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 explore the clinical and genetic characteristics of X-linked intellectual disability associated with HUWE1 gene variants.Methods:A cases series study retrospectively analyzed the clinical data of 6 children with HUWE1 gene variants. The children were identified from the Third Affiliated Hospital of Zhengzhou University, the First Affiliated Hospital of Zhengzhou University, the First Affiliated Hospital of Henan University of Chinese Medicine, and Guangzhou Women and Children′s Medical Center of Guangzhou Medical University between April 2021 and July 2023.The data included sex, age, dysmorphic features, intellectual and motor development, seizure history, neuroimaging findings, family history, and genetic results was analyzed.Results:A total of 6 children, including 5 boys and 1 girl. The age of onset ranged from 1 day to 3 years. All children presented with varying degrees of intellectual disability, with or without motor developmental delay. Dysmorphic features were observed in 4 children, including microcephaly in 3 children. Short stature were observed in 3 children. One child was diagnosed with autism spectrum disorders and 1 child had seizures. Two boys had relevant maternal family histories of febrile seizures and mild intellectual disability, respectively. Abnormal neuroimaging findings were presented in 4 children, including cerebral dysplasia (1 child), prominent supratentorial ventricles (1 child), and mild white matter demyelination (2 children). Whole-exome sequencing identified 5 missense variants and 1 in-frame deletion variant. Five variants were novel and previously unreported (c.12290C>T, c.12701T>C, c.9875C>T, c.9641A>T and c.10313_10315del). The variants in 4 boys were maternally inherited, while the remaining 2 children had de novo variants. The child with the in-frame deletion variant (c.10313_10315del) presented with the most severe phenotype, exhibiting symptoms from 1 day of age, absent cognitive development, feeding difficulties, and congenital laryngeal chondrodysplasia. He was lost to follow-up at 3 months of age after treatment was withdrawn. The age at the last follow-up for the remaining 5 children ranged from 2 years and 10 months to 17 years. A boy with seizures died at 2 years and 10 months of age. The remaining 4 children were able to walk independently at the last follow-up, although their developmental progress was slow. Conclusions:HUWE1 gene related X-linked intellectual disability is characterized by varying degrees of developmental delay and intellectual disability, frequently accompanied by microcephaly, short stature, and occasionally by seizures and autism spectrum disorders. Missense variants are more common and the in-frame deletion variant appears to be associated with a particularly severe phenotypic presentation.

Objective:To examine the relationship between college students'core self-evaluation and academic burnout,and to provide empirical support for intervention strategies.Methods:A two-point longitudinal study was conducted with 245 medical students over a period of 18 months(T1:May 2023,T2:November 2024)to assess participants'core self-evaluation level using the Core Self-Evaluation Scale(CSES),and the overall burnout level u-sing the Academic Study Burnout Inventory(ASBI).Cross-lagged panel model was applied to examine the bidirec-tional causal relationship.Results:The cross-lagged results showed that core self-evaluation score in T1 negatively predicted academic burnout score inT2(β=-0.21,P＜0.01),and academic burnout score in T1 also negatively predicted core self-evaluation score in T2(β=-0.20,P＜0.05).Conclusion:Core self-evaluations and academic burnout exhibit a reciprocal predictive relationship over time.

In recent years,using digital health technology can improve the quality and effect of nutrition management for patients with gestational diabetes mellitus(GDM).This article provides an overview of digital health technology,reviews the application form and effect of digital health technology in nutrition manage-ment of pregnant women with GDM,puts forward suggestions,in order to provide references and bases for promoting the more scientific,effective and standardized application of digital health technology in nutrition management of GDM patients.

Objective:To investigate the effect of olanzapine (OLZ) on the differentially-expressed circRNAs in prefrontal cortex of schizophrenia mouse models and predict the target genes.Methods:SPF grade C57BL/6 mice, 7~8 weeks-old, 20 male mice and 45 female mice were recruited and breeded offspring.Forty-four double-stimulation induced schizophrenia-like mouse models, the offspring mice exposed to dual stress were divided into the schizophrenia group(SZ group, n=23) and the olanzapine intervention group (SZ+ OLZ group, n=21), while the mice raised under normal conditions served as the control group (NC group, n=22). Whole transcriptome sequencing was used to sequence the expression level of RNAs from the prefrontal cortex of the mice. RT-qPCR was applied to verify the differentially-expressed circRNAs, then the target genes of miRNAs which have binding site to verified circRNAs were predicted. Results:RNA-seq results showed that there were 137 differentially-expressed circRNAs compared with NC group, 62 were significantly high-expressed and 75 were low-expressed. circRNA_06886 showed significant low-expressed in SZ group compared with NC group( Z=-3.259, P<0.01), and significant high-expressed in SZ+ OLZ group compared with SZ group( Z=-4.765, P<0.01). Bioinformatics analysis of miRNA target genes showed that the target genes were involved in the pathways related to neural pathways such as dopamine, glutamate and MAPK signaling pathways. Conclusions:There are differentially expressed circRNAs in the prefrontal cortex of schizophrenia mouse models, and circRNA_06886 is low-expressed in the prefrontal cortex of schizophrenia mice, Camk2b-201 and Plcb1-003 are the potential genes of circRNA_06886 involved in the regulation of schizophrenia pathogenesis by dopamine pathway.

Objective:To explore the clinical and genetic characteristics of X-linked intellectual disability associated with HUWE1 gene variants.Methods:A cases series study retrospectively analyzed the clinical data of 6 children with HUWE1 gene variants. The children were identified from the Third Affiliated Hospital of Zhengzhou University, the First Affiliated Hospital of Zhengzhou University, the First Affiliated Hospital of Henan University of Chinese Medicine, and Guangzhou Women and Children′s Medical Center of Guangzhou Medical University between April 2021 and July 2023.The data included sex, age, dysmorphic features, intellectual and motor development, seizure history, neuroimaging findings, family history, and genetic results was analyzed.Results:A total of 6 children, including 5 boys and 1 girl. The age of onset ranged from 1 day to 3 years. All children presented with varying degrees of intellectual disability, with or without motor developmental delay. Dysmorphic features were observed in 4 children, including microcephaly in 3 children. Short stature were observed in 3 children. One child was diagnosed with autism spectrum disorders and 1 child had seizures. Two boys had relevant maternal family histories of febrile seizures and mild intellectual disability, respectively. Abnormal neuroimaging findings were presented in 4 children, including cerebral dysplasia (1 child), prominent supratentorial ventricles (1 child), and mild white matter demyelination (2 children). Whole-exome sequencing identified 5 missense variants and 1 in-frame deletion variant. Five variants were novel and previously unreported (c.12290C>T, c.12701T>C, c.9875C>T, c.9641A>T and c.10313_10315del). The variants in 4 boys were maternally inherited, while the remaining 2 children had de novo variants. The child with the in-frame deletion variant (c.10313_10315del) presented with the most severe phenotype, exhibiting symptoms from 1 day of age, absent cognitive development, feeding difficulties, and congenital laryngeal chondrodysplasia. He was lost to follow-up at 3 months of age after treatment was withdrawn. The age at the last follow-up for the remaining 5 children ranged from 2 years and 10 months to 17 years. A boy with seizures died at 2 years and 10 months of age. The remaining 4 children were able to walk independently at the last follow-up, although their developmental progress was slow. Conclusions:HUWE1 gene related X-linked intellectual disability is characterized by varying degrees of developmental delay and intellectual disability, frequently accompanied by microcephaly, short stature, and occasionally by seizures and autism spectrum disorders. Missense variants are more common and the in-frame deletion variant appears to be associated with a particularly severe phenotypic presentation.

Objective:To examine the relationship between college students'core self-evaluation and academic burnout,and to provide empirical support for intervention strategies.Methods:A two-point longitudinal study was conducted with 245 medical students over a period of 18 months(T1:May 2023,T2:November 2024)to assess participants'core self-evaluation level using the Core Self-Evaluation Scale(CSES),and the overall burnout level u-sing the Academic Study Burnout Inventory(ASBI).Cross-lagged panel model was applied to examine the bidirec-tional causal relationship.Results:The cross-lagged results showed that core self-evaluation score in T1 negatively predicted academic burnout score inT2(β=-0.21,P＜0.01),and academic burnout score in T1 also negatively predicted core self-evaluation score in T2(β=-0.20,P＜0.05).Conclusion:Core self-evaluations and academic burnout exhibit a reciprocal predictive relationship over time.

In recent years,using digital health technology can improve the quality and effect of nutrition management for patients with gestational diabetes mellitus(GDM).This article provides an overview of digital health technology,reviews the application form and effect of digital health technology in nutrition manage-ment of pregnant women with GDM,puts forward suggestions,in order to provide references and bases for promoting the more scientific,effective and standardized application of digital health technology in nutrition management of GDM patients.

Objective:To investigate the effect of olanzapine (OLZ) on the differentially-expressed circRNAs in prefrontal cortex of schizophrenia mouse models and predict the target genes.Methods:SPF grade C57BL/6 mice, 7~8 weeks-old, 20 male mice and 45 female mice were recruited and breeded offspring.Forty-four double-stimulation induced schizophrenia-like mouse models, the offspring mice exposed to dual stress were divided into the schizophrenia group(SZ group, n=23) and the olanzapine intervention group (SZ+ OLZ group, n=21), while the mice raised under normal conditions served as the control group (NC group, n=22). Whole transcriptome sequencing was used to sequence the expression level of RNAs from the prefrontal cortex of the mice. RT-qPCR was applied to verify the differentially-expressed circRNAs, then the target genes of miRNAs which have binding site to verified circRNAs were predicted. Results:RNA-seq results showed that there were 137 differentially-expressed circRNAs compared with NC group, 62 were significantly high-expressed and 75 were low-expressed. circRNA_06886 showed significant low-expressed in SZ group compared with NC group( Z=-3.259, P<0.01), and significant high-expressed in SZ+ OLZ group compared with SZ group( Z=-4.765, P<0.01). Bioinformatics analysis of miRNA target genes showed that the target genes were involved in the pathways related to neural pathways such as dopamine, glutamate and MAPK signaling pathways. Conclusions:There are differentially expressed circRNAs in the prefrontal cortex of schizophrenia mouse models, and circRNA_06886 is low-expressed in the prefrontal cortex of schizophrenia mice, Camk2b-201 and Plcb1-003 are the potential genes of circRNA_06886 involved in the regulation of schizophrenia pathogenesis by dopamine pathway.

Objective:To serologically and genotypically analyze the pedigree of a case with a new allele c.175_176insGA of B el subtype and preliminarily explore the molecular mechanism of weak expression of glycosyltransferase B. Method:In the descriptive study,a 23-year-old male voluntary blood donor and his family members were selected for the study. The ABO and Le blood types of the proband and his family members was identified by the test tube method. The agglutination inhibition test was applied to detect the B and H antigens in saliva, and the Sanger sequencing and PacBio (Pacific Bioscience) third-generation haplotype sequencing were performed on the study subjects to identify genotypes. Finally, Expasy software were applied to amino acid translation of DNA sequences and prediction of protein length after gene alteration. ORF finder was applied to predict alternative start codons as well as open reading frames of mRNA, and protein expression mechanisms were analyzed.Results:The proband and her sister were B el subtype, her mother was AB el subtype, her father was normal O type, and all members of the family were Le(a+b+) phenotype. Sanger sequencing results showed that a new allele of c.175_176insGA was found in exon 4 of the proband, her mother, and her sister. Third-generation haplotype sequencing detected the haplotypes of the family members, which revealed that the proband was ABO*O.01.02/ABO*BEL.NEW (c.175_176insGA), the father was ABO*O.01.02/ABO*O.01.02, the mother was ABO*A1.02/ABO*BEL.NEW (c.175_176insGA), and the sister was ABO*O.01.02/ABO*BEL.NEW (c.175_176insGA). Analysis of the protein expression mechanism indicated that although the new allele of ABO*BEL.NEW was presumed to cause a frameshift mutation and result in a premature stop codon p.Asp59Glu*fs20 in exon 5, encoding an inactive glycosyltransferase, an alternative start codon could be utilized to initiate translation of B el subtype functional glycosyltransferase. Conclusion:Expression of the new allele of B el subtype is associated with the translation of B el subtype glycosyltransferase initiated by alternative start codons.