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 Investigate the efficacy of modified electroconvulsive therapy(MECT)in patients with schizophrenia across different genders.Methods From May 2018 to August 2022,481 patients with schizophrenia were recruited from three psychiatric hospitals in Luzhou,Zigong,and Yibin.According to gender grouping,both groups received adjunctive MECT treatment for two consecutive weeks for a total of six treatments.The differences in positive and negative syndrome scale(PANSS)scores before and after treatment,UKU adverse reaction rating scale(UKU),and gastrointestinal symptom rating scale(GSRS)scores were compared between the two groups.Results After quality control,463 cases were followed up for analysis including 246 males and 217 females.Compared with pre-treatment,the total PANSS score and scores on each subscale were significantly reduced in both genders after treatment(P<0.001).When comparing the reduction rates between the groups,the male patients showed a higher reduction rate in negative symptoms than the female patients(31.24%±30.24%vs.25.80%±33.96%,P<0.05).However,there were no significant differences between the two groups in the reduction rates of the total score,positive symptoms,and general psychopathology(P>0.05).The comparison of adverse reactions showed that the frequency of other types of adverse reactions was higher in female patients than in male patients(47.47%vs.37.80%,P<0.05).However,no significant differences were observed in the adverse reactions related to the mental,neurological,autonomic nervous system,and gastrointestinal systems(P>0.05).Correlation analysis revealed that the reduction rate of the PANSS total score was positively correlated with smoking history(r=0.135,P=0.034)and alcohol history(r=0.160,P=0.012)in male patients,while the reduction rate of the PANSS total score was negatively correlated with the disease duration(r=-0.210,P=0.002)and positively correlated with the age of onset(r=0.145,P=0.032)in female patients.Conclusion MECT is significantly effective for both male and female patients with schizophrenia.Compared to female patients,MECT shows a more pronounced effect on negative symptoms in male patients.Additionally,the factors related to the efficacy of MECT differ between genders,indicating that it is necessary to consider the clinical characteristics of patients comprehensively when selecting an MECT treatment plan.

Objective:To investigate effects of picroside Ⅱ(PⅡ)on proliferation,apoptosis and immune escape of lung cancer cells by regulating C-C motif chemokine ligand 2(CCL2)/C-C motif chemokine receptor 2(CCR2)signaling axis.Methods:Human lung cancer cells NCI-H292 were cultured and treated with 0,5,10,20,40 and 80 μmol/L PⅡ,MTT method was applied to detect cell viability.Experiment was separated into control group,low,medium and high concentrations PⅡ groups(PⅡ-L,PⅡ-M,PⅡ-H,10,20 and 40 μmol/L PⅡ),high concentration PⅡ+CCL2 overexpression negative control group(PⅡ-H+pcDNA-NC,40 μmol/L PⅡ+pcDNA-NC)and high concentration PⅡ+CCL2 overexpression group(PⅡ-H+CCL2,40 μmol/L PⅡ+pcDNA-CCL2).EdU method was applied to measure cell proliferation;flow cytometry was applied to measure cell apoptosis;immunoblotting was applied to determine expressions of CCL2,CCR2,B-cell lymphoma-2(Bcl-2)and Bcl-2 associated X protein(Bax).Lung can-cer cells in each group were co-cultured with CD8+T cells,Trypan blue staining was applied to measure CD8+T cell viability;ELISA was applied to determine levels of programmed death receptor-ligand 1(PD-L1),IL-10,IFN-γ and TGF-β.Results:Compared with 0 μmol/L,cell viability treated with 10,20,40 and 80 μmol/L PⅡ were significantly reduced(P<0.05),and 10,20 and 40 μmol/L PⅡ were selected for subsequent experiments.Compared with control group,positive rate of EdU and expressions of Bcl-2,CCL2 and CCR2 in PⅡ-L group,PⅡ-M group and PⅡ-H group were decreased sequentially(P<0.05),while apoptosis rate and expression of Bax were increased sequentially(P<0.05).Compared with PⅡ-H+pcDNA-NC group,positive rate of EdU and expressions of Bcl-2,CCL2 and CCR2 in PⅡ-H+CCL2 group were increased obviously(P<0.05),while apoptosis rate and expression of Bax were de-creased significantly(P<0.05).After co-culturing with CD8+T cells,compared with control group,levels of IL-10,TGF-β and PD-L1 in PⅡ-L group,PⅡ-M group and PⅡ-H group were decreased sequentially(P<0.05),while CD8+T cell viability and level of IFN-γ were increased sequentially(P<0.05).Compared with PⅡ-H+pcDNA-NC group,levels of IL-10,TGF-β and PD-L1 in PⅡ-H+CCL2 group were increased obviously(P<0.05),while CD8+T cell viability and level of IFN-γ were reduced significantly(P<0.05).Conclu-sion:PⅡ may inhibit proliferation and immune escape of lung cancer cells,and promote cell apoptosis by inhibiting CCL2-CCR2 sig-naling axis.

Objective To investigate the effects of asiaticoside(AS)on epithelial-mesenchymal transition(EMT)and radiotherapy sensitivity of esophageal cancer(EC)cells by its mechanism of regulating the hypoxia inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF)signaling pathway.Methods EC9706 cells were subjected to different concentrations of AS or different doses of radiation.Methyl thiazolyl tetrazolium method was used to detect cell proliferation and calculate the half-maximal inhibitory con-centration.EC9706 cells were divided into a control group,radiology group(X-ray irradiation),AS group,combined group(AS+X-ray irradiation),and activator group(AS+X-ray irradiation+HIF-1α/VEGF pathway activator dimethyloxallyl glycine).Plate cloning experi-ments were conducted to detect sensitivity,and Transwell assays were used to detect cell migration and invasion.Flow cytometry helped detect apoptosis,and real-time quantitative polymerase chain reaction detected the expression of HIF-1α and VEGF mRNA.Western blotting method was used to detect the expression of matrix metalloproteinase-2(MMP-2),vimentin,E-cadherin,Bcl-2 associated X protein(Bax),HIF-1α,and VEGF proteins.Results With the increase of AS concentration and radiation dose,the cell viability of EC9706 cells gradually decreased;compared with the control group,the survival fraction;the numbers of cells that had migrated and invaded;the expression of HIF-1α and VEGF mRNA;and the expression of MMP-2,vimentin,HIF-1α,and VEGF in the radiology group and AS group were reduced;further,the apoptosis rate and the expression of E-cadherin and Bax were increased(P＜0.05).Compared with the radiology group and AS group,the survival fraction;the numbers of cells that had migrated and invaded;the expression of HIF-1αand VEGF mRNA;and the expressions of MMP-2,vimentin,HIF-1α,and VEGF in the combined group were reduced;the apoptosis rate and the expression of E-cadherin and Bax were increased(P＜0.05).In comparison with the combined group,the changes in the above indicators in the activator group were reversed(P＜0.05).Conclusion AS may inhibit EMT by inhibiting the HIF-1α/VEGF signaling pathway,thus enhancing the radiotherapy sensitivity of EC cells.

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 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.

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.

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.

ObjectiveTo evaluate the clinical efficacy and safety of Baoshen prescription in the treatment of stage Ⅳ diabetic nephropathy （DN） in the patients with syndromes of Qi-Yin deficiency and kidney collateral stasis and obstruction， and to explore the mechanism of this prescription delaying the disease progression. MethodsA randomized， controlled， double-blind， multicenter clinical trial was conducted， in which 94 stage Ⅳ DN patients with syndromes of Qi-Yin deficiency and kidney collateral stasis and obstruction were randomly assigned into Baoshen prescription and control groups （47 cases）. The treatment lasted for 12 weeks. The primary efficacy indicators were mainly renal function indexes， including urine albumin-to-creatinine ratio （UACR）， 24-hour urine total protein （24 h-UTP）， serum creatinine （SCr）， and estimated glomerular filtration rate （eGFR）. The secondary efficacy indicators were metabolic memory of hyperglycemia， podocyte epithelial-to-mesenchymal transdifferentiation-related indexes， and TCM syndrome score. ResultsAfter 12 weeks of treatment， the Baoshen prescription group showed lowered levels of advanced glycation end products （lgAGEs）， connective tissue growth factor （CTGF）， type Ⅳ collagen （Col-Ⅳ）， receptor of AGEs （RAGE）， urinary fibroblast-specific protein-1 （FSP-1）， UACR， 24 h-UTP， and glycated hemoglobin （HbAlc） （P<0.05）， and an upward trend of miR-21 mRNA. The control group showed elevated levels of SCr and UREA and lowered levels of urinary FSP-1， eGFR， and HbAlc （P<0.05）. After treatment， the Baoshen prescription group had lower levels of lgAGEs， CTGF， urinary FSP-1， SCr， UACR， and 24 h-UTP and higher levels of Col-Ⅳ and eGFR than the control group （P<0.05）. In addition， the Baoshen prescription group showed statistically significant differences in SCr， eGFR， UACR， and 24 h-UTP before and after treatment （P<0.05）. ConclusionBaoshen prescription can effectively improve the renal function， reduce the urinary protein level， and alleviate clinical symptoms in stage Ⅳ DN patients with syndromes of Qi-Yin deficiency and kidney collateral stasis and obstruction. The mechanism may be related to the metabolic memory of hyperglycemia and epithelial-to-mesenchymal transdifferentiation of podocytes.