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.

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.

Aim To explore the mechanism of Epimedii folium-Astmgali radix activating the SCF/c-kit signa-ling pathway to activate the PI3K/Akt signaling path-way and its effect on sperm production and vitality in oligoasthenospermia.Methods Sixty male SD rats were used to establish a model of oligoasthenospermia with cyclophosphamide.They were randomly divided into six groups:experimental group(further divided into high,medium,and low dose group),model group,control group and blank group.The oligoasthenosper-mia model was established by using cyclophosphamide in experimental group,levocarnitine group and model group.The rats in the high,medium,and low dose group of the experimental group were orally adminis-tered Epimedii folium-Astmgali radix extract at doses of 800,400,and 200 mg·kg-1,respectively,Once daily for 35 days.Rats of the control group were orally ad-ministered 250 mg·kg-1·d-1 of levocarnitine,Once daily for 35 days.ELISA was used to detect serum of T,E2,FSH,and LH.Western blot and IHC staining were used to detect the expression of SCF,c-kit,Bcl-2,Bax,PI3K,and Akt proteins in rat testicular tissues.Sperm activity is examined by microscopy.The testicu-lar tissue structure and cell morphology of rats in each group were observed.Results Compared with the model group,Epimedii folium-Astmgali radix increased the sperm density,total viability rate,and vitality(P＜0.05,P＜0.01),decreased sperm apoptosis rate and LH,T,and E2 levels(P＜0.05,P＜0.01),decreased Bax protein expression in testicular tissue(P＜0.01),and increased Bcl-2,SCF,c-Kit,PI3K,and Akt protein expression(P＜0.05,P＜0.01);it increased the number of germ cells,thickened basement membrane,and significantly improved seminiferous tubule mor-phology,even showing germ cells at different develop-mental stages and mature sperm.Conclusions Epi-medii folium-Astmgali radix has a significant therapeu-tic effect on oligoasthenospermia in rats.Its mechanism may be related to the activation of the SCF/c-kit signa-ling pathway to activate the PI3K/Akt signaling path-way promoting the proliferation and differentiation of germ cells,and promoting sperm production,maturation and motility.

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 investigate the role of Sneathia sanguinegens(S.sanguinegens)in the development of unexplained recurrent spontaneous abortion(URSA).Methods A case-control study was conducted to analyze the vaginal flora characteristics of 65 patients with URSA and 18 healthy controls through 16S rRNA gene sequencing.Toxicity profile of S.sanguinegens on human cervical cancer cells(ME-180),human umbilical vein endothelial cells(HUVEC)and human placental choriocarcinoma cells(JEG-3)was analyzed at the cellular level to assess the mechanism of it in adverse pregnancy outcomes.And S.sanguinegens was used to infect C57BL/6J mice to explore the toxic effect on living organisms.Results The relative abundance of Sneathia was increased in patients with URSA compared with healthy controls.It was positively correlated with the number of miscarriages,and was attributed to S.sanguinegens.We also found that S.sanguinegens damaged ME-180,JEG-3 and HUVEC cells.The degree of cellular damage was related to the level of S.sanguinegens added.Intravenous infection with S.sanguinegens caused inflammatory damage in several organs and extramedullary hematopoiesis in the spleen.Conclusion S.sanguinegens is closely related to URSA and should be emphasized in patients with high vaginal bacterial load.

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.

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.

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.