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.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

Objective To systematically evaluate the clinical effects of remote ischaemic preconditioning (RIPC) in elective vascular surgery. Methods Electronic searches were conducted in The Cochrane Library, PubMed, EMbase, Web of Science, CNKI, Wanfang Data, VIP Database, and CBM. Relevant randomized controlled trials (RCTs) were screened according to inclusion and exclusion criteria. Meta-analysis was performed using RevMan 5.3 software, and the risk of bias was assessed using the Cochrane risk of bias tool. Results A total of 15 studies involving 1 382 patients were included. The meta-analysis results showed no statistically significant difference between RIPC and non-RIPC groups in reducing perioperative mortality in elective vascular surgery (P>0.05). There were also no statistically significant differences between the two groups of vascular surgery patients regarding the incidence of myocardial infarction, renal injury, postoperative stroke, postoperative length of hospital stay, duration of surgery or total anesthesia time, or the incidence of limb injury, arrhythmia, heart failure, and pneumonia (P>0.05). Conclusion For patients undergoing elective vascular surgery, there are no significant differences between RIPC and non-RIPC in terms of perioperative mortality and other clinical endpoint outcomes.

Objective: To explore the risk of endometrial polyp (EP) based on lipid metabolism and vaginal micro- ecology combined with uterine volume line drawing model. Methods: 143 EP patients treated by hysteroscopic sur- gery were selected as the experimental group , and 113 healthy women were selected as the control group at the same time. The data were randomly divided into training set and validation set according to the ratio of 7 : 3. The clinical data of the two groups were collected and recorded , and t/χ2 test , LASSO regression and multifactorial lo- gistic regression analysis were used to screen the independent risk factors , construct the prediction model , and draw the column line graph. The performance of the model was evaluated by applying subject operating characteristic (ROC) curves , calibration curves , Hosmer-Lemeshow test and clinical decision-making (DCA) curves. Results: Multifactorial logistic regression analysis showed that total cholesterol ( TC) , low-density lipoprotein cholesterol (LDL-C) , vaginal microecological balance , and uterine volume were independent risk factors for the development of EP. ROC curve analysis showed that the AUC values of the training and validation sets of the column line graph model were 0. 935 and 0. 887 , respectively , and its sensitivity and specificity were 90. 21% , 83. 46% and 86. 29% , 80. 66% respectively , The Hosmer-Lemeshow test showed that the model fits well ( training set : χ2 = 2. 261 , P = 0. 840 ; validation set : χ2 = 4. 837 , P = 0. 441) and the calibration curves of the training and validation sets were close to the ideal curves , which indicated that the model had good prediction accuracy; the analysis of DCA curves of the training and validation sets both showed that the column-line graph model had a good clinical benefit rate in predicting EP. Conclusion TC , LDL-C , vaginal microecological balance and uterine volume are independent risk factors for EP , and the column-line diagram model constructed by the model has high clinical ben- efit , calibration and accuracy in predicting the risk of EP.

Hyperuricemia(HUA)and gout became typical metabolic disorders characterized by multiple pathogenic factors.Their incidence increased annually,affecting younger populations.Given that uric acid(UA)and inflammation were the primary disease mechanisms,the search for effective and low-side-effect UA-lowering and anti-inflammatory drugs became a pressing scientific priority.Traditional Chinese medi-cine(TCM)encompassed a rich array of theoretical and practical experience,along with a diverse range of chemical substances,making herbs or their components potential sources for therapeutic drugs.Despite the significant role that modern herbal medicines played in treating HUA and gout,the existing research literature remained fragmented,lacking comprehensive and systematic reviews.In this review,we focused on the regulation of UA and summarized the discovery of UA-lowering pharmacodynamic components or ingredients derived from herbs and formulas,as well as their multi-targeted mechanisms of action.Emphasizing this focus,we proposed that,compared to acute inflammation,low-grade inflammation may play a relatively"unnoticed"role in the disease process.In contrast to Western medicine,we discussed the risks and benefits of herbal medicines and their ingredients for treatment,drawing from theoretical insights and clinical practice.This review offered comprehensive perspectives on the research into anti-HUA and gout treatments using herbal medicines and their natural products.Additionally,it provided a forward-looking view on natural product discovery,the exploration of ther-apeutic strategies,and new drug research in this field.

AIM To investigate the protective effects of the aqueous extract of Bulbophyllum kwangtungense Schltr.on D-galactose(D-gal),an oxidative stress-induced liver damage in rats.METHODS 60 Male SD rats were randomly divided into the normal control group,the model group,the resveratrol group(20 mg/kg),and low-dose,medium-dose,and high-dose B.kwangtungense aqueous extract groups(750,1 500 and 3 000 mg/kg).Except for those of the normal control group,the rats of the other groups were subcutaneously injected with D-gal(200 mg/kg)in the back of neck to establish a liver damage model.Simultaneously,each group underwent the corresponding drug administration by gavage(10 mL/kg)once daily for 42 days.After the treatment period,the rats had their peripheral blood and liver tissues collected for the calculation of the liver index;their serum AST and ALT activities,hepatic SOD and GSH-Px activities,and MDA levels measured;their hepatic pathological changes observed using HE staining;their hepatic mRNA expressions of Nrf2,NQO-1 and HO-1 detected by RT-qPCR;and their hepatic protein expressions of Nrf2,NQO-1,HO-1,Bax,Bcl-2 and cleaved Caspase-3 measured by Western blot.RESULTS Compared with the model group,the groups intervened with medium-dose or high-dose B.kwangtungense aqueous extract showed increased liver index level(P＜0.01);decreased serum AST and ALT activities(P＜0.01);increased hepatic SOD and GSH-Px activities(P＜0.05,P＜0.01);reduced MDA levels(P＜0.01);alleviated pathological liver damage and increased hepatic mRNA and protein expressions of Nrf2,NQO-1 and HO-1(P＜0.05,P＜0.01);and reduced protein expressions of cleaved Caspase-3 and the Bax/Bcl-2 ratio as well(P＜0.05,P＜0.01).CONCLUSION The aqueous extract of B.kwangtungense is protective of rats with D-gal-induced liver injury,and the underlying mechanism may associate with the inhibition of oxidative stress and the suppression of hepatocellular apoptosis mediated by the activation of the Nrf2/HO-1/NQO-1 signaling pathway.

Objective To explore the compatibility law of amenorrhea and commonly used local herbs in southwest China using hypergraph;To provide drug choice for the clinical treatment of modern TCM amenorrhea and promote the development and utilization of local Chinese materia medica resources.Methods In this study,the data of prescriptions for the treatment of amenorrhea in Southwest China were used as the data source.By constructing formulas related to amenorrhea-hypergraph(AFR-HG),the topological structure of AFR-HG was analyzed,and the core subnet was extracted according to the node weighted hypercentrality.Based on the sub-network AFR-HG-p1 extracted from the top 20 kinds of Chinese materia medica in AFR-HG,the Kumar algorithm was used to divide the efficacy community network.Results A total of 123 amenorrhea prescriptions were included in this study.Angelicae Sinensis Radix,Carthami Flos,Cyperi Rhizoma,Chuanxiong Rhizoma and other drugs with the efficacy of promoting blood circulation and removing blood stasis,soothing liver and regulating qi,and warming and tonifying were the main drugs with high frequency.Three layers of core subnets were extracted layer by layer through weighted hyper-centrality sorting.The first layer contained Angelicae Sinensis Radix,Chuanxiong Rhizoma,Hyperici Sampsonii Herba,etc.;the second layer of drugs were mainly Lycopi Herba,Rubiae Radix et Rhizoma,Bombycis Feculae,etc.;the third layer of drugs were mainly Ginseng Radix et Rhizoma Rubra,Moutan Cortex,Sargentodoxae Caulis and other drugs;based on the top 20 node overdose drugs,community drugs were obtained through community detection:the first community subnet was Armeniacae Semen Amarum,Draconis Sanguis,Corydalis Rhizoma,etc.,the second community subnet was Rubiae Radix et Rhizoma,Rosae Chinensis Flos,Hyperici Sampsonii Herba,etc.,and the third community subnet was Akebiae Caulis,Homalomenae Rhizoma,Bombycis Feculae,etc.Conclusion In prescriptions of amenorrhea in Southwest China,the treatment principles are basically consistent with modern clinical practice.In addition to commonly used drugs,local herbal medicines and similar medicines are also common.It is of great value to explore the rules of prescriptions for the development and utilization of Chinese materia medica resources.