The development of atherosclerosis （AS） is closely associated with endothelial dysfunction and mitochondrial metabolic abnormalities. These alterations are fundamentally characterized by metabolic reprogramming， in which the tricarboxylic acid （TCA） cycle serves as a central regulatory hub. Disruption of the homeostasis of TCA cycle intermediates， including succinate， α -ketoglutarate， and itaconate， contributes to AS progression through multiple mechanisms， such as the modulation of oxidative stress， inflammation， and glucose and lipid metabolic networks. Owing to their multi-target and multi-pathway regulatory properties， bioactive compounds derived from traditional Chinese medicine （TCM） have demonstrated unique advantages in correcting metabolic dysregulation. Flavonoids， glycosides， and other bioactive constituents of TCM can target key enzymes and metabolites involved in the TCA cycle， thereby restoring aberrant metabolic reprogramming， alleviating endothelial injury induced by oxidative stress， inflammation， and glucose and lipid metabolic disorders， ultimately improving metabolic homeostasis and attenuating the progression of AS.

The development of atherosclerosis （AS） is closely associated with endothelial dysfunction and mitochondrial metabolic abnormalities. These alterations are fundamentally characterized by metabolic reprogramming， in which the tricarboxylic acid （TCA） cycle serves as a central regulatory hub. Disruption of the homeostasis of TCA cycle intermediates， including succinate， α -ketoglutarate， and itaconate， contributes to AS progression through multiple mechanisms， such as the modulation of oxidative stress， inflammation， and glucose and lipid metabolic networks. Owing to their multi-target and multi-pathway regulatory properties， bioactive compounds derived from traditional Chinese medicine （TCM） have demonstrated unique advantages in correcting metabolic dysregulation. Flavonoids， glycosides， and other bioactive constituents of TCM can target key enzymes and metabolites involved in the TCA cycle， thereby restoring aberrant metabolic reprogramming， alleviating endothelial injury induced by oxidative stress， inflammation， and glucose and lipid metabolic disorders， ultimately improving metabolic homeostasis and attenuating the progression of AS.

Objective:To investigate the outcomes of natural cycle (NC) and modified natural cycle (MNC) assisted reproductive technology (ART) in patients with diminished ovarian reserve (DOR), and to provide a scientific basis for individualized treatment strategies for DOR patients.Methods:A retrospective cohort analysis was performed on the clinical data of DOR patients who underwent ART at the Center for Reproductive Medicine of the Department of Obstetrics and Gynecology, Peking University Third Hospital from January 1, 2015 to December 31, 2023. Patients were divided into the NC group ( n=801) and the MNC group ( n=385) based on their treatment protocol. The primary outcomes were cycle cancellation rate and oocyte retrieval rate. Secondary outcomes included clinical pregnancy rate and live birth rate per fresh embryo transfer cycle and frozen-thawed embryo transfer cycle, cumulative pregnancy rate and cumulative live birth rate per started cycle and per transfer cycle, as well as laboratory parameters such as the number of retrieved oocytes, the number of two pronuclei (2PN) fertilized oocytes, the number of transferable embryos, and transferable embryo formation rate. Further, multivariate logistic regression was used to analyze the impact of the treatment protocol on pregnancy and live birth outcomes. Results:There were no statistically significant differences between the NC and MNC groups in terms of general characteristics such as age, body mass index, and baseline hormone levels (all P>0.05). The cycle cancellation rate was significantly higher in the NC group [19.10% (153/801)] than in the MNC group [10.65% (41/385), P<0.001], and the oocyte retrieval rate was significantly lower in the NC group [66.31% (431/650)] than in the MNC group [74.86% (259/346), P=0.005]. The number of retrieved oocytes [1 (0,1)], the number of 2PN fertilized oocytes [1 (0,1)], and the number of transferable embryos [0 (0, 1)] were also significantly lower in the NC group than in the MNC group [1 (1, 2), P<0.001; 1 (1, 1), P<0.001; 0 (0, 1), P<0.001]. However, there were no statistically significant differences in 2PN fertilization rate and transferable embryo formation rate between the NC and MNC groups (all P>0.05). In both fresh embryo transfer cycles and frozen-thawed embryo transfer cycles, there were no statistically significant differences in clinical pregnancy rate and live birth rate between the NC and MNC groups (all P>0.05). The cumulative pregnancy rate per started cycle and transfer cycle, the cumulative live birth rate per started cycle and per transfer cycle were also not significantly different between the NC and MNC groups (all P>0.05). Multivariate logistic analysis showed no significant association between NC and clinical pregnancy or live birth compared with MNC. Conclusion:While MNC to some extent reduced the cycle cancellation rate and improved oocyte retrieval rates compared with NC, it did not ultimately improve pregnancy outcomes in DOR patients.

Objective:To explore the relationship between life events, anxiety, depression, and behavior problems in adolescents.Methods:From September to October 2022, the cluster sampling method was used to select 5 341 adolescents from 4 middle schools in Xinxiang urban area.The subjects and their parents were investigated by the adolescent self-rating life events check list (ASLEC), generalized anxiety disorder scale (GAD-7), patient health questionnaire (PHQ-9), and child behavior checklist (CBCL). SPSS 27.0 software was used for Spearman correlation analysis, and AMOS 28.0 software was used to construct the structural equation model.Results:The scores of anxiety, depression, and behavioral problems were 1 (0, 4), 1 (0, 4), and 3 (0, 10). The total score of life events was 5 (1, 13), and the dimensions scored as follows: interpersonal conflict 1 (0, 4), academic pressure 2 (0, 5), punishment 0 (0, 2), loss 0 (0, 0), health and adaptation problem 0 (0, 1), and others 0 (0, 2). There were positive correlations between life events and its dimensions, depression, anxiety and behavioral problems ( r=0.28-0.69, all P<0.01). In the overall population, anxiety and depression played parallel mediating roles in the impact of life events on behavior problems. Life events could positively predict anxiety ( β=0.68, P<0.01), and anxiety could positively predict behavior problems ( β=0.04, P=0.02). Life events could positively predict depression ( β=0.77, P<0.01), and depression could positively predict behavior problems ( β=0.18, P<0.01). The standardized total effect size of the impact of life events on behavioral problems was 0.622 (95% CI=0.564-0.675). The standardized direct effect size and indirect effect size were 0.460 (95% CI=0.374-0.539) and 0.162 (95% CI=0.108-0.218), accounting for 74.0% and 26.0%of the total effect, respectively. After stratification by gender, the results for male adolescents were consistent with the overall population, while the mediating effect of anxiety was not significant in the female adolescents. Conclusion:Life events can lead to anxiety and depression in adolescents, thereby increasing the risk of behavior problems.

Polygonatum sibiricum polysaccharide(PSP)is a polysaccharide with multiple pharma-cological activities that has been widely studied and used in the human body.However,there is cur-rently a lack of research investigating the potential advantages of PSP in poultry farming.This study investigated the effects of adding PSP to drinking water on the growth performance,antioxi-dant status,serum biochemical indicators,ileal tissue morphology,immune organs,and intestinal function of chicks.88 Hailan brown laying hens were randomly divided into 4 groups,with 22 hens in each group,namely the blank control group(CON),and fed with basic feed;The low-dose PSP group(250 mg/L),the medium dose PSP group(500 mg/L),and the high-dose PSP group(1 000 mg/L)were fed with corresponding doses of PSP through drinking water on the basis of basic feed,and the experimental period was 21 d.The initial and final body weight and immune or-gan relative quality of chicks,serum biochemical indicators,the activities of SOD,CAT,and GSH-Px,as well as the contents of T-AOC and MDA in the serum of chicks were measured;HE stai-ning method was used to observe the pathological changes of intestinal tissue slices in the ileum;Real time fluorescence quantitative PCR technology was used to detect the mRNA expression lev-els of cytokines ZO-1,Claudin-1,Occludin,Mucin-2,IL-1β,TNF-a,IFN-γ,IL-4,IL-8,and IL-10 in the ileum.The results showed that compared with the blank control group,the addition of medium dose PSP significantly increased the final relative quality(P＜0.01),the final body weight and ADG of PSP500 group chicks significantly increased(P＜0.01),and the F/G of PSP250 and PSP500 groups significantly decreased(P＜0.05 or P＜0.01).The villus height of the jejunum in the 200,500,and 1 000 mg/L PSP groups of chicks significantly increased(P＜0.05).The SOD ac-tivity significantly increased(P＜0.01),and the CAT activity in the PSP1000 group significantly increased(P＜0.01).The PSP500 and PSP1000 groups significantly reduced the mRNA expression of cytokines IL-1β,IL-4,and IFN-γ in the ileum(P＞0.05);PSP did not show significant changes in serum total protein(TP),albumin(ALB),glucose(GLU),cholesterol(T-CHO)content,and immune organ index(P＜0.05).In summary,PSP can improve growth performance,enhance an-tioxidant capacity,improve ileal morphology and epithelial barrier function,and regulate mucosal immune status.Considering the overall economic benefits,the recommended level of PSP addition is 500 mg/L.

AIM:Fine particulate matter(PM2.5)is closely associated with airway hyper-responsiveness(AHR).However,the underlying mechanism by which PM2.5 leads to AHR is still unclear.This study aimed to investi-gate the respiratory effects of ambient PM2.5 exposure.METHODS:Forty mice were randomly divided into five groups:control group(intranasal saline),lipopolysaccharide(LPS)group(100 mg/L),PM2.5 low-dose group(0.003 5 mg/d),PM2.5 medium-dose group(0.007 mg/d),and PM2.5 high-dose group(0.014 mg/d).They were treated with intranasal in-stillation for 30 d.Lung function and tracheal contractile responses were evaluated using whole-body plethysmography and sensitive wire myograph.Inflammatory mediators in serum and oxidative stress parameters were detected using enzyme-linked immunosorbent assay(ELISA).Lung tissues were subjected to HE and Masson staining.RT-qPCR and Western blot were used to determine the expression of contractile receptors and the phosphorylation of the mitogen-activated protein kinase(MAPK)signal pathway.RESULTS:Intranasal instillation of PM2.5 significantly increased airway resistance in mice and enhanced tracheal contractility in response to carbachol.PM2.5 elevated levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,and IL-6 in serum.PM2.5 instillation also led to a decrease in glutathione peroxidase(GSH-Px)levels and an increase in malondialdehyde(MDA)levels.Lung tissue exhibited notable pathological changes,including inflammatory cell infiltration,hyperplasia of alveolar epithelial cells,and collagen deposition.Mechanistically,exposure to PM2.5 increased the expression of muscarinic M3 receptor mRNA and protein,as well as the phosphorylation of p-ERK1/2 and p-p38 proteins following PM2.5 instillation.CONCLUSION:Intranasal instillation of PM2.5 induced inflammation and oxidative stress,along with the activation of the extracellular signal-regulated kinase 1/2(ERK1/2)and p38 MAPK pathways,resulting in the upregulation of M3 receptor-induced AHR.

This study aims to explore protective effects of Lycium barbarum polysaccharides(LBP)on intestinal damage caused by lipopolysaccharide(LPS)-induced inflammatory bowel disease(IBD)in chicks.Network pharmacology was initially employed to determine the target proteins of wolfberry in the prevention and treatment of IBD.Following this,protein-protein interaction analy-sis,GO and KEGG pathway enrichment analysis,and molecular docking studies were conducted.Subsequently,an animal study was conducted:a total of 100 one-day-old male Hy-line brown lay-ing hens were randomly divided into five groups:a blank control group(CON),an LPS treatment group(LPS),a low-dose LBP group(LPS+LBP 0.25 g/L,L-LBP),a medium-dose LBP group(LPS+LBP 0.5 g/L,M-LBP),and a high-dose LBP group(LPS+LBP 1 g/L,H-LBP).Upon reac-hing 21 days old,duodenal,jejunal,ileal,and cecal tissues were collected to determine SOD and GSH-Px levels.Furthermore,the mRNA expression levels of TNF-α,AKT1,IL-6,IL-1β and TP53 in the intestinal tissues were measured using quantitative real-time PCR.The results demonstrated that network pharmacology identified 45 active ingredients in wolfberry that target 116 key protein sites,including TNF,AKT1 and IL6.The primary objectives focus on signaling pathways including AGE-RAGE,IL-17,TNF,HIF-1,and NF-κB.Molecular docking showed excellent ligand-receptor docking scores,with stable binding facilitated by hydrogen bonds and hydrophobic interactions.Compared to the LPS group,the 0.5 g/L LBP exhibited notably higher levels of SOD and T-AOC.In comparison with the LPS group,the medium and high-dose LBP experimental groups showed notably decreased the mRNA expressions of TNF-α,AKT1,IL-6,and IL-1β,while TP53 mRNA expression was significantly upregulated(P＜0.01).In summary,wolfberry exerts preventive and therapeutic effects on IBD through a multi-component,multi-target,and multi-pathway mecha-nism.

Polygonatum sibiricum polysaccharide(PSP)is a polysaccharide with multiple pharma-cological activities that has been widely studied and used in the human body.However,there is cur-rently a lack of research investigating the potential advantages of PSP in poultry farming.This study investigated the effects of adding PSP to drinking water on the growth performance,antioxi-dant status,serum biochemical indicators,ileal tissue morphology,immune organs,and intestinal function of chicks.88 Hailan brown laying hens were randomly divided into 4 groups,with 22 hens in each group,namely the blank control group(CON),and fed with basic feed;The low-dose PSP group(250 mg/L),the medium dose PSP group(500 mg/L),and the high-dose PSP group(1 000 mg/L)were fed with corresponding doses of PSP through drinking water on the basis of basic feed,and the experimental period was 21 d.The initial and final body weight and immune or-gan relative quality of chicks,serum biochemical indicators,the activities of SOD,CAT,and GSH-Px,as well as the contents of T-AOC and MDA in the serum of chicks were measured;HE stai-ning method was used to observe the pathological changes of intestinal tissue slices in the ileum;Real time fluorescence quantitative PCR technology was used to detect the mRNA expression lev-els of cytokines ZO-1,Claudin-1,Occludin,Mucin-2,IL-1β,TNF-a,IFN-γ,IL-4,IL-8,and IL-10 in the ileum.The results showed that compared with the blank control group,the addition of medium dose PSP significantly increased the final relative quality(P＜0.01),the final body weight and ADG of PSP500 group chicks significantly increased(P＜0.01),and the F/G of PSP250 and PSP500 groups significantly decreased(P＜0.05 or P＜0.01).The villus height of the jejunum in the 200,500,and 1 000 mg/L PSP groups of chicks significantly increased(P＜0.05).The SOD ac-tivity significantly increased(P＜0.01),and the CAT activity in the PSP1000 group significantly increased(P＜0.01).The PSP500 and PSP1000 groups significantly reduced the mRNA expression of cytokines IL-1β,IL-4,and IFN-γ in the ileum(P＞0.05);PSP did not show significant changes in serum total protein(TP),albumin(ALB),glucose(GLU),cholesterol(T-CHO)content,and immune organ index(P＜0.05).In summary,PSP can improve growth performance,enhance an-tioxidant capacity,improve ileal morphology and epithelial barrier function,and regulate mucosal immune status.Considering the overall economic benefits,the recommended level of PSP addition is 500 mg/L.

Objective To analyze the effect of graded exercise rehabilitation in patients with acute exacerbation of chronic obstructive pulmonary disease,and to provide references for clinical nursing practice.Methods A total of 70 patients with acute exacerbation of chronic obstructive pulmonary disease who met the criteria in the Department of Respiratory Medicine of a tertiary hospital in Zunyi City from September to December 2023 were randomly divided into an experimental group and a control group(with 35 cases in each group).The experimental group implemented graded exercise rehabilitation based on the Global Chronic Obstructive Pulmonary Initiative guidelines,and the control group implemented routine exercise rehabilitation.After intervention,the lung function,blood gas analysis,oxygenation index,6 min walking test and the incidence of complications related to non-invasive mechanical ventilation were compared between the 2 groups.Results Finally,34 cases were included in the experimental group and 35 cases in the control group.After intervention,the forced expiratory volume in the first second of the experimental group was improved compared with the control group(P＜0.05).The 6-minute walking test of the experimental group was higher than that of the control group(P＜0.05).The total incidence of non-invasive mechanical ventilation-related complications in the experimental group was lower than that in the control group(P＜0.05).There was no significant difference in blood gas analysis and oxygenation index between the 2 groups(P＜0.05).Conclusion The implementation of graded exercise rehabilitation based on the Global Chronic Obstructive Pulmonary Initiative guidelines can help patients with acute exacerbation of chronic obstructive pulmonary disease improve their respiratory function,improve their exercise endurance,and reduce non-invasive mechanical ventilation-related complications.

Objective:To identify and validate secreted effector proteins of Chlamydia psittaci ( C. psittaci) through bioinformatic prediction and experimental verification, and to characterize their subcellular localization in host cells. Methods:Potential effector proteins were predicted using bioinformatics tools. Candidate effectors were fused to β-lactamase through the constructed expression vectors, and these vectors were transformed into C. psittaci. The secretion of these candidate effectors was evaluated by β-lactamase translocation assays. Eukaryotic expression vectors of confirmed effectors were transfected into host cells to determine their intracellular localization patterns. Results:Bioinformatic analysis identified 29 candidate effector proteins. Experimental validation confirmed the secretion of five effectors, with four exhibiting cytoplasmic localization and one displaying nuclear localization in host cells.Conclusion:This study characterizes five novel C. psittaci secreted effector proteins, providing critical insights for investigating the molecular pathogenesis of psittacosis.