Diabetic Nephropathy (DN) is the leading cause of end-stage renal disease (ESRD) globally, representing a major global health burden with limited disease-modifying therapies. Podocyte injury serves as the core pathological hallmark of DN, and conventional treatments targeting metabolic disorders or hemodynamic abnormalities fail to reverse the progressive decline of renal function. Accumulating evidence over the past decade has established that high glucose-induced podocyte pyroptosis—a pro-inflammatory form of programmed cell death—is a key driving force in DN progression. Its core molecular mechanism hinges on the activation of the TXNIP-NLRP3 inflammasome axis. Under sustained hyperglycemic conditions, excessive reactive oxygen species (ROS) are generated via pathways including the polyol pathway, advanced glycation end products (AGEs) accumulation, and mitochondrial dysfunction. Concurrently, methylglyoxal (a glucose metabolite) mediates post-translational modification of thioredoxin-interacting protein (TXNIP). These events collectively trigger the dissociation of TXNIP from thioredoxin (TRX), a redox-regulating protein. The free TXNIP then translocates to the mitochondria, where it binds to The NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) and promotes inflammasome assembly. This assembly activates cysteine-aspartic acid protease 1 (caspase-1), which cleaves Gasdermin D (GSDMD) to generate its N-terminal fragment (GSDMD-NT). GSDMD-NT oligomerizes to form membrane pores, leading to podocyte swelling, rupture, and the release of pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18). These cytokines amplify local inflammatory responses, induce mesangial cell proliferation, and accelerate extracellular matrix deposition, ultimately exacerbating glomerulosclerosis. MCC950, a highly selective NLRP3 inhibitor, exerts its therapeutic effects through a multi-layered mechanism: it binds to the NACHT domain (NAIP, CIITA, HET-E and TP1 domain) of NLRP3 with nanomolar affinity, forming hydrogen bonds with key residues (Lys-42 and Asp-166) within the ATP-hydrolysis pocket to block ATP hydrolysis, thereby locking NLRP3 in an inactive conformational state. Additionally, MCC950 interferes with the protein-protein interaction between TXNIP and NLRP3 and regulates mitochondrial homeostasis to reduce ROS production. Preclinical studies have demonstrated that MCC950 dose-dependently reduces proteinuria, restores the expression of podocyte-specific markers (nephrin and Wilms tumor 1 protein, WT1), and alleviates podocyte foot process fusion and glomerulosclerosis in both streptozotocin (STZ)-induced type 1 diabetic models (characterized by absolute insulin deficiency) and db/db type 2 diabetic models (driven by insulin resistance). However, discrepancies in therapeutic outcomes exist across different models—some studies report exacerbated renal inflammation and fibrosis in STZ-induced models—which may stem from differences in disease pathogenesis, intervention timing (early vs. mid-stage disease), and dosing duration. Despite its promising preclinical efficacy, MCC950 faces significant translational challenges, including low oral bioavailability, insufficient podocyte targeting, potential hepatotoxicity, and drug-drug interactions with statins (commonly prescribed to diabetic patients for cardiovascular risk management). Furthermore, off-target effects such as the inhibition of carbonic anhydrase 2 have been identified, raising concerns about its safety profile. Nevertheless, its unique mechanism of action—directly blocking podocyte pyroptosis by targeting the TXNIP-NLRP3 axis—endows it with substantial translational value. In the future, strategies to overcome these barriers are expected to advance its clinical application: targeted delivery via nanocarriers (e.g., PLGA-PEG nanoparticles or nephrin antibody-conjugated systems) to enhance renal accumulation and podocyte specificity; precise patient stratification based on biomarkers such as serum IL-18 and renal TXNIP/NLRP3 expression to identify “inflammatory-phenotype” DN patients most likely to benefit; and combination therapy with sodium-glucose cotransporter 2 (SGLT2) inhibitors—whose metabolic benefits synergize with MCC950’s anti-inflammatory effects. These approaches hold great potential to break through clinical translation bottlenecks, offering a novel, precise anti-inflammatory treatment option for DN and addressing an unmet clinical need for therapies targeting the inflammatory underpinnings of the disease.

Diabetic Nephropathy (DN) is the leading cause of end-stage renal disease (ESRD) globally, representing a major global health burden with limited disease-modifying therapies. Podocyte injury serves as the core pathological hallmark of DN, and conventional treatments targeting metabolic disorders or hemodynamic abnormalities fail to reverse the progressive decline of renal function. Accumulating evidence over the past decade has established that high glucose-induced podocyte pyroptosis—a pro-inflammatory form of programmed cell death—is a key driving force in DN progression. Its core molecular mechanism hinges on the activation of the TXNIP-NLRP3 inflammasome axis. Under sustained hyperglycemic conditions, excessive reactive oxygen species (ROS) are generated via pathways including the polyol pathway, advanced glycation end products (AGEs) accumulation, and mitochondrial dysfunction. Concurrently, methylglyoxal (a glucose metabolite) mediates post-translational modification of thioredoxin-interacting protein (TXNIP). These events collectively trigger the dissociation of TXNIP from thioredoxin (TRX), a redox-regulating protein. The free TXNIP then translocates to the mitochondria, where it binds to The NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) and promotes inflammasome assembly. This assembly activates cysteine-aspartic acid protease 1 (caspase-1), which cleaves Gasdermin D (GSDMD) to generate its N-terminal fragment (GSDMD-NT). GSDMD-NT oligomerizes to form membrane pores, leading to podocyte swelling, rupture, and the release of pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18). These cytokines amplify local inflammatory responses, induce mesangial cell proliferation, and accelerate extracellular matrix deposition, ultimately exacerbating glomerulosclerosis. MCC950, a highly selective NLRP3 inhibitor, exerts its therapeutic effects through a multi-layered mechanism: it binds to the NACHT domain (NAIP, CIITA, HET-E and TP1 domain) of NLRP3 with nanomolar affinity, forming hydrogen bonds with key residues (Lys-42 and Asp-166) within the ATP-hydrolysis pocket to block ATP hydrolysis, thereby locking NLRP3 in an inactive conformational state. Additionally, MCC950 interferes with the protein-protein interaction between TXNIP and NLRP3 and regulates mitochondrial homeostasis to reduce ROS production. Preclinical studies have demonstrated that MCC950 dose-dependently reduces proteinuria, restores the expression of podocyte-specific markers (nephrin and Wilms tumor 1 protein, WT1), and alleviates podocyte foot process fusion and glomerulosclerosis in both streptozotocin (STZ)-induced type 1 diabetic models (characterized by absolute insulin deficiency) and db/db type 2 diabetic models (driven by insulin resistance). However, discrepancies in therapeutic outcomes exist across different models—some studies report exacerbated renal inflammation and fibrosis in STZ-induced models—which may stem from differences in disease pathogenesis, intervention timing (early vs. mid-stage disease), and dosing duration. Despite its promising preclinical efficacy, MCC950 faces significant translational challenges, including low oral bioavailability, insufficient podocyte targeting, potential hepatotoxicity, and drug-drug interactions with statins (commonly prescribed to diabetic patients for cardiovascular risk management). Furthermore, off-target effects such as the inhibition of carbonic anhydrase 2 have been identified, raising concerns about its safety profile. Nevertheless, its unique mechanism of action—directly blocking podocyte pyroptosis by targeting the TXNIP-NLRP3 axis—endows it with substantial translational value. In the future, strategies to overcome these barriers are expected to advance its clinical application: targeted delivery via nanocarriers (e.g., PLGA-PEG nanoparticles or nephrin antibody-conjugated systems) to enhance renal accumulation and podocyte specificity; precise patient stratification based on biomarkers such as serum IL-18 and renal TXNIP/NLRP3 expression to identify “inflammatory-phenotype” DN patients most likely to benefit; and combination therapy with sodium-glucose cotransporter 2 (SGLT2) inhibitors—whose metabolic benefits synergize with MCC950’s anti-inflammatory effects. These approaches hold great potential to break through clinical translation bottlenecks, offering a novel, precise anti-inflammatory treatment option for DN and addressing an unmet clinical need for therapies targeting the inflammatory underpinnings of the disease.

Objective To investigate the impact of graft type on perioperative outcomes and long-term prognosis in patients undergoing surgical repair of post-myocardial infarction ventricular septal rupture (VSR) with concurrent coronary artery bypass grafting (CABG). Methods A retrospective analysis was conducted on clinical data from patients who underwent VSR repair and concurrent CABG at Fuwai Hospital between 2005 and 2022. Patients were divided into an arterial graft group and a saphenous vein graft (SVG)-only group based on the type of bypass grafts used. Clinical outcomes were compared between the two groups. Results A total of 92 patients were included, comprising 56 males and 36 females, with a mean age of (62.4±7.9) years. The arterial graft group consisted of 60 patients, and the SVG-only group consisted of 32 patients. There were no statistical differences between the two groups in age, gender, body mass index, past medical history, time interval from myocardial infarction to surgery, or culprit vessel distribution (P>0.05). A higher proportion of patients in the SVG-only group received preoperative intra-aortic balloon pump (IABP) support (56.3% vs. 35.0%, P=0.049). However, cardiopulmonary bypass time, aortic cross-clamp time, and early mortality rates were similar between the two groups (P>0.05). Follow-up data revealed no statistically significant differences in cumulative 10-year survival (82.8% vs. 80.0%, P=0.940) or freedom from major adverse cardiovascular and cerebrovascular events (49.6% vs. 58.6%, P=0.491) between the SVG-only and arterial graft groups. Furthermore, graft type did not significantly affect long-term mortality in patients with a culprit vessel in the left anterior descending artery or those with multivessel disease. Conclusion In patients undergoing delayed repair of VSR with concomitant CABG, the use of arterial or saphenous vein grafts does not significantly impact perioperative outcomes or long-term prognosis. Future research should further explore the benefits of different revascularization strategies to optimize treatment for this population.

The epidemiological and spatiotemporal clustering characteristics of dengue fever in Fujian Province were ana-lyzed,to provide a scientific basis for dengue fever prevention and control.Descriptive epidemiology,spatial autocorrelation a-nalysis,and spatiotemporal scanning were used to analyze dengue fever cases in Fujian Province from 2011 to 2023.In this peri-od,a total of 3 586 cases of dengue fever were reported in Fujian Province,including 2 360 local cases,1 134 imported cases from abroad,and 92 imported cases from China.Cases were reported in ten prefectures and cities of the province,and 81 out of 88 counties reported cases.Imported cases were reported throughout the year in Fujian Province,but the occurrence of local ca-ses showed clear seasonality.Local cases and domestic imports were concentrated in August to October,whereas overseas im-ports occurred primarily from June to October.The imported cases were mainly from Southeast Asian countries,but a trend of spreading from Southeast Asian countries to South Asia,Africa,the Americas,and other regions,was observed.Spatio-tem-poral clustering of dengue fever was found in Fujian Province(Moran's I value 0.14-0.66,P＜0.05),and the high-high ag-gregation areas were distributed primarily in Fuzhou,Quanzhou,and Putian.Spatio-temporal scanning detected three aggrega-tion areas:one main and two secondary.The aggregation time was from the end of July to October,and the distribution was primarily in Fuzhou,Quanzhou,Putian,Zhangzhou,and Xiamen.The distribution of dengue fever in Fujian Province showed clear spatial and temporal clustering from the end of July to October,and the distribution was primarily in Fuzhou,Quanzhou,Putian,Zhangzhou,and Xiamen.For high concentration areas,national health campaigns,mosquito prevention and control,epidemic surveillance,medical personnel training,and other relevant measures could be carried out in advance before local cases appear every year.Reduce local transmission of dengue fever due to importation.

Objective:To explore the value of contrast enhanced ultrasonography(CEUS) combined with shear wave elastography (SWE) in the diagnosis of urethral stricture.Methods:One hundred and twenty patients with urethral stricture were recruited, and preoperative retrograde urography, common urethral ultrasound, and CEUS were used to measure the length of the stricture site, and SWE was used to detect the elasticity value of the stricture site and its nearby spongiosum. Intraoperative urethral stricture lesion site measurements were performed to confirm the actual lesion location and length during surgery and to compare them with the lengths measured in the preoperative examination;4 months after surgery, SWE was used to detect the stiffness of the surgical site and to assess the surgical efficacy and prognosis.Results:The stenosis length measured by CEUS and intraoperative measurement had no statistical difference: (4.41 ± 1.47) cm vs. (4.37 ± 1.36) cm, t = 0.22, P>0.05. The elastic value in urethra stenosis in SWE was higher than that in normal urethra: (33.1 ± 6.7) kPa vs. (23.3 ± 4.1) kPa, there was statistical difference ( t = 13.67, P<0.05). The elastic value of unobstructed urethra and that of normal urethra after reconstruction had no statistical difference ( t = 0.95, P>0.05). Conclusions:CEUS combined with SWE is a safe, accurate and effective method to evaluate urethral stricture. SWE can be used to measure postoperative outcomes and recurrence.

Objective:To explore the relationships between physical activity and cognitive impairment in older adults aged ≥65 years in longevity areas in China.Methods:A total of 6 081 older adults aged ≥65 years from the Healthy Ageing and Biomarkers Cohort Study in China in 2021 were included in this study. Information about their demographic characteristics, lifestyles, and chronic disease histories were collected, the intensity of physical activity was evaluated by using Physical Activity Scale for the Elderly, and the cognitive function was evaluated by using Mini-Mental State Examination Scale (Chinese version). Multifactorial logistic regression model was used to analyze the associations between different levels and types of physical activity and cognitive impairment in older adults.Results:In the 6 081 older adults, 1 829 (30.1%) had cognitive impairment. After adjusting for confounders, older adults with T2 and T3 levels of physical activity had lower risks for cognitive impairment compared with those with T1 levels of physical activity, with ORs of 0.47 (95% CI: 0.40-0.55) and 0.22 (95% CI: 0.18-0.28). The results of different types of physical activities showed that the ORs in leisure activity T2 and T3 groups were 0.52 (95% CI: 0.44-0.63) and 0.49 (95% CI: 0.41-0.58), and the ORs in housework activity T2 and T3 groups were 0.36 (95% CI: 0.30-0.42) and 0.19 (95% CI: 0.16-0.24). There was no significant association between work-related activity and cognitive impairment. Conclusion:There is a negative association between the intensity level of physical activity and cognitive impairment, and active leisure and household activities might reduce the risk for cognitive impairment.

Objective To investigate the mechanism of action of Guizhi Fuling pill in treating chro-nic prostatitis(CP)using network pharmacology and molecular docking techniques.Methods Compo-nents of Guizhi Fuling pill were collected from the Traditional Chinese Medicines Systems Pharmacolo-gy Platform(TCMSP),and target information was obtained from the SwissTarget database.Targets for chronic prostatitis were screened from the GeneCards,OMIM,CTD,and DisGeNET disease data-bases.A protein-protein interaction(PPI)network was established and analyzed.Gene ontology(GO)functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway en-richment analysis were performed using the DAVID database.The Cytoscape software was employed to construct an association network linking the components of Guizhi Fuling Pill,their targets,and the targets of chronic prostatitis.Molecular docking was conducted using AutoDock Vina software to verify the binding stability between the components of Guizhi Fuling pill and their targets.Results After screening and deduplication in the TCMSP database,76 components of Guizhi Fuling Pill were iden-tified,and 655 component targets were retrieved from the SwissTarget database.There were 190 intersecting targets between GuizhiFuling Pill and chronic prostatitis.GO analysis indicated that Guizhi Fuling Pill may treat chronic prostatitis by participating in processes such asapoptosis,ATP binding,and signal transduction.KEGG analysis suggested that Guizhi Fuling Pill can regulate pathways such as phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)and mitogen-acti-vated protein kinase(MAPK)to intervene in chronic prostatitis.Molecular docking data demonstra-ted that the components of Guizhi Fuling pill exhibited stable conformations with their targets.Con-clusion The components of Guizhi Fuling Pill can stably bind to their targets and exert therapeutic effects on chronic prostatitis through multiple targets and pathways.

Osteosarcoma (OS) is the most prevalent primary malignant bone tumor affecting children and adolescents. Despite ongoing research efforts, the 5-year survival rate has remained stagnant for many years, highlighting the critical need for novel drug development to enhance current treatment protocols. Ziyuglycoside II (ZYG II), a triterpenoid saponin extracted from S. officinalis, has recently demonstrated antitumor properties. This study evaluates the antitumor effect of ZYG II on osteosarcoma and elucidates its mechanism of action through the co-regulation of p53 and estrogen-related receptor gamma (ESRRG), which inhibits disease progression. The research employs in vitro experiments using multiple established osteosarcoma cell lines, as well as in vivo studies utilizing a nude mouse model of orthotopic xenograft osteosarcoma. Additionally, ESRRG shRNA was used to construct stable ESRRG-reducing OS cell lines to investigate the molecular mechanism by which ZYG II exerts its anti-osteosarcoma effects through the co-regulation of ESRRG and p53. Results indicate that ZYG II administration led to decreased OS cell viability and reduced tumor volumes. Furthermore, cell cycles were arrested at the G₀/G₁ phase, while the proportion of apoptotic cells increased. Expression of p53, ESRRG, p21, Bax, Cleaved Caspase-9, and Cleaved Caspase-3 proteins increased, while expression of CDK4, Cyclin D1, and Bcl-2 proteins decreased. Multiple ZYG II and ESRRG docking patterns were simulated through molecular docking. Comparing the pharmacodynamic response of ZYG II to OS cell lines with reduced ESRRG and normal expression demonstrated that ZYG II inhibits osteosarcoma progression, induces cell cycle arrest, and promotes cell apoptosis through the coordination of p53 and ESRRG. In conclusion, ZYG II inhibits osteosarcoma progression, leads to cell cycle arrest, and promotes cell apoptosis through synergistic regulation of p53 and ESRRG.
Osteosarcoma/physiopathology* ; Tumor Suppressor Protein p53/genetics* ; Humans ; Animals ; Saponins/chemistry* ; Bone Neoplasms/physiopathology* ; Signal Transduction/drug effects* ; Cell Line, Tumor ; Mice, Nude ; Mice ; Apoptosis/drug effects* ; Receptors, Estrogen/genetics* ; Mice, Inbred BALB C ; Female ; Male ; Xenograft Model Antitumor Assays

Objective:To evaluate the diagnostic performance of resting echocardiography in detecting severe coronary artery stenosis.Methods:A total of 136 patients with suspected coronary artery disease（CAD）who presented to Sichuan Provincial People's Hospital between January 2021 and December 2024 were prospectively enrolled. All patients underwent both coronary computed tomography angiography（CCTA）and transthoracic echocardiography within one week. Based on CCTA results，the patients were divided into non-severe stenosis group（ n=78）and severe stenosis group（ n=58）. Echocardiographic parameters including left atrial maximum volume（LAVmax），left ventricular global longitudinal strain（GLS），left ventricular longitudinal strain of endo-myocardium，mid-myocardium，epi-myocardium（LSendo，LSmid，LSepi），early diastolic mitral inflow velocity（E），early diastolic mitral annular velocity of the lateral and septal walls（e'），and E/e' were measured. Predictive factors for severe coronary stenosis were identified using LASSO regression，and a nomogram model was developed via multivariate Logistic regression. Model performance was evaluated using ROC curves，calibration curves，and decision curve analysis. Results:Multivariate Logistic regression analysis revealed LSendo，LAVmax，and E/e' as independent predictors of severe coronary artery stenosis. The nomogram constructed based on these predictors achieved an area under the curve of 0.798（95% CI=0.723-0.873），with sensitivity and specificity of 0.756 and 0.759，respectively. Conclusions:The resting echocardiography-based nomogram model demonstrates good diagnostic efficacy for severe coronary artery stenosis. It may serve as a noninvasive tool to assist in risk stratification and clinical decision-making in patients with suspected CAD.

Objective:To analyze the clinical effects of an anterior cruciate ligament (ACL) tunnel locator applied in the arthroscopic reduction and fixation of Schatzker type Ⅳ tibial plateau fracture plus posterolateral column collapse.Methods:A retrospective study was conducted to analyze the clinical data of 12 patients with Schatzker type IV tibial plateau fracture combined with posterolateral column collapse who had undergone arthroscopic reduction and fixation assisted by an ACL locator at Department of Orthopedics and Trauma Surgery, The Hospital Affiliated to Yunnan University from January 2020 to December 2022. There were 8 males and 4 females with an age of (44.5±6.4) years (set as an observation group). According to a 1∶1 ratio, another contemporary 12 patients of the same category were selected as a control group who had been treated by double-plate-screw fixation through internal and external double incisions. They were 7 males and 5 females with an age of (42.6±6.3) years. The operation time, incision length, intraoperative blood loss, postoperative hospital stay, and postoperative complications were recorded and compared between the 2 groups. At the same time, the Rasmussen radiological and functional scores at 1, 3, and 12 months after operation were recorded for intergroup and intragroup comparisons.Results:There was no statistically significant difference in the preoperative general data between the 2 groups, showing the 2 groups were comparable ( P>0.05). All the 24 patients were followed up for (18.2±3.5) months after operation. In the observation group, the operation time [(96.3±6.3) min], incision length [(8.5±0.6) cm], and postoperative hospital stay [(8.1±1.3) d] were significantly shorter than those in the control group [(128.2±7.5) min, (15.9±0.8) cm, and (9.3±1.2) d], and the intraoperative blood loss [50.0 (41.5, 59.0) mL] was significantly less than that in the control group [135.0 (121.5, 147.5) mL] (all P<0.05). However, intergroup comparisons showed no statistically significant differences in Rasmussen radiographic scores or functional scores at 1 month, 3 months, or 12 months postoperatively between the 2 groups ( P>0.05). Additionally, no significant differences were observed in postoperative complications between the 2 groups ( P>0.05). Conclusions:In the arthroscopic reduction and fixation of Schatzker type Ⅳ tibial plateau fracture plus posterolateral column collapse, compared with the traditional double-plate-screw fixation through double incisions, assistance of an ACL tunnel locator leads to advantages of being more minimally invasive and more surgically efficient. However, the 2 techniques lead to comparable postoperative functional recovery.