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.

Objective To investigate the therapeutic efficacy of Erchen Decoction plus Sanzi Yangqin Decoction in the treatment of elderly patients with acute exacerbation of chronic obstructive pulmonary disease(COPD)of phlegm-dampness accumulation in lung syndrome,and to explore its possible therapeutic mechanism through the interleukin 33/soluble growth stimulation expressed gene 2(IL-33/ST2)signaling pathway.Methods A prospective trial was conducted on 92 elderly patients with acute exacerbation of COPD of phlegm-dampness accumulation in lung syndrome who were treated in Haikou Hospital of Traditional Chinese Medicine from January 2021 to June 2023.The patients were randomly divided into the control group and the observation group according to the random number table method,with 46 cases in each group.The control group was treated with conventional western medicine,while the observation group was treated with Erchen Decoction plus Sanzi Yangqin Decoction on the basis of treatment for the control group,and the course of treatment covered two weeks.The changes of traditional Chinese medicine(TCM)syndrome scores,lung function indicators,white blood cell count(WBC),neutrophil percentage(Neut%),and serum IL-33,ST2,interleukin 6(IL-6)and interleukin 8(IL-8)levels of patients in the two groups before and after the treatment were observed,and the clinical efficacy and medication safety of the patients in the two groups were evaluated.Results(1)After two weeks of treatment,the total effective rate of the observation group was 86.96%(40/46)and that of the control group was 67.39%(31/46),and the intergroup comparison(tested by chi-square test)showed that the therapeutic effect of the observation group was significantly superior to that of the control group(P<0.05).(2)After treatment,the TCM syndrome scores such as dyspnea,suppression in the chest,cough and expectoration in the two groups were decreased compared with those before treatment(P<0.05),and the decrease in the observation group was significantly superior to that in the control group(P<0.01).(3)After treatment,the lung function indicators such as forced vital capacity(FVC),forced expiratory volume in one second(FEV1),and peak expiratory flow(PEF)of the two groups all improved compared with those before treatment(P<0.05),and the improvement in the observation group was significantly superior to that in the control group(P<0.01).(4)After treatment,the levels of inflammatory indicators such as WBC,Neut%,and serum IL-33,ST2,IL-6 and IL-8 in the two groups were all decreased compared with those before treatment(P<0.05),and the decrease in the observation group was significantly superior to that in the control group(P<0.01).(5)The total incidence of adverse reactions in both groups was all 8.70%(4/46),and the intergroup comparison showed that the difference was not statistically significant(P>0.05).Conclusion The clinical efficacy of Erchen Decoction plus Sanzi Yangqin Decoction in the treatment of elderly patients with acute exacerbation of COPD of phlegm-dampness accumulation in lung syndrome is remarkable,and it is effective on improving the TCM syndromes,related inflammatory indicators and lung function.Its mechanism may be related to the reduction of the patients'serum IL-33 level,the inhibition of IL-33/ST2 signaling pathway and the expression of related inflammatory factors,so as to inhibit inflammatory response and improve the progression of COPD.

The interleukin-10 （IL-10） family is expressed in various types of cells and has a wide range of biological functions， and it plays an important role in the development and progression of hepatic fibrosis. Hepatic fibrosis is a chronic liver disease characterized by abnormal repair of hepatic tissues after injury， activation of hepatic stellate cells， and excessive accumulation of extracellular matrix. The IL-10 family members include IL-10， IL-19， IL-20， IL-22， IL-24， IL-26， IL-28， IL-29， and IL-35， with similarities in structure and function， and changes in their expression levels are closely associated with the progression of hepatic fibrosis. Moderate upregulation of the expression of IL-10 family members can help maintain the quiescent state of hepatic stellate cells， promote the transformation of macrophages to anti-inflammatory phenotype， and regulate the activity of natural killer cells， thereby inhibiting inflammatory response， regulating cell apoptosis and autophagy， and finally reversing the progression of hepatic fibrosis. This article discusses the mechanism of action of IL-10 family members and their application in traditional Chinese medicine and Western medicine therapies， in order to provide new thoughts for the treatment of hepatic fibrosis.

A 58-year-old female patient presented with red papules, plaques, and scabs on her right foot accompanied by pain and itching for 14 years. Dermatological examination revealed extensive red plaques on her right foot and ankle, with scattered red papules in between; some of the plaques were covered with a moderate amount of yellow-brown crusts, and a small amount of yellow exudate was observed at the junction of the toes and the dorsum of the foot. Histopathological examination of the skin lesions showed hyperkeratosis, parakeratosis, pseudoepitheliomatous hyperplasia, neutrophil aggregation in the epidermis, and mixed inflammatory cell infiltration in the dermis. Three different types of colonies were cultured from the skin lesion tissues: light brown granular colonies, black granular colonies, and white-brown filamentous colonies. Under the microscope, the filamentous colonies appeared as long chains of brown conidia with short cylindrical beaks, while the black and light brown granular colonies appeared as clusters of spores, with single or multiple septa inside, and some budding spores were observed. Electron microscopy further confirmed the above structures. Molecular biological analysis revealed that the three types of colonies were all identified as Alternaria alternata. The patient was diagnosed with cutaneous alternariosis caused by Alternaria alternata with special morphology. After 7 months of treatment with oral itraconazole, the skin lesions healed, and no recurrence was observed during a 3-year follow-up.

Objective:To evaluate the clinical efficacy and safety of an antioxidant gel containing tea polyphenols combined with narrow-band ultraviolet B in the treatment of vitiligo.Methods:A single-center, randomized controlled clinical trial was conducted. From April 25 to June 27, 2024, patients with vitiligo were selected from the Department of Dermatology, Hangzhou Third People's Hospital. An open-label and researcher-blinded design was used. The patients were divided into 3 groups: a phototherapy group receiving phototherapy alone, a tea polyphenols combined group treated with an antioxidant gel containing tea polyphenols combined with phototherapy, and a positive control group treated with an antioxidant gel containing superoxide dismutase combined with phototherapy, with the treatment duration being 3 months. The efficacy was evaluated using the Vitiligo Area Scoring Index (VASI), and when the VASI was improved by ≥ 10%, the treatment would be considered effective. Changes in skin aging and skin barrier function indicators before and after treatment were assessed for 72 vitiligo lesions in the tea polyphenols combined group and for 72 lesions in the phototherapy group. Comparisons between the groups were performed using one-way analysis of variance, Fisher's exact test, chi-square test, or t test. Results:A total of 171 vitiligo patients with 307 target lesions were successfully followed up in this study, including 74 males and 97 females, and their ages ranged from 1 to 64 years. Among the 307 lesions, 95 were treated with phototherapy alone, of which 35 showed improvement, resulting in a total response rate of 36.8% and an average VASI improvement rate of 10.9%; adverse reactions occurred in 29 lesions (30.5%). Of 138 lesions treated with the antioxidant gel containing tea polyphenols combined with phototherapy, 73 showed improvement, resulting in a total response rate of 52.9% and an average VASI improvement rate of 24.0%; adverse reactions occurred in 10 lesions (7.2%). In the positive control group, 74 lesions were treated, and 40 showed improvement, resulting in a total response rate of 54.1% and an average VASI improvement rate of 18.3%; adverse reactions occurred in 5 lesions (6.8%). Compared with the phototherapy group, the tea polyphenols combined group showed a significantly increased total response rate and a VASI improvement rate (both P < 0.01), but a significantly decreased incidence rate of adverse reactions ( P < 0.001). No significant differences in the above indicators were observed between the tea polyphenols combined group and the positive control group (all P > 0.05). In addition, the changes in skin barrier function and skin aging indicators (except for wrinkle depth) before and after treatment were significantly reduced in the tea polyphenols combined group compared to the phototherapy group (all P < 0.05). After the phototherapy alone, the transepidermal water loss significantly increased ( P = 0.004), and the water content of the stratum corneum significantly decreased ( P = 0.012). However, no significant differences in skin barrier function or skin aging indicators were found between pre- and post-treatment in the tea polyphenols combined group ( P > 0.05) . Conclusion:The antioxidant gel containing tea polyphenols could effectively improve the efficacy of narrow-band ultraviolet B in the treatment of vitiligo, and alleviate skin aging and barrier damage caused by phototherapy.

OBJECTIVES: Multiple myeloma (MM) is a hematologically malignant clonal plasma cell disease. This study aims to explore the association between immunophenotypes and prognosis in patients with MM, to determine whether the expression of CD45 and CD200 is related to the prognosis of newly diagnosed MM (NDMM) patients, and to evaluate the significance of the combined expression of CD45 and CD200 in NDMM. METHODS: A total of 123 NDMM patients admitted to Shengjing Hospital of China Medical University from July 2015 to August 2019 were enrolled. Five key immunophenotypic markers (including CD38, CD138, CD45, CD56, and CD200) were screened through flow cytometry and identified using random forest analysis and univariate Cox regression analysis. Patients were divided into 3 groups: Group A, CD45 and CD200 double-positive; Group B, CD45 or CD200 single-positive; Group C, CD45 and CD200 double-negative. Kaplan-Meier curves were used to analyze overall survival (OS) and progression-free survival (PFS) across groups. Multivariate Cox regression was performed to evaluate prognostic factors, and a nomogram was constructed based on these results. RESULTS: The OS and PFS of single-positive groups for CD38, CD138, CD45, CD56, and CD200 were all shorter than those of their respective single-negative groups (all P<0.05). Significant differences were observed in OS (P<0.001) and PFS (P=0.001) among Groups A, B, and C. Group A had shorter OS and PFS (all P=0.001) compared to the Group B+C (cases from Group B and Group C were combined). CD45 and CD200 double-positive was an independent prognostic factor for NDMM [hazard ratio (HR)=2.178, 95% confidence interval (CI) 1.048 to 4.529; P=0.037]. The nomogram and calibration curves constructed from multivariate Cox regression analysis demonstrated good concordance (concordance index=0.706; 95% CI 0.661 to 0.751). CONCLUSIONS NDMM patients with double-positive expression of CD45 and CD200 have significantly shorter OS and PFS. Compared with the use of either marker alone, the combined assessment of CD45 and CD200 may provide better prognostic stratification for MM patients.
Humans ; Multiple Myeloma/metabolism* ; Male ; Female ; Middle Aged ; Antigens, CD/metabolism* ; Prognosis ; Leukocyte Common Antigens/metabolism* ; Aged ; Adult ; Immunophenotyping ; Nomograms ; Biomarkers, Tumor ; Clinical Relevance

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.