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 evaluate the cost-utility of disitamab vedotin （DV） combined with toripalimab versus platinum-containing chemotherapy as first-line therapy for locally advanced or metastatic urothelial carcinoma（UC） with human epidermal growth factor receptor 2 （HER2） expression from the perspective of China’s health-care system.METHODS A cost-utility analysis was performed. A three-state partitioned survival model was constructed based on the RC48-C016 trial with a 1-week cycle length. The long-term health benefits [quality-adjusted life years（QALYs）] and costs of disitamab vedotin combined with toripalimab versus platinum-containing chemotherapy as first-line therapy for locally advanced or metastatic UC with HER2 expression were simulated. The simulation time horizon was set to 15 years， and the discount rate was 4.5%. The willingness-to-pay （WTP） threshold was defined as twice China’s per capita gross domestic product（GDP） in 2025 （199 330 yuan/QALY）. The incremental cost-effectiveness ratio （ICER） between the two groups was compared， and one-way sensitivity analysis and probabilistic sensitivity analysis were conducted.RESULTS Compared with platinum-containing chemotherapy regimen， the DV plus toripalimab regimen yielded an additional 1.01 QALYs with an incremental cost of 183 224.45 yuan， and the ICER was 181 728.15 yuan/QALY， which was below the WTP threshold. At the current threshold， the probability that the DV combination regimen had a cost-utility advantage was 79.9%.CONCLUSIONS Taking twice China’s per capita GDP in 2025 as the WTP threshold， DV combined with toripalimab exhibits a cost-utility advantage over platinum-containing chemotherapy as first-line treatment for HER2-expressing locally advanced or metastatic urothelial carcinoma.

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 MR imaging features of patients with general paresis of the insane(GPI),characterized by bilateral hippocampal atrophy,and to explore how to improve the accuracy of early GPI diagnosis.Methods A retrospective analysis was conducted on the clinical manifestations,brain imaging data,diagnosis and treatment of 11 patients with GPI.Results Among the 11 cases,MRI showed that 9 cases had varying degrees of brain atrophy,of which 7 cases showed age-inappropriate brain atro-phy,especially bilateral hippocampal atrophy as the main sign,and the remaining 2 cases showed brain atrophy accompanied by multi-ple abnormal intracranial signals;2 cases only showed multiple abnormal intracranial signals.Conclusion MR imaging findings of GPI often manifests only age-inappropriate brain atrophy,particularly bilateral hippocampal atrophy,a feature that holds significant diagnostic value for early detection with reducing missed diagnosis rate of GPI.

Objective To investigate the occurrence of dysphagia in patients with congenital esophageal atre-sia(EA)after surgery and study the associated risk factors.Methods A retrospective analysis was conducted on clinical data of 103 children who underwent surgery for congenital EA at Beijing Children's Hospital,Capital Medi-cal University,from July 2016 to August 2023.Results A total of 103 eligible cases of congenital EA were includ-ed in this study,among which 74 cases experienced dysphagia,with an incidence rate of 71.8％.Single-factor anal-ysis revealed that primary surgery(x2=4.017,P=0.045),endoscopic surgery(x2=8.315,P=0.004),long-seg-ment defects(x2=10.975,P＜0.001),gastroesophageal reflux(x2=16.973,P＜0.001),vocal cord paralysis(x2=4.017,P=0.045),tracheomalacia(x2=5.778,P=0.016),and arytenoid movement disorder(x2=10.420,P=0.001)were significantly associated with postoperative dysphagia.Further binary logistic regression analysis indi-cated that endoscopic surgery(OR=24.373,P=0.016),tracheomalacia(OR=17.556,P=0.010),and anasto-motic stenosis(OR=20.453,P=0.032)were independent risk factors for increased incidence of postoperative dys-phagia.Moreover,stratified analysis of dysphagia duration using unordered multinomial logistic regression revealed that tracheomalacia(OR=16.883,P=0.007;OR=4.337,P=0.045),long-segment defects(OR=0.040,P=0.049;OR=0.040,P=0.036),and arytenoid movement disorder(OR=0.127,P=0.039;OR=0.510,P=0.028)were closely associated with dysphagia duration.Conclusion Dysphagia is a common symptom in children with congenital EA after surgery across all age groups.Endoscopic surgery,long-segment defects,tracheomalacia,and anastomotic stenosis are independent factors contributing to postoperative dysphagia.Additionally,tracheoma-lacia,long-segment defects,and arytenoid movement disorder are closely related to the duration of dysphagia.

Objective:To establish a tumor tissue xenograft (PDX) model derived from liver cancer patients and explore the factors affecting tumorigenicity of liver cancer in the PDX model.Methods:The hepatocellular carcinoma tissues were inoculated subcutaneously in the axilla of NPG mice using the tissue block method to establish a PDX model. The demographic characteristics and related clinical examination data of 60 hepatocellular carcinoma patients were collected using the electronic medical record system and comprehensive medical information system of Beijing You'an Hospital, affiliated to Capital Medical University. The hepatocellular carcinoma samples of 24 cases were sequenced using the Oak Wing TM-808 gene detection reagent and high-throughput sequencing technology. SPSS 17.0 statistical software was used for statistical analysis, and the count data were analyzed using the χ2 test. Results:The tumorigenicity rate of PDX samples from 60 patients with liver cancer was 35% (21/60). The average tumorigenic duration in the PDX-P0 generation was 110.71±50.45 days. There were statistically significant differences ( P<0.05) corresponding to Edmondson grade ( χ2=5.910, P=0.015) and Ki67 expression ( χ2=4.615, P=0.032) among PDX with tumorigenicity and without tumorigenicity between the liver cancer samples. There was no statistically significant difference in gene mutation (TOP25) among PDX with tumorigenicity and without tumorigenicity between liver cancer samples. Conclusion:The factors affecting the tumorigenicity of liver cancer in PDX models are complex. The high pathological grade and strong Ki67 expression may be the key factors for the completion of liver cancer in PDX models.

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.

Objective To explore the biological functions and mechanisms of PIWI-interacting RNA(piRNA)in cervical cancer(CC).Methods RT-qPCR was used to detect the expression level of piRNA-2732 in CC tissue,CaSki cells and End1/E6E7 cells.EpiQuik m6A RNA methylation quantification kit was used to detect the methylation level of m6A RNA in CaSki cells.The expression levels of methyltransferases(METTL3,METTL14 and WTAP)and demethylases(FTO,ALKBH5)mRNA in CaSki cells were detected by RT-qPCR.After culturing CaSki cells to logarithmic growth stage,they were divided into six groups:piRNA-2732 mimic negative control group(mi-NC group),piRNA-2732 mimic group(mi-2732 group),piRNA-2732 inhibitor negative control group(in-NC group),piRNA-2732 inhibitor group(in-2732 group),piRNA-2732 mimic+METTL3 knockdown control group(mi-2732+si-NC group),and piRNA-2732 mimic+METTL3 knockdown group(mi-2732+si-METTL3 group).The viability of CaSki cells was detected by CCK8 assay.Colony formation assay was used to detect the proliferation ability of CaSki cells.Transwell experiment was used to detect the migration and invasion ability of CaSki cells.RT-qPCR and Western blot were used to detect the expression of methyltransferase like protein 3(METTL3).Transfected METTL3 wild-type(METTL3-WT)and METTL3 mutant(METTL3-MUT)in the mi-NC group,mi-2732 group,in-NC group,and in-2732 group respectively,and detected the effect of piRNA-2732 on METTL3 through dual luciferase reporter gene assay.Results Compared with the adjacent tissues,the expression of piRNA-2732(3.84±1.08 vs 1.32±0.53)was significantly higher in the cancer tissues of CC patients,and the difference was statistically significant(t=5.115,P<0.001).Compared with end1/E6E7 cells,the expression of piRNA-2732(1.00±0.13 vs 1.67±0.16)in CaSki cells was significantly higher,and the difference was statistically significant(t=5.632,P<0.01).Compared with mi-NC group,mi-2732 group promoted the viability,proliferation,migration and invasion of CaSki cells,and the differences were statistically significant(t=4.410～11.040,all P<0.01).Compared with mi-NC group,mi-2732 group increased m6A RNA methylation level and METTL3 mRNA and protein,the differences were statistically significant(t=6.176,9.211,12.550,all P<0.05).The results of dual luciferase reporter gene testing showed that compared with the mi-NC+METTL3-WT group,the relative luciferase activity of mi-2732+METTL3-WT group was significantly increased(t=11.850).Compared with mi-2732+METTL3-WT group,the relative luciferase activity of mi-2732+METTL3-MUT group was significantly lower(t=12.740),and the difference was statistically significant(all P<0.000 1).Compared with in NC+METTL3-WT group,the relative luciferase activity of in-2732+METTL3-WT group was significantly lower(t=7.828),compared with in-2732+METTL3-WT group,the relative luciferase activity of CaSki cells in in-2732+METTL3-MUT group was significantly increased(t=8.146),and the difference was statistically significant(all P<0.001).Compared with mi-2732+si-NC group,the expression level of m6A in mi-2732+si-METTL3 group was significantly lower,and the difference was statistically significant(t=7.630,P<0.01).Compared with mi-2732+si-NC group,the proliferation ability,colony number,cell migration and invasion ability of CaSki cells in mi-2732+si-METTL3 group were significantly decreased,and the differences were statistically significant(t=3.695～4.891,all P<0.001).Conclusion piRNA-2732 is overexpressed in CC tissues and cells,and piRNA-2732 promotes tumor development in CC through METTL3 mediated m6A methylation.

Objective To explore the relationship between the expression levels of serum long chain non coding RNA Kinectin 1 antisense RNA 1(LncRNA KTN1-AS1)and retinoblastoma binding protein 4(RBBP4)with postoperative recurrence and metastasis in esophageal cancer patients.Methods From May 2018 to May 2021,119 patients with esophageal cancer who underwent surgical treatment in our hospital were included as the study group.They were separated into an occurrence group(n=51)and a non occurrence group(n=68)based on whether there was recurrence or metastasis during a 3-year follow-up.Additionally,100 patients with benign esophageal tumors treated at the same stage were selected as the control group.ELISA method was applied to detect the expression levels of serum LncRNA KTN1-AS1 and RBBP4.Multivariate Logistic regression was applied to analyze the influencing factors of postoperative recurrence and metastasis in esophageal cancer patients.ROC curve was applied to analyze the predictive value of serum LncRNA KTN1-AS1 and RBBP4 for postoperative recurrence and metastasis in esophageal cancer patients.Results The expression levels of serum LncRNA KTN1-AS1 and RBBP4 in the study group were obviously higher than those in the control group(P＜0.05).The expression levels of serum LncRNA KTN1-AS1 and RBBP4,and the proportions of mucosal/submucosal infiltration depth,and low differentiation degree and proportion of lymph node metastasis in the occurrence group were obviously higher than those in the non occurrence group(P＜0.05).Serum LncRNA KTN1-AS1,RBBP4,proportion of lymph node metastasis,degree of differentiation,and depth of infiltration were influencing factors for postoperative recurrence and metastasis in esophageal cancer patients(P＜0.05).The area under the curve(AUC)of the combined prediction of serum LncRNA KTN1 AS1 and RBBP4 for postoperative recurrence and metastasis in esophageal cancer patients was 0.912,which was better than their individual predictions(Zcombination LncRNA KTN1 AS1=2.470,Zcombination-RBBp4=1.994,P=0.014,P=0.046),the sensitivity and specificity of the combined prediction were 90.20％and 85.29％,respectively.Conclusion The expression levels of serum LncRNA KTN1-AS1 and RBBP4 in esophageal cancer patients are obviously increased,which is closely related to postoperative recurrence and metastasis.The combined detection of the two has good predictive value for postoperative recurrence and metastasis in patients.