Objective To investigate the role of innate immune responses in acute lymphedema and their association with susceptibility to infection through a multidimensional approach integrating bioinformatics,clinical validation, and animal experiments. Methods The mouse acute lymphedema dataset GSE4333 was downloaded from the Gene Expression Omnibus （GEO）. Differentially expressed genes （DEGs） were identified using limma （|log₂FC|>1, P_adj<0.05）,and gene set enrichment analysis （GSEA） was performed with GO, KEGG, and Hallmark gene sets via clusterProfiler.Peripheral blood was collected from patients with lower-extremity lymphedema （experimental group, n=5） and healthy controls （n=5） at Traditional Chinese and Western Medicine Hospital of Wuhan （Wuhan First Hospital）（June-July 2025）.Serum levels of S100A8, S100A9, NT5E, IRF7, IFITM1, and CORO1A were measured by ELISA. A mouse tail lymphedema model was established （n=6）, and tail tissues were harvested on postoperative day 10 for qPCR analysis of the 6 target genes; LYVE-1 immunofluorescence was used to assess lymphangiogenesis. Results A total of 151 DEGs （58 upregulated,93 downregulated） were identified. GSEA revealed significant negative enrichment of the innate immune response,the regulation of inflammatory response,the chemokine signaling pathway,and the oxidative phosphorylation pathway in acute lymphedema. Clinical validation demonstrated that serum levels of S100A8,S100A9,NT5E,IRF7,IFITM1, and CORO1A were significantly lower in lymphedema patients than in healthy controls （all P<0.01）. Animal experiments confirmed that the mRNA expression levels of S100a8, S100a9, Nt5e, Irf7, Ifitm1, and Coro1a in mouse lymphedematous tail tissues were significantly downregulated （all P<0.01）. Conclusion Acute lymphedema profoundly suppresses innate immune-related signaling pathways. The systemic downregulation of key immune regulators including S100A8, S100A9, NT5E, IRF7, IFITM1, and CORO1A may represent a critical molecular basis for increased susceptibility to infection in lymphedema patients. These molecules may serve as potential biomarkers for assessing immune function and as candidate targets for immunomodulatory therapy.

Objective To identify the potential targets and key regulatory mechanisms underlying the neuroprotective effects of Pranlukast against cerebral ischemia-reperfusion （CIR） injury. Methods PharmMapper reverse virtual screening and molecular simulation were integrated with Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses to pinpoint the potential targets and regulatory pathways of Pranlukast. An oxygen-glucose deprivation/reperfusion （OGD/R） model was established in PC12 cells; cell viability was evaluated by the CCK-8 assay, and cell survival was assessed via PI and Hoechst 33342 double staining. A middle cerebral artery occlusion/reperfusion （MCAO/R） model was constructed in SD rats; the neuroprotective effects were evaluated by neurological deficit scores, TTC staining, and HE staining. Mechanistic validation was performed by using immunofluorescence staining for MPO, iNOS, and CD206; immunohistochemical staining for p-p65 and IL-6; and transmission electron microscopy （TEM） to observe myelin sheath structure. Results SRC, MAPK14, and ADAM17 were identified as high-affinity targets through which Pranlukast attenuates CIR injury, primarily by regulating the immune-inflammatory crosstalk network involving MAPK, PI3K-Akt, and other signaling pathways. In vitro and in vivo experiments demonstrated that Pranlukast significantly enhanced the viability of OGD/R-induced PC12 cells, ameliorated neurological deficits, reduced cerebral infarct volume, and attenuated neuronal damage in MCAO/R rats. Additionally, Pranlukast inhibited neutrophil infiltration, promoted M1 to M2 phenotypic switching of macrophages, downregulated p-p65 and IL-6 expression, and ameliorated myelin sheath structural damage. Conclusion Pranlukast attenuates CIR injury by modulating aberrant immune-inflammatory crosstalk, suppressing immune cell infiltration and neuroinflammatory cascades, and preserving myelin sheath integrity.

Objective To investigate the effects and mechanisms of EX-527, a specific SIRT1 inhibitor, on cardiac ion currents and arrhythmias in ventricular myocytes. Methods The whole-cell patch clamp technique was used to examine the effects of EX-527 on I_NaL and other ionic currents in mouse ventricular myocytes under normal conditions, as well as on the enhanced I_NaL induced by anemone toxinⅡ （ATXⅡ, an I_NaL enhancer） or by heart failure resulting from transverse aortic constriction （TAC）. In vivo electrocardiography was performed to evaluate the effects of EX-527 on ATXⅡ-induced ventricular arrhythmias in mice. The expression levels of p-CaMKⅡ and p-PKC were detected by Western blotting. Results ① EX-527 （10 µmol/L） inhibited the ATXⅡ-enhanced I_NaL in ventricular myocytes; ②EX-527 （10 µmol/L） had no significant effects on I_Na, I_CaL, I_K, I_K1 or I_to; ③Combined inhibition of CaMKⅡ（10 µmol/L KN-93） and PKC （2 µmol/L BIM） nearly completely eliminated the inhibitory effect of EX-527 on ATXⅡ-enhanced I_NaL; ④EX-527 inhibited the enhanced I_NaL induced by TAC; ⑤EX-527 shortened the prolonged action potential duration and completely eliminated early afterdepolarizations induced by ATXⅡ ⑥EX-527 significantly reduced the incidence and duration of ventricular tachycardia and ventricular fibrillation induced by ATXⅡ ⑦EX-527 reduced the expression levels of p-CaMKⅡ and p-PKC. Conclusion Acute application of EX-527 protects against ventricular arrhythmias by selectively inhibiting I_NaL in ventricular myocytes via both CaMKⅡ and PKC signaling pathways.

Objective To explore the mechanism by which internal heat acupuncture intervenes in peripheral sensitization of dorsal root ganglia （DRG） in chronic soft tissue pain, with a focus on the Wnt/β-catenin signaling pathway. Methods Forty-five clean-grade healthy adult New Zealand white rabbits were randomly divided into three groups （n=15）： control, model, and internal heat acupuncture group. A chronic soft tissue injury model was established using mechanical impact-induced contusion. After modeling, the acupuncture group received internal heat acupuncture once weekly for two weeks. At designated time points, spontaneous electromyographic activity frequency and spontaneous potential scores at the injured left hind limb were recorded. Local tissue thickness, color Doppler flow imaging （CDFI） signals, mean elastic modulus, and ultrasound images were also evaluated. Tissue samples were collected for histopathology, immunohistochemistry, Western blotting, and RT-PCR to assess pathological changes and the expression of vascular endothelial growth factor （VEGF）, basic fibroblast growth factor （bFGF）, brain-derived neurotrophic factor （BDNF）, and glial cell line-derived neurotrophic factor （GDNF）. In addition, the expression of Wnt pathway components,including active β-catenin, Wnt-5a, Frizzled8 protein, and their corresponding mRNAs,was assessed in the L4—L6 spinal DRG. Results In the internal heat acupuncture group, spontaneous activity frequency and potential scores were significantly lower than model group （both P<0.01）. Compared with both the pre-treatment values and the model group, the maximum thickness of the gastrocnemius, biceps femoris, and Achilles tendon in the injured area was significantly reduced （all P<0.01）, and the mean elastic modulus of the lesion also decreased markedly (P<0.01） in the acupuncture group. The expression levels of VEGF, bFGF, BDNF and GDNF in the acupuncture group were significantly lower than in the model group （all P<0.01）. Moreover, the expression of active β-catenin, Wnt-5a, Frizzled8 protein, and their mRNAs in L4-L6 DRG were significantly reduced compared with the model group （all P<0.01）. Conclusion Internal heat acupuncture exerts its analgesic effect by modulating the expression of Wnt-related signaling molecules in the L4-L6 DRG and adjusting local neurotrophic factors in chronic soft tissue lesions, thereby decreasing spontaneous muscle activity, relieving spasms, normalizing muscle tone and elasticity, promoting tissue repair, and alleviating pain.

Objective To investigate the protective effects and mechanisms of catechins （Cat） against isoprenaline （ISO）-induced chronic sympathetic stress-related myocardial injury, using network pharmacology, molecular docking, and in vivo and in vitro experiments. Methods Potential targets of Cat were predicted from the BATMAN, DrugBank, TargetNet, TCMSP, and CTD databases. Genes associated with excessive sympathetic nerve activation and myocardial injury were retrieved from the OMIM and GeneCards databases. The overlapping targets between the two datasets were identified as potential therapeutic targets. A protein-protein interaction （PPI） network was constructed using the STRING database and Cytoscape 3.9.1, and core targets were screened out. Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis was performed to predict relevant signaling pathways. Molecular docking was conducted using AutoDock Vina 1.5.6, and the target-ligand interactions were further validated by visualization with PyMOL. In vivo myocardial injury models were established in mice, and in vitro models were established in AC16 cells, both induced by ISO. The protective effects of Cat and its underlying mechanisms were evaluated by histopathological analysis, TUNEL assay, Annexin Ⅴ-FITC/PI flow cytometry, ELISA, and Western blotting. Results A total of 155 intersecting targets were identified among catechins, sympathetic overactivation, and myocardial injury. KEGG enrichment analysis suggested that the phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） pathway might play a key role. Molecular docking results showed that Cat exhibited strong binding affinity to the core targets, namely phosphoinositide-3-kinase catalytic subunit alpha （PIK3CA） and protein kinase B1 （Akt1）. In vivo experiments demonstrated that Cat significantly reversed ISO-induced myocardial fiber disarray, elevated myocardial enzyme levels, and cell apoptosis （P<0.01）. In vitro experiments further confirmed its ability to alleviate ISO-induced myocardial cell apoptosis （P<0.05, P<0.01）. However, after intervention with the PI3K inhibitor LY294002, the anti-apoptotic effect of Cat was markedly attenuated （P<0.05）, suggesting that its action depends on the PI3K/Akt pathway. Conclusion Catechins mitigate sympathetic stress-induced myocardial injury by activating PI3K/Akt signaling and inhibiting cardiomyocyte apoptosis, supporting their potential role in myocardial protection.

Objective this study investigated the feasibility of real-time nitric oxide （NO） monitoring for distinguishing between esophageal squamous cell carcinoma （ESCC） and normal esophageal epithelial cells at the cellular and organoid levels, and for preliminary assessment of chemotherapy response. Methods An electrochemical sensor was used to monitor NO release levels in the ESCC cell lines KYSE30 and KYSE150, as well as in normal esophageal epithelial cells （NE6-T）, upon L-arginine stimulation.An in vitro chemotherapy model with ESCC cells and organoids was established to assess changes in NO release after paclitaxel （PTX） treatment. Pearson correlation analysis was performed between relative viability derived from NO signals and that obtained via the CCK-8 assay. Results NO levels in ESCC cells were higher than those in normal esophageal epithelial cells （P<0.05）, and this elevation may be associated with the activation of the HIF-1α-iNOS pathway. Following PTX treatment, cell viability estimated from NO measurements showed a strong positive correlation with that determined by the CCK-8 assay （r= 0.9579, P<0.05）, and organoid viability also showed a strong positive correlation （r=0.9116, P<0.05）, indicating good consistency between the two methods. Conclusion Dynamic NO release can distinguish ESCC cells from normal esophageal epithelial cells in vitro and reflect changes in the viability of tumor cells and organoids following treatment with chemotherapeutic agents. This suggests that dynamic NO detection holds value in the in vitro discrimination of ESCC and drug sensitivity screening.

Objective To explore the association between attention-deficit/hyperactivity disorder （ADHD） symptoms and multidimensional obesity phenotypes defined by BMI and body composition indicators in school-aged children, and further analyze the potential mediating role of unhealthy eating behaviors. Methods A cross-sectional study was conducted among 6624 children aged 6–18 years from Zhuhai, China, recruited via stratified cluster sampling in 2023. Height and weight were measured to calculate BMI, and body composition indicators, including body fat percentage and waist-to-hip ratio, were assessed by bioelectrical impedance analysis. ADHD symptoms were evaluated with the parent-rated Swanson Nolan and Pelham-Ⅳ （SNAP-Ⅳ）, while eating behaviors were assessed with the children's self-reported Dutch Eating Behavior Questionnaire. Four obesity phenotypes were defined：obesity by BMI;obesity with a high waist-to-hip ratio;obesity with high body fat percentage; and obesity with high trunk fat percentage. Multilevel logistic regression was performed for association analysis, and mediation effects were tested using the bootstrap method. Results The positive screening rate for ADHD symptoms was 6.9%, and the detection rate of obesity was 10.3%. Among all participants,hyperactive-impulsive symptom scores were positively associated with obesity （OR=1.31） and obesity with a high waist-to-hip ratio （OR=1.31）. Among girls, these scores were also significantly positively associated with obesity with high body fat percentage （OR=1.40） and obesity with high trunk fat percentage （OR=1.38）,whereas no significant associations of these indicators were found in boys. Restrained eating scores showed a potential mediating effect in these associations, explaining 61.0%-72.2% of the total effect in the overall sample and 35.9%-39.1% in girls. Conclusion ADHD symptoms in school-aged children are associated not only with the risk of obesity but also with multidimensional obesity phenotypes characterized by central fat accumulation. Restrained eating may be an important potential mediator in this association. For obesity prevention and control, attention should be paid to children with hyperactive-impulsive symptoms and their eating behaviors. Body composition indicators may facilitate refined phenotyping, yet their value in routine monitoring requires validation in prospective studies.

Objective To systematically assess the burden of cardiovascular diseases （CVDs） globally and in China from 1990 to 2021 using data from the Global Burden of Disease （GBD） 2021 study, and to evaluate temporal trends, cause-of-death composition, years of life lost （YLL） contribution, and age-period-cohort effects, so as to provide a scientific basis for differentiated prevention and treatment strategies. Methods CVD data for the globe and China from 1990 to 2021 were extracted from the GBD 2021 database, including incidence, mortality, age-standardized mortality rate （ASMR）, disability-adjusted life years （DALYs）, YLL, and years lived with disability （YLD）. The annual percentage change （APC） and average annual percentage change （AAPC） were calculated to analyze temporal trends. Pareto analysis was used to identify leading causes of death. YLL contribution was calculated to assess the contribution of each cause of death. An age-period-cohort model was constructed to quantify the effects of age, period, and birth cohort on CVD mortality. Results Temporal trend analysis： From 1990 to 2021, the relative changes in ASMR and age-standardized DALY rate for CVDs were negative for both the globe and China. The ASMR for CVDs showed a declining trend, with a greater decline globally （AAPC=-1.336%） than in China （AAPC=-1.216%）. In both regions, the decline in mortality was smaller in males than in females. Cause-of-death composition analysis： From 1990 to 2021, CVDs were the leading cause of death globally and in China. Ischemic heart disease, stroke, and hypertensive heart disease were the top three causes of CVD deaths, collectively accounting for more than 80% of total CVD mortality; however, their rankings differed （globally： ischemic heart disease > stroke > hypertensive heart disease; in China： stroke > ischemic heart disease > hypertensive heart disease）. Premature mortality burden analysis： Although the contribution of YLL showed a gradual decline over the years, it consistently remained at a high level of 90%.Age-period-cohort effects analysis： The results showed that the net drift, age, period, and cohort effects for global CVD mortality were all statistically significant （all P<0.05）. The age effect exhibited a J-shaped increase with advancing age. Both period and cohort effects showed a sustained downward trend over time and across successive birth cohorts. Conclusion Although the age-standardized mortality burden of CVDs has declined overall in both the globe and China, the absolute burden continues to increase, and the problem of premature death remains substantial. China faces distinct challenges in terms of leading causes （stroke vs. ischemic heart disease） and gender disparities compared with the globe. Future prevention and control efforts should take into account the risk characteristics associated with specific ages, periods, and birth cohorts to develop precise and differentiated intervention strategies.

Objective To investigate the molecular mechanism by which heme oxygenase-1 （HMOX1） regulates ferroptosis in endometriosis. Methods Human immortalized endometrial ectopic epithelial cells （hEM15A） were divided into blank control （Con） group, sh-NC group, and sh-HMOX1 group. The hEM15A cells in the sh-NC and sh-HMOX1 groups were transfected with negative control and interfering plasmids targeting HMOX1, respectively. Normal human endometrial stromal cells （hESCs） were divided into blank control （Con） group, FeSO₄ group, FeSO₄+sh-NC group, and FeSO₄+sh-HMOX1 group. Cells in the FeSO₄, FeSO₄+sh-NC, and FeSO₄+sh-HMOX1 groups were exposed to FeSO₄ （100 μmol/L） solution for 24 hours. The hESCs in the FeSO₄+sh-NC and FeSO₄+sh-HMOX1 groups were transfected with negative control and interfering plasmids targeting HMOX1 prior to FeSO₄ exposure. Cell viability was assessed using the Cell Counting Kit-8 （CCK-8） assay. Lipid peroxidation was measured by flow cytometry. Intracellular Fe²⁺ levels were analyzed by FeRhoNox-1 fluorescence staining. Cell migration ability was evaluated by Transwell assay, and pro-angiogenic activity was assessed by HUVECs tube formation assay. Expression of iron metabolism-related proteins was analyzed by Western blotting. Results Compared with hESCs, HMOX1 protein expression was upregulated in hEM15A cells. Compared with the sh-NC group, the sh-HMOX1 group exhibited decreased hEM15A cell viability, number of migrated cells, number of HUVEC tube formation,lipid ROS levels, Fe²⁺ levels, and ACSL4 protein expression （all P<0.05）, while SLC7A11 and GPX4 protein expression was increased （both P<0.05）. Compared with the Con group, the FeSO₄ and FeSO₄+sh-NC groups showed increased lipid ROS, Fe²⁺ levels, and HMOX1 and ACSL4 protein expression in hESCs （all P<0.05）, whereas SLC7A11 and GPX4 protein expression was decreased （both P<0.05）. Compared with the FeSO₄+sh-NC group, the FeSO₄+sh-HMOX1 group showed decreased lipid ROS, Fe²⁺ levels, and HMOX1 and ACSL4 protein expression in hESCs （all P<0.05）, while SLC7A11 and GPX4 protein expression was increased （both P<0.05）. Compared with the Con group, the FeSO₄ and FeSO₄+sh-NC groups exhibited increased numbers of migrated hESCs and HUVEC tube formation（all P<0.05）. Compared with the FeSO₄+sh-NC group, the FeSO₄+sh-HMOX1 group showed decreased cell viability, number of migrated cells, and number of HUVEC tube formation in hESCs （all P<0.05）. Conclusion Knockdown of HMOX1 may inhibit the progression of endometriosis by regulating ferroptosis, providing new evidence for HMOX1 as a potential therapeutic target for endometriosis.

Objective To investigate the effect of bony tunnels created by pedicle screw implantation on the load-bearing capacity of vertebral bodies in thoracolumbar fracture surgery, and to clarify the biomechanical effects of the “tunnel shield” phenomenon in the surgical treatment of thoracolumbar fractures. Methods Ten 3-month-old Bama miniature pigs were randomly divided into a unilateral screw placement group （n=5） and a bilateral screw placement group （n=5）. Posterior lumbar surgery was performed, and screws with a diameter of 2.5 mm were implanted into the pedicles of L1-L5 （unilateral placement in the unilateral group, bilateral placement in the bilateral group）. Spinal specimens were obtained at staged time points postoperatively. The degree of corticalization of the screw tunnel walls was quantified by CT scanning, and three-dimensional finite element models of the L2 vertebral body were established to analyze stress distribution within the screw tunnels. A hydraulic testing machine was used to compare the biomechanical strength between screwed vertebrae and normal vertebrae. A total of 83 patients with thoracolumbar fractures who underwent pedicle screw removal were enrolled and divided into three groups based on the screw placement method in the injured vertebrae： unilateral screw placement group, bilateral screw placement group, and non-screw placement group. Spinal X-ray and CT scans were performed before internal fixation removal, immediately after removal, and at the final follow-up to measure the morphology of the injured vertebrae and adjacent vertebrae, as well as screw tunnel parameters. The effects of different screw placement methods on spinal stability and screw tunnels were analyzed. Results After pedicle screw implantation into the vertebral bodies of miniature pigs, the “tunnel shield” effect led to corticalization of the screw tunnel walls. With prolonged screw retention time, the corticalization of the tunnel walls became more pronounced, and the maximum load-bearing stress of the vertebrae gradually increased, though it remained lower than that of normal vertebrae. Under the same screw tunnel diameter, as the tunnel wall thickness increased, the stress on cortical bone in both the unilateral and bilateral tunnel models gradually decreased, while the stress on cancellous bone gradually increased, and the stress on the tunnel walls gradually decreased. Clinical data analysis revealed that at the final follow-up, the loss of anterior vertebral height ratio in the bilateral screw placement group was significantly lower than those in the other two groups [bilateral group （4.14±3.79）%, unilateral group （7.95±5.85）%, non-screw group （8.89±2.54）%; P=0.022], and the increase in segmental kyphotic Cobb angle was also significantly smaller than those in the other two groups [bilateral group （3.64±2.68）°, unilateral group （6.38±3.48）°, non-screw group （4.74±1.51）° P=0.019]. Conclusion The bony tunnel created by the “tunnel shield” effect can enhance vertebral stability. Bilateral screw placement demonstrates a tendency to be superior to unilateral screw placement in maintaining anterior vertebral height and segmental Cobb angle.

Objective To investigate the associations of galectin-4 （Gal-4） and histone deacetylase 6 （HDAC6） with cardiac functional class and Meta-Analysis Global Group in Chronic Heart Failure （MAGGIC） score in patients with chronic heart failure （CHF） and to evaluate their prognostic value. Methods This retrospective study included 218 patients with CHF hospitalized at Xinxiang Central Hospital from June 2018 to June 2021. Prognosis was assessed based on the occurrence of major adverse cardiovascular events （MACE） over a 3-year period, and patients were divided into a MACE group （n=74） and a non-MACE group （n=144）. Serum levels of Gal-4 and HDAC6 were measured via enzyme-linked immunosorbent assay （ELISA）. Pearson and Spearman's correlation analysis was used to assess the correlations of serum Gal-4 and HDAC6 levels with cardiac function, MAGGIC score, and prognosis in patients with CHF. Multivariate Cox regression and Kaplan-Meier analysis were used to evaluate prognosis. Receiver operating characteristic （ROC） curve analysis was used to evaluate the predictive value of each biomarker for the occurrence of MACE within 3 years in patients with CHF. Results Serum Gal-4 and HDAC6 levels in patients with CHF increased significantly as NYHA class increased （both P<0.01）. In patients with CHF, Gal-4 was weakly to moderately positively correlated with the MAGGIC score （r=0.428）, BUN （r=0.247）, and Scr （r=0.178）. HDAC6 was also weakly to moderately positively correlated with the MAGGIC score （r=0.416）, UA （r=0.284）, and NT-proBNP （r=0.191） （all P<0.05）. Serum Gal-4 and HDAC6 levels were significantly higher in the MACE group than in the non-MACE group （both P<0.01）. High serum levels of Gal-4 （HR=1.524, 95%CI：1.238-1.876） and HDAC6 （HR=1.037, 95%CI：1.006-1.070） were independent risk factors for MACE within 3 years in patients with CHF （both P<0.05）. The cumulative incidence of MACE over 3 years was significantly higher in the group with high expression of both Gal-4 and HDAC6 compared with both the group with low expression of both markers and the group with high expression of one marker and low expression of the other （all P<0.01）. The combined Gal-4 and HDAC6 model （Gal-4+HDAC6, AUC=0.824） and the MAGGIC score （AUC=0.840） both exhibited predictive performance for MACE within 3 years in patients with CHF,and there was no significant difference between them （Z=0.488, P=0.626）. Conclusion Serum Gal-4 and HDAC6 may serve as potential biomarkers reflecting disease severity and long-term risk of MACE in patients with CHF. Combined measurement of Gal-4 and HDAC6 provides a novel and effective tool for risk stratification and prognostic assessment in this population.

Objective To develop and validate a machine learning prediction model for post-stroke cognitive impairment （PSCI） and to identify key predictive factors. Methods We retrospectively enrolled 1070 patients with acute ischemic stroke admitted to the Department of Neurology at the Affiliated Lianyungang Hospital of Xuzhou Medical University from January 2020 to August 2023, and randomly divided them into a training set （n=749） and a validation set （n=321） in a 7∶3 ratio. LASSO regression was used for feature selection. Based on selected variables, seven machine learning models were built： Logistic Regression （LR）, Decision Tree （DT）, Random Forest （RF）, Support Vector Machine （SVM）, eXtreme Gradient Boosting （XGBoost）, Light Gradient Boosting Machine （LightGBM）, and K-Nearest Neighbors （KNN）. Model performance was evaluated using the area under the receiver operating characteristic curve （AUC）, calibration curves, and decision curve analysis （DCA）. The SHapley Additive exPlanations （SHAP） method was applied for interpretability of the optimal model. Results LASSO regression identified 11 core predictive variables： atrial fibrillation, speech clarity impairment, depression, TOAST classification, medial temporal lobe atrophy, white matter hyperintensities, multiple lesions, years of education, age, the National Institutes of Health Stroke Scale （NIHSS） score, and infarct volume. The XGBoost model demonstrated optimal and stable predictive performance, with an AUC of 0.863 in the training set and 0.854 in the validation set, differing by only 0.009. Calibration curves yielded Brier scores of 0.141 and 0.155 for the training and validation sets, respectively. DCA showed that the XGBoost model provided a higher clinical net benefit within the threshold probability range of 20%-70%. SHAP analysis revealed that infarct volume, depression, multiple lesions, age, and NIHSS score were the top predictors of PSCI, while years of education had a protective effect. Conclusion The XGBoost-based PSCI prediction model demonstrates good discrimination, calibration, and clinical utility, providing a data-driven decision-support tool for early risk stratification and clinical management of PSCI.

Objective To investigate the association between serum cystatin C and hyperuricemia in overweight/obese populations in the United States and China, and to evaluate whether sex, age, and BMI modify this association. Methods We analyzed data from the National Health and Nutrition Examination Survey （NHANES） 1999-2002, including 1149 participants with overweight or obesity. Additionally, we included 2157 individuals with overweight or obesity who underwent physical examinations or sought medical care at the Third People's Hospital of Chengdu, China, between November 2020 and August 2022. Logistic regression with interaction terms was used to assess associations and restricted cubic spline （RCS） analysis was used to characterize the nonlinear relationship between serum cystatin C and hyperuricemia. Results Weighted logistic regression based on the NHANES data showed that participants in the highest quartile of serum cystatin C had an increased risk of hyperuricemia （OR=5.60; 95% CI： 2.51-12.50）. This association was consistently observed in the Chengdu cross-sectional sample （OR=2.67; 95% CI： 1.77-4.03）. RCS analysis showed no significant nonlinear dose-response relationship between serum cystatin C and hyperuricemia in either study population. Subgroup analyses demonstrated no statistically significant differences in the association between cystatin C and hyperuricemia across strata of sex, age, and BMI （all P for interaction >0.05）. Conclusion In two independent populations with overweight/obesity, higher serum cystatin C levels were consistently associated with a higher prevalence of hyperuricemia, and this association was not significantly modified by sex, age, or BMI.

Objective Given the high cost of imported reagents for community-based latent tuberculosis infection （LTBI） screening and the lack of local data on domestic reagents in the elderly population, this study aimed to evaluate the diagnostic performance and clinical applicability of domestic interferon-gamma release assay （IGRA） reagents for LTBI screening in the community-dwelling elderly population, within the implemented “three-tier screening and closed-loop management” pathway in Huangpu District, Shanghai. Methods A retrospective study was conducted based on the data from the TB-free community screening program in Huangpu District. A total of 2019 permanent residents aged ≥42 years were enrolled from April to November 2025 and screened for LTBI using a domestic Biotron IGRA kit. A subset of 278 samples （all positive samples and randomly selected negative samples） was tested head-to-head against the international reference standard QuantiFERON-TB Gold Plus （QFT-Plus） to evaluate concordance. Primary-care adaptability was assessed in the context of the existing screening pathway. Results The overall LTBI positivity rate was 6.3% （128/2019） among the community-dwelling elderly population. Male sex was an independent risk factor for LTBI positivity （adjusted OR = 2.231, 95% CI： 1.53-3.26）. The overall concordance rate between the domestic Biotron IGRA kit and QFT-Plus was 91.4% with a kappa value of 0.83. Sensitivity was 92.2% and specificity was 90.7%. IFN-γ release levels were strongly positively correlated （ρ=0.929, P<0.01）, and discordant samples were concentrated in the critical gray zone of 0.2-0.6 U/mL. The assay can be seamlessly integrated into the existing community-based three-tier screening process and is compatible with the integrated chronic disease management service model. Conclusion The domestic Biotron IGRA kit showed reliable diagnostic performance in the community-dwelling elderly population and has significant cost advantages. It can replace imported reagents for large-scale community-based LTBI screening in low-prevalence areas and support the cost-effective development of TB-free communities.

Cerebral amyloid angiopathy （CAA） is an age-related cerebral small vessel disease characterized by β-amyloid deposition in the walls of small vessels in the cerebral cortex and the leptomeninges, leading to vascular dysfunction and perivascular brain injury. Its incidence increases significantly with age, and CAA is a major cause of lobar hemorrhage and dementia in the elderly. Currently, there are no disease-modifying treatments for CAA, and clinical management focuses primarily on reducing the occurrence and recurrence of intracerebral hemorrhage. However, the increasing prevalence of ischemic stroke with advancing age necessitates a comprehensive risk-benefit assessment of anticoagulant or antiplatelet therapies in CAA patients with concurrent ischemic stroke. Current research lacks adequate exploration of therapeutic strategies for this population. This review systematically addresses epidemiology, imaging biomarkers, hemorrhage risk stratification, antithrombotic approaches, and strategies to monitor bleeding risks.

Postoperative delirium （POD） is a common neurocognitive disorder in elderly patients after surgery, and its pathogenesis has not yet been fully elucidated. Evidence suggests that POD does not result from a single pathological pathway, but rather from the combined effects of a vulnerable brain predisposed to the condition and perioperative stress. The gut microbiota may be involved in this process and contribute to the onset and progression of POD through multilayered mechanisms. Based on a synthesis of current experimental and clinical evidence, this review proposes that the gut microbiota plays an integrative role in POD, participating in its development through mechanisms involving inflammation, barrier dysfunction, gut microbiota-derived metabolites, neurotransmitters, and vagal reflex pathways. This review also discusses the potential translational value of gut microbiota-targeted strategies for preventing and early intervention for POD. The aim is to provide new insights for developing mechanism-oriented, individualized perioperative management strategies.

Progressive pulmonary fibrosis （PPF） is a group of interstitial lung diseases （ILD） characterized by a progressive phenotype and poor prognosis. It is based on a comprehensive assessment of symptoms, lung function and imaging findings. PPF is not limited to specific etiologies, but encompasses patients with ILD presenting with progressive fibrosis, with the exception of idiopathic pulmonary fibrosis.Currently, it remains difficult to identify early-stage patients at risk of progression and provide timely intervention. Existing antifibrotic treatments only slow disease progression without reversing it, and some patients exhibit poor tolerability. Therefore, this article reviews the pathogenesis, clinical identification, and treatment strategies for PPF, aiming to provide new insights into early prediction and precision-targeted therapy for patients with PPF.

Vascular remodeling is a pivotal pathological process in numerous cardiovascular diseases. Peroxisome proliferator-activated receptor delta （PPARδ）, a key member of the nuclear receptor family, not only plays a crucial role in regulating physiological processes such as energy metabolism, inflammatory responses, and oxidative stress, but also influences the vascular remodeling process by modulating various complex pathophysiological mechanisms, including the proliferation and migration of vascular smooth muscle cells and extracellular matrix remodeling. In-depth exploration of the specific mechanisms by which PPARδ affects vascular remodeling can help elucidate the pathogenesis of cardiovascular diseases, identifying novel intervention targets, mitigating the risk of cardiovascular events, and improving patient prognosis. This article reviews the structure and function of PPARδ and its recent research on the impact and mechanisms in vascular remodeling, aiming to offer new therapeutic targets for cardiovascular diseases.

mRNA delivery technology, an emerging strategy for cancer treatment, achieves therapeutic objectives by precisely delivering protein-encoding mRNA into cells to express target proteins. Delivery vehicles include lipid nanoparticles（LNPs）, polymeric nanoparticles, and exosomes. Component optimization and targeted modifications significantly enhance organ- and cell-specific delivery efficiency and facilitate efficient endosomal escape. PTEN mRNA delivered to non-small cell lung cancer cells combined with PD-1 antibody treatment normalizes the immunosuppressive microenvironment and overcomes primary resistance. Intratumoral injection of OX40L mRNA-LNPs into hepatocellular carcinoma cells inhibits tumor growth by activating T-cell immune responses. pH-responsive nanoparticles encapsulating PTEN mRNA delivered to trastuzumab-resistant breast cancer cells block the PI3K/Akt pathway, thereby inhibiting tumor growth. All-trans retinoic acid-modified LNPs-encapsulating mRNA delivered to colorectal cancer cells more effectively penetrates the mucosal barrier, driving T-cell homing to tumor sites. Liposomal delivery of p53 mRNA to ovarian cancer cells restores p53 activity, regulating apoptosis and cell cycle to reverse chemotherapy resistance. However, clinical translation remains hindered by challenges such as suboptimal delivery efficiency, immunogenicity, and personalized production. Future efforts should integrate single-cell omics, novel degradable carriers, and combination immunotherapies to drive breakthroughs for mRNA-based precision cancer therapy.

Cerebral ischemia-reperfusion injury （CIRI） occurs when cerebral blood flow is restored following an ischemia episode. Although oxygen and nutrients are depleted during ischemia, the subsequent rapid reperfusion can paradoxically cause irreversible neuronal damage. CIRI involves multiple programmed cell death （PCD） pathways, including apoptosis, pyroptosis, and necroptosis. The recently proposed concept of PANoptosis highlights the close integration and molecular crosstalk among these three PCD modalities in inflammatory injury settings, offering a novel perspective for elucidating cell death mechanisms in CIRI. This review summarizes the definition of PANoptosis, the molecular composition of PANoptosomes, and the potential roles of different PANoptosome subtypes in CIRI, aiming to open new avenues for therapeutic intervention and drug development.