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 evaluate the efficacy and safety of plasma exchange (PE) in thymoma-associated myasthenia gravis (MG), thereby to provide theoretical support for its application in the treatment of thymoma-associated MG. Methods: A total of 133 patients with thymoma-associated MG admitted from January 2018 to September 2024 were retrospectively analyzed. Patients were matched using propensity score to reduce selection bias, yielding 22 matched pairs for both PE group (n=22) and non-PE group (n=22). Patient characteristics including gender, age of disease onset, course of disease, history of thymoma resection, clinical absolute scores [clinical absolute scores (CAS) and clinical relative scores (CRS)], and synchronized immunotherapy regimen of the two groups were analyzed. The CAS scores before and after treatment were compared between the two groups, and the CRS was used to assess the treatment efficiency. Safety of the two treatment regimens were also compared. Continuous variables were compared using the t-test or ANOVA, while categorical data were compared by the chi-square test. Results: A total of 133 patients were included and divided into two groups according to whether they underwent plasma exchange treatment: the PE group (n=22) and the non-PE group (n=111). To exclude bias caused by large difference in the number of cases between the two groups, we performed propensity score matching. After matching, the number of cases in both groups was 22. There was no significant difference in baseline clinical characteristics between the two groups (P>0.05), including gender, age of onset, duration of disease course, history of thymectomy and baseline CAS score before treatment. Compared to the non-PE group, patients in the PE group showed more significant improvement in CAS score (5.09±1.95 vs 3.59±1.50, P<0.05) and a higher CRS score (75.00% vs 50.00%, P<0.001). Compared to the non-PE group, PE group had significantly longer ICU stay, longer hospital stay and higher hospitalization cost (P<0.05). There was no statistically significant difference in adverse events between the two groups during treatment (P>0.05). During long-term follow-up, both the PE and non-PE groups showed relatively low 1-, 3-, and 5-year recurrence rate, with no significant difference between the two groups (P>0.05). Conclusion: This study indicates that plasma exchange has clear value in the treatment of patients with thymoma-associated myasthenia gravis. It can not only significantly improve patients' muscle strength to alleviate motor dysfunction and enhance quality of life, but also does not significantly increase the incidence of adverse reactions. Therefore, it can be regarded as one of the preferred treatment options that achieve a "balance between efficacy and safety" for such patients, and provides an important basis for optimizing treatment strategies, improving prognosis, and promoting the application of subsequent treatment regimens.

AIM To study the chemical constituents from the water fraction of rhizoma of Smilax trinervula Miq.and their biological activities.METHODS Polyamide,silica gel,Sephadex LH-20,ODS and semi-preparative HPLC were used for isolation and purification,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The antitumor activities were determined by MTT mothod,and the inhibitory activities on α-glucosidase were determined by PNPG method.RESULTS Eleven compounds were isolated and identified as tyrosine(1),uridine(2),2-(2',3',4'-trihydroxybutyl)-6-(2",3",4"-trihydroxybutyl)-pyrazine(3),2-(1',2',3',4'-tetrahydroxybutyl)-6-(2",3",4"-trihydroxybutyl)-pyrazine(4),2-(1',2',3',4'-tetrahydroxybutyl)-5-(2",3",4"-trihydroxybutyl)-pyrazine(5),uracil(6),2-(1',2',3',4'-tetrahydroxybutyl)-5-(1",2",3",4"-tetrahydroxybutyl)-pyrazine(7),dioscin(8),shikimic acid(9),pyrazine(10),3,4-dihydroxyphenyethyl alcohol 8-O-β-D-glycopyranoside(11).The IC50 values of compounds 8 to human breast cancer cell MCF-7 was(2.36±0.26)μg/mL,and the IC50 values of compounds 3-5 and 7 to α-glucosidase were(1.54±0.15)-(10.53±0.38)μg/mL.CONCLUSION Compounds 1-7,10 are isolated from Smilax genus for the first time,and compound 9,11 are first isolated from this plant.Compound 8 has anti-tumor activity,and compounds 3-5,7 have α-glucosidase inhibitory activities.

Objective:To explore the correlation between the post-traumatic stress disorder(PTSD)level and postoperative fear disease progression and quality of life in patients undergoing laparoscopic myomectomy,and to analyze the related factors affecting the occurrence of PTSD in patients.Methods:120 patients who underwent laparoscopic myomectomy in Ruijin People's Hospital from April 2022 to April 2024 were selected,the PTSD occurrence was assessed with the Civilian version of PTSD checklist-civilian version(PCL-C)1 month after operation,and the progression of fear of Disease was assessed with the fear of progression questionnaire-short form(FoP-Q-SF),the quality of life was assessed with uterine fibroid symptoms and health-related quality of life questionnaire(UFS-QOL).The correlation between PTSD level and postoperative fear disease progression and quality of life in patients undergoing laparoscopic myomectomy was analyzed,and the factors of PTSD in patients undergoing laparoscopic myomectomy were analyzed by multivariate Logistic regression.Results:PTSD scores of in patients undergoing laparoscopic myomectomy was(36.93±5.69)score,fear of disease progression was(26.00±1.66)score,quality of life was(54.27±4.82)score.The total score of PCL-C was positively correlated with the total score of FoP-Q-SF,and negatively correlated with the total score of UFS-QOL(P＜0.05).The patients were divided into PTSD group(n=30)and non-PTSD group(n=90)according to whether or not occurrence of PTSD at 1 month after operation.Univariate analysis showed that,there were significant differences in age,education level,family income,number of fibroids,operation time and preoperative anxiety level between the PTSD group and the non-PTSD group(P＜0.05).Multivariate Logistic regression analysis showed that age ≥35 years old,operation time ≥90 min,preoperative anxiety level of moderate to severe,and increased total score of FoP-Q-SF were independent risk factors for PTSD in patients undergoing laparoscopic myomectomy(P＜0.05),and increased total score of UFS-QOL were protective factors(P＜0.05).Conclusion:The PTSD level in patients undergoing laparoscopic myomectomy is positively correlated with fear disease progression and negatively correlated with quality of life.Age,operation time,preoperative anxiety,fear disease progression and quality of life were the factors that influenced the occurrence of PTSD.

A 58-year-old female patient with breast cancer received treatment with pegylated recombinant human granulocyte colony-stimulating factor(PEG-rhG-CSF)injection after adjuvant chemotherapy.The serum creatinine level of the patient gradually increased from the normal baseline value to 199.3 μmol·L-1.The patient was diagnosed as acute kidney injury(AKI),after stopping the medication and providing symptomatic treatment,the patient's renal function gradually improved.The patient completed subsequent chemotherapy as planned without reusing PEG-rhG-CSF injection,and other medications and dosages remained unchanged.Renal function remained stable during follow-up.Naranjo's Assessment Scale was used to evaluate the association between PEG-rhG-CSF injection and AKI,the result was"probable."There are few reports of AKI occuring with PEG-rhG-CSF injection,and this case provides evidence for clinical safe medication.

Objective To observe the value of contrast-enhanced ultrasound(CEUS)for diagnosing malignant adnexal tumors.Methods Totally 112 patients with single adnexal masse were retrospectively enrolled and divided into benign adnexal tumor group(benign group,n=73)and malignant adnexal tumor group(malignant group,n=39).Clinical data,laboratory indicators,ovarian-adnexal ultrasound reporting and data system(O-RADS)classification based on conventional ultrasound(US),CEUS manifestations and CEUS classification of benign and malignant tumors were compared between groups.Multivariable logistic regression analysis of clinical and laboratory indicators being statistically different between groups,as well as US O-RADS classification and CEUS classification was performed to screen the independent predictors of malignant adnexal tumors,and combined models were constructed using forward stepwise regression method.The efficacy of each independent predictor and combined model for diagnosing malignant adnexal tumors was analyzed.Results Statistical differences of carbohydrate antigen 125(CA125),US O-RADS classification,enhancement time and level of CEUS,as well as CEUS classification were found between groups(all P＜0.05).CA125,US O-RADS classification and CEUS classification were all independent predictors of malignant adnexal tumors(all P＜0.05).Combined model Ⅰ,Ⅱ and Ⅲ were constructed based on CA125+CEUS classification,US O-RADS classification+CEUS classification and CA125+US O-RADS classification+CEUS classification,respectively.The area under the curve(AUC)of single CA125 level,US O-RADS classification,CEUS classification and combined model Ⅰ,Ⅱ and Ⅲ for diagnosing malignant adnexal tumor was 0.708,0.809,0.908,0.918,0.945 and 0.954,respectively.AUC of combined model Ⅲ was higher than that of combined model Ⅰ(Z=-2.142,P=0.032),while no significant difference of AUC was found between combined model Ⅱ and Ⅰ nor Ⅱ and Ⅲ(both P＞0.05).Conclusion CEUS could be used to effectively diagnose malignant adnexal tumor.Combining with CA125 level and US O-RADS classification could significantly improve its diagnostic efficacy.

Objective To explore the quality markers of Puerariae Lobatue Radix;To predict its"efficacy component group"with alcohol detoxification and liver protection effects.Methods Fingerprints of 26 batches of Puerariae Lobatue Radix samples from different origins in China was established.Multivariate statistical analysis was employed to identify quality markers,while network pharmacology and molecular docking were used to predict the potential"efficacy component group".Results UPLC fingerprint analysis calibrated 11 common peaks.Clustering analysis classified 26 batches of samples into 3 categories,and 7 quality markers were ultimately screened through multivariate statistical analysis,including mirificin,puerarin,puerarin-6''-O-xyloside,3'-methoxypuerarin,ononin,genistin and daidzin.Network pharmacology revealed that all 7 markers interacted with targets related to alcohol-associated liver disease,identifying 19 core targets such as TNF,CASP3,BCL2,MMP9,IL2,and 93 signaling pathways involving IL-17 and PI3K-Akt signaling pathways.Molecular docking demonstrated strong binding affinity between the 7 markers and target proteins,with binding energies<-5 kcal/mol.Conclusion The"efficacy component group",main targets and signaling pathways predicted in this study can provide support for the research on the mechanism,material basis and quality control of the alcohol detoxification and liver protection effects of Puerariae Lobatue Radix.

Objective To evaluate the efficacy and safety of enteric-coated metformin hydrochloride capsules(Junlida?)in patients with T2DM and poor glycemic control under lifestyle interventions.Methods In this study,419 patients with T2DM were recruited from 15 research centers from July 2020 to March 2022,and randomly divided into observation(Obs)group(n=209)and control group(Con,n=210)using a multicenter,randomized,double-blind,non-inferiority trial design.Patients in the Obs group were treated with enteric-coated Metformin hydrochloride capsules(Junlida?),and patients in the Con group were treated with Metformin hydrochloride tablets(Glucophage?).The optimal effective dose of 2 g/d was achieved within 4 weeks,and the reasonable dose was maintained until the end of treatment.The treatment period was 24 weeks.HbA1c and its compliance rate,FPG,and body weight were compared between the two groups in full analysis set(FAS)and protocol set(PPS).Safety and adverse events(AE)were evaluated in safety set(SS).Results A total of 414 participants were randomized(207 cases in Obs group and 207 cases in Con group).414 cases in FAS population(207 cases in Obs group and 207 cases in Con group),and 328 cases in PPS population(164 cases in Obs group and 164 cases in Con group),and 414 cases in SS population(207 cases in Obs group and 207 cases in Con group).After treatment,HbA1c,FPG and body weight were lower in both groups(P<0.05)in FAS and PPS.HbA1c compliance rate was not significantly different between the two groups in FAS and PPS(P>0.05).The results of non-inferiority test showed that the lower limit was>-0.4%in both FAS(-0.154,95%CI-0.384～0.069)and PPS(-0.139,95%CI-0.390～0.112),and the Obs group reached non-inferiority end point.The achievement rate,compliance rate,safety index and incidence of AE were not significantly different between the two groups(P>0.05).Conclusions Junlida? demonstrated non-inferiority to Glucophage? in glycemic control and can be safely and effectively used in patients with diabetes.

A 58-year-old female patient with breast cancer received treatment with pegylated recombinant human granulocyte colony-stimulating factor(PEG-rhG-CSF)injection after adjuvant chemotherapy.The serum creatinine level of the patient gradually increased from the normal baseline value to 199.3 μmol·L-1.The patient was diagnosed as acute kidney injury(AKI),after stopping the medication and providing symptomatic treatment,the patient's renal function gradually improved.The patient completed subsequent chemotherapy as planned without reusing PEG-rhG-CSF injection,and other medications and dosages remained unchanged.Renal function remained stable during follow-up.Naranjo's Assessment Scale was used to evaluate the association between PEG-rhG-CSF injection and AKI,the result was"probable."There are few reports of AKI occuring with PEG-rhG-CSF injection,and this case provides evidence for clinical safe medication.