ObjectiveTo investigate the effect and mechanism of Bukan Yilidan on perimenopausal psycho-cardiac disease by mitochondrial autophagy mediated by dynamin-related protein 1（Drp1）/phosphatase and tensin homolog（PTEN） induced putative kinase 1（PINK1）/Parkin pathway. MethodsSixty rats were randomly divided into the blank group， model group， western medicine group（isosorbide mononitrate 7.2 mg·kg^-1+sertraline hydrochloride tablets 18 mg·kg^-1）， Bukan Yilidan low， medium and high dose groups（2.59， 5.18， 10.35 g·kg^-1）， with 10 rats in each group. Except for the blank group， the rat model of perimenopausal psycho-cardiac disease was prepared by ovariectomy（OVX） combined with high-fat feeding， chronic unpredictable mild stress（CUMS） and subcutaneous multi-point injection of isoproterenol hydrochloride. After successful modeling， the general state and tongue image of rats were observed. The depression status of rats in vivo was evaluated by open field test， sucrose preference test， forced swimming immobility time and grip strength value， and the cardiac function of rats was evaluated by electrocardiogram and echocardiography. The levels of serum norepinephrine（NE）， dopamine（DA） and 5-hydroxytryptamine（5-HT） were detected by enzyme-linked immunosorbent assay（ELISA）， and biochemical detection was used to assess myocardial injury by measuring serum levels of high-density lipoprotein cholesterol（HDL-C）， low-density lipoprotein cholesterol（LDL-C）， triglyceride（TG）， total cholesterol（TC）， aspartate aminotransferase（AST）， alanine aminotransferase（ALT）， lactate dehydrogenase（LDH） and creatine kinase isoenzyme（CK-MB）. Hematoxylin-eosin（HE） and Nissl staining were used to observe the pathological status of hippocampus and myocardial tissue in rats， the status of mitophagosomes in hippocampus and myocardium was observed by transmission electron microscope（TEM）， and Western blot was used to detect the contents of Drp1， mitochondrial fusion protein 2（Mfn2）， optic atrophy protein 1（OPA1）， PINK1， Parkin， p62 and microtubule-associated protein light chain 3B（LC3B） in hippocampus and myocardium. ResultsCompared with the blank group， the food intake and water intake of rats in the model group decreased， the hair was dark yellow， the gloss and smoothness decreased， the spirit was depressed， the tongue was light purple or dark purple， accompanied by petechiae or ecchymosis， the sublingual collaterals were purple and black， and the tongue coating was white and smooth. The indexes of open field test， grip strength and sucrose preference of rats decreased significantly， and the immobility time of forced swimming increased significantly（P<0.01）. Electrocardiogram and echocardiography showed that ST segment was significantly depressed， and left ventricular fractional shortening（LVFS） and left ventricular ejection fraction（LVEF） were significantly decreased（P<0.05， P<0.01）. Pathological observation showed that the number of hippocampal neurons and myocardial cells decreased， and the structural damage was obvious. The levels of serum TC， TG， LDL-C， CK-MB， LDH， AST and ALT increased， while the levels of HDL-C， 5-HT， DA and NE decreased（P<0.05， P<0.01）. TEM showed obvious mitochondrial damage in hippocampus and myocardial tissue. The protein expressions of Drp1， PINK1， Parkin and p62 in hippocampus and myocardium were increased， while the protein expressions of OPA1， Mfn2 and LC3BⅡ/Ⅰ were decreased（P<0.05， P<0.01）. Compared with the model group， the mental state， body curling up， fear of cold and other symptoms of rats in each administration group were improved， and the degree of pale purple or dark purple tongue was reduced. The scores of open field test， grip strength， sucrose preference， LVFS and LVEF were increased， and the immobility time of forced swimming was shortened（P<0.05， P<0.01）. The ST segment of electrocardiogram had a significant recovery（P<0.01）， pathological observation showed that the damage of nerve cells and myocardial tissue was improved. The levels of serum TC， TG， LDL-C， CK-MB， LDH， AST and ALT decreased， while the levels of HDL-C， 5-HT， DA and NE increased（P<0.05， P<0.01）. TEM showed that mitochondrial damage was reduced in hippocampal neurons and cardiomyocytes with visible mitochondrial autophagosomes. The protein expressions of Drp1， PINK1， Parkin and p62 in hippocampus and myocardium were decreased， while the protein expressions of OPA1， Mfn2 and LC3BⅡ/Ⅰ were increased（P<0.05， P<0.01）. ConclusionBukan Yilidan can alleviate depression， lipid metabolism disorder and myocardial ischemia injury in rats with perimenopausal psycho-cardiac disease， and its mechanism may be related to inhibiting Drp1/PINK1/Parkin signaling pathway and enhancing mitochondrial autophagy.

Under the background of the Healthy China strategy， the integration of traditional Chinese medicine （TCM） into the public health emergency response system has become an important measure to enhance the capacity for coping with public health emergencies. In recent years， the role of TCM in responding to such emergencies has become increasingly prominent. Taking major emerging epidemics as an example， TCM has developed a rich theoretical system and practical experience in epidemic prevention and treatment over thousands of years， and has played a significant role in successive outbreaks with its unique advantages. Based on the concept of ''preventing disease before its onset'' and the theoretical framework of treatment based on syndrome differentiation， TCM has achieved remarkable results through early intervention and full participation in the integrated model of TCM and Western medicine， from severe acute respiratory syndrome （SARS） to corona virus disease-2019 （COVID-19）， in improving clinical symptoms and outcomes， reducing adverse reactions， and promoting recovery. From the perspective of the Healthy China strategy， this paper systematically reviews the historical development of TCM in epidemic prevention and treatment， with particular attention to recent epidemics such as SARS， influenza A （H1N1）， and COVID-19. It further examines the similarities and differences between TCM and Western medicine in responding to major emerging epidemics， as well as relevant policies related to TCM in epidemic prevention and control. In addition， it summarizes the existing problems in TCM's role in the prevention and treatment of major emerging epidemics， and explores measures to improve its rapid response capacity under the Healthy China strategy. This study not only provides a ''Chinese solution'' for the prevention and control of newly emerging infectious diseases worldwide， but also offers theoretical and practical references for strengthening the public health emergency response system， carrying strategic significance for promoting the modernization and internationalization of TCM.

Objective To investigate the factors influencing the severity of cerebral white matter hyperintensity in hypertensive patients with acute cerebral infarction,and focus on the independ-ent roles of treatment adherence,advanced age,and multidimensional risk factors.Methods A single-center cross-sectional study was conducted on 262 hypertensive patients with acute cerebral infarction admitted to our department from January 2020 to June 2023.According to their score of Morisky Medication Adherence Scale(MMAS-8),they were divided into an adherence group(116 cases)and a non-adherence group(146 cases).Their demographic data,medical history,and blood pressure data were collected through electronic medical records.Fazekas score was assessed blind-ly to quantify the severity of white matter hyperintensity.MMAS-8 and Montreal Cognitive Assessment Scale(MoCA)were used to assess the behavioral indicators,and modified Rankin Scale(mRS)was employed to evaluate the neurological function.Univariate and multivariate logistic regression analyses were performed to screen the risk factors.Results There were statis-tical differences in marital status,mRS score and Fazekas score between the adherence group and the non-adherence group(P＜0.05,P＜0.01).The non-adherence group had significantly higher diastolic blood pressure than the adherence group[(87.29±7.51)mm Hg(1 mm Hg=0.133 kPa)vs(83.98±8.11)mm Hg,P=0.001].Univariate logistic regression analysis showed age of≥80 years,duration of hypertension≥5 years,systolic blood pressure,and MoCA score＜10 were no-tably correlated with severity of white matter hyperintensity(P＜0.01).Multivariate logistic re-gression analysis indicted that age of≥80 years(OR=3.305,95％CI:1.560-7.001,P=0.002),systolic blood pressure(OR=1.026,95％CI:1.008-1.044,P=0.003),MoCA score＜10(OR=5.210,95％CI:2.060-13.176,P=0.000),and treatment non-adherence(OR=2.380,95％CI:1.346-4.209,P=0.003)were independent risk factors for white matter hyperintensity severity,and duration of hypertension showed no significance in the multivariate model(P＞0.05).Conclusion Poor treatment adherence and advanced age are core factors for white matter hyper-intensity progression in hypertensive patients with acute cerebral infarction.

Objective To explore causal relationship between 25-hydroxyvitamin D[25(OH)D]and ankylosing spondylitis(AS).Methods Genetic data of 25(OH)D and AS were extracted from the genome-wide association study.The causal effect of 25(OH)D on AS was estimated by MR-Egger regression method,weighted median,inverse variance weighted(IVW),simple mode and weighted mode,and sensitivity analysis was conducted for verification.Results The IVW results indicated that there was a causal relationship between 25(OH)D concentration and AS(OR=0.805,95％CI:0.686-0.944,P=0.008),and the maximum likelihood ratio(OR=0.799,95％CI:0.678-0.940,P=0.007)showed consistent results.The IVW results of the reverse Mendelian randomization study showed that there was no causal relationship between the two(OR=1.019,95％CI:0.995-1.043,P=0.110).In addition,MR-Egger intercept,Cochran Q test,"leave-one-out"and MR-PRESSO analysis showed no horizontal pleipotency or heterogeneity.Conclusion There may be a genetic causal relationship between the concentration of 25(OH)D and the onset of AS.AS cannot cause changes in the concentration of 25(OH)D in the body.

Objective:To analyze the epidemiological characteristics and changing trends of elderly patients with drug-resistant pulmonary tuberculosis(DR-PTB)at Beijing Chest Hospital, Capital Medical University, in order to provide references for clinical prevention and treatment.Methods:Data were retrospectively collected from all DR-PTB cases hospitalized in the electronic medical record system of Beijing Chest Hospital from 2019 to 2023.The epidemiological characteristics including classification, gender, age, occupation and their changing trends among elderly DR-PTB patients were analyzed.Results:Among 1 981 hospitalized DR-PTB patients, 400(20.19%)were elderly[aged 60-92 years, mean(68.67±7.01)years], showing an overall increasing trend from 2019 to 2023.Mono-resistant PTB was the most common(198 cases, 49.50%), followed by multidrug-resistant PTB(170 cases, 42.50%), extensively drug-resistant PTB(21 cases, 5.25%), and polyresistant PTB(11 cases, 2.75%).Among the elderly DR-PTB patients, 287 cases(71.75%)were male, 200 cases(50.00%)were initial treatment cases, 377 cases(94.25%)were Han nationality, 165 cases(41.25%)were Beijing residents, 185 cases(46.25%)were employees of enterprises and institutions, 109 cases(27.25%)were farmers, 68 cases(17.00%)were unemployed individuals, 202 cases(50.50%)were pathogen-positive cases(smear and culture positive), and 228 cases(57.00%), 331 cases(82.75%), 196 cases(49.00%)were patients with comorbidities, complications, and extrapulmonary tuberculosis, respectively.There were no significant differences between elderly and non-elderly groups in ethnicity, treatment classification, or comorbidities(all P>0.05).However, significantly differences were found in gender ( χ2=12.718, P<0.001), occupation ( χ2=97.500, P<0.001), patient origin ( χ2=119.771, P<0.001), pathogen detection results ( χ2=10.101, P=0.001), and drug resistance patterns ( χ2=15.990, P=0.001).The proportion of elderly DR-PTB patients showed an overall increasing trend, with rises in females(25.64%-28.70%), unemployed individuals(7.69%-20.37%), other occupations(5.13%-19.40%), Han ethnicity(91.03%-99.07%), initial treatment(33.33%-57.41%), smear-negative but culture-positive cases(46.15%-53.70%), polyresistant PTB(1.28%-9.26%), and extensively drug-resistant PTB(1.28%-3.70%). Conclusions:Among elderly DR-PTB patients, the proportions of female, unemployed individuals and other occupations, initial treatment cases, smear-negative but culture-positive cases, polyresistant PTB, and extensively drug-resistant PTB are increasing annually.Future efforts should focus on targeted prevention and treatment for key populations to further reduce the rate of elderly DR-PTB.

BACKGROUND:Hydroxy safflower yellow A has anti-ischemia,anti-oxidation,anti-thrombotic and anti-inflammatory effects.Whether it affects neuronal pyroptosis after glucose-oxygen deprivation/reglucose-reoxygenation is still unclear. OBJECTIVE:To investigate the protective effect of hydroxy safflower yellow A on neuronal pyroptosis and its mechanism. METHODS:HT22 cells in logarithmic growth phase were randomly divided into five groups:normal group,model group,hydroxy safflower yellow A group,colivelin group,and colivelin+hydroxy safflower yellow A group.HT22 cells were treated with glucose-oxygen deprivation/reglucose-reoxygenation to establish neuronal pyroptosis model,and then treated with STAT3 agonist Colivelin and hydroxy safflower yellow A.JC-1 probe was employed to assess changes in mitochondrial membrane potential.Reactive oxygen species kit was used to determine the content of reactive oxygen species in cells.GSDMD/TUNEL staining was conducted to observe cell pyroptosis.Immunofluorescence analysis was performed to detect STAT3 and GSDMD protein expression.RT-PCR was utilized for assessing mRNA expression levels of STAT3,NLRP3,and Caspase-1.Western blot assay was utilized to measure the protein expression levels of p-STAT3,NLRP3,GSDMD,Cleaved-caspase-1,and interleukin-1β. RESULTS AND CONCLUSION:(1)Compared with the normal group,the number of pyroptotic cells increased in HT22 cells in the model group along with a significant increase in protein expression levels of p-STAT3,NLRP3,Cleaved-caspase-1,GSDMD,and interleukin-1β.Compared with the model group,the number of pyroptotic cells reduced,and the expression of pyroptosis-related proteins significantly decreased in the hydroxy safflower yellow A group.(2)In comparison with the model group,pyroptosis worsened in the colivelin group where mitochondrial membrane potential decreased along with elevated reactive oxygen species content and increased mRNA expression levels of STAT3,NLRP3,and Caspase-1,as well as increased protein expression levels of p-STAT3,NLRP3,GSDMD,Cleaved-caspase-1,and interleukin-1β.Compared with the Colivelin group,above indexes were improved in the colivelin+hydroxy safflower yellow A group.These results suggest that hydroxy safflower yellow A plays a neuroprotective role through STAT3 signaling pathway to inhibit HT22 pyroptosis after glucose-oxygen deprivation/reglucose-reoxygenation treatment.

Purpose To investigate the sex differences of white matter damage in Alzheimer's disease(AD)and their association with cognitive impairment.Materials and Methods This retrospective study included 88 AD patients(48 females),71 amnestic mild cognitive impairment(aMCI)patients(39 females),and 95 healthy controls(63 females)recruited from the Memory Disorder Clinic at the First Affiliated Hospital of Anhui Medical University from September 2017 to July 2024.High-resolution three-dimensional T1 structure images and diffusion tensor imaging images were all obtained from each participant.The mean diffusivity(MD)and fractional anisotropy(FA)values of each white matter region were obtained,and the two-way ANOVA analysis was conducted to investigate brain regions with interaction effects between groups and sexes,those brain regions were then chosen as regions of interest for further correlation analysis with a series of cognitive scale scores.Results In terms of FA values,the right posterior corona radiata,right anterior limb of the internal capsule and left corticospinal tract showed interaction between sexes and cognitive groups(F=4.764,3.812,5.937,all P<0.05).The FA value of AD group was significantly lower than that of healthy control and aMCI group(all P<0.05),but there was no significant difference between healthy control and aMCI group(except the right anterior limb of the internal capsule,P=0.018).In AD group,FA values were significantly higher in women than in men in the previously described brain regions(all P<0.05),while there was no significant difference in FA values between male and female in healthy control and aMCI groups(except the left corticospinal tract,P<0.001).In terms of MD values,the right anterior limb of the internal capsule,right superior corona radiata and left external capsule showed interaction effect between sexes and cognitive groups(F=8.581,3.680,7.218,all P<0.05).The MD value of AD group was significantly higher than that of aMCI group(P<0.001),and aMCI group was higher than that of healthy control group(all P<0.05).In AD group,the MD values in the above brain regions were significantly higher in males than those in females(all P<0.01),while no significant difference was found between males and females in healthy control and aMCI groups(except for the left external capsule,P<0.05).For correlation analysis,the AD group was dimidiated into two groups by sex,the scores of the Montreal cognitive assessment,the Mini Mental state examination and the verbal fluency test of the female patient group were positively correlated with the FA values of the right posterior corona radiate(r=0.372,P=0.009;r=0.345,P=0.016;r=0.383,P=0.007),while the Mini Mental state examination and the verbal fluency test scores of female AD patient group were negatively correlated with the MD values of the right superior corona radiata(r=-0.360,P=0.012;r=-0.360,P=0.003).Conclusion Compared to the healthy control and MCI groups,white matter damage in AD patients shows sex differences and is associated with general cognitive and language functions impairment in female AD patients.

AIM:To investigate the effects and underlying mechanisms of paeoniflorin(PF)on lipopolysac-charide(LPS)-induced intestinal injury in septic mice,using a combination of network pharmacology,molecular docking,and animal experiments.METHODS:Network pharmacology was used to identify key active components and therapeutic targets of Red Peony for treating sepsis.Molecular docking was performed to explore the binding affinity be-tween PF and silent information regulator 1(SIRT1).An LPS-induced mouse model of sepsis with intestinal injury was es-tablished.Samples were collected 24 h after modeling,and hematoxylin-eosin(HE)staining was performed to observe pathological changes in intestinal tissues.Chiu's scoring system was utilized to evaluate the extent of intestinal injury.En-zyme-linked immunosorbent assay(ELISA)was employed to measure levels of inflammatory factors in intestinal tissues,including interleukin-1β(IL-1β)and IL-18,as well as indicators of intestinal permeability such as diamine oxidase(DAO)and intestinal-type fatty acid-binding protein(I-FABP),alongside serum levels of D-lactate and the aerobic gly-colysis product L-lactate.Western blot analysis was performed to assess changes in protein levels of SIRT1,M2-type pyru-vate kinase(PKM2),and NOD-like receptor protein 3(NLRP3)in intestinal tissues.RESULTS:Network pharmacolo-gy suggested that paeoniflorin,an active component of Red Peony,treats sepsis by targeting SIRT1 among other proteins.Molecular docking revealed a strong binding affinity of PF with SIRT1.In vivo experimentation revealed significant patho-logical damage in intestinal tissues in the LPS group compared to the control group as evidenced by HE staining.Chiu's score,along with levels of IL-1β,IL-18,D-lactate,and L-lactate were significantly elevated,while DAO and I-FABP levels were reduced(P＜0.05).SIRT1 expression decreased,while PKM2 and NLRP3 levels increased(P＜0.05).In contrast,the LPS+PF group displayed reduced intestinal histopathological injury,lower Chiu's scores,and decreased levels of IL-1β,IL-18,D-lactate,and L-lactate,along with increased DAO and I-FABP levels(P＜0.05).Notably,SIRT1 protein expression increased while PKM2 and NLRP3 levels decreased(P＜0.05).Furthermore,compared to the LPS+PF group,the LPS+PF+EX527 group exhibited exacerbated intestinal histopathological injury,increased Chiu's scores,as well as elevated levels of IL-1β,IL-18,D-lactate,and L-lactate,alongside reduced DAO and I-FABP levels(P＜0.05),decreased SIRT1 expression,and increased PKM2 and NLRP3 levels(P＜0.05).CONCLUSION:Paeoni-florin effectively alleviates intestinal injury in mice with sepsis,potentially through the upregulation of SIRT1 expression and the inhibition of PKM2-mediated aerobic glycolysis,which subsequently reduces the activation of NLRP3 inflamma-somes,mitigates the release of inflammatory factors,and lessens intestinal inflammation.

Objective:To investigate the immunological mechanism by which grifola frondosa extract improves colonic tissue inflammation in rats with ulcerative colitis(UC)through the sphingosine kinase 1(SPHK1)/sphingosine-1-phosphate(S1P)signaling pathway.Methods:Forty male SD rats were randomly divided into five groups:blank group,model group,sulfasalazine treatment group(SASP group),grifola frondosa extract treatment group(GF group),and sulfasalazine combined with grifola frondosa extract treatment group(SASP+GF group).UC model was established using a 3%dextran sulfate sodium(DSS)free drinking method.After one week,each treatment group received sulfasalazine 0.3 g/(kg·d),grifola frondosa extract 10 mg/(kg·d),and combination of both drugs by gavage.During the experiment,the general condition of the rats was observed,the disease activity index(DAI)score was re-corded and the protein content and positive expression levels of SPHK1,S1P,tumor necrosis factor receptor-associated factor 2(TRAF2)and TNF-α in rat colon tissue were detected by immunohistochemistry.mRNA and protein expression levels of SPHK1,S1P,TRAF2 and TNF-α in rat colon tissue were measured by RT-qPCR and Western blot.Results:Compared with the blank group,the general condition of the model group rats were poor,the DAI score was significantly increased,and the protein positive expres-sion,mRNA and protein expression levels of SPHK1,S1P,TRAF2 and TNF-α in colon tissue were significantly increased(P<0.01).Compared with the model group,the general condition of the rats in each treatment group improved significantly,the DAI score was decreased(P<0.01),and the positive expression of each target protein was significantly reduced(P<0.01),especially in the GF group and SASP+GF group;the mRNA and protein expression levels of SPHK1 and TRAF2 were reduced to varying degrees(P<0.01 or P<0.05),while the mRNA and protein expression levels of S1P and TNF-α only decreased significantly in the GF group and SASP+GF group(P<0.01).Compared with the SASP group,the GF group only showed a decrease in SPHK1 protein expression,TNF-α mRNA,and protein expression levels,while the SASP+GF group showed significant reductions in all targets(P<0.01 or P<0.05).Compared with the GF group,the SASP+GF group showed significant reductions in SPHK1 protein positive expression and content,S1P mRNA expression levels,and TNF-α protein content(P<0.05 or P<0.01).Conclusion:Grifola frondosa extract may alleviate co-lonic tissue inflammation in rats with UC by inhibiting the activation of the SPHK1/S1P pathway,restoring intestinal mucosal barrier function,and improving symptoms of UC.

Autophagy is a fundamental biological metabolic process involved in immune defense, material metabolism, and homeostasis and closely linked to immune regulation. Systemic lupus erythematosus (SLE) is a widespread connective tissue disorder primarily resulting from immune system imbalance. Due to the immune system's failure to recognize its own substances, it generates autoantibodies that can affect various tissues and organs, leading to diverse clinical manifestations. The pathogenesis and treatment of SLE are currently under extensive investigation. In normal metabolic processes, autophagy engages in both innate and adaptive immunity, regulates the immune response, and is crucial for maintaining normal immune function and the body's internal homeostasis. Research has indicated that SLE patients exhibit immune dysfunction and altered autophagy levels. Modulating autophagy expression can influence immune system functionality and alleviate SLE symptoms. Additionally, autophagy aids in the innate immune response and adaptive immunity by clearing metabolites and regulating the life cycle of immune cells. Studies suggest that drugs targeting autophagy can positively influence the progression of SLE. This article reviews advancements in research regarding the impact of autophagy on the pathogenesis of SLE through the regulation of immune system functions.
Lupus Erythematosus, Systemic/pathology* ; Autophagy/immunology* ; Humans ; Animals ; Immunity, Innate ; Adaptive Immunity ; Disease Progression ; Immune System/immunology*