OBJECTIVE To explore the effects and potential mechanism of Huangqi jianzhong decoction on intestinal inflammation in the rats of irritable bowel syndrome with diarrhea （IBS-D） based on the mitogen-activated protein kinase （MAPK）/ nuclear factor-κB （NF-κB） signaling pathway. METHODS Male SD rats were selected. Ten rats were randomly chosen as the control group， and the remaining rats （50 rats） were used to prepare the IBS-D model by acetic acid enema+restraint stress. The rats with successful modeling were randomly divided into the IBS-D group， the traditional Chinese medicine （TCM） group （Huangqi jianzhong decoction 15 g/kg）， the positive control drug group （Rifaximin tablets 150 mg/kg）， the activator group （anisomycin 125 μg/kg， the activator of p38 MAPK）， and the TCM+activator group （Huangqi jianzhong decoction 15 g/kg+ anisomycin 125 μg/kg）， with 10 rats in each group. Rats in each group were given a gavage or tail vein injection of the corresponding medicine liquid or the same volume of normal saline， once a day for two consecutive weeks. After the last administration， feces within 24 hours were collected for the calculation of fecal water content and fecal trait score， and the minimum volume threshold was detected. The levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and IL-6 in serum were detected； the pathological changes of colonic tissue were observed； the expressions of tight junction protein ZO-1， occludin mRNAs and proteins related to the MAPK/NF- κB signaling pathway in colonic tissue were determined. RESULTS Compared with the control group， obvious edema and inflammatory cell infiltration could be observed in the colonic tissue of rats in the IBS-D group. The fecal water content and trait score， serum levels of inflammatory factors， as well as the protein phosphorylation levels of p38 MAPK and NF-κB p65 in the colonic tissue were significantly increased， while the minimum volume threshold and the mRNA expressions of ZO-1 and occludin were significantly decreased or down-regulated （P＜0.05）. Compared with the IBS-D group， the pathological changes of colonic tissue in the TCM group and positive control drug group were alleviated， and the above indicators improved significantly （P＜0.05）， while the above indicators in the activator group deteriorated further （P＜0.05）. Compared with the TCM group， the above indicators in the TCM+activator group were significantly reversed （P＜0.05）. CONCLUSIONS Huangqi jianzhong decoction can alleviate colonic inflammation in IBS-D rats， relieve visceral hypersensitivity， and has a certain protective effect on their intestinal barrier function. The above-mentioned effects may be related to the inhibition of the MAPK/NF- κB signaling pathway.

ObjectiveTo multidimensionally analyze the clinical effects of Qianyang Yuyin granules on elderly hypertensive patients through an "energy-inflammation-aging" network. MethodsRelevant datasets were retrieved from the GEO database. Gene set enrichment analysis （GSEA） was performed on the gene expression profiles of peripheral blood cells from patients with essential hypertension in dataset GSE24752. The GSEA referenced "GO gene sets" and "KEGG gene sets" to identify significantly enriched gene sets. A clinical trial was conducted using a randomized controlled study design. A total of 40 patients meeting the inclusion criteria were enrolled. The control group received standard antihypertensive treatment with angiotensin receptor blockers （ARBs） or combined calcium channel blockers （CCBs）. In contrast，the treatment group received Qianyang Yuyin Granules in addition to the standard treatment for 12 weeks. Blood pressure levels and clinical efficacy were observed，and changes in energy metabolism indicators，DNA damage markers，and senescence-associated secretory phenotype （SASP） in blood were measured using ELISA before and after treatment. ResultsGSEA results indicated significant energy metabolism dysregulation in hypertensive patients. Clinical findings showed that both groups achieved blood pressure control without significant intergroup differences. In terms of clinical efficacy，the treatment group had a significantly higher effective rate compared to the control group （95% vs 65%，P0.05）. After treatment，the treatment group showed a significant increase in NAD⁺ levels （P0.01），with higher levels compared to the control group （P0.05）. The treatment group also exhibited a greater reduction in DNA damage marker 8-OHdG （P0.01） and cell adhesion factors ICAM-1 and VCAM-1 （P0.01） compared to the control group. Pro-inflammatory cytokines IL-1β and IL-6 were significantly reduced in the treatment group （P0.01），with greater reductions compared to the control group （P0.05，P0.01）. Anti-inflammatory cytokines IFN-α，IL-4，and IL-10 were significantly elevated in the treatment group （P0.01），with higher levels compared to the control group （P0.01）. No significant adverse reactions were reported in either group. ConclusionThe "energy- inflammation- aging" network plays an important role in the pathological mechanism of hypertension patients. Qianyang Yuyin granules may delay the aging process by increasing patients' energy metabolism levels，reducing DNA oxidative damage，and maintaining the balance of inflammatory factors.

Objective To investigate the diagnostic value of 4 novel inflammatory markers related to routine blood tests,namely neutrophil-to-lymphocyte ratio(NLR),red blood cell distribution width(RDW),hemoglobin-to-RDW ratio(HRR)and systemic immune-inflammation index(SII),in elderly patients with chronic cardiovascular disease(CVD)complicated with frailty.Methods Retrospectively analyze 110 patients with chronic stable CVD who were hospitalized in the cadre ward of cardiovascular medicine at the Air Force Characteristic Medical Center from January 2022 to June 2023.According to the assessment results of the Fried scale,they were divided into three groups:non-frailty group(Fried score=0,n=30),the pre-frailty group(Fried score 1 or 2,n=40)and frailty group(Fried score≥3,n=40).The differences in general information,the impairment rate of daily living activities,miniature nutritional assessment-short form(MNA-SF)scores,mini-mental state examination(MMSE)scores,and the indicators such as NLR,RDW,HRR,and SII among the three groups were compared.Spearman rank correlation was used to analyze the correlation between NLR,RDW,HRR,SII and frailty scores as well as each frailty indicator.Multivariate logistic regression analysis was performed to identify the independent risk factors for frailty in elderly patients with chronic CVD,and the receiver operating characteristic(ROC)curve was used to assess the clinical diagnostic value of NLR and HRR in elderly patients with chronic CVD complicated with frailty.Results Compared with non-frailty group and pre-frailty group,patients in frailty group were older,with higher impaired rates of daily living activities,NLR,RDW,and SII,and lower MNA-SF scores,MMSE scores,and HRR,and differences were statistically significant(P<0.05).Spearman rank correlation analysis showed that the frailty score was positively correlated with NLR(rs=0.354,P<0.001),and RDW(rs=0.448,P<0.001),negatively correlated with HRR(rs=-0.232,P=0.024),and had no significant correlation with SII(rs=0.144,P=0.167).Further analysis of the correlation between the above novel inflammatory markers and the 5 components of frailty showed that NLR was positively correlated with fatigue(rs=0.228,P=0.017),slowed walking speed(rs=0.299,P<0.001),and low physical function(rs=0.319,P<0.001);RDW was positively correlated with decreased grip strength(rs=0.321,P<0.001),slowed walking speed(rs=0.422,P<0.001),and low physical function(rs=0.246,P=0.001);and HRR was negatively correlated with slowed walking speed(rs=-0.230,P=0.025),and low physical function(rs=-0.299,P=0.003).Multivariate logistic regression analysis showed that MNA-SF score(OR=0.577,95%CI 0.342-0.973)was an independent protective factor for pre-frailty in elderly patients with chronic CVD(P<0.05);NLR(OR=7.866,95%CI 1.101-56.185)was an independent risk factor for frailty,while HRR(OR=0.344,95%CI 0.120-0.983)and MNA-SF score(OR=0.292,95%CI 0.146-0.580)were independent protective factors for frailty in elderly CVD patients(P<0.05).The area under the ROC curve of NLR and HRR for diagnosing frailty in elderly patients with chronic CVD were 0.778 and 0.749,respectively.Conclusion NLR and HRR have high clinical diagnostic value for frailty in elderly patients with chronic CVD,and are expected to become effective inflammatory markers for screening elderly patients with chronic CVD complicated with frailty.

Objective To explore the role of miR-429 in synovial mesenchymal stem cell-derived exosomes(SMSC-Exos)in repairing cartilage damage in temporomandibular joint osteoarthritis(TMJ OA)by extracting SMSC-Exos from human synovial tissue and screening differentially expressed microRNA(miRNA)through transcriptome sequencing.Methods Human synovial tissues were obtained from 6 patients who underwent surgery at the First Medical Center of the Chinese PLA General Hospital from June to December 2023,including 3 patients with osteoarthritis(OA group)and 3 control patients(control group),all of whom were male.SMSC-Exos were extracted from the synovial tissues for miRNA sequencing and differential expression analysis.Further,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed on the target genes of differentially expressed miRNA to identify key functional miRNA and construct miRNA-target gene regulatory networks and protein-protein interaction(PPI)networks of target genes.An in vitro model of rabbit condylar cartilage cell inflammatory microenvironment induced by interleukin-1β(IL-1β)was established,with the control group cultured in DMEM/F12 basic medium and the inflammation-induced group cultured in DMEM/F12 basic medium containing 10 ng/ml IL-1β.RT-qPCR was used to detect the effects of overexpressed target miRNA on the mRNA expression levels of cartilage phenotype factors such as type Ⅱ collagen α1 chain(Col2a1),aggrecan(Acan),as well as inflammatory factors including a disintegrin and metalloproteinase with thrombospondin motifs 5(Adamts5)and cyclooxygenase-2(Cox-2).Results(1)SMSC-Exos were successfully isolated,cultured,and identified.(2)miRNA sequencing of SMSC-Exos from OA and control groups revealed 16 differentially expressed miRNAs(|log2FC|>2,P<0.05).Compared with control group,7 miRNAs were up-regulated and 9 were down-regulated in OA group.GO and KEGG analysis indicated that the target genes of miR-429 were mainly involved in development process,anatomical structure development,system development,cell development and differentiation,and were enriched in inflammation-related pathways such as mitogen-activated protein kinase(MAPK)and phosphatidylinositol 3-kinase-protein kinase B(PI3K-Akt).(3)Functional validation of miR-429 in the rabbit condylar cartilage cell inflammatory model showed that overexpression of miR-429 increased the mRNA expression levels of Col2a1 and Acan(P<0.05)and decreased the mRNA expression levels of Adamts5 and Cox-2(P<0.05)in the inflammation-induced group.Conclusions miRNA sequencing of SMSC-Exos isolated and identified from human synovial tissues reveals a specific miRNA expression profile in OA patients,with miR-429 significantly down-regulated.Functional validation demonstrates that overexpression of miR-429 has reparative and anti-inflammatory effects on condylar cartilage cells in an inflammatory microenvironment.

Objective:To describe the prevalence of non-alcoholic fatty liver disease (NAFLD) in people living with HIV in Taizhou, Zhejiang Province, and identify the factors associated with NAFLD in this population.Methods:A cross-sectional survey was conducted from 2021 to 2023. Based on the routine follow-up management of people living with HIV, liver ultrasound examination, physical examination and laboratory test were conducted to collect the information about the diagnosis of NAFLD and biochemical indicators in this population. Logistic regression model was used to identify the factors associated with the prevalence of NAFLD.Results:In the 2 550 study participants, the prevalence of NAFLD was 21.5% (548/2 550), abnormal liver function was found in 23.7% (604/2 550) of the study participants, and liver fibrosis was found in 45.2% (1 152/2 550) of the study participants. Multivariable logistic regression analyses showed that being women (a OR=0.55, 95% CI: 0.42-0.73), being overweight or obese (a OR=3.22, 95% CI: 2.59-4.01), having diabetes (a OR=3.37, 95% CI: 2.15-5.29), having dyslipidemia (a OR=2.96, 95% CI: 2.25-3.89), CD4 + T lymphocyte (CD4) counts <200 cells/μl (a OR=0.61, 95% CI: 0.42-0.88), and receiving Efavirenz (EFV) + Lamivudine (3TC) + Zidovudine (AZT) for antiretroviral therapy (ART)(a OR=1.52, 95% CI: 1.17-1.98) were associated with NAFLD. NAFLD was positively associated with abnormal liver function (a OR=2.01, 95% CI: 1.60-2.52) and inversely associated with liver fibrosis (a OR=0.76, 95% CI: 0.59-0.98). The 45-59 age group (a OR=7.05, 95% CI: 5.65-8.80), CD4 counts <200 cells/μl (a OR=1.45, 95% CI: 1.06-1.97) and receiving Nevirapine (NVP)+3TC+AZT of ART (a OR=1.87,95% CI: 1.44-2.43) were the main factors associated with liver fibrosis. Conclusions:The prevalence of NAFLD in people living with HIV Taizhou was more than 20.0%, with a significant proportion of them having abnormal liver function and liver fibrosis. Being overweight or obese, suffering from diabetes, having dyslipidemia, low CD4 counts, and receiving specific ART were associated with NAFLD. NAFLD, CD4 counts and specific ART were the main factors associated with abnormal liver function and liver fibrosis.

Objective:To analyze the cerebral hemodynamic characteristics of uremic patients complicated with depressive symptoms by transcranial color-coded Doppler(TCCD),and explore the correlation between cerebral hemodynamic indicators and uremia complicated with depressive symptoms.Methods:A total of 70 uremic patients received hemodialysis in our hospital from Dec 2022 to Dec 2023 were enrolled,in which 37 patients complicated with depressive symptoms were selected as the research group,and 40 patients without depressive symptoms were selected as the control group.Peak systolic velocity(PSV),end diastolic velocity(EDV),mean velocity(MV),and pulsatility index(PI)of bilateral middle cerebral artery(MCA)were compared.Binary logistic regression was used to analyze risk factors for uremia complicated with depressive symptoms,and receiver operating characteristic(ROC)curves were generated for key parameters.Results:There was no significant difference in PSV between the two groups(P＞0.05),while EDV and MV of bilateral MCA in the research group were lower but PI was higher than those in the control group(P＜0.05).Age was positively correlated with the depressive symptoms in uremic patients,while EDV,MV of bilateral MCA and left PSV were negatively correlated with depressive symptoms of uremic patients(P＜0.05).The elevated level of HCO3-in blood increased the risk of uremia complicated with depressive symptoms(OR=1.245,95%CI:1.024-1.513).When the left EDV was 41.25 cm/s,the predicted occurrence rate of depressive symptoms in uremic patients was 74.6%,with a specificity of 62%and a sensitivity of 85%.Conclusions:EDV and MV of bilateral MCA in patients with uremia complicated with depressive symptoms were lower than those in patients with uremia without depressive symptoms.Age,EDV and MV of bilateral MCA and PSV of left MCA were associated with depressive symptoms.Left EDV＜41.25 cm/s may serve as a hemodynamic marker for early clinical detection of depressive symptoms in uremia.TCCD can provide a reference for early clinical detection of uremic patients complicated with depressive symptoms.

This study assessed the role and mechanism of the recombinant Bacillus Calmette-Gue?rin vaccine(rBCG)with c-di-AMP adjuvant in regulating metabolism and immunity in epididymal white adipose(eWAT)in mice.Male C57BL/6 mice were intravenously immunized with BCG and rBCG,and their body weights were monitored.eWAT was isolated from the mice,and the stromal vascular fractions(SVFs)cell number was counted with a hemocytometer.Sections of mouse adipose tissue were prepared,and the size,number,and morphology of eWAT adipocytes and crown-like structure(CLS)formation were compared under a microscope after HE staining.The transcription levels of lipid metabolism-associated factors,cytokines and aging-associated genes in each group were determined with qRT-PCR.The body weights of mice gradually increased after immunization with BCG and rBCG.The proportions of eWAT increased,and the SVFs cell number decreased,in rBCG immunized mice.HE staining indicated that BCG immunization promoted hyperplasia,whereas rBCG immunization promoted hypertrophy of eWAT adipocytes;moreover,both BCG and rBCG immunization induced CLS formation in eWAT.The qRT-PCR results indicated that rBCG immunization inhibited the expression of genes associated with lipolysis and energy expenditure in eWAT.BCG immunization had little effect on cytokine transcription,whereas rBCG significantly induced the transcription of IFN-γ and IL-1Ra,and inhibited that of IL-15 and IL-2,but did not induce the expression of aging-associated genes.Thus,rBCG immunization induced eWAT adipocyte hypertrophy,which was associated with the inhibition of eWAT lipolysis and the regulation of cytokine expression.

Hypertension remains a major global health challenge and a leading threat to cardiovascular health. Among the key mechanisms contributing to the development of hypertension, impaired autonomic regulation of the cardiovascular system is particularly prominent. Extensive evidence supports the pivotal role of the autonomic nervous system in maintaining cardiovascular homeostasis. This review integrates findings from experimental and clinical studies to elucidate the complex relationship between autonomic dysfunction and hypertension. It further analyzes the underlying physiological and molecular mechanisms, summarizes recent research advances, and highlights the fundamental factors that contribute to the onset of hypertension. These insights aim to support the development of innovative prevention and treatment strategies for hypertension.

Objective:To explore the predictive value of atherogenic index of plasma(AIP)combined with neutro-phil/HDL-C ratio(NHR),lymphocyte/HDL-C ratio(LHR)and monocyte/HDL-C ratio(MHR)for major adverse cardiovascular events(MACE)in patients with acute coronary syndrome(ACS).Methods:This retrospec-tive study enrolled 320 patients underwent coronary angiography in Department of Cardiovascular Medicine,Harri-son International Peace Hospital between January 2021 and December 2022,including 215 ACS patients and 105 pa-tients without ACS;according to Gensini score,ACS patients were divided into low risk group(n=50),medium risk group(n=70)and high risk group(n=95).According to the presence of MACE within 1 year,patients were divided into MACE group(n=55)and no MACE group(n=160).After admission,blood routine,blood lipids,C-reactive protein(CRP)and endothelin-1(ET-1)levels were measured,then NHR,LHR,MHR and AIP were calculated.Spearman method was used to analyze the association of above-mentioned indexes with Gensini score;stepwise Logistic regression was used to analyze the influencing factors of MACE within 1 year in ACS patients;and ROC curve was used to analyze the predictive value of single and combined detection of above indexes for MACE within 1 year in ACS patients.Results:Compared to patients in no ACS group,those in ACS group had significantly higher BMI[(23.59±0.85)kg/m2 vs.(21.57±1.16)kg/m2],proportions of hypertension(57.67％vs.13.33％),diabetes(23.26％vs.8.57％),NHR[(12.09±3.46)vs.(3.81±1.29)],MHR[(0.70±0.18)vs.(0.33±0.10)],LHR[(0.79±0.21)vs.(0.40±0.09)],AIP[(0.21±0.06)vs.(0.11±0.02)],CRP[(9.82±3.09)mg/L vs.(2.20±0.58)mg/L],ET-1[(31.25±10.34)μg/L vs.(10.60±1.96)μg/L](P＜0.001 all).Compared to those in no MACE group,patients in MACE group had significantly higher NHR[(17.33±3.87)vs.(10.12±2.68)],MHR[(0.93±0.24)vs.(0.61±0.13)],LHR[(1.05±0.27)vs.(0.71±0.16)],AIP[(0.28±0.04)vs.(0.17±0.02)],CRP[(15.52±3.83)mg/L vs.(7.69±2.40)mg/L],ET-1[(46.68±9.51)μg/L vs.(25.47±4.66)μg/L]levels(P＜0.001 all).Spearman correlation analysis showed that NHR,MHR,LHR and AIP were significant positively correlated with Gensini score(r=0.837～0.868,P＜0.001 all).Stepwise Logistic regression analysis showed that NHR(OR=1.225,95％CI 1.016～1.550,P=0.035),AIP(OR=2.632,95％CI 1.055～6.566,P=0.038)were independent risk factors for MACE within 1 year in ACS patients.ROC curve shows that AUC of AIP combined with NHR,MHR and LHR predicting MACE within 1 year in ACS patients was 0.786(95％CI 0.725～0.839),which was significantly higher than those of NHR(AUC 0.768,95％CI 0.706～0.823),LHR(AUC 0.749,95％CI 0.686～0.806)and AIP(AUC 0.764,95％CI 0.701～0.819)alone(Z=2.597,2.687,1.965,P＜0.05 or＜0.01).Conclusion:AIP combined with NHR,MHR and LHR have certain predictive value for MACE within 1 year in ACS patients.