ObjectiveTo investigate the possible mechanism of Jishe Qushi Capsule （脊蛇祛湿胶囊， JQC） in treating rheumatoid arthritis （RA） from the perspective of macrophage polarization mediated by neutrophil extracellular traps （NETs）. MethodsTwenty-four female SD rats were randomly divided into four groups， blank control group， model group， JQC group， and peptidylarginine deiminase 4 （PAD4） inhibitor group with 6 rats in each group. All groups but the blank control group were subjected to the induction of collagen-induced arthritis （CIA）. After successful model establishment， rats in the JQC group received intragastric administration of JQC 1.47 g/kg daily； rats in the PAD4 inhibitor group received intraperitoneal injections of the PAD4 inhibitor 4 mg/kg weekly. Rats in the blank， model， and PAD4 inhibitor groups received 2 ml of pure water daily by gavage. All treatments lasted 4 weeks. Joint lesions of each group were assessed on day 7， 14， 21， 28， and 35 after model establishment， and arthritis index （AI） scores were recorded. At 24 h after the final administration， histopathology of knee joints， including HE staining， safranin O-fast green staining， and TRAP staining， was performed. Flow cytometry was used to detect the counts of M1 and M2 macrophages in peripheral blood. ELISA was used to determine serum levels of TRACP， NETs， TNF-α， IL-1β， and iNOS. Western Blotting and qRT-PCR were used to measure MPO， NE， RANKL， OPG， and p65 protein and mRNA expression in knee cartilage tissue. ResultsCompared with the blank control group， the model group showed increased AI scores （P＜0.05）， marked synovial inflammatory infiltration， angiogenesis， and bone-cartilage destruction， increased TRAP-positive osteoclasts， increased M1 macrophages and decreased M2 macrophages， elevated serum TRACP， NETs， TNF-α， IL-1β， and iNOS （P＜0.05）， elevated MPO， NE， RANKL， and p65 protein/mRNA expression and decreased OPG protein/mRNA expression in knee cartilage tissue （P＜0.05）. Compared with the model group， the JQC group exhibited improved synovial inflammation， angiogenesis， and bone-cartilage damage， reduced AI scores on day 21， 28， and 35， decreased osteoclast counts， decreased M1 macrophages and increased M2 macrophages， reduced serum TRACP， NETs， TNF-α， IL-1β， and iNOS （P＜0.05）， decreased MPO， NE， RANKL， and p65 protein/mRNA expression and increased OPG expression （P＜0.05）. Compared with the PAD4 inhibitor group， the JQC group showed significantly lower AI scores， reduced M1 macrophages， increased M2 macrophages （P＜0.05）， reduced serum TRACP， TNF-α， IL-1β， and iNOS， decreased MPO， RANKL， and p65 expression， and increased OPG levels （P＜0.05）. ConclusionThe therapeutic mechanism of JQC for RA may involve inhibition of NETs formation， downregulation of the RANKL/NF-κB signaling pathway， and regulation of macrophage M1/M2 polarization imbalance， thereby suppressing osteoclastogenesis and inflammatory bone destruction.

OBJECTIVE To evaluate the efficacy and safety of total glucosides of paeonia （TGP） in the treatment of systemic lupus erythematosus （SLE）. METHODS Randomized controlled trial （RCT） about TGP combined with western medicine versus western medicine alone for SLE treatment were retrieved from PubMed， Embase， Cochrane Library， Web of Science， CNKI， VIP， Wanfang Data， and CBM. The search period spanned from the inception of each database to June 1， 2025. After literature screening， data extraction， and quality assessment of the included studies， Meta-analysis was performed using RevMan 5.4 software. RESULTS Fifteen RCTs， involving 1 318 patients， were included. Meta-analysis results showed that compared with western medicine alone， TGP combined with western medicine significantly improved clinical efficacy [OR＝4.96， 95%CI（3.41， 7.23）， P＜0.000 01]， complement 3 [MD＝0.18， 95%CI （0.13， 0.23）， P＜0.000 01] and complement 4[MD＝0.08， 般021） 95%CI （0.04， 0.11）， P＜0.000 01]， and reduced the levels of immunoglobulin G （IgG） [MD＝－3.10， 95%CI （－3.59，－2.62）， P＜0.000 01]， IgA [MD＝－0.68， 95%CI （－0.78， －0.58）， P＜0.000 01]， IgM [MD＝－0.43， 95%CI （－0.53，－0.34）， P＜0.000 01]， systemic lupus erythematosus disease activity index （SLEDAI） [MD＝－1.59， 95%CI （－2.20， －0.99）， P＜0.000 01]， recurrence rate [OR＝0.23， 95%CI （0.13， 0.42）， P＜0.000 01] and the incidence of adverse drug reactions [OR＝ 0.54， 95%CI （0.36， 0.82）， P＝0.004]. CONCLUSIONS TGP therapy can improve clinical efficacy of SLE patients， promote the restoration of immunoglobulins and complements， reduce SLEDAI and recurrence rate and has good safety.

Objective: To examine the prevalence of e-cigarette use and associated factors among primary and secondary school students in Pudong New Area, Shanghai, and to explore the pathways linking harm perception of e-cigarettes, interpersonal social influence, and attitudes toward e-cigarette use with experimentation behavior, in order to provide scientific basis for further optimizing the prevention and control strategies of e-cigarette among adolescents. Methods: From September to October 2025, a multi stage cluster random sampling method was used to select 5 144 primary and secondary school students aged 8-19 years from 47 primary and secondary schools in Pudong New Area, Shanghai, to conduct an anonymous questionnaire survey. The questionnaire collected information on e-cigarette use, harm perception of e-cigarette, interpersonal social influence, and attitudes toward e-cigarette use. The Chi-square test was applied to analyze the differences in cigarette and e-cigarette use behavior among primary and secondary school students with different demographic characteristics. Structural equation modeling (SEM) was constructed using Mplus 8.3 software, and the bootstrap method was utilized to test the mediating effects. Results: The reported rates of cigarette experimentation, e-cigarette experimentation, and current e-cigarette use among primary and secondary school students were 1.85%, 2.10%, and 0.70%, respectively. Higher reporting rates of e-cigarette experimentation were observed among boys (2.82%), secondary school students aged 16-19 (3.39%), senior high school students (3.05%), and those with weekly pocket money >100 yuan ( 6.11% ) ( χ 2=11.67, 8.61, 8.00, 54.18, all P <0.05). Structural pathway analysis results demonstrated that e-cigarette harm perception positively predicted interpersonal social influence ( β =0.61) and e-cigarette use attitude ( β = 0.53 ), and interpersonal social influence ( β =0.65) and e-cigarette use attitude ( β =0.25) further promoted e-cigarette experimentation behavior among primary and secondary school students (all P <0.01), with interpersonal social influence playing a major mediating role (indirect effect=0.40). Conclusions E-cigarette experimentation behavior among primary and secondary school students in Pudong New Area is jointly influenced by multiple psychosocial factors. Intervention strategies should strengthen interpersonal social factors such as family and peers on the basis of health education, thereby constructing a comprehensive prevention and control strategy for e-cigarette use among primary and secondary school students.

Objective To explore the influencing factors of immune-associated thyroid dysfunction caused by sintilimab treatment in solid tumors and construct a prediction model.Methods Medical records of patients diagnosed with solid tumors and treated with sintilimab at Peking University People's Hospital(Xizhimen Campus,Tongzhou Campus,Shijiazhuang Campus)from January 2023 to September 2024 were collected to explore the influencing factors that caused immune-related thyroid dysfunction using univariate and multifactorial binary logistic regression analyses and to establish a prediction model.The predictive effect of the model was assessed using the receiver operating characteristic(ROC)curve.Results A total of 120 patients were included,and 33 presented with immune-related thyroid dysfunction.Multifactorial logistic regression analysis revealed that thyroid-stimulating hormone(TSH)[OR=2.470,95%CI=(1.279,4.771)]and treatment cycles[OR=1.298,95%CI=(1.117,1.509)]were independent risk factors for the occurrence of immune-associated thyroid dysfunction,and the difference was statistically significant(P＜0.05).The area under the ROC curve was(0.897±0.043)[95%CI=(0.813,0.981)],the Yoden index was 0.703,and the model prediction accuracy was 86.5%.Conclusion The risk of immune-related thyroid dysfunction caused by sintilimab is high,and TSH and treatment cycle are the influencing factors,and the constructed model has certain predictive value and is of reference significance.

OBJECTIVE To investigate the neuroprotective effects of Ditan Decoction(DTD)on ischemic stroke.METHODS A mouse middle cerebral artery occlusion(MCAO)model was used to induce cerebral ischemia and assess the role of DTD in post-stroke NVU injury.DTD was gavaged once a day for 3 days after MCAO.Transwell neutrophil chemotaxis assay was used to explore the role of DTD in the neutrophil chemotaxis.RESULTS In the MCAO model,DTD treatment significantly reduced infarct volume(P<0.01)and attenuated blood-brain barrier disruption,as evidenced by decreased IgG leakage and preserved laminin expression(P<0.05).Furthermore,DTD suppressed neutrophil infiltration into ischemic brain tissue,as demonstrated by reduced neutrophil elastase(P<0.01)and myeloperoxidase(P<0.05)levels.Mechanistically,DTD inhibited neutrophil chemotaxis in a dose-dependent manner and downregulated phosphodiesterase 4B(PDE4B),a key regulator of neutrophil migration(P<0.05).Molecular docking analysis i-dentified four active DTD components-apigenin,vitexin,chlorogenic acid,and orientin-with strong binding affinities to PDE4B(bind-ing energies<-5 kcal·mol-1),suggesting their potential role in mediating DTD's therapeutic effects.CONCLUSION These find-ings highlight DTD as a promising intervention for ischemic stroke,targeting NVU preservation and PDE4B-dependent neutrophil mod-ulation.

OBJECTIVE: Peritoneal fibrosis (PF) is an adverse event that occurs during long-term peritoneal dialysis, significantly impairing treatment efficiency and adversely affecting patient outcomes. Astragaloside IV (AS-IV), a principal active component derived from Astragalus membranaceus (Fisch.) Bunge, has exhibited anti-inflammatory and antifibrotic effects in various settings. This study aims to investigate the potential therapeutic efficacy and mechanism of AS-IV in the treatment of PF. METHODS: The PF mouse model was established by intraperitoneal injection of 4.25% peritoneal dialysis fluid (100 mL/kg). The epithelial-mesenchymal transition (EMT) of HMrSV5 cells was induced by the addition of 10 ng/mL transforming growth factor β (TGF-β). The differentially expressed genes in HMrSV5 cells treated with AS-IV were screened using transcriptome sequencing analysis. The potential targets of AS-IV were screened using network pharmacology and analyzed using molecular docking and molecular dynamics simulations. RESULTS: Administration of AS-IV at doses of 20, 40, or 80 mg/kg effectively mitigated the increase in peritoneal thickness and the development of fibrosis in mice with PF. The expression of the fibrosis marker α-smooth muscle actin in the peritoneum was significantly decreased in AS-IV-treated mice. The treatment of AS-IV (10, 20, and 40 μmol/L) significantly delayed the EMT of HMrSV5 cells induced by TGF-β, as demonstrated by the decreased number of 5-ethynyl-2'-deoxyuridine-positive cells, reduced migrated area, and decreased expression of fibrosis markers. A total of 460 differentially expressed genes were detected in AS-IV-treated HMrSV5 cells through transcriptome sequencing, with notable enrichment in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-AKT serine/threonine kinase 1 (AKT) signaling pathway. The reduced levels of phosphorylated PI3K (p-PI3K) and p-AKT were detected in HMrSV5 cells with AS-IV treatment. Epidermal growth factor receptor (EGFR) was predicted as a direct target of AS-IV, exhibiting strong hydrogen bond interactions. The activation of the PI3K-AKT pathway by the compound 740Y-P, and the activation of the EGFR pathway by NSC 228155 each partially counteracted the inhibitory effect of AS-IV on the EMT of HMrSV5 cells. CONCLUSION AS-IV delayed the EMT process in peritoneal mesothelial cells and slowed the progression of PF, potentially serving as a therapeutic agent for the early prevention and treatment of PF. Please cite this article as: Huang Y, Chu CL, Qiu WH, Chen JY, Cao LX, Ji SY, Zhu B, Wang GK, Shen QQ. Astragaloside IV delayed the epithelial-mesenchymal transition in peritoneal fibrosis by inhibiting the activation of EGFR and PI3K-AKT pathways. J Integr Med. 2025; 23(6):694-705.
Epithelial-Mesenchymal Transition/drug effects* ; Animals ; Saponins/pharmacology* ; Triterpenes/pharmacology* ; Mice ; Peritoneal Fibrosis/pathology* ; Proto-Oncogene Proteins c-akt/metabolism* ; ErbB Receptors/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Signal Transduction/drug effects* ; Male ; Humans ; Molecular Docking Simulation ; Cell Line ; Mice, Inbred C57BL

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

The engineering application of microbially induced carbonate precipitation(MICP)is limited by pH-dependent conformational dynamics of urease.Focusing on the α-subunit urease from Sporosarcina pasteurii,this study integrated conductivity experiments and constant-pH molecular dynamics simulations to analyze active site conformational dynamics and catalytic function across pH 3-11.Results showed that under neutral conditions(pH 7-8),key histidine residues(HIS139/HIS249)exhibited minimal dis-placement(＜0.5 ?),the longest hydrogen bond lifetime(＞8 ps),highest conformational stability(root mean square deviation,RMSD:0.15-0.18 nm),and optimal catalytic activity(conductivity change rate:0.03 mS/cm·min-1,CaCO3 precipitation:3.84 g).Extreme pH(pH 3/11)induced structural collapse(displacement up to 1.8 ?)and complete activity loss.Simulations revealed that neutral pH sta-bilizes a protonation-dependent cooperative allosteric network by maintaining active site cavity volume(～120 ?3)and moderate conformational coherence(correlation coefficient～0.8).This work deciphers the molecular mechanism of pH-regulated urease dynamics through protonation states,providing theoreti-cal support for MICP applications in acidic mine tailing remediation and alkaline soil stabilization.

OBJECTIVE To investigate the neuroprotective effects of Ditan Decoction(DTD)on ischemic stroke.METHODS A mouse middle cerebral artery occlusion(MCAO)model was used to induce cerebral ischemia and assess the role of DTD in post-stroke NVU injury.DTD was gavaged once a day for 3 days after MCAO.Transwell neutrophil chemotaxis assay was used to explore the role of DTD in the neutrophil chemotaxis.RESULTS In the MCAO model,DTD treatment significantly reduced infarct volume(P<0.01)and attenuated blood-brain barrier disruption,as evidenced by decreased IgG leakage and preserved laminin expression(P<0.05).Furthermore,DTD suppressed neutrophil infiltration into ischemic brain tissue,as demonstrated by reduced neutrophil elastase(P<0.01)and myeloperoxidase(P<0.05)levels.Mechanistically,DTD inhibited neutrophil chemotaxis in a dose-dependent manner and downregulated phosphodiesterase 4B(PDE4B),a key regulator of neutrophil migration(P<0.05).Molecular docking analysis i-dentified four active DTD components-apigenin,vitexin,chlorogenic acid,and orientin-with strong binding affinities to PDE4B(bind-ing energies<-5 kcal·mol-1),suggesting their potential role in mediating DTD's therapeutic effects.CONCLUSION These find-ings highlight DTD as a promising intervention for ischemic stroke,targeting NVU preservation and PDE4B-dependent neutrophil mod-ulation.

Objective:To explore the construction method of a resistant multiple myeloma(MM)patient-derived xenotransplantation(PDX)model.Methods:1.0 × 107 MM patient-derived mononuclear cells(MNCs),2.0 × 106 MM.1S cells and 2.0 × 106 NCI-H929 cells were respectively subcutaneously inoculated into NOD.CB17-Prkdcscid Il2rgtml/Bcgen(B-NDG)mice with a volume of 100 p1 per mouse to establish mouse model.The morphologic,phenotypic,proliferative and genetic characteristics of PDX tumor were studied by hematoxylin-eosin staining,immunohistochemical staining(IHC),cell cycle analysis,flow cytometry and fluorescence in situ hybridization(FISH).The sensitivity of PDX tumor to bortezomib and anlotinib monotherapy or in combination was investigated through cell proliferation,apoptosis and in vitro and in vivo experiments.The effects of anlotinib therapy on tumor blood vessel and cell apoptosis were analyzed by IHC,TUNEL staining and confocal fluorescence microscope.Results:MM PDX model was successfully established by subcutaneously inoculating primary MNCs.The morphologic features of tumor cells from MM PDX model were similar to those of mature plasma cells.MM PDX tumor cells positively expressed CD138 and CD38,which presented 1q21 amplification,deletion of Rb1 and IgH rearrangement,and had a lower proliferative activity than MM cell lines.In vitro,PDX,MM.1S and NCI-H929 cells were treated by bortezomib and anlotinib for 24 hours,respectively.Cell viability assay showed that the IC50 value of bortezomib were 5 716.486,1.025 and 2.775 nmol/L,and IC50 value of anlotinib were 5 5107.337,0.706 and 5.13 μmol/L,respectively.Anlotinib treatment increased the apoptosis of MM.1S cells(P＜0.01),but did not affect PDX tumor cells(P＞0.05).In vivo,there was no significant difference in PDX tumor growth between bortezomib monotherapy group and control group(P＞0.05),while both anlotinib monotherapy and anlotinib combined with bortezomib effectively inhibited PDX tumor growth(both P＜0.05).The vascular perfusion and vascular density of PDX tumor were decreased in anlotinib treatment group(both P＜0.01).The apoptotic cells in anlotinib treatment group were increased compared with those in control group(P＜0.05).Conclusion:Bortezomib-resistant MM PDX model can be successfully established by subcutaneous inoculation of MNCs from MM patients in B-NDG mice.This PDX model,which retains the basic biological characteristics of MM cells,can be used to study the novel therapies.