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.

Liver cancer is one of the most common malignant tumors worldwide. Currently, the available treatment methods cannot fully control its recurrence and mortality rate. Establishing appropriate animal models for liver cancer is crucial for developing new treatment technologies and strategies. The patient-derived xenograft (PDX) model preserves the tumor's microenvironment and heterogeneity, which makes it advantageous for biological research, drug evaluation, personalized medicine, and other purposes. This article reviews the development, preparation techniques, application fields, and challenges of PDX models in liver cancer, providing insights for the research and exploration of PDX models in diagnostic and therapeutic strategies of liver cancer.
Liver Neoplasms/drug therapy* ; Animals ; Humans ; Xenograft Model Antitumor Assays/methods* ; Mice ; Disease Models, Animal

OBJECTIVES: 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. CONCLUSIONS QJZ can improve renal damage in MRL/lpr mice possibly by inhibiting overactivation of the MyD88/NF-κB pathway.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Female ; Mice, Inbred C57BL ; Mice, Inbred MRL lpr ; Myeloid Differentiation Factor 88/metabolism* ; Mice ; NF-kappa B/metabolism* ; Signal Transduction/drug effects* ; Kidney/metabolism* ; Interleukin-17

OBJECTIVES: 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. CONCLUSIONS QJZ inhibits B cell differentiation and alleviates renal damage in systemic lupus erythematosus possibly by suppressing the AIM2/Blimp-1/Bcl-6 signaling pathway.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Mice, Inbred MRL lpr ; Female ; Mice ; Mice, Inbred C57BL ; Cell Differentiation/drug effects* ; B-Lymphocytes/drug effects* ; Proto-Oncogene Proteins c-bcl-6/metabolism* ; Kidney/drug effects* ; DNA-Binding Proteins/metabolism* ; Signal Transduction ; Lupus Nephritis

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 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 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 correlation and lag effects of environmental factors on pediatric respiratory disease visits at hospital, so as to provide scientific basis for disease prediction and optimizing clinical diagnosis and treatment. Methods: Data from 503 889 pediatric respiratory disease outpatient and emergency visits a central hospital in Minhang District of Shanghai between 2017 and 2019, along with concurrent meteorological data were collected. A distributed lag non-linear models (DLNM) was constructed to explore the specific relationship between pediatric respiratory disease consultations and various environmental factors and to quantify the cumulative lag effects of environmental factors on respiratory disease consultations. Results: Among the environmental factors, temperature, fine particulate matter (PM 2.5 ), inhalable particulate matter (PM 10 ), nitrogen dioxide (NO 2), and sulfur dioxide (SO 2) were associated with pediatric respiratory disease visits. After adjusting for temperature, PM 2.5 and PM 10 concentrations did not show significant immediate or lag effects. The relative risk (RR) of pediatric respiratory disease visits increased with rising NO 2 concentrations. When NO 2 concentration ≥55 μg/m 3, significant immediate and lagged effects (lag 3, 5, and 7 days) were observed. The RR values were 1.05, 1.13, 1.17, and 1.21( P <0.05). The RR values showed an inverted “U” shaped relationship with SO 2 concentrations. When SO 2 concentration ≥5 μg/m 3, significant lagged effects (lag 3, 5, and 7 days) were observed. The RR values were 1.03 , 1.03, and 1.04 ( P <0.05). Conclusion High concentrations of NO 2 and SO 2 increase the risk of pediatric respiratory disease visits, with observable lag effects.