Antibody-drug conjugates （ADCs） are a novel class of anti-tumor agents composed of a targeted monoclonal antibody， a cytotoxic drug， and a linker connecting the two. They combine the high specificity of antibodies with the potent cytotoxicity of chemotherapeutic agents. Triple-negative breast cancer （TNBC） is characterized by high aggressiveness， elevated risks of recurrence and metastasis， and poor prognosis， largely due to the lack of effective therapeutic targets. This review summarizes the research progress of ADCs in the treatment of TNBC. It has been found that ADCs targeting human epidermal growth factor receptor 2 （such as trastuzumab deruxtecan）， trophoblast cell surface antigen 2 （such as sacituzumab govitecan and datopotamab deruxtecan）， zinc transporter LIV-1 （such as ladiratuzumab vedotin）， HER-3 （such as patritumab deruxtecan）， epidermal growth factor receptor （such as AVID100）， and glycoprotein non-metastatic melanoma protein B （such as glembatumumab vedotin） have all demonstrated promising therapeutic effects against TNBC. Despite challenges including acquired resistance and treatment-related toxicities， ADCs are undoubtedly reshaping the therapeutic landscape for TNBC and are expected to occupy a more central position in TNBC treatment in the future.

Objective: To analyze the school tuberculosis (TB) outbreaks and preventive treatment in Hefei from 2022 to 2024, so as to provide reference for TB prevention and control in schools. Methods: Data were collected on all school based TB outbreaks occurring during 2022-2024 in Hefei, defined as ≥2 epidemiologically linked TB cases within the same school during a single semester. Statistical analyses were performed using the Chi square test. Results: Close contacts exhibited significantly higher TB incidence (2.88%) and latent mycobacterium tuberculosis infection (LTBI) rates (13.80%) in the school TB outbreaks, compared to non close contacts (0.12% and 2.63%, respectively). Among close contacts, secondary school students showed lower TB incidence (0.48%) and LTBI prevalence (3.42%) than both primary school or younger children (0.68%, 6.95%) and college students ( 0.78% , 6.50%), with statistically significant differences ( χ 2=360.91, 6.37; 791.71, 102.03, all P <0.05). The proportion of LTBI individuals recommended for preventive therapy was higher in primary school or younger groups (98.59%) than in secondary (95.25%) or college students (86.34%) ( χ 2=25.86, P <0.01). However, among those recommended, close contacts had higher uptake (85.82%) and completion rates (87.25%) of preventive therapy than non close contacts (69.63% and 70.57%); similarly, secondary school students demonstrated higher uptake (91.21%) and completion rates (86.45%) compared to primary school or younger (88.57%, 83.87%) and college students (57.28%, 64.08%) ( χ 2=30.52, 26.72; 125.17, 38.84, all P <0.01). Subsequent TB incidence among LTBI close contacts (13.30%) and among those who did not complete preventive therapy (22.73%) were significantly higher than among non close contacts (2.80%, 2.41%), respectively ( χ 2=32.19, 13.87, both P <0.05). Conclusions In school TB outbreaks, close contacts face higher LTBI prevalence and subsequent TB risk than non close contacts. College students show notably low adherence to preventive therapy. It is necessary to take targeted measures to improve the compliance of preventive measures among students.

BACKGROUND:Erythropoietin has anti-inflammatory,anti-apoptotic,and pro-bone defect repair effects.To date,fewer studies have been conducted on its effects and molecular mechanism underlying restorative dentin formation after pulp injury. OBJECTIVE:To explore the effect of erythropoietin on restorative dentin formation after pulp injury. METHODS:(1)Animal experiment:Thirty-two rats were randomly divided into control group(n=16)and experimental group(n=16).In the experimental group,collagen sponges containing erythropoietin were used to directly cap the pulp at the pulp injury,and in the control group,collagen sponges containing PBS were used to directly cap the pulp at the exposed pulp injury.The cavity was then closed with glass ionomer adhesive.After 2 and 4 weeks of treatment,the maxillary bones of the two groups were collected,and the expression of nestin in dentin was detected by immunohistochemistry,and the reparative dentin production was observed by hematoxylin-eosin staining.The maxillae of four Sprague-Dawley rats were taken for immunohistochemical detection of erythropoietin expression in molar and incisor teeth.(2)Cell experiment:Human dental pulp cells,human periodontal ligament cells and human gingival fibroblasts were obtained from human dental tissue,periodontal ligament,and gingival tissue.Real-time reverse transcription PCR(RT-PCR)was used to detect the mRNA expression of erythropoietin.Erythropoietin,dentin sialophosphoprotein,dentin matrix protein 1,and nestin mRNA levels in human pulp cells were detected by RT-PCR under induced or uninduced odontoblastic differentiation.After down-regulation of erythropoietin expression or exogenous administration of erythropoietin intervention under induced or uninduced differentiation odontoblastic differentiation,the relative mRNA expression of dentin sialophosphoprotein and dentin matrix protein 1 in human pulp cells was detected by RT-PCR,and the formation of mineralized nodules was detected by alizarin red S staining,and mRNA and protein expressions of bone morphogenetic protein 2 were detected by RT-PCR and western blot,respectively. RESULTS AND CONCLUSION:(1)Animal experiment:Compared with the control group,the restorative dentin production and nestin expression were higher in the experimental group after 2 and 4 weeks of treatment.The expression of erythropoietin was weakly positive in pulp,odontoblastic cell layer and periodontal membrane of the rat's first maxillary molar,and strongly positive in odontoblasts.(2)Cell experiment:The mRNA expression of erythropoietin was higher in human dental pulp cells than in the other two types of cells.The mRNA expressions of dentin sialophosphorin,dentin matrix protein 1,nestin,erythropoietin and bone morphogenetic protein 2 in human pulp cells increased and the formation of mineralized nodules during odontoblastic differentiation under induction compared with non-induction conditions.The mRNA expression of dentin sialophosphoprotein,dentin matrix protein 1,nestin,bone morphogenetic protein 2 and the formation of mineralized nodules were decreased in human pulp cells after downregulation of erythropoietin under induced odontoblastic differentiation,and the protein expression of bone morphogenetic protein 2 was also decreased.After exogenous erythropoietin intervention,the expression of the above indexes in human dental pulp cells increased.To conclude,erythropoietin can promote the formation of dentin to some extent.

Community general practitioners are the main force of primary health care, however, the lack of effective incentive mechanisms would affect their work enthusiasm. Therefore, to enhance incentive mechanisms,particularly from the perspective of the career development,will improve the work enthusiasm and post competeny of general practitioners in primary health care services. This article summarizes five major influencing factors of the incentives for community general practitioners, namely salary and benefits, performance evaluation, promotion and development, working conditions and interpersonal relationships, and proposes the operational strategies of incentive improvement, to provide reference for improving working conditions and strengthening incentive measures for community general practioners in primary community hospitals.

Objective:To investigate the preventive efficacy of triamcinolone acetonide injection on esophageal stenosis after endoscopic submucosal dissection (ESD).Methods:From February 1, 2021 to October 31, 2023, 82 patients who underwent ESD for esophageal lesions at the Affiliated Cancer Hospital of Nanjing Medical University (Jiangsu Cancer Hospital) were enrolled. According to the treatment of the surface after ESD, the patients were divided into the triamcinolone acetonide group (49 cases) and the no-special-treatment group (33 cases). The patients of triamcinolone acetonide group received multiple injections of triamcinolone acetonide solution post-ESD (immediate), week 1, and week 4, while the patients of no-special-treatment group did not receive additional pharmacological intervention. The patients were followed up for 3 months after ESD. The occurrence of esophageal stenosis after ESD was observed under endoscopy. The incidence of esophageal stenosis and the improvement of dysphagia after ESD were compared between the triamcinolone acetonide group and no-special-treatment group. Univariate and multivariate logistic regression analyes were performed to identify influencing factors of esophageal stenosis after ESD. Chi-square test was used for statistical analysis.Results:The incidence of esophageal stenosis after ESD in the triamcinolone acetonide group was lower than that in the no-special-treatment group (16.3% (8/49) vs. 66.7% (22/33)), and the proportion of patients without dysphagia (Stooler′s grading score of 0) was higher than that in the no-special-treatment group (83.7% (41/49) vs. 33.3% (11/33)), and the differences were statistically significant ( χ2=19.42 and 24.31, both P<0.001). In 42 patients with circumferential esophageal lesions involving >75%, the incidence of esophageal stenosis in the triamcinolone acetonide group was lower than that in the no-special-treatment group (28.6% (6/21) vs. 85.7% (18/21)), and the proportion of patients without dysphagia (Stooler′s grading score of 0) was higher than that in the no-special-treatment group (71.4% (15/21) vs. 14.3% (3/21)), and the differences were statistically significant ( χ2=11.76 and 15.33, both P<0.001). There was no statistically significant differences in the incidence of adverse events between the triamcinolone acetonide group and no-special-treatment group (4.1% (2/49) vs. 0; χ2=0.20, P=0.656), and no serious adverse reactions occurred in 2 groups. The results of multivariate logistic regression analysis showed that the long distance from the proximal lesion margin to the incisors was a protective factor of whether esophageal stenosis occured or not after ESD ( OR=0.795, 95% confidence interval (95% CI): 0.652 to 0.947, P=0.014), while the incidence of esophageal stenosis increased in patients with circumferential lesions involving >75% ( OR=7.064, 95% CI: 1.893 to 32.408, P=0.006), and the incidence of esophageal stenosis effectively reduced after the use of triamcinolone acetonide post ESD ( OR=0.062, 95% CI: 0.013 to 0.229, P<0.001). Conclusion:After ESD, triamcinolone acetonide can reduce the incidence of esophageal stenosis and improve patients′ dysphagia.

Purpose To explore the expression of SHIP2 in esophageal squamous cell carcinoma and its effect on the malignant biological behavior of ESCC cells.Methods The UALCAN database was used to analyze the expression of SHIP2 in esophageal cancer.qRT-PCR and immunohistochemistry SP method were used to measure the expression of SHIP2 in tumor tissues of ESCC patients.SHIP2 mRNA and protein were examined by qRT-PCR and Western blot in human normal esophageal epithelial cells(HEEC)and ESCC cells(KYSE150 and EC109).KYSE150 and EC109 were divided into the NC group and the si-SHIP2 group respectively.Cell proliferation,migration,and invasion were observed by CCK-8 assay,EdU assay,scratch assay,and Transwell assay.The expression of epithelial-mesenchymal transition-related proteins(E-cadherin,N-cadherin,and vimentin)was detected by Western blot.Results The UAL-CAN database showed that SHIP2 expression was higher in esophageal cancer than in normal tissues(P＜0.05).SHIP2 had higher mRNA(2.19±3.20)expression and staining scores(5.33±3.83)in ESCC tumor tissues than in paracarcinoma tissues(1.00±0.80;0.87±1.07,all P＜0.05).SHIP2 had higher mRNA(KYSE150,EC109:1.91±0.22,3.73±1.06)and protein(KYSE150,EC109:0.93±0.12,1.05±0.13)expression in ESCC cells than in HEEC(1.06±0.40;0.31±0.04,all P＜0.05).Cell function experiments showed that compared with the NC group(CCK-8 assay:KYSE150,EC109:2.44±0.12,3.56±0.07;EdU assay:KYSE150,EC109:44.46±4.74,38.82±3.79;scratch assay:KYSE150,EC109:0.85±0.07,0.70±0.06;Transwell migration assay:KYSE150,EC109:130.30±9.53,39.25±3.30;Transwell invasion assay:KYSE150,EC109:121.00±9.54、88.67±6.66);cell proliferation(CCK-8 assay:KYSE150,EC109:1.56±0.03,2.85±0.02,EdU assay:KYSE150,EC109:19.34±6.24,17.39±1.14);migration(scratch assay:KYSE150,EC109:0.51±0.09,0.36±0.02;Transwell migration assay:KYSE150,EC109:71.50±12.07,20.75±2.99),and invasion(Transwell in-vasion assay:KYSE150,EC109:73.33±4.04,12.67±2.31)ability in the si-SHIP2 group was significantly re-duced(all P＜0.05).Western blot results showed that compared with the NC group(0.48±0.21,0.42±0.24;1.00±0.04,1.17±0.18;1.34±0.10,1.00±0.13),the expression of E-cadherin protein(1.10±0.22,1.02±0.20)in the si-SHIP2 group was increased(P＜0.05),while the expression of N-cadherin protein(0.59±0.20,0.84±0.08)and vimentin protein(0.41±0.06,0.338±0.19)was decreased(P＜0.05).Conclusion SHIP2 is overexpressed in ESCC,and the down-regulation of SHIP2 can inhibit the proliferation,migration,and invasion of ES-CC cells.

Objective To investigate the efficacy of Qihuang Jianpi Zishen Granules(QJZ)for inhibiting renal B cell differentiation in MRL/lpr mice and explore its underlying mechanism.Methods Thirty 8-week-old female MRL/lpr mice were randomly divided into model group,QJZ group,prednisone(Pred)group,QJZ+Pred group,and AIM2 inhibitor group(n=6),with 6 8-week-old female C57BL/6 mice as the normal control group.After treatments with normal saline,QJZ,Pred,or AIM2 inhibitor for 8 weeks,the mice were examined for urinary total protein-to-creatinine ratio(TPCR)and albumin-to-creatinine ratio(ACR),serum creatinine(Cr)and blood urea nitrogen(BUN)levels,and renal histopathology(with HE,Masson,and PAS staining)and ultrastructural changes(with electron microscopy).ELISA,immunohistochemistry,immunofluorescence staining and flow cytometry were used to detect blood levels of anti-dsDNA antibodies,cytokines and chemokines,renal deposition of complement components C3 and C4,renal expressions of AIM2,CD19,CD27 and CD138,and changes in splenic B lymphocyte subsets.The effect of QJZ on the AIM2/Blimp-1/Bcl-6 signaling axis was examined using Western blotting.Results QJZ treatment significantly improved Cr,BUN,TPCR and ACR in MRL/lpr mice,ameliorated renal pathologies,reduced the expressions of ds-DNA,BAFF,IL-21,CXCL12,CXCL13,C3 and C4,and increased IL-10 levels.QJZ significantly downregulated renal expressions of the key B-cell transcription factors Blimp-1 and XBP-1,upregulated Bcl-6 and PAX5 expressions,inhibited B-cell differentiation,and lowered the expressions of AIM2,CD27,CD138 and CD69.Inhibition of AIM2 similarly reduced renal Blimp-1 and XBP-1 expressions,increased Bcl-6 and PAX5 levels,suppressed B-cell differentiation,decreased IgG production,reduced C3 and C4 deposition,and alleviated renal pathology in MRL/lpr mice.Conclusion QJZ inhibits B cell differentiation and alleviates renal damage in systemic lupus erythematosus possibly by suppressing the AIM2/Blimp-1/Bcl-6 signaling pathway.

Objective To investigate the mechanism of Qihuang Jianpi Zishen Granules(QJZ)for ameliorating renal damage in MRL/lpr mice.Methods With 6 female C57BL/6 mice as the normal control group,30 female MRL/lpr mice were randomized into model group,QJZ treatment groups at low,moderate and high doses,and prednisone treatment group(n=6).After 8 weeks of treatment,the mice were examined for 24-h urine protein,creatinine and albumin levels,serum levels of IgG,complement 3(C3),C4,anti-dsDNA,interferon γ(IFN-γ)and interleukin 17(IL-17).Kidney tissues were sampled for histopathological examination with HE staining and observation of glomerular ultrastructure changes using transmission electron microscopy(TEM).The expressions of MyD88/NF-κB pathway-related molecules in the kidney tissue were detected using RT-qPCR,Western blotting and immunohistochemistry.Results Compared with those in the model group,the mice treated with QJZ at the 3 doses and prednisone showed significant reductions in the renal injury biomarkers and serum IgG,anti-dsDNA,IFN-γ and IL-17 levels and elevation of serum C3 and C4 levels.HE staining revealed lessened glomerular endothelial cell proliferation and mesangial thickening in all the treatment groups.TEM observation further demonstrated reduced electron-dense deposits and diminished inflammatory cell infiltration in the glomeruli in the intervention groups.QJZ at the 3 doses and prednisone treatment all significantly lowered renal expression levels of MyD88,NF-κB,p65 and p52 in the mouse models.Conclusion QJZ can improve renal damage in MRL/lpr mice possibly by inhibiting overactivation of the MyD88/NF-κB pathway.

Objective:To analyze the trend of infertility disease burden from 1990 to 2019 and predict the age-standardized prevalence rate (ASPR) and age-standardized disability-adjusted life-year (DALY) rate of male and female infertility for 2020—2029, providing a certain reference for the prevention and treatment of infertility diseases.Methods:Based on the Global Burden of Disease 2019, prevalence, ASPR, DALY rate, and age-standardized DALY rate were used to evaluate the global burden of infertility comprehensively. The estimated annual percentage change was used to describe trends in the disease burden of infertility in 21 regions worldwide. The Bayesian age period cohort model was used to predict the ASPR and age-standardized DALY rate for male and female infertility in 204 countries and regions from 2020 to 2029. Sensitivity analysis was performed using the autoregressive integrated moving average model.Results:The prevalence, DALY rate, ASPR and age-standardized DALY rate of global male infertility increased from 319.52 per 100 000,1.82 per 100 000, 2 856.53 per 100 000, and 16.19 per 100 000 in 1990 to 565.30 per 100 000, 3.22 per 100 000, 3 398.53 per 100 000, and 19.36 per 100 000 in 2019, respectively. The prevalence, DALY rate, ASPR, and age-standardized DALY rate of global female infertility increased from 656.67 per 100 000, 3.53 per 100 000, 6 036.36 per 100 000, and 32.27 per 100 000 in 1990 to 1 223.78 per 100 000, 6.59 per 10 000, 7 483.12 per 100 000, and 40.33 per 100 000 in 2019, respectively. The burden of infertility disease was the highest in men and women aged 30-34 years, and the ASPR and age-standardized DALY rates were 4 407.47 per 100 000, 25.08 per 100 000, 10 270.55 per 100 000 and 55.65 per 100 000, respectively. Only in 45-49 years of age, the prevalence of infertility (11.31 per 100 000) and DALY rate (0.06 per 100 000) in women were lower than those in men (15.68 per 100 000 and 0.08 per 100 000). In addition, the burden of infertility was the lowest in high socio-demographic index regions. Cameroon had the highest ASPR (7 652.40 per 100 000) and age-standardized DALY rate (43.94 per 100 000) for male infertility. Chinese women had the highest ASPR (20 402.30 per 100 000) and age-standardized DALY rate (106.16 per 100 000) of infertility. The forecast results show that the burden of male and female infertility diseases will increase in 204 countries and regions from 2020 to 2029.Conclusion:The burden of infertility diseases in men and women increased in 204 countries and regions from 1990 to 2019, and it is predicted that the global burden of infertility diseases will continue to rise in 2020—2029. Preliminary screening of infertility should be carried out as soon as possible, health education should be strengthened and effective prevention and treatment strategies should be formulated.

Mechanical pain is one of the most common causes of clinical pain, but there remains a lack of effective treatment for debilitating mechanical and chronic forms of neuropathic pain. Recently, neurotoxin GsMTx4, a selective mechanosensitive (MS) channel inhibitor, has been found to be effective, while the underlying mechanism remains elusive. Here, with multiple rodent pain models, we demonstrated that a GsMTx4-based 17-residue peptide, which we call P10581, was able to reduce mechanical hyperalgesia and neuropathic pain. The analgesic effects of P10581 can be as strong as morphine but is not toxic in animal models. The anti-hyperalgesic effect of the peptide was resistant to naloxone (an μ-opioid receptor antagonist) and showed no side effects of morphine, including tolerance, motor impairment, and conditioned place preference. Pharmacological inhibition of TRPV4 by P10581 in a heterogeneous expression system, combined with the use of Trpv4 knockout mice indicates that TRPV4 channels may act as the potential target for the analgesic effect of P10581. Our study identified a potential drug for curing mechanical pain and exposed its mechanism.