drugs, nonsteroidal anti-inflammatory drugs, and glucocorticoid therapy were protective factors for readmission. HQC treatment was closely associated with improvements in many factors, including erythrocyte sedimentation rate, C-reactive protein, C3, rheumatoid factor levels, visual analog scale, depression self-assessment scale, and patient-reported activity index scores with RA. Conclusion: HQC treatment can reduce the risk of readmission and significantly improve immune inflammatory indicators and SPP in patients with RA, with no risk of hepatorenal toxicity.

Aureane-type sesquiterpene tetraketides as a novel class of immunomodulators with interleukin-17A inhibitory activity.

Interleukin (IL)-17A, a pro-inflammatory cytokine, is a fundamental function in the onset and advancement of multiple immune diseases. To uncover the primary compounds with IL-17A inhibitory activity, a large-scale screening of the library of traditional Chinese medicine constituents and microbial secondary metabolites was conducted using splenic cells from IL-17A-GFP reporter mice cultured under Th17-priming conditions. Our results indicated that some aureane-type sesquiterpene tetraketides isolated from a wetland mud-derived fungus, Myrothecium gramineum, showed remarkable IL-17A inhibitory activity. Nine new aureane-type sesquiterpene tetraketides, myrogramins A-I (1, 4-11), and two known ones (2 and 3) were isolated and identified from the strain. Compounds 1, 3, 4, 10, and 11 exhibited significant IL-17A inhibitory activity. Among them, compound 3, with a high fermentation yield dose-dependently inhibited the generation of IL-17A and suppressed glycolysis in splenic cells under Th17-priming conditions. Strikingly, compound 3 suppressed immunopathology in both IL-17A-mediated animal models of experimental autoimmune encephalomyelitis and pulmonary hypertension. Our results revealed that aureane-type sesquiterpene tetraketides are a novel class of immunomodulators with IL-17A inhibitory activity, and hold great promise applications in treating IL-17A-mediated immune diseases.

Association between air pollutants and initiation of biological therapy in patients with ankylosing spondylitis: a nationwide, population-based, nested case-control study.

BACKGROUND: Outdoor air pollution has been found to trigger systemic inflammatory responses and aggravate the activity of certain rheumatic diseases. However, few studies have explored the influence of air pollution on the activity of ankylosing spondylitis (AS). As patients with active AS in Taiwan can be reimbursed through the National Health Insurance programme for biological therapy, we investigated the association between air pollutants and the initiation of reimbursed biologics for active AS. METHODS: Since 2011, hourly concentrations of ambient air pollutants, including PM2.5, PM10, NO2, CO, SO2, and O3, have been estimated in Taiwan. Using Taiwanese National Health Insurance Research Database, we identified patients with newly diagnosed AS from 2003 to 2013. We selected 584 patients initiating biologics from 2012 to 2013 and 2336 gender-, age at biologic initiation-, year of AS diagnosis- and disease duration-matched controls. We examined the associations of biologics initiation with air pollutants exposure within 1 year prior to biologic use whilst adjusting for potential confounders, including disease duration, urbanisation level, monthly income, Charlson comorbidity index (CCI), uveitis, psoriasis and the use of medications for AS. Results are shown as adjusted odds ratio (aOR) with 95% confidence intervals (CIs). RESULTS: The initiation of biologics was associated with exposure to CO (per 1 ppm) (aOR, 8.57; 95% CI, 2.02-36.32) and NO2 (per 10 ppb) (aOR, 0.23; 95% CI, 0.11-0.50). Other independent predictors included disease duration (incremental year, aOR, 8.95), CCI (aOR, 1.31), psoriasis (aOR, 25.19), use of non-steroidal anti-inflammatory drugs (aOR, 23.66), methotrexate use (aOR, 4.50; 95% CI, 2.93-7.00), sulfasalazine use (aOR, 12.16; 95% CI, 8.98-15.45) and prednisolone equivalent dosages (mg/day, aOR, 1.12). CONCLUSIONS: This nationwide, population-based study revealed the initiation of reimbursed biologics was positively associated with CO levels, but negatively associated with NO2 levels. Major limitations included lack of information on individual smoking status and multicollinearity amongst air pollutants.

Effect of Supplementing Vitamin E, Selenium, Copper, Zinc, and Manganese during the Transition Period on Dairy Cow Reproductive Performance and Immune Function.

The transition dairy cows are challenged by various stresses such as decreased dry matter intake, liver dysfunction, increased inflammation, and oxidative stress, particularly in subtropical regions. These might increase the requirement for vitamin E and trace elements. To examine whether supplementation of vitamin E, selenium or copper, zinc, and manganese complex would help transition dairy cows to achieve greater reproduction performance by overcoming the immune function and postpartum disorders in subtropical Taiwan. A total of 24 Holstein Friesian dairy cows were enrolled in this study and divided into three groups (n = 8 cows/group): treatment 1 supplemented with organic selenium and vitamin E (SeE), treatment 2 supplemented with organic copper, zinc, and manganese complex (CZM) and control (CON). The results showed SeE supplementation improved immune function, reproductive performance, and milk yield, but not negative energy balance status. Supplementation of CZM improved milk yield and energy regulation through antioxidative capacity and immune function, but had no influence on reproductive performance.

Expression and significance of histone methyltransferase SET domain containing 2 with histone H3 lysine 36 trimethylation in mouse hepatic oval cells differentiated into bile duct epithelial cells in vitro.

The present study aimed to identify the function and expression of trimethylated protein histone H3 lysine 36 (H3K36)me3 and the upstream specific enzyme histone methyltransferase SET domain containing 2 (SETD2), during the differentiation of hepatic oval cells (HOCs) into cholangiocytes in mice following partial liver resection and fed with 2­acetamidofluorene. HOCs were isolated from Kunming male mice fed with 2­acetamidofluorene for 10 days. Their liver tissues were then isolated following partial liver resection and another week of 2­acetamidofluorene treatment. HOCs were collected following a two­step enzyme digestion procedure involving protease E and collagenase 4. The target cells were cultured in DMEM/F12 supplemented with 10 µg/ml EGF, 5 µg/ml stem cell growth factor and 5 µg/ml leukemia inhibitory factor. Target cells using the markers OV­6, CK­19, SETD2, H3K36me3, were detected with flow cytometry and immunofluorescence microscopy; reverse transcription­quantitative PCR and western blotting were used to quantify the protein levels of SETD2 and H3K36me3. The retrieved primary hepatocytes developed into cholangiocytes with increasing CK­19 and decreasing OV­6 expression in each subsequent passage, whereas the SETD2 and H3K36me3 levels gradually increased, suggesting the possible involvement of both of these factors in differentiation.

The treatment of high-concentration garlic processing wastewater by UASB-SBR.

The treatment of garlic processing wastewater was investigated in a UASB-SBR system. The experimental results showed that UASB was successfully started up after 64 days of continuous operation with COD removal rate of 45%. SBR start-up phase went through 60 days and the COD removal rate achieved 96%. UASB ran under optimal conditions (HRT of 45 h, pH of 7.5, and temperature of 35 ± 2°C) for 14d and performed well in organic matter treatment. SBR played a major part in nitrogen and phosphorus removal when running under optimal conditions (cycle time of 12 h, temperature of 25°C, organic loading of 0.72 kgCOD/(m3·d), and COD of 6000 mg/L) for 18d. Secondly, the microbial community structure indicated that the abundance of ß-Proteobacteria and α-Proteobacteria in the sludge reached 30.05% and 47.57%, respectively, and played a crucial part for the organic matter, nitrogen and phosphorus removal in the SBR. After UASB-SBR system had been stabilised with influent COD of 9800 mg/L, the average COD, TP, NH3-N and TN removal rates were 99%, 94.82%, 87.07% and 94.87%, respectively, which were 3%, -2%, 1% and 3.5% higher than SBR running alone under optimal conditions. UASB coupled with SBR process had an excellent performance for high-concentration garlic processing wastewater.

Enhanced biological phosphorus removal in low-temperature sewage with iron-carbon SBR system.

This study proposed an AO-SBR (Anaerobic Aerobic Sequencing Batch Reactor) combined with iron-carbon micro-electrolysis (ICME) particles system for sewage treatment at low temperature and explored the dephosphorisation mechanism and microbial community structure. The experimental results illustrated that ICME particles contributed to phosphorus removal, metabolic mechanism of poly-phosphorus accumulating organism (PAO) and microbial community structure in the AO-SBR system. The optimal treatment effect was achieved under the conditions of pH 7, DO 3.0 mg/L and particle dosage of 2.6 g Fe-C/g MLSS, and the removal rates of COD, TP, NH4+-N and TN reached 80.56%, 91.46%, 69.42% and 57.57%. The proportion of phosphorus accumulating organisms (PAOs) increased from 4.54% in the SBR system to 10.89% in the ICME-SBR system at 10°C. Additionally, the metabolic rate of PAOs was promoted, and the activities of DHA and ETS both reached the maximum value of 13.34 and 102.88 µg·mg-1VSS·h-1. These results suggest that the ICME particles could improve the performance of activated sludge under low-temperature conditions. This technology provides a new way for upgrading the performance of sewage treatment in the cold area.

Effect of Inonotus obliquus Extract Supplementation on Endurance Exercise and Energy-Consuming Processes through Lipid Transport in Mice.

Inonotus obliquus (IO) is used as functional food to treat diabetes. This study investigated the effect of IO supplementation on body composition in relation to changes in energy expenditure and exercise performance. Male Institute of Cancer Research mice were divided into four groups (n = 8 per group) and orally administered IO once daily for 6 wk at 0 (vehicle), 824 (IO-1×), 1648 (IO-2×), and 2472 mg/kg (IO-3×). IO supplementation increased muscle volume, exhaustive treadmill time, and glycogen storage in mice. Serum free fatty acid levels after acute exercise improved in the IO supplementation group, which exhibited changes in energy expenditure through the peroxisome proliferator-activated receptor (PPAR) pathway. RNA sequencing revealed significantly increased PPAR signaling; phenylalanine, ascorbate, aldarate, and cholesterol metabolism; chemical carcinogenesis; and ergosterol biosynthesis in the IO group compared with the vehicle group. Thus, IO supplements as nutraceuticals have a positive effect on lipid transport and exercise performance. In addition, this study was only IO supplementation without training-related procedures.

Efficacy and safety of total glucosides of paeony in the treatment of systemic lupus erythematosus: A systematic review and meta-analysis.

Background: Total glucosides of paeony (TGP), extracted from the Chinese medicine Paeonia lactiflora Pall., have been proven to be effective in various autoimmune diseases. We aim to systematically evaluate the efficacy and safety of TGP combined with different conventional therapeutic agents in the treatment of systemic lupus erythematosus (SLE). Methods: Eight databases were searched for randomized controlled studies of TGP for SLE. The search time was set from the establishment of the databases to March 2022. The risk of bias was assessed by the Cochrane Evaluation Manual (5.1.0), RevMan 5.3 software was used for meta-analysis, and the certainty of the evidence was assessed by the GRADE methodology. Results: A total of 23 articles were included, including 792 patients overall in the treatment group and 781 patients overall in the control group. The meta-analysis results showed that TGP combined with conventional treatments was superior to the conventional treatments in reducing the SLE disease activity and the incidence of adverse reactions (SMDTGP+GC+CTX = -1.98, 95% Cl = [-2.50, -1.46], p < 0.001; SMDTGP+GC+HCQ = -0.65, 95% Cl = [-1.04, -0.26], p <0.001; SMDTGP+GC+TAC = -0.94, 95% Cl = [-1.53, -0.34], p < 0.05; SMDTGP+GC = -1.00, 95% Cl = [-1.64, -0.36], p < 0.05; and RRTGP+GC+CTX = 0.37, 95% Cl = [0.21, 0.64], p < 0.001). The results also showed that TGP helped improve other outcomes related to SLE disease activity, such as complement proteins (C3 and C4), immunoglobulins (IgA, IgM and, IgG), ESR, CRP, 24 h urine protein, and recurrence rate. In addition, TGP may also be effective in reducing the average daily dosage of glucocorticoids (GCs) and the cumulative dosage of cyclophosphamide (CTX). The certainty of the evidence was assessed as moderate to low. Conclusion: TGP is more effective and safer when used in combination with different conventional therapeutic agents. It helped reduce the disease activity of SLE and the incidence of adverse reactions. However, we should be cautious about these conclusions as the quality of the evidence is poor. Future studies should focus on improving the methodology. High-quality randomized controlled trials (RCTs) will be necessary to provide strong evidence for the efficacy of TGP for SLE. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42021272481.

Predictors for self-discontinuation of anti-osteoporosis medication: A hospital-based real-world study.

Osteoporotic fractures have a tremendous impact on quality of life and may contribute to fatality, but half of patients may discontinue their anti-osteoporosis medication. The study aimed to investigate the factors associated with the persistence of anti-osteoporosis medication. Between June 2016 and June 2018, we recruited 1195 participants discontinuing prior anti-osteoporosis medication. Telephone interviews were conducted to discern the reasons for discontinuation. Comparisons among groups and risks of self-discontinuation were analyzed. Among 694 patients who have no records of continuing anti-osteoporosis medication, 374 (54%) self-discontinued, 64 (9.2%) discontinued due to physicians' suggestion, and 256 (36.8%) with unintended discontinuation. Among patients with self-discontinuation, 173 (46.3%) forgot to visit outpatient clinics; 92 (24.5%) discontinued because of medication-related factors; 57 (15.2%) thought the severity of osteoporosis had improved and therefore discontinued; 30 (8%) stopped due to economic burden; 22 (5.9%) were lost to follow-up because of newly diagnosed diseases other than osteoporosis. Additionally, older age, male gender, calcium supplement, teriparatide therapy and hip fractures in teriparatide users were associated with adherence to anti-osteoporosis drugs. In conclusion, our results indicate that younger age, female gender, non-use of calcium supplements, and anti-resorptive medication were independent risk factors associated with drug discontinuation. Identifying high-risk patients and providing timely health education are crucial for adherence to anti-osteoporosis medication.

Maternal Folic Acid Supplementation, Dietary Folate Intake, and Low Birth Weight: A Birth Cohort Study.

Objectives: To investigate the independent and collective effects of maternal folic acid supplementation or dietary folate intake on the risk of low birth weight (LBW), and to further comprehensively examine the joint associations of folic acid supplementation and dietary folate intake with LBW by various clinical subtypes. Design: Participants were recruited from Gansu Provincial Maternity and Child Care Hospital. A standardized and structured questionnaire was distributed to collect demographic factors, reproductive and medical history, occupational and residential history, physical activity, and diet. Data on pregnancy-related complications and birth outcomes were extracted from medical records. Unconditional logistic regression models were used to estimate the odds ratio (OR) and 95% confidence interval (95% CI) for single and joint associations of folic acid supplementation and dietary folate intake with LBW. Setting: A birth cohort data analysis using the 2010-2012 Gansu Provincial Maternity and Child Care Hospital in Lanzhou, China. Participants: In total, 9,231 pregnant women and their children were enrolled in the study. Results: Compared with non-users, folic acid supplementation was associated with a reduced risk of LBW (OR: 0.80, 95% CI: 0.66-0.97), and the reduced risk was mainly seen for term-LBW (OR: 0.59, 95% CI: 0.41-0.85), and multiparous-LBW (OR: 0.72, 95% CI: 0.54-0.94). There were no significant associations between dietary folate intake and LBW, and there was no interaction between folic acid supplement and dietary folate intake on LBW. Conclusions: Our study results indicated that folic acid supplementation was associated with a reduced risk of LBW, and there was no interaction between folic acid supplements and dietary folate intake on LBW.

Investigating the efficiency and tolerability of traditional Chinese formulas combined with antiarrhythmic agents for paroxysmal atrial fibrillation: A systematic review and Bayesian network meta-analysis.

BACKGROUND: The combination of antiarrhythmic drugs with traditional Chinese formulas are used treatments for the management of paroxysmal atrial fibrillation (PAF). However, the most effective treatment for PAF has yet to be been determined. A Bayesian network meta-analysis study was thus performed for comparing the relative efficacy and tolerability of different treatment alternatives. METHODS: A comprehensive literature review of randomized controlled trials (RCTs) is performed from eight database. Maintenance rate of sinus rhythm (MRSR), p-wave dispersion (Pd), left atrium diameter (LAD), left ventricular ejection fraction (LVEF), and adverse events (AEs) were used as outcomes. We also estimated treatment rank based on the surface under the cumulative ranking curve (SUCRA). This study was performed using a Bayesian network meta-analysis with a random-effects model. FINDINGS: After screening, 59 RCTs involving 5,543 patients and 16 treatments were included. The results showed that Shensong-Yangxin capsule (SSYX) plus amiodarone (81%) was the most effective treatment for MRSR according to the value of SUCRA, followed by Wenxin-Keli granules (WXKL) plus amiodarone (73%). Meanwhile, SSYX plus amiodarone (7%) was most likely to reduce Pd, followed by SSYX plus metoprolol (23%), WXKL plus amiodarone (26%), WXKL plus bisoprolol (27%). Furthermore, SSYX plus amiodarone (4%) was more effective in improving LAD. WXKL plus amiodarone was preferred because it had the lowest toxicity. For benefit-risk ratio, amiodarone combined with WXKL or SSYX appeared to be the best option. CONCLUSION: Antiarrhythmic agents combined with traditional Chinese formulas had higher efficacy and lower toxicity than other treatment alternatives. This study might provide reference to help find the better treatment options for PAF.

A protocol for the integration of multi-omics bioinformatics: Mechanism of acupuncture as an adjunctive therapy for alcohol use disorder.

Background: Alcohol use disorder (AUD) has become a significant global factor in various diseases. As a non-pharmacological therapy, certain therapeutic potential has been found in acupuncture; however, in-depth mechanistic studies related to acupuncture for patients with AUD are still insufficient. Methods: Based on a randomized control design and a multi-omics analysis plan, this protocol details the recruitment (42 AUD patients), group allocation (21 in acupuncture group vs. 21 in sham acupuncture group), intervention and follow-up (replacement drugs as a normal treatment, 2 weeks acupuncture duration, and 3 month follow-up), and data collection and analytical processes. For the clinical outcomes, in addition to the time required for alcohol withdrawal symptoms to subside as the primary outcome, changes in the alcohol withdrawal symptoms, alcohol craving, mood dysfunction, sleep disorder, fatigue, self-efficacy, gastrointestinal symptoms, the quality of life, and the relapse outcomes will be compared between the groups to confirm the acupuncture clinical effectiveness on alcohol withdraw. The gut microbiome and the fecal metabolomics will also be assessed to explore the association of the structure and the function of gut microflora and the mediation of acupuncture effect on AUD fully utilizing gut microflora multi-modal data and clinical information, via the combination of multi-omics methods, feature screening algorithms and appropriate models. Discussion: The results of this study may help to strengthen clinical evidence of the mechanism of acupuncture intervention in patients with AUD, through understanding of the regulatory mechanism of acupuncture in the gut microbiome and its metabolism as well as AUD-related clinical manifestations. Trial registration: Chinese Clinical Trial Registry ChiCTR2200058120. Registered on 24 Mar 2022.

Effects of Traditional Chinese Acupuncture Compared with Sham Acupuncture on the Explosive Force Production by the Forearm Muscles in Female: A Randomized Controlled Trial.

BACKGROUND: Acupuncture can effectively enhance musculoskeletal rehabilitation, with effects such as reduced pain intensity and muscle tension and decreased disability. OBJECTIVE: The purpose of this study was to determine the efficacy of traditional Chinese acupuncture (TCA) compared with sham acupuncture (SA) in explosive force production by the forearm muscles in females. METHODS: A total of 32 subjects were included and randomly assigned to two groups: TCA group (n = 16): stimulated specific acupoints including Quchi (LI11), Shousanli (LI10), Hegu (LI4), Xiaohai (SI8), Tianjing (SJ10), and Waiguan (SJ5) for 15 minutes; SA group (n = 16): using superficial needle insertion at nonacupoints without stimulation. The subjects warmed up for the 3-time isokinetic test with an angular velocity of 30°/s and then performed a set of 15 full flexion (Flex) and extension (Ext) with an angular velocity of 180°/s using the CON-TREX isokinetic test training system recorded as the pretest. After acupuncture for 15 min, perform a set of the same isokinetic movement isokinetic records as the posttest. The average max torque, average work, average power, average peak power, average max speed, and total work were collected to evaluate the forearm explosive force changes. Use two-way repeated measures ANOVA to compare the difference before and after acupuncture between two groups. RESULTS: The results showed that acupuncture conditions (sham acupuncture as well as true acupuncture) and the intervention times (not acupuncture or acupuncture for 15 min) have a significant interaction effect on forearm explosive force and joint stiffness (P < 0.05). The simple main effect showed that the selected parameters of the TCA group increased significantly after acupuncture (P < 0.05), while the SA group did not (P > 0.05). We speculate that the activation of muscle may be related to the selected acupuncture points. CONCLUSION: Acupuncture can produce excitation in motor nerves and muscles, and nerve stimulation increases the recruitment of motor units, thus improving the muscle explosive force.

Discovery of an Orally Efficacious MYC Inhibitor for Liver Cancer Using a GNMT-Based High-Throughput Screening System and Structure-Activity Relationship Analysis.

Glycine-N-methyl transferase (GNMT) downregulation results in spontaneous hepatocellular carcinoma (HCC). Overexpression of GNMT inhibits the proliferation of liver cancer cell lines and prevents carcinogen-induced HCC, suggesting that GNMT induction is a potential approach for anti-HCC therapy. Herein, we used Huh7 GNMT promoter-driven screening to identify a GNMT inducer. Compound K78 was identified and validated for its induction of GNMT and inhibition of Huh7 cell growth. Subsequently, we employed structure-activity relationship analysis and found a potent GNMT inducer, K117. K117 inhibited Huh7 cell growth in vitro and xenograft in vivo. Oral administration of a dosage of K117 at 10 mpk (milligrams per kilogram) can inhibit Huh7 xenograft in a manner equivalent to the effect of sorafenib at a dosage of 25 mpk. A mechanistic study revealed that K117 is an MYC inhibitor. Ectopic expression of MYC using CMV promoter blocked K117-mediated MYC inhibition and GNMT induction. Overall, K117 is a potential lead compound for HCC- and MYC-dependent cancers.

Effect of Acupuncture on Timeliness of Male Shoulder Joint Endurance.

Acupuncture as a traditional and commonly used treatment has been used to improve the performance of athletes. In the improvement of female shoulder joint explosive force and muscle endurance also has an immediate effect. However, whether the effect of acupuncture therapy can be maintained after improving athletic performance still worth further discussion. The purpose of this study was to explore the timeless of the physical neurophysiological response induced by acupuncture at specific acupoints in improving endurance performance. Seventeen healthy male participants completed six groups of shoulder joint isokinetic exercises. The isokinetic exercise completed in the first group was taken as the baseline. After acupuncture for 15 min, the following 5 isokinetic experiments were completed. Acupuncture acupoints included Binao (LI14), Jianliao (SJ14), Naohui (SJ13), Zhongfu (LU1), Xiabai (LU4), Tianfu (LU3) and Xiaoluo (SJ12). The results show that acupuncture can improve physical performance for 10-20 min. After acupuncture, the maximum torque, average power, average work and total work values significantly increased (p < 0.05). Stimulation of acupoints can effectively improve the performance of periarticular muscle endurance around the shoulder, but this improvement is limited by time.