Assessment of the therapeutic potential of probiotics against carbon quantum dots-induced neurotoxicity in common carp (Cyprinus carpio).

Carbon quantum dots (CQDs) have received increasing attention in recent years for their potential toxicity. However, little is known about their neurobehavioral toxicity. This study aimed to investigate the potential mechanisms by which probiotics reduce CQDs neurotoxicity from a brain-gut axis perspective by exposing carp to CQDs and/or probiotics for five weeks. The results showed that CQDs accumulation in the brain reduces the expression of blood-brain-barrier (BBB) related genes in carp, leading to brain damage. In addition, CQDs impaired motor behavior and inhibited acetylcholinesterase activity. These abnormalities were alleviated by probiotic supplementation. Microbiomic analysis showed that probiotics improved the imbalance of intestinal flora caused by CQDs and increased the abundance of Firmicutes. Serum metabolomic analysis showed that probiotic supplementation restored the abnormal metabolic levels associated with neurological, inflammatory, and apoptotic cell death caused by CQDs. Overall, probiotic supplementation improved the CQDs-induced changes in brain damage, gut microbiology, and systemic metabolism. These results suggests that CQDs may cause neurotoxicity via the brain-gut microbial axis.

Andrographolide in atherosclerosis: integrating network pharmacology and in vitro pharmacological evaluation.

OBJECTIVE: Andrographis paniculata (Burm.f.) Nees is a medicinal plant that has been traditionally used as an anti-inflammatory and antibacterial remedy for several conditions. Andrographolide (AG), the active constituent of A. paniculata (Burm.f.) Nees, has anti-lipidic and anti-inflammatory properties as well as cardiovascular protective effects. The present study aimed to explore the effects of AG on the progression of atherosclerosis and to investigate related mechanisms via network pharmacology. MATERIALS AND METHODS: Compound-related information was obtained from the PubChem database. Potential target genes were identified using STITCH, SwissTargetPrediction, Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine, and Comparative Toxicogenomics Database. Genes involved in atherosclerosis were obtained from DisGeNet and compared with AG target genes to obtain an overlapping set. Protein-protein interactions were determined by STRING. Gene ontology (GO) analysis was performed at WebGestalt, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment was analyzed using Metascape. The final network showing the relationship between compounds, targets, and pathways was constructed using Cytoscape. After that, oxLDL-induced RAW264.7 cells were used to further validate a part of the network pharmacology results. RESULT: Eighty-one potential AG target genes were identified. PPI, GO, and KEGG enrichment revealed genes closely related to tumor progression, lipid transport, inflammation, and related pathways. AG improves the reverse cholesterol transport (RCT) through NF-κB/CEBPB/PPARG signaling in oxLDL-induced RAW264.7 cells. CONCLUSION: We successfully predict AG's potential targets and pathways in atherosclerosis and illustrate the mechanism of action. AG may regulate NF-κB/CEBPB/PPARG signaling to alleviate atherosclerosis.

Effect of Qingfei Paidu decoction combined with Western medicine treatments for COVID-19: A systematic review and meta-analysis.

BACKGROUND: Qingfei Paidu decoction (QFPDD) showed to be beneficial for the treatment of coronavirus disease 2019 (COVID-19) in China. PURPOSE: This study aimed to systematically assemble the evidence on the efficacy and safety of QFPDD combined with Western medicine treatments (WMT) for COVID-19. STUDY DESIGN: Systematic review and meta-analysis. METHODS: A comprehensive literature search was conducted in PubMed, Embase, Cochrane Library, CNKI, CSTJ, CBM, Wanfang Data for clinical trials with a control arm until January 13, 2022. Studies matched the selection criteria were included. Data extraction and quality assessment of the included studies were independently conducted by two reviewers. Review Manager 5.4 was used for meta-analysis. RESULTS: A total of 9 trials including 1108 COVID-19 patients met the selection criteria. Meta-analysis demonstrated that QFPDD combined with WMT reduced aggravation rate (AR) by 71% [risk ratio (RR) = 0.29, 95% confidence intervals (CI) (0.17, 0.51)], increased effective rate (ER) by 13% [RR = 1.13, 95%CI (1.04, 1.22)], shortened 4.78 days of viral shedding [95%CI (-5.79, -3.77)] and 4.45 days of hospital stay [95%CI (-6.05, -2.86)], also decreased the incidence of adverse events (AE) by 56% [RR = 0.44, 95%CI (0.22, 0.89)]. CONCLUSION: QFPDD combined with WMT might reduce the proportion of severe cases and the incidence of AE, shorten the duration of viral shedding and length of hospital stay. More randomized controlled trials (RCTs) are required to confirm our findings in the future.

Medical expenditure and its influencing factors of patients with hypertension in Shanxi Province, China: a study based on 'System of Health Accounts 2011' and multiple-layer perceptron neural network.

OBJECTIVES: To study the medical expenditure and influencing factors of patients with hypertension in Shanxi Province, China. DESIGN: A cross-sectional study. SETTING: 1088 medical institutions, including general hospitals, traditional Chinese medicine hospitals, special hospitals, basic medical institutions and public health institutions. PARTICIPANTS: 180 441 hypertensive outpatients and 14 763 inpatients from 1 January to 31 December 2017. PRIMARY AND SECONDARY OUTCOME MEASURES: Curative care expenditure for hypertension (CCEht) was measured based on System of Health Accounts 2011. Influenced factors were analysed by univariate analysis and multiple layer perceptron neural network. RESULTS: In 2017, CCEht was US$307.71 million, accounting for 3.63% of total CCE and 0.14% of gross domestic product (GDP) in Shanxi Province of China. CCE of hypertensive outpatients (CCEht-out) and inpatients (CCEht-in) accounted for 44.49% and 55.51% of CCEht. Drug fee accounted for 81.55% of CCEht-out and 22.50% of CCEht-in, respectively. The top three influencing factors were drug fee, surgical fee and hospitalisation days for inpatients, and drug fee, examination fee and test fee for outpatients. CONCLUSIONS: The medical expenditure of hypertension is still heavy for individuals and society. The diagnosis and treatment capacities of primary healthcare system has been enhanced. New rural cooperation medical insurance and urban employee basic medical insurance have a trend of overusing, and the burden of family healthcare expenditure is still heavy. To ease the economic burden of patients with hypertension and improve the efficiency of social resources utilisation, policymakers should pay more attention to key groups, further increase support for primary healthcare system, standardise the treatment and reimbursement of hypertension and incline the reimbursement policy to outpatient service.

Medication Rule Analysis of the Diagnosis and Treatment Programs of Chinese Medicine for the Prevention and Treatment of COVID-19 in China.

OBJECTIVES: To summarize the measures and rules of Chinese medicine (CM) and provide reference for clinical application in the prevention and treatment of coronavirus disease (COVID-19). METHODS: The data source was from CM COVID-19 prevention and treatment programs on government websites and official media websites of the different provinces and cities. The search lasted from December 8, 2019 to March 10, 2020. Main variables were medication frequency and combinations of medicines. Cluster analysis and complex network analysis were used by prevention and treatment stage and by area. RESULTS: Among 27 CM diagnosis and treatment plans, 203 therapeutic prescriptions were enrolled, of which the top 4 herbs were: Radix glycyrrhizae, Semen armeniacae amarum, Herba ephedrae, and Herba agastachis, respectively. The core combinations were Herba ephedrae and Semen armeniacae amarum. Forty-eight preventive formulae were identified. Ten herbs, including Radix Astragali seu hedysari, Radix glycyrrhizae, Radix saposhnikoviae, Flos lonicerae, etc. were most frequently used. The core prescription of CM compatibility was Radix astragali seu hedysari, Radix glycyrrhizae, and Radix saposhnikoviae, which is the main component of Yu Ping Feng San. There were 45 prevention and treatment prescriptions in East China; the most used CM was Radix glycyrrhizae, Herba agastachis, Pericarpium citri reticulatae, and Gypsum fibrosum. Fifty prescriptions were identified in North China. According to CM analyses, Herba agastachis, Semen armeniacae amarum, Herba ephedrae, and Poria were most frequently used. CONCLUSIONS: CM for COVID-19 prevention mainly focuses on improving human immunity; for treatment, prescription focuses on clearing the lungs and removing dampness. Prescriptions vary with regions, perhaps due to climatic and environmental differences, which help clinicians to quickly make CM plans and treat patients according to clinical status, further minimizing resource wastage.

[Effects of Bupleurum chinense on the diversity of intestinal flora in depressed mice].

Bupleuri Radix, serving as the sovereign medicinal in many antidepressant compound preparations, has been proved effective in treating depression in mice, but its effect on the intestinal flora remains unclear. The present study aimed to investigate the effects of Bupleurum chinense(one of the original materials of Bupleuri Radix) on the behaviors and the diversity of intestinal flora of depressed mice. A depression mouse model was induced by repeated social defeat stress. Specifically, C57 BL/6 J male mice were exposed to the attack from the CD-1 mice. Then, C57 BL/6 J male mice were divided into a depression group and a B. chinense group, with normal saline and B. chinense administered(ig) respectively. Sucrose preference test and tail suspension test were conducted during and after the experiment respectively, to analyze the effects of B. chinense on the behaviors of the depressed mice. The feces were collected after the experiment. The V3-V4 16 S rDNA regions of intestinal flora of mice in each group were sequenced by Ion S5 TMXL for the analysis of the number of operational taxonomic units(OTUs), richness, alpha and beta diversity indexes, and differential phyla and genera. The results indicated that B. chinense could decrease depressive-like behaviors of mice, increase sucrose preference, and shorten the time of immobility in tail suspension test. After B. chinense intervention, the relative abundance of Firmicutes was significantly decreased, while that of Bacteroidetes was increased at the phylum level. At the genus level, the relative abundance of Lactobacillus and Lachnoclostridium decreased(P<0.05), while that of Bacteroides, Alistopes, etc. was elevated(P<0.05). The findings demonstrate that B. chinense can regulate the intestinal flora and improve the depressive-like behaviors of mice with depression.

Mechanisms of traditional Chinese medicine in modulating gut microbiota metabolites-mediated lipid metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: The gut microbiome plays an important role in advancing the process of host lipid metabolism directly or indirectly. Traditional Chinese medicine (TCM) can improve the intestinal environment by intervening with gut microbiota metabolites to potentially regulate lipid levels. However, the underlying mechanisms remain unclear. Therefore, we examined the current databases to search for studies related to influence of TCM on the gut microbiota metabolites-mediated lipid metabolism. AIM OF THE STUDY: This paper aims to review the TCM that could regulate lipid metabolism mediated by microbial metabolites and their pharmacological targets and provides perspectives for future investigation. METHODS: Electronic databases including PubMed, Web of Science, EMBASE, the Cochrane Library, Chinese Biological Medicine Database, and China National Knowledge Infrastructure were searched up to April 2021 to identify eligible studies. RESULTS: A total of 30 active compounds, five Chinese herbal formulae, and three proprietary Chinese medicines were included in this review. We found that TCM can effectively improve lipid metabolism by increasing short chain fatty acids (SCFA) levels, regulating bile acid (BA) metabolism, reducing the production of trimethylamine N-oxide (TMAO), alleviating the release of inflammatory factors, and altering branched-chain amino acids (BCAA) biosynthesis. This process is accompanied by changes in the structure of the gut microbiota, blood lipids, and expression of lipid metabolism genes. CONCLUSION: In summary, studies on the regulation of lipid metabolism by microbial metabolites in TCM will provide a new approach for better management of dyslipidemia, which may facilitate future clinical treatments.

Clinical characteristics and treatment outcome of COVID-19 patients with stroke in China: A multicenter retrospective study.

OBJECTIVE: Previous studies mainly reported the clinical characteristics of novel coronavirus 2019 (COVID-19) infections, but the research on clinical characteristics and treatment outcomes of COVID-19 patients with stroke is still rare. METHODS: A multi-center retrospective study was conducted at 11 hospitals in 4 provinces of China, and COVID-19 patients with stroke were enrolled from February 24 to May 4, 2020. We analyzed epidemiological, demographic, and clinical characteristics of cases as well as the laboratory test results, treatment regimens and outcomes, and the clinical characteristics and therapeutic outcomes were compared between severe and nonsevere patients, and by age group, respectively. RESULTS: A total of 27 patients [mean age: 66.41 (SD 12.1) years] were enrolled. Among them, 9 (33.3%) were severe patients and 18 (66.7%) were nonsevere patients; 17 (63.0%) were female; 19 (70.4%) were aged 60 years and above. The most common symptoms were fever [19 (70.4%)], fatigue [12 (44.4%)] and cough [11 (40.7%)], respectively. Abnormal laboratory findings of COVID-19 patients with stroke included high levels of C-reactive protein [19 (73.1%)], D-dimer [14 (58.3%)], blood glucose [14 (53.8%)], fibrinogen [13 (50.0%)], and decreased lymphocytes [12 (44.4%)]. Comparing to nonsevere cases with stroke, severe patients with stroke were likely to be older, susceptible to receiving oxygen inhalation, and had more complications (p < 0.05). In addition, there were significant differences in lymphocytes, neutrophils, lactate dehydrogenase, C-reactive protein, creatine kinase between the severe cases and nonsevere cases (p < 0.05). The older patients had a decreased platelet count and elevated fibrinogen, compared with the younger (p < 0.05). All patients (100%) received antiviral treatment, 12 (44.4%) received antibiotics treatment, 26 (96.3%) received Traditional Chinese Medicine (Lung cleansing & detoxifying decoction), and oxygen inhalation was in 18 (66.7%). The median duration of hospitalization was 16 days. By May 4, 2020, a total of 26 (96.3%) patients were cured and discharged, and 1 (3.7%) patients died. CONCLUSION: COVID-19 patients with stroke had poor indicators of coagulation system, and severe and older patients might have a higher risk of complications and unfavorable coagulation system. However, the overall treatment outcome is favorable.

Synergistic effects of anti-MRSA herbal extracts combined with antibiotics.

MRSA is a super drug-resistant bacterium. Developing new drug or therapeutic strategies against MRSA is urgently needed. Increasing evidence has shown that herbal extracts and antibiotics can have synergistic effects against MRSA. This review focuses on commonly used antibiotics combined with herbal extracts against MRSA and the corresponding mechanisms. Through systematic analysis, we found that herbal extracts combined with antibiotics, such as ß-lactams, quinolones, aminoglycosides, tetracyclines and glycopeptides, could greatly enhance the antibacterial effects of the antibiotics, reduce the dosage and toxic side effects, and reverse MRSA resistance. Therefore, we conclude that herbal extracts combined with antibiotics may be a promising strategy to combat MRSA. This review provides a novel idea for overcoming antibiotic resistance.

[Toxicity-reducing effect of compatibility of Tripterygium and licorice in animals: systematic review].

The aim of this paper was to systematically evaluate the toxicity-reducing effect of Tripterygium-licorice in animal experiments,and also to provide evidence for basic research on the toxicity reduction of Tripterygium wilfordii. The PubMed,EMbase,Web of Science,CBM,CNKI and Wan Fang Databases from their establishment to August 31 th,2018 were searched. Two independent reviewers screened the papers,extracted the data,assessed the risk of bias using SYRCLE assessment tool and conducted Meta-analysis with Rev Man 5. 3 software. A total of 10 papers involving 31 studies were finally included,15 studies of which were used for Meta-analysis. Four studies were included for chronic hepatotoxicity animal model. In experimental group( 34 animals),Tripterygium was administered at dose of 0. 09-0. 1 mg·kg-1·d-1,and glycyrrhizic acid was administered at dose of 90-100 mg·kg-1,both for 2 weeks; in control group( 34 animals),glycyrrhizic acid was replaced with equal volume of normal saline. Eleven studies were included for acute hepatotoxicity animal model. In experimental group( 66 animals),glycyrrhizic acid was administered at dose of 75-480 mg·kg-1 for 7 days,then glycyrrhizic acid was stopped,and Tripterygium began to be administered at dose of 0. 6-1. 0 mg·kg-1 per 24 h or 48 h for a total of 1-2 times; in control group( 66 animals),glycyrrhizic acid was replaced with equal volume of normal saline or corresponding solvent. The results of Meta-analysis showed that in both chronic hepatotoxicity animal model and acute hepatotoxicity animal model,the transaminase levels in the experimental group were lower than those in the control group( P < 0. 05). Subgroup analysis of acute hepatotoxicity animal model showed that the transaminase levels in the experimental group were lower than those in the control group for every subgroup except " glycyrrhizic acid 75 mg·kg-1" subgroup. However,in terms of the mean difference( MD) and confidence interval( CI),there was no significant difference in transaminase decline between each subgroup. Low dose of glycyrrhizic acid( 90-100 mg·kg-1) has a toxicity-reduction effect on chronic hepatotoxicity induced by tripterygium( 0. 09-0. 10 mg·kg-1). Middle and high doses of glycyrrhizic acid( 120-480 mg·kg-1) have a toxicity-reduction effect on acute hepatotoxicity induced by tripterygium( 0. 6-1. 0 mg·kg-1),but with no significant dose-effect relationship.

Acupuncture for patients with myasthenia gravis: A systematic review protocol.

BACKGROUND: The objective of this systematic review protocol is to provide the methods for evaluating the effectiveness and safety of acupuncture on the treatment of myasthenia gravis (MG). METHODS AND ANALYSIS: We will search randomized controlled trials (RCTs) on this subject in 8 electronic databases and they are Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PubMed, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), the Wan-Fang Database, and Chinese Scientific Journal Database (VIP database). Other relevant literatures will be manually searched as a complement. Only RCTs related to acupuncture for MG will be included, without Language restrictions and limitation of publication types. The risk of bias and trial quality will be assessed by the Cochrane collaboration tool. The study inclusion, data extraction and quality assessment will be conducted independently by 2 reviewers. All data from the studies included will be analyzed by RevMan V.5.3 statistical software. RESULTS: This study will provide a high-quality synthesis of RCTs on the efficacy and safety of acupuncture as an adjuvant therapy in the treatment of MG. CONCLUSION: This systemic review will provide high quality evidence to evaluate acupuncture as adjuvant therapy in patients with MG. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42019133577.

Bioactive compounds from herbal medicines to manage dyslipidemia.

Dyslipidemia is a key risk factor for cardiovascular diseases, which are a major cause of morbidity and mortality worldwide. However, despite the advancement of the treatment and prevention of dyslipidemia, medications used to treat dyslipidemia are limited to chemical drugs. Herbal medicine, as an alternative treatment, has a long history of usage and provides more treatment options, and related studies have revealed intervention targets for dyslipidemia. Four lipid-lowering mechanisms of herbal medicines have been proposed and are discussed in this paper. These mechanisms are the inhibition of cholesterol absorption in enterocytes, reduction of cholesterol synthesis, elevation of reverse cholesterol transport, and promotion of cholesterol excretion in the liver. This review elaborates on the underlying molecular pathways involved in plasma lipid balance via bioactive compounds from herbal medicines.