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.

ObjectiveTo perform a genome-wide association study of rubella virus vaccine strain BRD-Ⅱ, so as to fully grasp the sequence characteristics of this genome. MethodsSecond-generation sequencing method was used to conduct the whole-genome sequencing on the vaccine strain BRD-Ⅱ, and the affinity tree of this genome with some vaccine strains and wild-type rubella virus strains was analyzed using the maximum likelihood method. The average genetic distance of nucleic acid sequence of each vaccine strain protein was determined. And homology comparison of structural proteins of each rubella vaccine strain, plus the comparison between this genome with the AY258323.1 genome sequence, were conducted to analyze the homology of E1 protein between the wild-type rubella virus reference strain and vaccine strain BRD-Ⅱ. ResultsThe sequencing results showed that the BRD-Ⅱ strain was a single-molecule single-stranded positive-strand ribonucleic acid (RNA), composed of 9 778 nucleotides, with a GC content of 69.35 %. The C protein was composed of 300 amino acids, the E2 glycoprotein was composed of 282 amino acids, and the E1 glycoprotein was composed of 481 amino acids. The results of preliminary analysis showed that the average genetic distances of nucleic acid sequences were 0.066 700 for the P150 protein, 0.061 933 for the P90 protein, 0.057 850 for the C protein, 0.068 167 for the E2 protein, and 0.068 833 for the E1 protein, respectively. The amino acid sequences in the E2 protein and E1 protein regions of the two BRD-Ⅱ strains did not change, confirming the conserved regions of the E1 protein by comparison. ConclusionThe sequence characteristics of the genome are clarified, which have laid a broad foundation for the subsequent detection of the genetic stability of the main antigen genes.

Objective:To explore the effects of IFN-γ on IL-8 secretion by human liver cancer cells and the impact on their malignant biological functions in vitro. Methods:HuH7 and Hep3B cells were treated with different concentrations of IFN-γ for 24 or 48 h. Changes in the cellular activity, IL-8 secretion, and the proportion of CD133 + liver cancer stem cells were evaluated using CCK8 kit and flow cytometry. Western blot was used to detect the effects of IFN-γ on the expression of several molecules such as phosphorylated protein kinase B (p-Akt), phosphorylated c-Jun N-terminal kinase (p-JNK), vimentin, and E-cadherin in the liver cancer cells. Effects of IFN-γ with or without IL-8 on the migration of liver cancer cells were detected by transwell assay. Additionally, effects of IFN-γ combined with IL-8 or IL-8 receptor inhibitor repertaxin on the differentiation of liver cancer stem cells were detected by flow cytometry. One-way analysis of variance and Tukey-Kramer test were used for statistical analysis. Results:HuH7 and Hep3B cells secreted significantly higher levels of IL-8 than normal hepatocytes LO2 ( P<0.01) and high expression level of IL-8 gene ( CXCL8) was closely correlated with the expression levels of vimentin gene ( VIMENTIN), CD133 gene ( PRCM1), PD-L1 gene ( CD274), PD-1 gene ( PDCD1), and CD163 gene ( CD163), as well as the poor prognosis of liver cancer patients ( P<0.01). IFN-γ (1-100 ng/ml) had no significant effect on the proliferative activity of HuH7 and Hep3B cells ( P>0.05), but could significantly inhibit IL-8 secretion, cell migration, CD133 + liver cancer stem cell differentiation and suspension tumor sphere formation through the Akt and JNK pathways ( P<0.01). IFN-γ combined with IL-8 could significantly reversed the inhibitory effects of IFN-γ on liver cancer cell migration, stem cell differentiation, and suspension tumor sphere formation ( P<0.01). IFN-γ in combination with repertaxin could synergistically inhibited the differentiation of CD133 + liver cancer stem cells ( P<0.01). Conclusion:IFN-γ inhibits the differentiation and migration of human liver cancer cells through the Akt/JNK-IL-8 signaling pathway, providing a new strategy for future clinical immunotherapy of liver cancer.

Objective To determine the relationship between the triglyceride-glucose(TyG)index and subclinical left ventricular dysfunction(SLVD)in patients with type 2 diabetes mellitus(T2DM).Methods A total of 148 patients with T2DM who were admitted to Anyang Regional Hospital of Puyang were enrolled in this study from January to December 2023.They were divided into simple T2DM group with global longitudinal strain(GLS)value≥18%(n=89)and SLVD group with GLS value<18%(n=59)according to the left ventricular function.The general data,biochemical indexes,TyG index and homeostatic model 2 assessment for insulin resistance(HOMA2-IR)were compared between the two groups.Pearson correlation analysis was used to analyze the correlation between clinical indicators and TyG index.Receiver operating characteristic(ROC)curve was used to analyze the predictive value of TyG index and HOMA2-IR for SLVD in T2DM patients.Results BMI,WC,HOMA2-IR,end-diastolic interventricular septal thickness(IVSTD),left ventricular end-diastolic diameter(LVDD),left ventricular end-systolic diameter(LVDS),left ventricular end-diastolic posterior wall thickness(LVPWTD),left atrial diameter(LAD),HbA1c,FPG,FC-P,TG and TyG were higher(P<0.05),while GLS and LVEF were lower in SLVD group than in T2DM group(P<0.05).Pearson correlation analysis showed that TyG index was positively correlated with BMI,WC,IVSTD,LVDS,LVPWTD,HbA1c,FPG,FC-P,TG,HOMA2-IR(P<0.05),and negatively correlated with GLS and LVEF(P<0.05).ROC curve analysis showed that the area under the curve(AUC)of TyG index was 0.810,the sensitivity was 54.2%,the specificity was 98.9%,and the cut-off value was 9.45 for predicting SLVD in T2DM patients.The AUC of HOMA2-IR was 0.651,the sensitivity was 42.4%,the specificity was 84.2%,and the cut-off value was 1.85 for predicting SLVD in T2DM patients.Conclusions The TyG index was independently associated with SLVD in patients with T2DM and was a more reliable indicator of SLVD than HOMA2-IR.

Benign prostatic hyperplasia （BPH） is a common chronic progressive disease in middle-aged and elderly men， characterized by prostate enlargement and bladder outlet obstruction， leading to symptoms such as frequent urination， urgency， and difficulty urinating. The pathogenesis of BPH involves factors such as aging， hormonal metabolic abnormalities， inflammatory responses， and imbalances in cell proliferation and apoptosis. Currently， the main treatment methods for BPH include medication， physical therapy， and surgical intervention. However， medication may cause side effects like sexual dysfunction and hypotension， physical therapy has limited efficacy， and surgery carries risks and postoperative complications. Therefore， there is an urgent need to find safer and more effective treatment options. Traditional Chinese medicine （TCM）， with its focus on treatment based on syndrome differentiation and a holistic approach， offers therapeutic advantages through multiple pathways and mechanisms. Recent studies have shown that TCM regulates pathways such as phosphoinositide-3-kinase/protein kinase B （PI3K/Akt）， nuclear factor-κB （NF-κB）， mitogen-activated protein kinases （MAPK）， nuclear factor E₂-related factor 2/antioxidant response element （Nrf2/ARE）， androgen receptor （AR）， transforming growth factor-β （TGF-β）/Smad， and hypoxia-inducible factor-1α/vascular endothelial growth factor （HIF-1α/VEGF） to inhibit oxidative stress and inflammatory response， reduce prostate cell proliferation， and promote apoptosis， thus exerting therapeutic effects. This article summarizes and analyzes the roles of these signaling pathways in the occurrence and development of BPH and the mechanisms of TCM intervention， aiming to provide scientific evidence for clinical treatment and drug development for BPH.

Benign prostatic hyperplasia （BPH） is a common chronic progressive disease in middle-aged and elderly men， characterized by prostate enlargement and bladder outlet obstruction， leading to symptoms such as frequent urination， urgency， and difficulty urinating. The pathogenesis of BPH involves factors such as aging， hormonal metabolic abnormalities， inflammatory responses， and imbalances in cell proliferation and apoptosis. Currently， the main treatment methods for BPH include medication， physical therapy， and surgical intervention. However， medication may cause side effects like sexual dysfunction and hypotension， physical therapy has limited efficacy， and surgery carries risks and postoperative complications. Therefore， there is an urgent need to find safer and more effective treatment options. Traditional Chinese medicine （TCM）， with its focus on treatment based on syndrome differentiation and a holistic approach， offers therapeutic advantages through multiple pathways and mechanisms. Recent studies have shown that TCM regulates pathways such as phosphoinositide-3-kinase/protein kinase B （PI3K/Akt）， nuclear factor-κB （NF-κB）， mitogen-activated protein kinases （MAPK）， nuclear factor E₂-related factor 2/antioxidant response element （Nrf2/ARE）， androgen receptor （AR）， transforming growth factor-β （TGF-β）/Smad， and hypoxia-inducible factor-1α/vascular endothelial growth factor （HIF-1α/VEGF） to inhibit oxidative stress and inflammatory response， reduce prostate cell proliferation， and promote apoptosis， thus exerting therapeutic effects. This article summarizes and analyzes the roles of these signaling pathways in the occurrence and development of BPH and the mechanisms of TCM intervention， aiming to provide scientific evidence for clinical treatment and drug development for BPH.

Objective To determine the relationship between the triglyceride-glucose(TyG)index and subclinical left ventricular dysfunction(SLVD)in patients with type 2 diabetes mellitus(T2DM).Methods A total of 148 patients with T2DM who were admitted to Anyang Regional Hospital of Puyang were enrolled in this study from January to December 2023.They were divided into simple T2DM group with global longitudinal strain(GLS)value≥18%(n=89)and SLVD group with GLS value<18%(n=59)according to the left ventricular function.The general data,biochemical indexes,TyG index and homeostatic model 2 assessment for insulin resistance(HOMA2-IR)were compared between the two groups.Pearson correlation analysis was used to analyze the correlation between clinical indicators and TyG index.Receiver operating characteristic(ROC)curve was used to analyze the predictive value of TyG index and HOMA2-IR for SLVD in T2DM patients.Results BMI,WC,HOMA2-IR,end-diastolic interventricular septal thickness(IVSTD),left ventricular end-diastolic diameter(LVDD),left ventricular end-systolic diameter(LVDS),left ventricular end-diastolic posterior wall thickness(LVPWTD),left atrial diameter(LAD),HbA1c,FPG,FC-P,TG and TyG were higher(P<0.05),while GLS and LVEF were lower in SLVD group than in T2DM group(P<0.05).Pearson correlation analysis showed that TyG index was positively correlated with BMI,WC,IVSTD,LVDS,LVPWTD,HbA1c,FPG,FC-P,TG,HOMA2-IR(P<0.05),and negatively correlated with GLS and LVEF(P<0.05).ROC curve analysis showed that the area under the curve(AUC)of TyG index was 0.810,the sensitivity was 54.2%,the specificity was 98.9%,and the cut-off value was 9.45 for predicting SLVD in T2DM patients.The AUC of HOMA2-IR was 0.651,the sensitivity was 42.4%,the specificity was 84.2%,and the cut-off value was 1.85 for predicting SLVD in T2DM patients.Conclusions The TyG index was independently associated with SLVD in patients with T2DM and was a more reliable indicator of SLVD than HOMA2-IR.

Objective To investigate the prognostic value of mitochondrial autophagy-related genes(MRGs)in prostate cancer(PCa),and to reveal their regulatory relationship with interstitial epidermal transforming factor(C-Met)based on the Gene Expression Database(GEO).Methods Single-cell RNA sequencing(scRNA-seq)data of three PCa samples were obtained from the GSE153892 dataset of GEO,and MRGs were collected from the Genecards database and previous literature.The scRNA-seq data were processed and analyzed using the Seurat software package,including quality control,gene expression screening,cell type annotation,differentially expressed genes(DEGs)identification,and intersection analysis with MRGs.The transcriptome data of PCa and control samples were downloaded from the Cancer Genome Atlas Database(TCGA)-PRAD cohort,and differential expression analysis and copy number variation analysis were conducted.The non-negative matrix factorization algorithm is adopted to conduct cluster analysis on PCa samples to identify different PCa subtypes.A prognostic risk model based on intersection genes was constructed,and the predictive ability of the model was analyzed through Kaplan-Meier survival curve analysis and time-dependent receiver operating characteristic(ROC)curve analysis.Conduct independent prognostic analysis,construct a nomogram model based on risk scores and clinical characteristics,and evaluate its ability to predict patient survival rates.The possibility of immune infiltration and tumor immune escape in PCa samples was evaluated by using the single-sample Gene Set Enrichment analysis(ssGSEA)algorithm and the TIDE database.The relationship between intersection genes and C-Met expression was analyzed using Pearson correlation analysis.Results scRNA-seq data analysis identified five cell types including B lymphocytes,epithelial cells,monocytes,natural killer cells and T lymphocytes,and discovered the intersection genes that were highly expressed in different cell types.Through differential expression analysis,genes significantly related to the prognosis of PCa patients were screened out,and a prognostic risk model was constructed.Six genes such as ADH5 and CAT were retained through LASSO analysis.A diagnostic model was constructed and grouped.There was a significant difference in survival time between the two groups in the internal test set(P<0.05).ROC curve evaluation showed that the model had a good predictive ability for 1-,3-,and 5-year survival rates.The external test set verified that there was a statistically significant difference in the expression of intersection genes(P<0.05).Independent prognostic analysis identified T stage and risk score as independent prognostic factors.A nomogram model was constructed.Calibration curve and ROC curve analyses showed that the predictive ability of this model was superior to that of the simple risk model.ssGSEA analysis revealed differences in the abundance of immune cell inflammation and immune function scores between the two groups.Most immune cells,immune function,and risk scores were related to the modeling genes.There were significant differences in TIDE scores and multiple immune checkpoints between the high-risk and low-risk groups(P<0.05).BCAT2,DCXR,OGT and FUS were positively correlated with the expression of C-Met,while ADH5 and CAT were negatively correlated with the expression of C-Met(P<0.05).Conclusion The prognostic risk model based on intersection genes can effectively predict the prognosis of patients with PCa,and the risk score and T stage are independent prognostic factors for PCa.The correlation analysis of intersection genes and C-Met expression provides a new idea for the targeted therapy of PCa.

Objective:To compare the consistency and efficacy of ultrasound and CT in the preoperative diagnosis of cervical lymph node metastasis in patients with thyroid cancer, and to explore the clinical value of the combined application of multimodal imaging.Methods:The 119 thyroid cancer patients underwent surgical treatment from January to September 2023 in Zhongshan Hospital Affiliated to Dalian University were retrospectively analyzed. All patients underwent ultrasound and CT examinations before operation. The results of postoperative histopathology examination were taken as the gold standard, the efficacy of ultrasound and CT in preoperative diagnosis of cervical lymph node metastasis was compared.Results:A total of 1 721 cervical lymph nodes were detected in 119 patients with thyroid cancer, among which 1 378 lymph nodes were benign, and 343 lymph nodes were malignant, the rate of malignant lymph nodes was 19.93% (343/1 721). Among them, the proportion of malignant lymph nodes in area Ⅵ was the highest, 22.58% (245/1 085), followed by area Ⅲ, 21.26% (37/174). The sensitivity of CT in diagnosing cervical lymph node metastasis in patients with thyroid cancer was significantly higher than that of ultrasound diagnosis: 58.46% (38/65) vs. 38.46% (25/65), the specificity was significantly lower than that of ultrasound diagnosis: 85.19% (46/54) vs. 96.30% (52/54), and there were statistical differences ( P<0.01 and <0.05); there was no statistical difference in accuracy between CT and ultrasound ( P>0.05). Conclusions:In the preoperative diagnosis of cervical lymph node metastasis in patients with thyroid cancer by ultrasound and CT, ultrasound examination has no radiation risk, while CT examination has a higher diagnostic efficiency.

Objective To establish a rapid immunological detection method for MPT64 protein based on red microspheres and select highly-sensitive and highly-specific antibody pairs.Methods A His-tagged prokaryotic expression vector was constructed for expression of MPT64 protein that was used to immunize New Zealand white rabbits after purification and validation.Peripheral blood mononuclear cells(PBMCs)were isolated from the rabbits,and antigen-specific B cells expressing antibodies were sorted using single B-cell flow cytometry.mRNA in B cells was reverse-transcribed into cDNA,and paired antibody heavy-and light-chain sequences were amplified via nested PCR.Expression vectors were constructed,and recombinant antibodies were produced in Expi293F cells.Fluorescent immunochromatography was employed to screen for matched antibody pairs.The selected antibodies were used to establish a rapid detection method based on red microsphere immunochromatography.Results Ten high-affinity monoclonal antibodies against MPT64 were generated.Two antibody pairs were selected for MPT64 immunodetection that reached a sensitivity of 0.0125 ng/mL.Conclusion High-affinity rabbit monoclonal antibodies against MPT64 are obtained via single B-cell technology,and a rapid red microspheres-based immunodetection method is established,enabling highly sensitive detection of Mycobacterium tuberculosis MPT64 protein.