The study was conducted to investigate the mechanism of Xinyang Tablets( XYP) in modulating the fat mass and obesity-associated protein(FTO)/N6-methyladenosine(m6A) signaling pathway to ameliorate ventricular remodeling in heart failure(HF). A mouse model of HF was established by transverse aortic constriction(TAC). Mice were randomized into sham, model, XYP(low, medium, and high doses), and positive control( perindopril) groups(n= 10). From day 3 post-surgery, mice were administrated with corresponding drugs by gavage for 6 consecutive weeks. Following the treatment, echocardiography was employed to evaluate the cardiac function, and RT-qPCR was employed to determine the relative m RNA levels of key markers, including atrial natriuretic peptide( ANP), B-type natriuretic peptide( BNP), β-myosin heavy chain(β-MHC), collagen type I alpha chain(Col1α), collagen type Ⅲ alpha chain(Col3α), alpha smooth muscle actin(α-SMA), and FTO. The cardiac tissue was stained with Masson's trichrome and wheat germ agglutinin(WGA) to reveal the pathological changes. Immunohistochemistry was employed to detect the expression levels of Col1α, Col3α, α-SMA, and FTO in the myocardial tissue. The m6A modification level in the myocardial tissue was measured by the m6A assay kit. An H9c2 cell model of cardiomyocyte injury was induced by angiotensin Ⅱ(AngⅡ), and small interfering RNA(siRNA) was employed to knock down FTO expression. RT-qPCR was conducted to assess the relative m RNA levels of FTO and other genes associated with cardiac remodeling. The m6A modification level was measured by the m6A assay kit, and Western blot was employed to determine the phosphorylated phosphatidylinositol 3-kinase(p-PI3K)/phosphatidylinositol 3-kinase(PI3K) and phosphorylated serine/threonine kinase(p-Akt)/serine/threonine kinase(Akt) ratios in cardiomyocytes. The results of animal experiments showed that the XYP treatment significantly improved the cardiac function, reduced fibrosis, up-regulated the m RNA and protein levels of FTO, and lowered the m6A modification level compared with the model group. The results of cell experiments showed that the XYP-containing serum markedly up-regulated the m RNA level of FTO while decreasing the m6A modification level and the p-PI3K/PI3K and p-Akt/Akt ratios in cardiomyocytes. Furthermore, FTO knockdown reversed the protective effects of XYP-containing serum on Ang Ⅱ-induced cardiomyocyte hypertrophy. In conclusion, XYP may ameliorate ventricular remodeling by regulating the FTO/m6A axis, thereby inhibiting the activation of the PI3K/Akt signaling pathway.
Animals ; Ventricular Remodeling/drug effects* ; Heart Failure/physiopathology* ; Signal Transduction/drug effects* ; Mice ; Male ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred C57BL ; Humans ; Adenosine/analogs & derivatives* ; Myocytes, Cardiac/metabolism* ; Disease Models, Animal

This study investigates the effect and underlying mechanism of Guizhi Tongluo Tablets(GZTL) in treating atherosclerosis(AS) in a mouse model. Apolipoprotein E-knockout(ApoE~(-/-)) mice were randomly assigned to the following groups: model, high-, medium-, and low-dose GZTL, and atorvastatin(ATV), and age-matched C57BL/6J mice were selected as the control group. ApoE~(-/-) mice in other groups except the control group were fed with a high-fat diet for the modeling of AS and administrated with corresponding drugs via gavage for 8 weeks. General conditions, signs of blood stasis, and body mass of mice were monitored. Aortic plaques and their stability were assessed by hematoxylin-eosin, Masson, and oil red O staining. Serum levels of total cholesterol(TC), triglycerides(TG), and low-density lipoprotein cholesterol(LDL-C) were measured by biochemical assays, and those of interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6) were determined via enzyme-linked immunosorbent assay. Apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL). Single-cell RNA sequencing(scRNA-seq) was employed to analyze the differential expression of CD72hi macrophages(CD72hi-Mφ) in the aortas of AS patients and mice. The immunofluorescence assay was employed to visualize CD72hi-Mφ expression in mouse aortic plaques, and real-time fluorescence quantitative PCR was utilized to determine the mRNA levels of IL-1β, TNF-α, and IL-6 in the aorta. The results demonstrated that compared with the control group, the model group exhibited significant increases in body mass, aortic plaque area proportion, necrotic core area proportion, and lipid deposition, a notable decrease in collagen fiber content, and an increase in apoptosis. Additionally, the model group showcased elevated serum levels of TC, TG, LDL-C, IL-1β, TNF-α, and IL-6, alongside marked upregulations in the mRNA levels of IL-1β, TNF-α, and IL-6 in the aorta. In comparison with the model group, the GZTL groups and the ATV group showed a reduction in body mass, and the medium-and high-dose GZTL groups and the ATV group demonstrated reductions in aortic plaque area proportion, necrotic core area proportion, and lipid deposition, an increase in collagen fiber content, and a decrease in apoptosis. Furthermore, the treatment goups showcased lowered serum levels of TC, TG, LDL-C, IL-1β, TNF-α, and IL-6. The data of scRNA-seq revealed significantly elevated CD72hi-Mφ signaling in carotid plaques of AS patients compared with that in the normal arterial tissue. Animal experiments confirmed that CD72hi-Mφ expression, along with several pro-inflammatory cytokines, was significantly upregulated in the aortas of AS mice, which were downregulated by GZTL treatment. In conclusion, GZTL may alleviate AS by inhibiting CD72hi-Mφ activity.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Atherosclerosis/immunology* ; Mice ; Mice, Inbred C57BL ; Macrophages/immunology* ; Male ; Humans ; Apolipoproteins E/genetics* ; Tablets ; Tumor Necrosis Factor-alpha/genetics* ; Apoptosis/drug effects* ; Interleukin-1beta/genetics* ; Interleukin-6/genetics* ; Disease Models, Animal ; Mice, Knockout

This study aimed to investigate the ameliorative effect of Xinyang Tablets on myocardial fibrosis in uremic cardiomyopathy(UCM) using single-cell sequencing technology. UCM mouse models were established by 5/6 nephrectomy(NPM) and randomly divided into the model group, Xinyang Tablets group, and sham-operated(sham) group as the control. The Xinyang Tablets group received postoperative interventions of Xinyang Tablets(0.34 g·kg~(-1)). After eight weeks, the hearts of the mice in each group were disassociated and subjected to 10×Genomics single-cell sequencing. The data were subjected to t-SNE dimensionality reduction, K-means clustering, and CellMarker annotation prior to analyzing differential expression and cell differentiation trajectories using the Seurat and Monocle3 tools. Additionally, the CellChat tool was used to parse intercellular signaling communication. The results showed that a total of nine types of cells including fibroblasts, endothelial cells, and immune cells were identified in this study. The single-cell expression results of fibroblasts and Gene Ontology(GO) enrichment analysis showed that Xinyang Tablets regulated myocardial fibrosis factors and related signals. Mimetic timing analysis identified three major differentiation trajectories of mouse cardiac fibroblasts and identified the expression of secreted phosphoprotein 1(Spp1) as consistent with the fibroblast differentiation trajectory. Cellular interaction network analysis showed that the communication signals between mouse cardiac fibroblasts and other cells were weakened in the Xinyang Tablets group compared with the model group. The results of ligand-receptor interaction analysis showed that the interaction between myeloid cell-derived osteopontin(OPN) and cardiac fibroblasts and between myeloid cell Spp1 ligand and cardiac fibroblast receptor of mice in the Xinyang Tablets group was weakened compared with the model group. In conclusion, Xinyang Tablets may improve myocardial fibrosis in UCM by inhibiting both endogenous and exogenous OPN at the single-cell level.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Cardiomyopathies/pathology* ; Single-Cell Analysis ; Male ; Fibrosis/drug therapy* ; Myocardium/metabolism* ; Uremia/metabolism* ; Tablets ; Mice, Inbred C57BL ; Humans

Antineoplastic Agents, Immunological/adverse effects* ; Humans ; Immune Checkpoint Inhibitors ; Myocarditis/chemically induced*

Objective:To study the clinical features and prognostic risk factors of gastrointestinal (GI) involvement in systemic lupus erythematosus (SLE), and improve clinicians' understanding of GI involvement in SLE.Methods:The clinical data of SLE patients admitted to the First Affiliated Hospital of Guangxi Medical University from September 1, 2012 to September 1, 2019 were retrospectively analyzed. Two hundred and forty-three patients with GI system involvement were the GI system affected group, and 486 patients with-out GI system involvement at the same period were randomly selected as the control group. The clinical mani-festations, laboratory tests and treatment effects of the two groups were compared by t test, Wilcoxon signed-rank test and χ2 test and Logistic regression was used to analyze the prognostic risk of SLE with GI system involvement. Results:① There were 243 SLE patients with GI involvement, with the proportion of GI involvement in SLE patients of 6.4%(243/3 820), and as the first manifestation with GI system symptoms accounted for 20.2%(49/243). The common causes were lupus hepatitis accounted for 52.3%(127/243), lupus mesenteric vasculitis (LMV) for 35.0%(85/243), pseudo Intestinal obstruction (IPO) for 9.9%(24/243), lupus-related pancreatitis for 8.6%(21/243), and protein-losing enteropathy (PLE) as 7.0%(17/243). ② Compared with the control group, the group with GI involvement had a lower average age [(38±14) year vs(32±15) year, t=-2.47, P=0.014], a shorter median duration of illness [12.0(3.0, 72.0) months vs 5.0(1.1, 24.8) months, Z=-5.67 , P<0.001], a higher median systemic lupus erythematosus disease activity index (SLEDAI) score [10(6,28) vs 16(9, 37), Z=2.24 , P<0.001], the occurrence of skin rash (38.7% vs 53.5%, χ2=14.46), arthritis (36.4% vs 46.7%, χ2=7.12 , P=0.008), myositis (43.0% vs 56.4%, χ2=11.53 , P=0.001), pericarditis [(216±111)×10 9/L vs (175±114)×10 9/L, t=-4.69 , P<0.001], thrombocytopenia, and hydroureterosis (1.0% vs 12.8%, χ2=47.47 , P<0.001) were high, but the incidence of pulmonary arterial hypertension (PAH) (31.2% vs 10.7%, χ2=36.99 , P<0.001) was low; Serum alanine aminotransferase (ALT) [17(10, 29) U/L vs 59(16, 127) U/L, Z=9.65 , P<0.001], aspartate aminotransferase (AST) [25.0 (18.0, 37.0) U/L vs 82.5(25.0, 289.0) U/L, Z=10.57 , P<0.001], alkaline phosphatase (ALP) [58(46, 76) U/L vs 82(56, 187)U/L, Z=8.42 , P<0.001], Creatine kinase (CK) [44.0(28.0, 83.0) U/L vs 58.5(34.0, 176.0) U/L, Z=4.46 , P<0.001], lactate dehydrogenase (LDH) [(309±206) U/L vs (443±332) U/L, t=5.64 , P<0.001], fasting blood glucose (FBS) [(5.0±1.5) mmol/L vs (5.3±1.7) mmol/L, t=2.16 , P=0.031], triglyceride (TG) [(2.0±1.3) mmol/L vs (2.7±2.2) mmol/L, t=4.55 , P<0.001] increased, albumin (ALB) [(30±7) g/L vs (27±7) g/L, t=5.87 , P<0.001)] and high-density lipoprotein (HDL) [(1.1±0.8) mmol/L vs (0.9±0.5) mmol/L, t=-4.20 , P<0.001] decrease, and anti SSB antibody positive rate (16.0% vs 9.5%, χ2=5.60 , P=0.018) decreased.③ After 3 months' follow-up, 203 patients with SLE GI involvement were relieved, 30 patients (12.3%) died, and 9 patients (1.8%) died in the control group. Ninety-five (46.8%) patients in the remission group had a significantly higher rate of cyclophosphamide treatment when compared with 5(12.5%) in the non-remission group ( χ2=16.23, P<0.001) . Logistic regression analysis showed that no increase of PAH, elevated erythrocyte sedimentation rate (ESR), ALT, glutamyl transpeptidase (GGT), indirect bilirubin (IBIL) and high SLEDAI scores, hydroureteral dilatation, decreased ALB and HDL were independent related factors for SLE GI involvement, while ascites and elevated FBS were SLE GI involvement factors of poor prognosis. Conclusion:SLE patients with GI involvement have a high mortality rate, and lupus hepatitis and LMV are common. Hydroureterosis, high SLEDAI score, abnormal liver function are risk factors for GI involvement. Jaundice and elevated FBS are the risk factors for poor prognosis, and treatment with cyclophosphamide is the protective factor.

Objective: To investigate death and attrition in HIV-infected children under initial antiretroviral therapy (ART) and associated factors in Guangxi Zhuang autonomous region. Methods: This retrospective cohort study was conducted in HIV-infected children under initial ART in Guangxi from 2004 to 2019, data from ART information system of National comprehensive AIDS prevention and treatment information system. Cox proportional hazards models were used to assess factors associated with the death and attrition. Results: In 943 HIV-infected children, the overall mortality and attrition rates were 1.00/100 person-years and 0.77/100 person-years, respectively. The mortality and attrition rates within the first year of ART were 3.90/100 person-years and 1.67/100 person-years, respectively. The cumulative survival rate during the first, second, fifth and tenth year after ART was 96.14%, 95.80%, 93.68% and 91.54%, respectively. Multivariate Cox proportional hazards models results showed that being female (aHR=2.00, 95%CI: 1.17-3.40), CD4⁺T lymphocytes (CD4) counts before ART <200 cells/μl (aHR=2.79, 95%CI: 1.54-5.06), weight-for-age Z score before ART <-2 (aHR=2.38, 95%CI: 1.32-4.26), hemoglobin before ART <80 g/L (aHR=2.47, 95%CI: 1.24-4.92), initial ART with LPV/r (aHR=5.05, 95%CI: 1.15-22.12) were significantly associated with death; being female (aHR=2.23, 95%CI: 1.22-4.07) and initial ART with LPV/r (aHR=2.02, 95%CI: 1.07-3.79) were significantly associated with attrition. Conclusions: The effect of ART in HIV-infected children in Guangxi was better, but the mortality and attrition rates were high within the first year of treatment. It is necessary to strengthen the training in medical staff and health education in HIV-infected children and their parents in order to improve the treatment effect.
Anti-HIV Agents/therapeutic use* ; Child ; China/epidemiology* ; Female ; HIV Infections/drug therapy* ; Humans ; Male ; Proportional Hazards Models ; Retrospective Studies

Objective: To investigate the impact of pretreatment drug resistance (PDR) on virological effect among HIV-infected patients having received antiretroviral therapy (ART) after three years. Methods: The baseline survey of PDR among HIV-infected patients was conducted in 2018, with a three-year follow up study. The clinic data and virological laboratory test variables were statistically analyzed. Results: Of the 2 433 participants, 41.6% (1 012/2 433) were aged between 18 and 34, 82.8% (2 015/2 433) were males, 46.9% (1 142/2 433) had education of high school or above, 22.4% (544/2 433) were farmers, 33.8% (823/2 433) were unmarried, 48.1% (1 169/2 433) were infected heterosexually and 41.3% (1 004/2 433) were with CRF07_BC. The prevalence of PDR was 4.5% (109/2 433). The prevalence of virological suppression failure (viral load ≥50 copies/ml) and drug resistance at three years follow up after ART was 8.1%(196/2 433) and 2.5%(60/2 433) respectively. The prevalence of virological suppression failure and drug resistance at three years follow up after ART were 18.3% (20/109) and 7.6% (176/2 324), and 4.6% (5/109) and 2.4% (55/2 324) among participants with PDR and non-PDR, respectively. The results of multivariate logistic regression model showed that illiteracy (aOR=3.26, 95%CI: 1.82-5.86), primary and junior high school education (aOR=1.54, 95%CI: 1.09-2.18), CD4⁺T lymphocyte count <200/μl (aOR=2.77, 95%CI: 1.75-4.37) and CD4⁺T lymphocyte count 200-499/μl (aOR=1.55, 95%CI: 1.10-2.18) at a three year follow up visit after ART, missed drugs in the past month (aOR=4.24, 95%CI: 2.92-6.17), and PDR (aOR=2.84, 95%CI: 1.67-4.85) were statistically significant with virological suppression failure on treatment. Conclusions: The prevalence of PDR in China at a low level currently, and the virological suppression failure rate is low after three years of ART. It is necessary to strengthen drug resistance monitoring of HIV-infected patients and pay attention to the influence of PDR on treatment effect.
Male ; Humans ; Adolescent ; Female ; Follow-Up Studies ; Viral Load ; Treatment Failure ; Drug Resistance ; HIV Infections/drug therapy*

Traditional Chinese Medicine (TCM) has become an important part of the health system in the Sultanate of Oman. Although there is no independent law, the local health department has implemented the administrative measures such as the admittance assessment system of TCM doctors and the standardized examination and approval of TCM clinics. The development of TCM in the Sultanate of Oman is supported by the policies of the two governments, with the characteristics likemedical cooperation starting with high-level personnel, the cooperation in economy, trade and medical treatment, TCM and local traditional medicine showing inclusive with good base, and the advantages of TCM theory and treatment meeting the needs of the local medical market. The prospect of cooperation in TCM market is broad. It is suggested that the local government should promote the legislation of traditional medicine and improve the admittance system of practitioners. China needs to promote the formulation of international standards of TCM and optimize the cooperation platform of TCM by using Internet and other technologies. The practitioners in China need to carry out medical activities on the premise of understanding and respecting the local cultural background.In order to promote the development of TCM in Arab countries, the Sultanate of Oman will radiate the whole Middle East through the above strategies.

To evaluate the application of outcome indicators in randomized controlled trials(RCTs) concerning the treatment of tension-type headache(TTH) with traditional Chinese medicine(TCM) in recent five years, so as to provide a basis for the study of core outcome set(COS) for TCM intervention in TTH. The RCTs on TCM treatment of TTH in recent five years were systematically retrieved from CNKI, Wanfang, VIP, CBM, EMbase, PubMed, Cochrane Library, Web of Science, ClinicalTrials.gov and China Clinical Trial Registry. After literature screening, data extraction and evaluation of the risk of bias, the outcome indicators in the included RCTs were subjected to qualitative analysis. The preliminary search yielded 19 042 articles, and 10 983 were left after the elimination of duplication. Finally, 52 RCTs(48 in Chinese and 4 in English) were included for qualitative analysis. The outcome indicators of RCTs included in this study were classified into seven domains: TCM syndrome, symptom and sign, physical and chemical detection, quality of life, long-term prognosis, economic evaluation, and safety event. The findings demonstrated that headache characteristic index in the symptom and sign domain was the index with the highest reporting frequency and reporting rate. Seventeen RCTs used TCM syndrome score as the outcome indicator. Further analysis revealed that there existed such problems in research design as non-distinction between primary and secondary outcome indicators, great difference in the adopted measurement tools for outcome indicators, and the neglect of measurement time of outcome indicators. Moreover, the syndrome indicators reflecting TCM advantages, objective evaluation indicators, safety and health-economic indicators were lacking. These limitations have affected the quality and reliability of RCTs on TTH treatment with TCM. It is suggested that the efficacy and characteristics of TCM should be combined into current clinical research, and the COS in RCTs regarding TCM treatment of TTH should be established according to internationally recognized standard procedures.
Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Quality of Life ; Randomized Controlled Trials as Topic ; Reproducibility of Results ; Tension-Type Headache/drug therapy*