ObjectiveThis study aims to compare the modeling effects of submaxillary gland antigen and salivary gland antigen in the establishment of Sjögren syndrome (SS) mouse models, and to characterize the phenotypic and immunological features of these models in comparison with spontaneous SS-prone non-obese diabetic (NOD)/LtJ mice. MethodsAdult C57BL/6J mice (equal numbers of males and females) were immunized with submaxillary gland antigen or salivary gland antigen, respectively, combined with Freund's adjuvant to induce SS models. Mice immunized with phosphate-buffered saline (PBS) combined with Freund's adjuvant served as the control group. Immunization was induced via multiple subcutaneous injections in the back with antigen combined with Freund's complete adjuvant (FCA) on Days 1 and 7. A booster immunization was administered via multiple subcutaneous injections in the back with antigen combined with Freund's incomplete adjuvant (FIA) on Day 14. Female NOD/LtJ mice were used as the spontaneous SS model group, with ICR mice as the corresponding control strain for comparative analysis. Body weight, water intake, and salivary flow rate of mice were dynamically monitored for 4 weeks. At the end of the experiment, tissue and serum samples were collected, the weights of submaxillary glands, thymus, and spleen were measured, and organ indices (organ-to-body weight ratios) were calculated. Pathological morphological analysis of the submaxillary gland and spleen was performed with hematoxylin and eosin (HE) staining. Serum interleukin-17 (IL-17) level was detected using enzyme-linked immunosorbent assay (ELISA). Real-time quantitative polymerase chain reaction was used to detect the mRNA expression levels of SS type A (SSA) and SS type B (SSB) in submaxillary gland tissues. ResultsFemale mice in the submaxillary gland antigen group exhibited significantly increased water intake (P<0.05) and reduced salivary flow rate (P<0.05) compared with the female control group. No statistically significant differences were observed in the submaxillary gland index, thymus index and spleen index (P>0.05). Focal lymphocytic infiltration was observed in the submaxillary glands, and the splenic marginal zone was enlarged. Serum IL-17 levels were significantly increased (P<0.05). There was no significant difference in submaxillary gland SSA/SSB expression levels (P>0.05). Compared with the female control group, female mice in the salivary gland antigen group showed no statistically significant differences in water intake, salivary flow rate, submaxillary gland index, and spleen index (P>0.05), whereas the thymus index was significantly reduced (P<0.01). Mild inflammatory cell infiltration and glandular atrophy were observed in the submaxillary glands, and the splenic white pulp and marginal zone were slightly enlarged. Serum IL-17 levels and submaxillary gland SSB mRNA expression levels were significantly increased (P<0.01), whereas no significant change was observed in submaxillary gland SSA expression levels (P>0.05). Compared with the male control group, mild submaxillary gland atrophy was observed in male mice in the submaxillary gland antigen group, whereas no obvious changes were found in other modeling-related indicators (P>0.05). Compared with the ICR control group, NOD/LtJ model mice exhibited elevated water intake (P<0.05), significantly reduced salivary flow rate (P<0.01), no significant differences in the submaxillary gland index or spleen index (P>0.05), but a significantly increased thymus index (P<0.05). Marked focal infiltration was observed in the submaxillary glands, the splenic marginal zone was obviously enlarged, and serum IL-17 concentrations as well as submaxillary gland SSA/SSB expression levels were significantly increased (P<0.05). ConclusionSubmaxillary gland antigen and salivary gland antigen can induce SS-related features in female C57BL/6J mice. The SS-related phenotype is more pronounced in the submaxillary gland antigen group than in the salivary gland antigen group, but weaker than that in spontaneously SS-prone female NOD/LtJ mice. Immunization of male C57BL/6J mice with submaxillary or salivary gland antigens fails to induce an obvious SS phenotype.

The Chinese Pharmacopoeia 2025 Edition added the 9213 Guideline for validation,verification,and transfer of microbiological analytical methods.Based on the characteristics of pharmaceutical microbiological analyt-ical methods and practical applications,it specified definitions of relevant terms and application scenarios,estab-lished technical indicators and acceptance criteria for methodological evaluation,and introduced key statistical tools and evaluation principles.This article systematically elaborates on the drafting background and process of the Guideline,and interprets its key content,aiming to offer theoretical guidance and practical reference for relevant practitioners in applying this guideline.This guideline strengthens the foundation of pharmaceutical microbial analytical methods in China and enhances the scientificity and accuracy of the pharmaceutical microbial standards system.

Objective To evaluate the predictive efficacy of individualized dosage support software-Smart Dose,PharmVan and JPKD-on vancomycin plasma concentration in patients undergoing infective endocarditis(IE)surgery,and to analyze the influencing factors.Methods A retrospective analysis was conducted in IE patients who received intravenous vancomycin in our hospital from January 2019 to December 2022.The above softwares were used to predict the steady-state trough concentration of vancomycin,and the relative prediction error and absolute weight deviation(AWE)between the predicted and measured values were compared.According to the AWE value,the results were divided into accurate prediction group(AWE＜30％)and the inaccurate prediction group(AWE≥30％).Univariate analysis and Logistic regression analysis were used to explore the influencing factors,and to evaluate the predictive value through the receiver operating characteristic curve(ROC).Results A total of 27 patients were enrolled,with 27 concentrations of initial regimen and 35 of adjustment regimen.When PharmVan predicted the adjusted concentration,the AWE was 24.84(11.54,39.78)％,with higher accuracy than other predicted results.The Univariate analysis of factors influencing the performance of PharmVan in predicting the adjusted concentration showed that patients in the accurate prediction group was significantly younger than that in the inaccurate prediction group(P＜0.05).Multivariate analysis showed that advanced age was an independent risk factor for the inaccurate prediction of PharmVan for adjustment concentration[OR=0.856,95％CI was(0.757,0.969),P=0.014].ROC curve analysis indicated that when patients were older than 48.5 years old,the risk of inaccurate prediction was increased with a sensitivity of 78.9％and a specificity of 93.7％.Conclusions Only the PharmVan software has a higher accuracy in predicting the adjusted concentration among the three softwares,but it is still need to be cautious in combination with the analysis results of ROC curve.Therefore,when using vancomycin in IE patients,attention should be paid to renal function and plasma concentration should be actively monitored.

Objective:To explore the predictive value of atherogenic index of plasma(AIP)combined with neutro-phil/HDL-C ratio(NHR),lymphocyte/HDL-C ratio(LHR)and monocyte/HDL-C ratio(MHR)for major adverse cardiovascular events(MACE)in patients with acute coronary syndrome(ACS).Methods:This retrospec-tive study enrolled 320 patients underwent coronary angiography in Department of Cardiovascular Medicine,Harri-son International Peace Hospital between January 2021 and December 2022,including 215 ACS patients and 105 pa-tients without ACS;according to Gensini score,ACS patients were divided into low risk group(n=50),medium risk group(n=70)and high risk group(n=95).According to the presence of MACE within 1 year,patients were divided into MACE group(n=55)and no MACE group(n=160).After admission,blood routine,blood lipids,C-reactive protein(CRP)and endothelin-1(ET-1)levels were measured,then NHR,LHR,MHR and AIP were calculated.Spearman method was used to analyze the association of above-mentioned indexes with Gensini score;stepwise Logistic regression was used to analyze the influencing factors of MACE within 1 year in ACS patients;and ROC curve was used to analyze the predictive value of single and combined detection of above indexes for MACE within 1 year in ACS patients.Results:Compared to patients in no ACS group,those in ACS group had significantly higher BMI[(23.59±0.85)kg/m2 vs.(21.57±1.16)kg/m2],proportions of hypertension(57.67％vs.13.33％),diabetes(23.26％vs.8.57％),NHR[(12.09±3.46)vs.(3.81±1.29)],MHR[(0.70±0.18)vs.(0.33±0.10)],LHR[(0.79±0.21)vs.(0.40±0.09)],AIP[(0.21±0.06)vs.(0.11±0.02)],CRP[(9.82±3.09)mg/L vs.(2.20±0.58)mg/L],ET-1[(31.25±10.34)μg/L vs.(10.60±1.96)μg/L](P＜0.001 all).Compared to those in no MACE group,patients in MACE group had significantly higher NHR[(17.33±3.87)vs.(10.12±2.68)],MHR[(0.93±0.24)vs.(0.61±0.13)],LHR[(1.05±0.27)vs.(0.71±0.16)],AIP[(0.28±0.04)vs.(0.17±0.02)],CRP[(15.52±3.83)mg/L vs.(7.69±2.40)mg/L],ET-1[(46.68±9.51)μg/L vs.(25.47±4.66)μg/L]levels(P＜0.001 all).Spearman correlation analysis showed that NHR,MHR,LHR and AIP were significant positively correlated with Gensini score(r=0.837～0.868,P＜0.001 all).Stepwise Logistic regression analysis showed that NHR(OR=1.225,95％CI 1.016～1.550,P=0.035),AIP(OR=2.632,95％CI 1.055～6.566,P=0.038)were independent risk factors for MACE within 1 year in ACS patients.ROC curve shows that AUC of AIP combined with NHR,MHR and LHR predicting MACE within 1 year in ACS patients was 0.786(95％CI 0.725～0.839),which was significantly higher than those of NHR(AUC 0.768,95％CI 0.706～0.823),LHR(AUC 0.749,95％CI 0.686～0.806)and AIP(AUC 0.764,95％CI 0.701～0.819)alone(Z=2.597,2.687,1.965,P＜0.05 or＜0.01).Conclusion:AIP combined with NHR,MHR and LHR have certain predictive value for MACE within 1 year in ACS patients.

Aim To explore the neuroprotective effects of salidroside on Parkinson's disease(PD)through modulation of inflammatory responses and the underly-ing mechanisms.Methods Mice were divided into five groups:healthy control group,1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)disease group,low-dose Rhodioloside intervention group,medium-dose salidroside intervention group,and high-dose salidro-side intervention group.MPTP-induced PD mouse model was established,and salidroside intervention was administered.Behavioral changes,inflammatory cyto-kine levels,autophagy-related protein expression,and neurons were observed through histological analysis and immunohistochemical staining.Results After MPTP treatment,mice exhibited significant behavioral chan-ges,increased pro-inflammatory cytokines,decreased anti-inflammatory cytokines,reduced autophagy-related proteins,and evident pyroptosis.Salidroside interven-tion alleviated these changes in a dose-dependent man-ner.Conclusions Salidroside exerts neuroprotective effects on PD by alleviating inflammatory responses and promoting autophagy,thereby protecting neurons.

Objective:To investigate the relationship between fibroblast growth factor receptor-2(FGFR2)gene polymorphisms and the risk of breast cancer and its protein expression in Han women from Heilongjiang,China.Meth-ods:Using the Snapshot technique for multiplex single nucleotide polymorphism genotyping,the polymorphisms rs3135718 and rs1219648 of FGFR2 were analyzed in 747 breast cancer patients and 716 healthy controls.Logistic re-gression was used to examine the association between these genotypes and breast cancer susceptibility.In a subset of 338 cases,immunohistochemistry was performed to assess FGFR2 protein expression,and chi-square tests was used to analyze the relationship between polymorphisms and protein expression.Results:The genotype frequencies of FGFR2 rs3135718 and rs1219648 showed significant differences between the breast cancer and control group.Logistic regression revealed that,for rs3135718,the CT,CC,and CT+CC genotypes were associated with increased breast cancer risk compared to the TT genotype(OR=1.280,95%CI:1.003-1.633;OR=1.500,95%CI:1.112-2.023;OR=1.341,95%CI:1.066-1.688).For rs1219648,the GA,GG,and GA+GG genotypes were significantly associated with higher breast cancer risk compared to the AA genotype(OR=1.352,95%CI:1.063-1.719;OR=1.826,95%CI:1.361-2.504;OR=1.475,95%CI:1.175-1.852).However,no significant association was found between FGFR2 rs3135718 and rs1219648 polymorphisms and FGFR2 protein expression(χ2=0.052,P=0.820;χ2=0.117,P=0.732).Conclusion:FGFR2 gene poly-morphisms rs3135718 and rs1219648 are significantly associated with breast cancer susceptibility in Han women from Heilongjiang,China,but these polymorphisms do not show a clear relationship with FGFR2 protein expression.

Background and Aims:Gastroesophageal reflux disease(GERD)is a common complication following sleeve gastrectomy(SG),particularly in patients with concomitant hiatal hernia,where symptoms tend to be more persistent and refractory,significantly impairing postoperative quality of life.This study aimed to evaluate the efficacy of laparoscopic hiatal hernia repair combined with gastroesophageal fixation in SG patients with severe GERD and hiatal hernia,providing clinical reference for revisional surgical strategies.Methods:The clinical data of 9 patients with severe GERD after SG who underwent laparoscopic hiatal hernia repair and gastroesophageal fixation at Huashan Hospital,Fudan University,between January 2023 and June 2024 were retrospectively analyzed.GerdQ scores,proportion of endoscopically confirmed reflux esophagitis,and proton pump inhibitor(PPI)usage were compared before and after surgery.Surgical parameters and follow-up outcomes were also recorded.Results:All patients successfully completed the surgery without major intraoperative complications,and the mean postoperative hospital stay was 5.22 d.After a mean follow-up period of 15.27 months,the GerdQ score significantly decreased from 11.67±2.00 to 7.22±1.48.The proportion of patients with GerdQ score≥8 decreased from 100.00％to 44.44％,and the rate of endoscopically confirmed GERD dropped from 88.89％to 11.11％;PPI use also significantly declined,with all differences reaching statistical significance(all P＜0.05).Conclusion:Laparoscopic hiatal hernia repair combined with gastroesophageal fixation can effectively alleviate reflux symptoms in SG patients with coexisting hiatal hernia,demonstrating favorable short-term efficacy and high safety.This approach may be a preferable surgical option for selected patients.

Aim To explore the mechanism of action of Guizhi Jia Gegen decoction(GGD)in treating pneu-monia-enteritis induced by H1N1 influenza virus infec-tion in a mouse model,using network pharmacology and molecular docking techniques,followed by in vivo verification.Methods A pneumonia-enteritis mouse model was established,and the intervention effects of GGD on the model mice were evaluated using indica-tors such as body weight,rectal temperature,lung in-dex,colon length,H1N1 M gene expression,relative mRNA expression levels of inflammatory cytokines,and pathological sections of the lung and intestine.The targets of the blood-absorbed components of GGD were identified using the Swiss Target Prediction platform,and the disease targets were retrieved from the Gene-Cards platform.The intersecting targets were analyzed through PPI network analysis using the STRING data-base to identify core targets.GO analysis and KEGG pathway enrichment analysis were performed using the Metascape database.RT-qPCR was employed to vali-date the core targets and pathways.Molecular docking was conducted using AutoDock Tools software to verify the interactions between blood-absorbed components and key targets.Results GGD demonstrated signifi-cant therapeutic effects on the pneumonia-enteritis mouse model.The results of network pharmacology in-dicated that the therapeutic effects of GGD were strong-ly associated with targets such as TNF,ALB,PTGS2,MMP9,EGFR,ESR1,SRC,HSP90AA1,PPARG and MMP2.RT-qPCR results indicated that GGD could intervene in pneumonia-enteritis by regulating the targets TNF,ALB,EGFR and the related targets of the NF-κB pathway.Molecular docking results re-vealed that blood-absorbed components such as puerar-in and liquiritin could stably bind to TNF,ALB and EGFR.Conclusion Components such as puerarin and liquiritin in GGD may exert therapeutic effects on pneumonia-enteritis induced by H1N1 influenza virus infection by acting on targets such as TNF,ALB and EGFR.

Objective To explore the microstructural characteristics of white matter in patients with acute ischemic stroke and their relationship with collateral circulation.Methods In all,150 patients with acute ischemic stroke admitted to our hospi-tal from January 2023 to May 2024 were selected as the study subjects,and another 150 healthy volunteers during the same peri-od were selected as the control group to compare the general clinical data of the two groups.All subjects underwent head MRI examination to extract microstructural features of brain white matter and analyze the correlation between microstructural fea-tures of brain white matter and brain white matter lesions.According to the formation status of collateral circulation,150 pa-tients with acuteischemic stroke were divided into good collateralcirculation group(n=91)and poor collateral circulation group(n=59).The general clinical data and microstructure characteristics of white matter were compared between the two groups.The predictive value of microstructurecharacteristics of white matter for stroke,white matter lesions,and poor collater-al circulation were analyzed using ROC curves.Results Comparing the general information between the healthy group and the stroke group,it could be seen that there were significant differences between the two groups in terms of smoking history,hyper-lipidemia history,hypertension history,LDL-C,HDL-C,FIB,and D-D(all P<0.05);The brain white matter fiber bundles with statistically significant FA values in the healthy and stroke groups included:cerebellar peduncle,pontine chiasmatic tract,corpus callosum,fornix column and fornix body,right corticospinal tract,left corticospinal tract,right cerebellar peduncle,left cerebellar peduncle,right anterior radial crown,and left anterior radial crown;The brain white matter fiber bundles with statistically sig-nificant MD values in the healthy and stroke groups included:cerebellar peduncle,pontine chiasmatic tract,right cerebellar pe-duncle,left cerebellar peduncle,right external capsule,left external capsule,and right frontal occipital bundle;The brain white matter fiber bundles with statistically significant RD values in the healthy and stroke groups included:cerebellar peduncle,pon-tine chiasmatic tract,left corticospinal tract,right cerebellar peduncle,left cerebellar peduncle,right cerebellar peduncle,left cer-ebellar peduncle,right external capsule,and left external capsule;The brain white matter fiber bundles with statistically signifi-cant AD values in the healthy and stroke groups included:midcerebellar peduncle,right medial thalamus,left medial thalamus,right superior cerebellar peduncle,left superior cerebellar peduncle,right posterior thalamic radiation,right sagittal layer,right external capsule,left external capsule,right cingulate and left cingulate.Correlation analysis showed that the FA values of the cerebellar peduncle,pontine chiasmatic tract,corpus callosum,fornix column and fornix body,right corticospinal tract,left corti-cospinal tract,right cerebellar peduncle,left cerebellar peduncle,right anterior radial crown,and left anterior radial crown were significantly negatively correlated with the white matter lesion score(all P<0.05);The MD values of the cerebellar peduncle,pontine chiasmatic tract,right cerebellar peduncle,left cerebellar peduncle,right external capsule,left external capsule,and right frontal occipital tract were significantly positively correlated with the white matter lesion score(all P<0.05);The RD values of the cerebellar peduncle,pontine chiasmatic tract,left corticospinal tract,right cerebellar peduncle,left cerebellar peduncle,right cerebellar peduncle,left cerebellar peduncle,right external capsule,and left external capsule were significantly positively correla-ted with the white matter lesion score(all P<0.05);The AD values of the cerebellar peduncle,right cerebellar peduncle,left cerebellar peduncle,right external capsule,and left external capsule were significantly positively correlated with the white matter lesion score(all P<0.05),while the AD values of the right medial thalamus,left medial thalamus,right posterior thalamus radi-ation,right sagittal layer,right cingulate and left cingulate were significantly negatively correlated with the white matter lesion score(all P<0.05).Comparing the general information between good collateral circulation group and poor collateral circulation group,it could be seen that there was a significant difference in the white matter lesion score between the two groups of patients(P<0.05).The ROC analysis showed that FA,MD,RD,and AD values in the cerebellar midfoot had good predictive value for stroke,white matter injury,and collateral circulation disorders,and the combined diagnostic efficacy of the four values was high-er than the diagnostic efficacy of each value alone.Conclusion The microstructure of white matter in patients with acute ische-mic stroke exhibits varying degrees of damage.Changes in FA,MD,AD,and RD values in the white matter of the cerebellar pe-duncle can be used to differentiate collateral circulation status,and the combined diagnostic efficacy of the four is better.

Objective:To explore whether anti-dsDNA antibodies can activate podocyte NLRP3 inflammasomes through FcRn,enhance the antigen-presenting function of podocytes,and promote podocyte damage.Methods:Kidney biopsies from lupus nephritis(LN)patients and lupus model mice were collected.Immunofluorescence was used to detect podocyte MHC Ⅱ,CD80,and FcRn levels.The NLRP3 inhibitor MCC950 was used to intervene in lupus model mice(MRL/lpr),and immunofluorescence was per-formed to assess changes in glomerular MHC Ⅱ and CD80 expressions.Podocytes pretreated with MCC950 were stimulated with anti-dsDNA antibodies,and Western blot was used to measure MHC Ⅱ and CD80 expression.FcRn was knocked down in podocytes using siRNA,and after stimulation with anti-dsDNA antibodies,Western blot was conducted to evaluate NLRP3 and caspase-1 p20 expres-sion levels.CD4+T cells from peripheral blood of SLE patients were sorted and co-cultured with podocytes pretreated with serum from SLE patients,and flow cytometry was used to analyze the proportions of IFN-γ+CD4+T cells and IL-17+CD4+T cells.Immunofluores-cence was used to observe the cytoskeletal changes in podocytes.Results:Podocytes from LN patients and lupus model mice ex-pressed high levels of MHC Ⅱ,CD80,and FcRn.MCC950 intervention significantly reduced MHC Ⅱ and CD80 levels in podocytes of MRL/lpr mice.Anti-dsDNA antibodies induced elevated MHC Ⅱ and CD80 expression in podocytes,which were reduced by NLRP3 inhibitor MCC950(P<0.05).Knockdown of FcRn in podocytes resulted in significant decreases in NLRP3 expression and active cas-pase-1 p20 levels(P<0.05).Co-culturing SLE patient CD4+T cells with podocytes pretreated with SLE patient serum led to a signifi-cant increase in the proportion of IFN-γ+CD4+T cells(P<0.05).There were notable changes in the podocyte cytoskeleton,including a significant reduction in stress fibers and cellular morphological remodeling.Conclusion:Anti-dsDNA antibodies can activate podo-cyte NLRP3 inflammasomes via FcRn,enhancing the antigen-presenting function of podocytes.The activated CD4+T cells further con-tribute to the remodeling of podocyte cytoskeleton.