Gut microbiota regulation of T lymphocyte subsets during systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by disturbance of pro-inflammatory and anti-inflammatory lymphocytes. Growing evidence shown that gut microbiota participated in the occurrence and development of SLE by affecting the differentiation and function of intestinal immune cells. The purpose of this study was to investigate the changes of gut microbiota in SLE and judge its associations with peripheral T lymphocytes. METHODS: A total of 19 SLE patients and 16 HCs were enrolled in this study. Flow cytometry was used to detect the number of peripheral T lymphocyte subsets, and 16 s rRNA was used to detect the relative abundance of gut microbiota. Analyzed the correlation between gut microbiota with SLEDAI, ESR, ds-DNA and complement. SPSS26.0 software was used to analyze the experimental data. Mann-Whitney U test was applied to compare T lymphocyte subsets. Spearman analysis was used for calculating correlation. RESULTS: Compared with HCs, the proportions of Tregs (P = 0.001), Tfh cells (P = 0.018) and Naïve CD4 + T cells (P = 0.004) significantly decreased in SLE patients, and proportions of Th17 cells (P = 0.020) and γδT cells (P = 0.018) increased in SLE. The diversity of SLE patients were significantly decreased. Addition, there were 11 species of flora were discovered to be distinctly different in SLE group (P < 0.05). In the correlation analysis of SLE, Tregs were positively correlated with Ruminococcus2 (P = 0.042), Th17 cells were positively correlated with Megamonas (P = 0.009), γδT cells were positively correlated with Megamonas (P = 0.003) and Streptococcus (P = 0.004), Tfh cells were positively correlated with Bacteroides (P = 0.040), and Th1 cells were negatively correlated with Bifidobacterium (P = 0.005). As for clinical indicators, the level of Tregs was negatively correlated with ESR (P = 0.031), but not with C3 and C4, and the remaining cells were not significantly correlated with ESR, C3 and C4. CONCLUSION: Gut microbiota and T lymphocyte subsets of SLE changed and related to each other, which may break the immune balance and affect the occurrence and development of SLE. Therefore, it is necessary to pay attention to the changes of gut microbiota and provide new ideas for the treatment of SLE.

MiR-182-5p: A Novel Biomarker in the Treatment of Depression in CSDS-Induced Mice.

BACKGROUND: Depression is a neuropsychiatric disease with a high disability rate and mainly caused by the chronic stress or genetic factors. There is increasing evidence that microRNAs (miRNAs) play a critical role in the pathogenesis of depression. However, the underlying molecular mechanism for the pathophysiology of depression of miRNA remains entirely unclear so far. METHODS: We first established a chronic social defeat stress (CSDS) mice model of depression, and depression-like behaviors of mice were evaluated by a series of behavioral tests. Next, we detected several abundantly expressive miRNAs suggested in previous reports to be involved in depression and found miR-182-5p was selected as a candidate for analysis in the hippocampus. Then western blotting and immunofluorescence were used together to examine whether adeno-associated virus (AAV)-siR-182-5p treatment alleviated chronic stress-induced decrease in hippocampal Akt/GSK3ß/cAMP-response element binding protein (CREB) signaling pathway and increase in neurogenesis impairment and neuroinflammation. Furthermore, CREB inhibitor was adopted to examine if blockade of Akt/GSK3ß/CREB signaling pathway abolished the antidepressant actions of AAV-siR-182-5p in mice. RESULTS: Knockdown of miR-182-5p alleviated depression-like behaviors and impaired neurogenesis of CSDS-induced mice. Intriguingly, the usage of agomiR-182-5p produced significant increases in immobility times and aggravated neuronal neurogenesis damage of mice. More importantly, it suggested that 666-15 blocked the reversal effects of AAV-siR-182-5p on the CSDS-induced depressive-like behaviors in behavioral testing and neuronal neurogenesis within hippocampus of mice. CONCLUSIONS: These findings indicated that hippocampal miR-182-5p/Akt/GSK3ß/CREB signaling pathway participated in the pathogenesis of depression, and it might give more opportunities for new drug developments based on the miRNA target in the clinic.

Aging-related upregulation of the homeobox gene caudal represses intestinal stem cell differentiation in Drosophila.

The differentiation efficiency of adult stem cells undergoes a significant decline in aged animals, which is closely related to the decline in organ function and age-associated diseases. However, the underlying mechanisms that ultimately lead to this observed decline of the differentiation efficiency of stem cells remain largely unclear. This study investigated Drosophila midguts and identified an obvious upregulation of caudal (cad), which encodes a homeobox transcription factor. This factor is traditionally known as a central regulator of embryonic anterior-posterior body axis patterning. This study reports that depletion of cad in intestinal stem/progenitor cells promotes quiescent intestinal stem cells (ISCs) to become activate and produce enterocytes in the midgut under normal gut homeostasis conditions. However, overexpression of cad results in the failure of ISC differentiation and intestinal epithelial regeneration after injury. Moreover, this study suggests that cad prevents intestinal stem/progenitor cell differentiation by modulating the Janus kinase/signal transducers and activators of the transcription pathway and Sox21a-GATAe signaling cascade. Importantly, the reduction of cad expression in intestinal stem/progenitor cells restrained age-associated gut hyperplasia in Drosophila. This study identified a function of the homeobox gene cad in the modulation of adult stem cell differentiation and suggested a potential gene target for the treatment of age-related diseases induced by age-related stem cell dysfunction.

Mendelian randomization analysis suggests no associations of herpes simplex virus infections with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) characterized by immune dysfunction is possibly more vulnerable to herpes simplex virus (HSV) infection. The infection has been intensively considered a common onset and exacerbation of SLE. This study is aimed at elucidating the causal association between SLE and HSV. A bidirectional two-sample Mendelian Randomization (TSMR) analysis was systematically conducted to explore the causal effect of SLE and HSV on each other. The causality was estimated by inverse variance weighted (IVW), MR-Egger and weighted median methods based on the summary-level genome-wide association studies (GWAS) data from a publicly available database. Genetically proxied HSV infection exhibited no causal association with SLE in the forward MR analysis using IVW method (odds ratio [OR] = 0.987; 95% confidence interval [CI]: 0.891-1.093; p = 0.798), nor did HSV-1 IgG (OR = 1.241; 95% CI: 0.874-1.762; p = 0.227) and HSV-2 IgG (OR = 0.934; 95% CI: 0.821-1.062; p = 0.297). Similar null results with HSV infection (OR = 1.021; 95% CI: 0.986-1.057; p = 0.245), HSV-1 IgG (OR = 1.003; 95% CI: 0.982-1.024; p = 0.788) and HSV-2 IgG (OR = 1.034; 95% CI: 0.991-1.080; p = 0.121) were observed in the reverse MR where SLE served as the exposure. Our study demonstrated no causal association between the genetically predicted HSV and SLE.

Deep stratification by transcriptome molecular characters for precision treatment of patients with systemic lupus erythematosus.

OBJECTIVES: To leverage the high clinical heterogeneity of systemic lupus erythematosus (SLE), we developed and validated a new stratification scheme by integrating genome-scale transcriptomic profiles to identify patient subtypes sharing similar transcriptomic markers and drug targets. METHODS: A normalized compendium of transcription profiles was created from peripheral blood mononuclear cells (PBMCs) of 1046 SLE patients and 86 healthy controls (HCs), covering an intersection of 13 689 genes from six microarray datasets. Upregulated differentially expressed genes were subjected to functional and network analysis in which samples were grouped using unsupervised clustering to identify patient subtypes. Then, clustering stability was evaluated by the stratification of six integrated RNA-sequencing datasets using the same method. Finally, the Xgboost classifier was applied to the independent datasets to identify factors associated with treatment outcomes. RESULTS: Based on 278 upregulated DEGs of the transcript profiles, SLE patients were classified into three subtypes (subtype A-C) each with distinct molecular and cellular signatures. Neutrophil activation-related pathways were markedly activated in subtype A (named NE-driving), whereas lymphocyte and IFN-related pathways were more enriched in subtype B (IFN-driving). As the most severe subtype, subtype C [NE-IFN-dual-driving (Dual-driving)] shared functional mechanisms with both NE-driving and IFN-driving, which was closely associated with clinical features and could be used to predict the responses of treatment. CONCLUSION: We developed the largest cohesive SLE transcriptomic compendium for deep stratification using the most comprehensive microarray and RNA sequencing datasets to date. This result could guide future design of molecular diagnosis and the development of stratified therapy for SLE patients.

Specific enterotype of gut microbiota predicted clinical effect of methotrexate in patients with rheumatoid arthritis.

OBJECTIVE: The most used drug for the treatment of rheumatoid arthritis (RA) remains methotrexate (MTX). Unfortunately, up to 50% of patients do not achieve a clinically adequate outcome. Here we study whether the gut microbiota patterns can aid in the prediction of MTX efficacy for RA. METHOD: To dissect gut microbiome profiles of RA patients (n = 145), 16S rRNA gene sequencing was performed. Dirichlet multinomial mixture (DMM) clustering was used to identify enterotypes at genus level. The relationships between enterotypes and clinical measures (such as lymphocyte subsets and cytokines detected by flow cytometry) were explored. Then, enterotype stability was evaluated by the stratification of the RA patient cohort (n = 66) in Shanghai, China, using the same method. Finally, the enterotype-based gut microbial human index classifier was applied to another independent RA patient cohort (n = 27) to identify the factors associated with MTX clinical response. RESULTS: Our analysis revealed that the RA patients always displayed two different dysbiotic microbiota patterns: RA E1 comprised predominantly Prevotella and RA E2 comprised predominantly Bacteroides. Among all of the lymphocyte subsets and cytokines, only the number of CD8+ T cells showed a significant difference between RA E1 and RA E2. These results were validated in the RA patient cohort in Shanghai, China. Significant associations of RA E1 with clinical response to subsequent MTX treatment were confirmed by another independent RA patient cohort. CONCLUSION: Together, the enterotype-based gut microbial human index (EGMI) classifier was useful to precisely and effectively identify enterotypes of individual RA patients, which could effectively evaluate MTX clinical responses.

Reduced circulating Tregs and positive pANCA were robustly associated with the occurrence of antiphospholipid syndrome in patients with systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a typical chronic immune disorder with clinical heterogeneity. The systemic abnormal immune response not only challenges the diagnosis and treatment of the disease itself but also the secondary antiphospholipid syndrome (APS), characterized by recurrent arterial or venous thrombosis, recurrent spontaneous abortion, or stillbirth. Clinical interest has primarily focused on primary APS's pathological and clinical features. However, differences in clinical features and laboratory indicators between SLE with or without APS are still lacking, especially differences between circulating lymphocytes, which are critical in the pathogenesis of SLE and its complications. METHODS: In this retrospective study, we collected and analyzed clinical characteristics, general laboratory indicators, immunological indicators, and circulating lymphocyte subsets of SLE with or without APS. RESULTS: Systemic lupus erythematosus with APS (SLE-APS) had elevated SLEDAI scores, hospitalization costs and time, and frequencies of central nervous system symptoms and spontaneous abortion compared with those without APS. SLE-APS had higher positive anti-Cardiolipin antibodies, anti-ß2 Glycoprotein 1 antibodies, and perinuclear antineutrophil cytoplasmic antibody (pANCA) than none-APS patients. Compared with healthy controls (HCs), the circulating lymphocyte subsets were altered to some extent in all patients, especially in patients with SLE-APS. Reduced Tregs and positive pANCA were independent risk factors for SLE secondary APS. CONCLUSION: The present study revealed a robust association between APS secondary to SLE and reduced Tregs and positive pANCA, which provides essential information regarding the diagnosis and therapeutic possibilities of APS secondary to SLE.

First-principles study of the structures and superconductivity of H-S-La systems under high pressure.

Recent experimental and theoretical studies have shown that a La-H system displays remarkable superconducting properties, and it is also possible to improve the superconducting state by introducing other elements into this system. In this study, we systematically investigated the crystal structures and physical properties of an H-S-La system by using first-principles calculations combined with the CALYPSO structure exploration technique. We predicted four stable stoichiometries containing H2SLa, H3SLa, H4Sla, and H6SLa. These compounds undergo a series of phase transitions under 50-300 GPa. The bonding characters and electronic properties were calculated. It was found that Cm-H2SLa, C2/c-H2SLa, and Cmcm-H6SLa exhibit good metallic nature, which stimulates us to further study their superconducting properties. The calculated superconducting transition temperatures (Tc) of Cm-H2SLa, C2/c-H2Sla, and Cmcm-H6SLa are 15.0 K at 200 GPa, 6.9 K at 300 GPa, and 23.6 K at 300 GPa, respectively.

Identifying cellular senescence associated genes involved in the progression of end-stage renal disease as new biomarkers.

BACKGROUND: Cellular senescence plays an essential role in the development and progression of end-stage renal disease (ESRD). However, the detailed mechanisms phenomenon remains unclear. METHODS: The mRNA expression profiling dataset GSE37171 was taken from the Gene Expression Omnibus (GEO) database. The cell senescence-associated hub genes were selected by applying protein-protein interaction (PPI), followed by correlation analysis, gene interaction analysis, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. We next explored the relationships of hub genes with miRNAs, TFs, and diseases. The absolute abundance of eight immune cells and two stromal cells were calculated by MCPcount and the correlation of hub genes with these ten cells was analyzed. Lasso was used to selecting for trait genes. ROC curves and DCA decision curves were used to assess the accuracy and predictive power of the trait genes. RESULTS: A total of 65 cellular senescence signature genes were identified among patients and controls. The PPI network screened out ten hub genes. GO and KEGG indicated that ten hub genes were associated with ESRD progression. Transcription factor gene interactions and common regulatory networks of miRNAs were also identified in the datasets. The hub genes were significantly correlated with immune cells and stromal cells. Then the lasso model was constructed to screen out the five most relevant signature genes (FOS, FOXO3, SIRT1, TP53, SMARCA4). The area under the ROC curve (AUC) showed that these five characteristic genes have good resolving power for the diagnostic model. CONCLUSIONS: Our findings suggested that cellular senescence-associated genes played an important role in the development of ESRD and immune regulation.

A Ratiometric Fluorescent Probe for N2H4 Having a Large Detection Range Based upon Coumarin with Multiple Applications.

Although hydrazine (N2H4) is a versatile chemical used in many applications, it is toxic, and its leakage may pose a threat to both human health and environments. Consequently, the monitoring of N2H4 is significant. This study reports a one-step synthesis for coumarin-based ratiometric fluorescent probe (FP) CHAC, with acetyl as the recognition group. Selected deprotection of the acetyl group via N2H4 released the coumarin fluorophore, which recovered the intramolecular charge transfer process, which caused a prominent fluorescent, ratiometric response. CHAC demonstrated the advantages of high selectivity, a strong capacity for anti-interference, a low limit of detection (LOD) (0.16 µM), a large linear detection range (0-500 µM), and a wide effective pH interval (6-12) in N2H4 detection. Furthermore, the probe enabled quantitative N2H4 verifications in environmental water specimens in addition to qualitative detection of N2H4 in various soils and of gaseous N2H4. Finally, the probe ratiometrically monitored N2H4 in living cells having low cytotoxicity.

LncRNA nuclear-enriched abundant transcript 1 aggravates cerebral ischemia/reperfusion injury through activating early growth response-1/RNA binding motif protein 25 axis.

Ischemic stroke is a major global health issue. Ischemia and subsequent reperfusion results in stroke-related brain injury. Previous studies have demonstrated that nuclear-enriched abundant transcript 1 (NEATa and early growth response 1 (EGR1) are involved in ischemia reperfusion (IR) injury). In this study, we aimed to explore the roles of NEAT1/EGR1 axis as well as its downstream effector RNA binding motif protein 25 (RBM25) in cerebral IR injury. Oxygen-glucose deprivation/reperfusion (OGD/R) and middle cerebral artery occlusion (MCAO) were used to establish in vitro and in vivo models of cerebral IR injury, respectively. According to our data, NEAT1, EGR1, and RBM25 levels were elevated in OGD/R-exposed SK-N-SH and SH-SY5Y cells and cerebral cortex of MCAO mice. NEAT1, EGR1, or RBM25 knockdown effectively reduced infarct volumes and apoptosis, and improved neurological function. Mechanistically, NEAT1 directly interacted with EGR1, which restrained WW domain containing E3 ubiquitin protein ligase 1 (WWP1)-mediated ubiquitination of EGR1 and subsequently caused EGR1 accumulation. EGR1 bound to RBM25 promoter and transcriptionally activated RBM25. Rescue experiments indicated that RBM25 overexpression abolished the therapeutic effects of NEAT1 knockdown. In conclusion, this work identified a novel NEAT1/EGR1/RBM25 axis in potentiating brain injury after IR insults, suggesting a potential therapeutic target for ischemic stroke.

Safety, tolerance, pharmacokinetic and pharmacodynamic properties of thrombopoietin mimetic peptide for injection in Chinese healthy volunteers: a randomized, placebo-controlled, double-blind study.

The thrombopoietin mimetic peptide for injection is a second-generation thrombopoietin receptor agonist (TPO-RA) used in the treatment of patients with immune thrombocytopenia. The aim of the present study was to assess the safety, tolerance, pharmacokinetic and pharmacodynamic properties of thrombopoietin mimetic peptide for injection in Chinese healthy volunteers. A randomized, placebo-controlled, double-blind, dose-escalation study was conducted in healthy Chinese subjects aged 18-50 years. Thirty subjects received single subcutaneous injection of 0.3 µg/kg, 1.0 µg/kg, 2.0 µg/kg thrombopoietin mimetic peptide or placebo. Thrombopoietin mimetic peptide was safe and well tolerated at doses of 0.3-2.0 µg/kg. There was no significant change in mean platelet count (PLT) from baseline at the 0.3 µg/kg or placebo groups. The mean PLT of subjects in the 1.0 µg/kg and 2.0 µg/kg groups peaked at day 12 (± 1), began to decline around day 17, and returned to the baseline level at day 28 (± 1). Platelet aggregation rates of the three dose groups showed no significant change before and after administration. Serum concentrations of thrombopoietin mimetic peptide in all subjects were below the quantization limit. This was the first study to demonstrate that subcutaneous injection of thrombopoietin mimetic peptide at doses of 0.3-2.0 µg/kg was safe and well tolerated in Chinese healthy subjects. As a second-generation TPO-RA, thrombopoietin mimetic peptide is effective at improving PLT after single subcutaneous injection at dose of ≥1 µg/kg.P lain l anguage s ummaryWhat is the context?● Immune thrombocytopenia (ITP) is a rare, serious autoimmune disorder characterized by low platelet count (PLT) without an alternate cause. The treatment goal of ITP is to increase the platelet count to a safe level that can stop active bleeding and reduce the risks of future bleeding.● Thrombopoietin receptor agonists (TPO-RAs, e.g. eltrombopag, avatrombopag, hetrombopag, and romiplostim) have shown high response rates in stimulating platelet production and reducing the risk of bleeding. TPO-RAs provide ITP patients with well-tolerated, long-term treatment choices.What is new?● The thrombopoietin mimetic peptide for injection is a new TPO-RAs developed by Shandong Quangang Pharmaceutical Co., Ltd. (China).● This study showed that thrombopoietin mimetic peptide is effective at improving PLT after a single subcutaneous injection.● The thrombopoietin mimetic peptide is safe and well-tolerated in Chinese healthy subjects.What is the impact?● This study provides evidence for the further development potential of the thrombopoietin mimetic peptide.

High-Dose Clopidogrel versus Ticagrelor in CYP2C19 intermediate or poor metabolizers after percutaneous coronary intervention: A Meta-Analysis of Randomized Trials.

WHAT IS KNOWN AND OBJECTIVE: For patients after percutaneous coronary interventions (PCI), clopidogrel combined with aspirin is a conventional dual antiplatelet therapy (DAPT) method. Because the genetic polymorphism of CYP2C19 gene leads to clopidogrel resistance, guidelines for antiplatelet recommendations in CYP2C19 of ultrarapid metabolizers (UM), extended metabolizers (EM) and poor metabolizers (PM) are clear. However, there is no clear recommendation as to whether ticagrelor or double dose clopidogrel is the best antiplatelet regimen for CYP2C19 of intermediate metabolizers (IM). To evaluate the efficacy and safety of ticagrelor (combined with aspirin) and high-dose clopidogrel (combined with aspirin) in patients after PCI with CYP2C19 loss-of-function (LOF) alleles. METHODS: We searched the following databases to select RCTs of comparing ticagrelor with high-dose clopidogrel in patients after PCI with CYP2C19 LOF alleles: CNKI, Wanfang Data, PubMed, Clinical trials, Cochrane, Web of Science and Embase. Major adverse cardiovascular events (MACEs), platelet function and TIMI bleeding event were defined as the outcomes. revman 5.3 software was used to perform meta-analysis. RESULTS AND DISCUSSION: A total of 14 RCTs with 2351 patients were enrolled. Meta-analysis showed that compared with high-dose clopidogrel, ticagrelor had reduced incidence of MACEs (OR = 0.32, 95% Cl: 0.23-0.44, p < 0.00001), stent thrombosis (OR: 0.24, 95%CI: 0.13-0.44, p < 0.00001), myocardial infarction OR: 0.42, 95%CI: 0.22-0.80, p = 0.008), revascularization (OR: 0.29, 95%CI: 0.10-0.82, p = 0.02) and unstable angina (OR: 0.47, 95%CI: 0.29-0.77, p = 0.003) in patients after PCI with CYP2C19 LOF alleles. A subgroup analysis showed that ticagrelor reduced the risk of MACEs compared with high-dose clopidogrel regardless of the type of metabolizer. Compared with high-dose clopidogrel, ticagrelor significantly reduced the risk of MACE with longer follow-up period (more than 3 months) without increasing the risk of bleeding (OR: 0.89, 95%CI: 0.53-1.49, p = 0.30), while elevated dyspnoea (OR: 5.62, 95%CI: 3.07-10.28, p < 0.00001). WHAT IS NEW AND CONCLUSIONS: For patients carrying CYP2C19 LOF alleles after PCI, ticagrelor may be better than high-dose clopidogrel in reducing the risk of MACEs, while dyspnoea incidents should be alerted.

Nutritional complexity in children with ADHD related morbidities in China: A cross-sectional study.

BACKGROUND AND OBJECTIVES: To assess the general and nutritional health of children with attention deficit/ hyperactivity disorder (ADHD). METHODS AND STUDY DESIGN: The National Multicenter Sleep Research Database for 23791 school-age children in grades 1-6 from 9 cities in China was accessed. Children with a specialist diagnosis of ADHD or not (non-ADHD) in 2005 were studied. National anthropometric growth standards for children aged 2-18 years classified children as underweight, wasted, stunted (short stature presumed nutritional), or overweight/obesity. Independent variables were preterm birth, sleep quality and prior disease and ADHD was the dependent variable. Binary logistic regression models were developed along with interaction analyses for associated disorder or disease on overweight/obesity, and stunted. RESULTS: Some 18731 records were analyzed for 808 children with ADHD. The comparative prevalences for ADHD with non-ADHD children were stunted 9.8% vs 5.9% (p<0.001) and overweight/ obesity (32.6% vs 29.6%, p=0.002) respectively. ADHD boys were more often underweight (7.5% vs 5.3%, p=0.027), but not in girls. ADHD likelihood Odds Ratios, ORs (with 95%CI) were for premature birth 1.838, (1.393-2.423), allergic diseases 1.915 (1.526-2.399), otitis media 1.54 (1.118- 2.146), tonsillar or adenoid hypertrophy1.662 (1.348-2.050), gastroesophageal reflux 3.008(1.792-1.792-5.049), and sleep disorder 2.201(1.847-2.623) were ADHD risk factors. Only poor sleep quality and ADHD exhibited an interaction for stunted with OR=0.409 (0.233-0.719). CONCLUSIONS: Compromised and complex nutritional health in ADHD children challenges clinical nutrition with a range of health problems, albeit coherent with the needed nutritional emphasis in the 'first 1000 days'.

[Network Meta-analysis of efficacy and safety of oral Chinese patent medicines combined with conventional western medicine in treatment of hypertension].

This study aims to systematically evaluate the effect of oral Chinese patent medicines on hypertension with network Meta-analysis. Randomized controlled trials on the treatment of hypertension with oral Chinese patent medicine combined with conventional western medicine were retrieved from China National Knowledge Infrastructure(CNKI), Wanfang, VIP, SinoMed, PubMed, EMbase, and Cochrane Library(from establishment of the database to August 2021). Two researchers independently screened the articles, extracted the data, and evaluated article quality. Then R 4.1.0 was employed for data analysis. Finally, 195 eligible articles were screened out, involving 22 546 patients and 18 oral Chinese patent medicines. The results of the network Meta-analysis are as follows. In terms of reducing systolic blood pressure(SBP) and diastolic blood pressure(DBP), Xuesaitong, Qiangli Dingxuan Tablets, Songling Xuemaikang Capsules combined with conventional western medicine are superior. In improving blood lipids, the overall effects of Xinmaitong Capsules, Compound Xueshuantong Capsules, Ginkgo Folium preparations, Yindan Xinnaotong Soft Capsules, and Naoxintong Capsules combined with conventional western medicine are outstanding. In terms of regulating endothelial function, Yindan Xinnaotong Soft Capsules, Xinmaitong Capsules, Zhenju Jiangya Tablets, Compound Danshen Dripping Pills, Xuesaitong with conventional western medicine have certain advantages. As for the safety, the incidence of adverse reactions of conventional western medicine combined with oral Chinese patent medicines is lower than that of conventional western medicine alone. In summary, compared with conventional western medicine alone, the 18 oral Chinese patent medicines combined with conventional western medicine in the treatment of hypertension show advantages in improving blood pressure, blood lipids, and endothelial function. Among them, Xuesaitong, Qiangli Dingxuan Tablets, and Songling Xuemaikang Capsules may be the best oral Chinese patent medicines for lowering blood pressure. The conclusion needs to be further verified by more high-quality studies.

[Clinical trials and evaluation of Chinese patent medicine for influenza].

The clinical randomized controlled trial(RCT) of Chinese patent medicine in the treatment of influenza were reviewed and analyzed to provide basic information for clinical decision and related research. On the basis of the collection in the Traditional Chinese Medicine(TCM) Clinical Evidence Database System(EVDS), CNKI, Wanfang, VIP, SinoMed, EMbase, PubMed, and Cochrane Library were searched for RCTs of Chinese patent medicine for influenza published from database inception to July 25, 2021. The publication time, sample size, intervention and control measures, course of treatment, outcome indicators, and methodological quality of the trials were analyzed and evaluated. Ninety-two RCTs of Chinese patent medicine for influenza published between 2005 and 2021, were included, among which 17 RCTs(18.48%) had a sample size higher than 200 and the average sample size was about 145. Twenty-seven Chinese patent medicines were involved, including twenty-one oral medicines and six injections. The Chinese patent medicines in trials reported in more than five papers included Lianhua Qingwen Capsules/Gra-nules, Tanreqing Injection, and Reduning Injection. Fourteen intervention protocols were reported, of which Chinese patent medicine+western medicine+conventional treatment vs western medicine+conventional treatment(20.65%) was the most frequently employed. Additionally, 85.87% of the RCTs reported the course of treatment, and 80.43% of the RCTs determined 3-7 d as the intervention course. Forty-five outcome indicators were extracted, which were used 434 times, including symptoms/signs, physicochemical detection, safety events, TCM symptoms/syndromes, quality of life, long-term prognosis, and economic evaluation. Symptoms/signs(61.52%) exhibited the highest frequency. Methodological problems were prevalent in the included trials. The findings reveal that there are few clinical trials on influenza treatment by Chinese patent medicine, and the methodological problems are prominent, affec-ting the reliability and practicability of the trials. In the future research, the value characteristics of Chinese patent medicine should be highlighted and the quality control in the whole process should be strengthened based on the scientific and rigorous design.

[Analysis of outcome indexes in randomized controlled trials of traditional Chinese medicine for rheumatic heart disease].

The present study analyzed the efficacy evaluation indexes of the randomized controlled trials(RCTs) of Chinese medi-cine in the treatment of rheumatic heart disease to lay the foundation for the construction of the corresponding core outcome index set. Clinical RCTs with a definite diagnosis of rheumatic heart disease were retrieved from CNKI, Wanfang, VIP, Sino Med, Pub Med, EMbase, and Cochrane Library from January 1, 2010, to December 31, 2020. Thirty-five RCTs were included, involving 3 314 patients and 41 efficacy evaluation indexes, which covered seven domains [traditional Chinese medicine(TCM) symptoms/syndromes, symp-toms/signs, physical and chemical examination, quality of life, long-term prognosis, economic evaluation, and safety events]. Physi-cal and chemical examination(56. 91%) and symptoms/signs(29. 27%) were the more frequently applied. The number of indexes used in a single trial ranged from 1 to 15, with an average of 4. The measurement time points of the top five indexes in the frequency of use were as follows: total response rate was reported at five measurement time points, ranging from 14 days to 6 months; left ventri-cular ejection fraction was measured at eight time points ranging from 5 days to 6 months; left ventricular end systolic diameter was measured at six time points, ranging from 5 days to 6 months; interleukin-2(IL-2) and tumor necrosis factor-α(TNF-α) were repor-ted 28 days after treatment. At present, there are many problems in the efficacy outcome indexes of RCTs in the treatment of rheumatic heart disease with TCM, such as large difference in quantity, unclear primary and secondary indexes, unreasonable selection of " surro-gate indexes", insufficient attention to long-term prognostic indexes and safety event indexes, non-standard application of composite in-dexes, long measurement period, and lack of TCM characteristics. It is urgent to establish the core outcome set for TCM treatment of rheumatic heart disease.

Potential new therapeutic target for Alzheimer's disease: Glucagon-like peptide-1.

Increasing evidence shows a close relationship between Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM). Recently, glucagon-like peptide-1 (GLP-1), a gut incretin hormone, has become a well-established treatment for T2DM and is likely to be involved in treating cognitive impairment. In this mini review, the similarities between AD and T2DM are summarised with the main focus on GLP-1-based therapeutics in AD.

Identification of novel hub genes associated with gastric cancer using integrated bioinformatics analysis.

BACKGROUND: Gastric cancer (GC) is one of the most common solid malignant tumors worldwide with a high-recurrence-rate. Identifying the molecular signatures and specific biomarkers of GC might provide novel clues for GC prognosis and targeted therapy. METHODS: Gene expression profiles were obtained from the ArrayExpress and Gene Expression Omnibus database. Differentially expressed genes (DEGs) were picked out by R software. The hub genes were screened by cytohubba plugin. Their prognostic values were assessed by Kaplan-Meier survival analyses and the gene expression profiling interactive analysis (GEPIA). Finally, qRT-PCR in GC tissue samples was established to validate these DEGs. RESULTS: Total of 295 DEGs were identified between GC and their corresponding normal adjacent tissue samples in E-MTAB-1440, GSE79973, GSE19826, GSE13911, GSE27342, GSE33335 and GSE56807 datasets, including 117 up-regulated and 178 down-regulated genes. Among them, 7 vital upregulated genes (HMMR, SPP1, FN1, CCNB1, CXCL8, MAD2L1 and CCNA2) were selected. Most of them had a significantly worse prognosis except SPP1. Using qRT-PCR, we validated that their transcriptions in our GC tumor tissue were upregulated except SPP1 and FN1, which correlated with tumor relapse and predicts poorer prognosis in GC patients. CONCLUSIONS: We have identified 5 upregulated DEGs (HMMR, CCNB1, CXCL8, MAD2L1, and CCNA2) in GC patients with poor prognosis using integrated bioinformatical methods, which could be potential biomarkers and therapeutic targets for GC treatment.

Absolute reduction of peripheral regulatory T cell in patients with relapsing polychondritis.

OBJECTIVES: Although relapsing polychondritis (RP) is considered as an immune-mediated systemic disease, the levels of peripheral lymphocyte subpopulations are rarely studied in patients with RP. In this study, we focused on changes of peripheral CD4+T cell subsets in patients with RP. METHODS: Absolute numbers and percentages of CD4+T cell subsets including helper T(Th)1, Th2, Th17 cells and regulatory T (Treg) cells in peripheral blood (PB) from 19 RP patients, healthy controls and RA patients respectively were assessed by flow cytometry combined a microbead-based single-platform method. We compared the CD4+T cell levels in all RP patients and healthy controls. In addition, we analysed the difference of the absolute number and percentage of Treg cells between RP and RA patients. RESULTS: Compared with healthy controls, all RP patients had significantly both lower absolute number and proportion of Treg cells (absolute number, 45.10/µl vs. 22.48/µl, p<0.001; proportion, 5.19% vs. 3.78%, p<0.001) no matter whether they had received treatment or not. Similarly, the absolute number of Th2 cells in all RP patients was decreased (10.19/µl vs. 7.44/µl, p=0.030). However, there were no significant differences in percentages and absolute numbers of Th1 and Th17 cells between RP patients and healthy controls. The above results led to increased ratios of Th1/Treg (3.68 vs. 2.06, p=0.020), Th2/Treg (0.29 vs. 0.21, p=0.037) and Th17/Treg (0.25 vs. 0.14, p<0.001) in RP patients, and untreated RP patients were mainly characterised by the imbalance of Th17/Treg (0.25 vs. 0.14, p<0.01). There was no significant difference in Treg cells between RP and RA patients (p>0.05). CONCLUSIONS: Our data suggest that the reduction of Treg cells and its imbalance with Th cells play an important role in the pathogenesis of RP.