Objective: To characterize the sequence polymorphism of HLA-A, -B, and -C loci in the northern Han Chinese population and to evaluate their selection signals and phylogenetic patterns based on long-read sequencing data. Methods: A total of 408 unrelated healthy blood donors were enrolled. Long-read sequencing of HLA-A, -B, and -C loci was performed using the PacBio Sequel II platform. The Ewens-Watterson neutrality test, sliding-window nucleotide diversity (π) and Tajima′s D analyses were conducted, together with genetic distance heatmaps, principal coordinates analysis (PCoA), and maximum likelihood phylogenetic analysis to assess polymorphism distribution, selection signals, and phylogenetic structure across the three loci. Results: The analyzed sequence lengths for the HLA-A, -B, and -C loci were 3 257 bp, 3 794 bp, and 3 831 bp, respectively; the numbers of locus-specific sequence types were 44, 82, and 56, with corresponding locus-specific sequence type diversities of 0.905 2, 0.964 9, and 0.939 8, respectively. The Ewens-Watterson test showed no significant deviation from neutrality (P>0.05). Sliding-window analysis revealed elevated π and Tajima′s D values in exons 2 and 3 as well as in certain intronic regions of HLA-A and HLA-B, whereas HLA-C exhibited relatively lower overall diversity. Genetic distance heatmaps, PCoA, and phylogenetic analysis consistently showed clear clustering in HLA-A and HLA-C, while HLA-B displayed the highest phylogenetic heterogeneity. Conclusion: HLA-A, -B, and -C gene sequences in the northern Chinese Han population exhibit high levels of polymorphism and marked regional heterogeneity. HLA-B shows greater diversity, stronger signals of selection, and more complex phylogenetic structure compared with HLA-A and HLA-C.

Objective To understand the serologic prevalence and infection status of Cytomegalovirus(CMV)in children aged 0～1 years,and explore the risk factors of CMV infection for clinical reference.Methods The data of 4 938 children aged 0～1 years who underwent chemiluminescence enzyme immunoassay for TORCH in Department of Inpatient and Department of Pediatrics Outpatient of Maternal and Child Health Hospital of Inner Mongolia from January 2020 to December 2022 were retrospectively analyzed to understand the seroprevalence of human CMV(HCMV)among children in the region,and analyzed the risk factors associated with HCMV infections by combining the results of laboratory tests and clinical information.Results In 4 938 children,the total antibody positivity rate was 94.01%(4 642/4 938),the total IgG antibody positivity rate was 93.86%(4 635/4 938),the total IgM antibody positivity rate was 8.10%(400/4 938),and the positive rate of the two simultaneous detections was 7.96%(393/4 938).The difference in HCMV-IgG and HCMV-IgM antibodies positivity rates beteen different age groups were statistically significant(χ2=36.350,1 043.199,all P<0.05),and the differences in HCMV-IgG and IgM antibodies between boys and girls were not statistically significant(χ2=0.215,1.184,all P＞0.05).According to univariate analysis,the breast-feeding and vaginal delivery rates in the infected group were higher than those in the control group,and the differences in feeding and birth methods were statistically significant(χ2=10.777,5.725,all P<0.05).Multifactorial analysis found that breast-feeding and transvaginal delivery were independent risk factors for HCMV infection,and the differences was statistically significant(Wald χ2=6.247,10.057,all P<0.05).Conclusion The serologic antibody positivity rate of HCMV in children within 1 year of age is as high as 94.01%,and infants aged 3 months to 6 months are most susceptible to infection.Breastfeeding and transvaginal delivery are independent risk factors for HCMV infection in children within 1 year of age.

Objective:To investigate the clinical manifestations and genetic characteristics of a Chinese Han family with Axenfeld-Rieger syndrome (ARS).Methods:A pedigree study was conducted.Three people from a Chinese Han family with ARS who visited Henan Eye Hospital in January 2024 were included, including 1 patient.Clinical data of the proband and her parents were collected.Comprehensive ophthalmic examination and general physical examination were performed on the proband and her parents.Peripheral blood samples were obtained from family members for DNA extraction.Whole exome sequencing was performed on the proband, and the copy number of the ZBED1P1, ENPEP, PITX2, and FAM241A genes in family members were validated using the real-time fluorescent quantitative PCR.Axenfeld-Rieger syndrome, Axenfeld-Rieger Syndrome, and PITX2 were used as keywords to search across databases such as OMIM, ClinVar, PubMed, CNKI, Wanfang, VIP, DECIPHER, and Google Scholar.The clinical manifestations and microdeletion types of different patients in ARS literature related to PITX2 microdeletions in China population were summarized, and the relationship between genotype and clinical phenotype was analyzed.The study followed the Declaration of Helsinki, and the study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEEC-2024[34]).All subjects understood the purpose of the study and voluntarily signed the informed consent form. Results:The proband was a 25-year-old female, exhibiting diminutive cornea in both eyes, polycoria, deformation and displacement of pupils, a flat mid-face, maxillary dysplasia, tooth loss, and a protruding umbilicus, among other symptoms.Parents of the proband were phenotypically normal.DNA sequencing identified a 1.06 MB microdeletion on chromosome 4q25 in the proband.Real-time quantitative PCR confirmed that this microdeletion encompassed the PITX2 and ENPEP genes, and it was absent in the proband's parents.The ClinGen CNV pathogenicity scoring indicated that the deletion involving the PITX2 gene represented a novel pathogenic copy number variation (CNV).Five studies related to 4q25 microdeletion in Chinese families with Axenfeld-Rieger syndrome was screened, including 13 patients.Clinical manefestations of the 13 patients included corneal disorders (accounting for 100%), umbilical hernia and dental anomalies (accounting for 92%), irregular intraocular pressure (accounting for 62%), iris atrophy (accounting for 46%), and posterior corneal embryotoxon (accounting for 31%). Conclusions:For this Chinese family diagnosed with ARS, a novel pathogenic 4q25 microdeletion variant encompassing the PITX2 gene was found in the proband, which is associated with characteristic phenotypes including microcornea, congenital iris dysplasia, polycoria, tooth loss, and a protruding umbilicus.

Objective To understand the serologic prevalence and infection status of Cytomegalovirus(CMV)in children aged 0～1 years,and explore the risk factors of CMV infection for clinical reference.Methods The data of 4 938 children aged 0～1 years who underwent chemiluminescence enzyme immunoassay for TORCH in Department of Inpatient and Department of Pediatrics Outpatient of Maternal and Child Health Hospital of Inner Mongolia from January 2020 to December 2022 were retrospectively analyzed to understand the seroprevalence of human CMV(HCMV)among children in the region,and analyzed the risk factors associated with HCMV infections by combining the results of laboratory tests and clinical information.Results In 4 938 children,the total antibody positivity rate was 94.01%(4 642/4 938),the total IgG antibody positivity rate was 93.86%(4 635/4 938),the total IgM antibody positivity rate was 8.10%(400/4 938),and the positive rate of the two simultaneous detections was 7.96%(393/4 938).The difference in HCMV-IgG and HCMV-IgM antibodies positivity rates beteen different age groups were statistically significant(χ2=36.350,1 043.199,all P<0.05),and the differences in HCMV-IgG and IgM antibodies between boys and girls were not statistically significant(χ2=0.215,1.184,all P＞0.05).According to univariate analysis,the breast-feeding and vaginal delivery rates in the infected group were higher than those in the control group,and the differences in feeding and birth methods were statistically significant(χ2=10.777,5.725,all P<0.05).Multifactorial analysis found that breast-feeding and transvaginal delivery were independent risk factors for HCMV infection,and the differences was statistically significant(Wald χ2=6.247,10.057,all P<0.05).Conclusion The serologic antibody positivity rate of HCMV in children within 1 year of age is as high as 94.01%,and infants aged 3 months to 6 months are most susceptible to infection.Breastfeeding and transvaginal delivery are independent risk factors for HCMV infection in children within 1 year of age.

Objective:To investigate the clinical manifestations and genetic characteristics of a Chinese Han family with Axenfeld-Rieger syndrome (ARS).Methods:A pedigree study was conducted.Three people from a Chinese Han family with ARS who visited Henan Eye Hospital in January 2024 were included, including 1 patient.Clinical data of the proband and her parents were collected.Comprehensive ophthalmic examination and general physical examination were performed on the proband and her parents.Peripheral blood samples were obtained from family members for DNA extraction.Whole exome sequencing was performed on the proband, and the copy number of the ZBED1P1, ENPEP, PITX2, and FAM241A genes in family members were validated using the real-time fluorescent quantitative PCR.Axenfeld-Rieger syndrome, Axenfeld-Rieger Syndrome, and PITX2 were used as keywords to search across databases such as OMIM, ClinVar, PubMed, CNKI, Wanfang, VIP, DECIPHER, and Google Scholar.The clinical manifestations and microdeletion types of different patients in ARS literature related to PITX2 microdeletions in China population were summarized, and the relationship between genotype and clinical phenotype was analyzed.The study followed the Declaration of Helsinki, and the study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEEC-2024[34]).All subjects understood the purpose of the study and voluntarily signed the informed consent form. Results:The proband was a 25-year-old female, exhibiting diminutive cornea in both eyes, polycoria, deformation and displacement of pupils, a flat mid-face, maxillary dysplasia, tooth loss, and a protruding umbilicus, among other symptoms.Parents of the proband were phenotypically normal.DNA sequencing identified a 1.06 MB microdeletion on chromosome 4q25 in the proband.Real-time quantitative PCR confirmed that this microdeletion encompassed the PITX2 and ENPEP genes, and it was absent in the proband's parents.The ClinGen CNV pathogenicity scoring indicated that the deletion involving the PITX2 gene represented a novel pathogenic copy number variation (CNV).Five studies related to 4q25 microdeletion in Chinese families with Axenfeld-Rieger syndrome was screened, including 13 patients.Clinical manefestations of the 13 patients included corneal disorders (accounting for 100%), umbilical hernia and dental anomalies (accounting for 92%), irregular intraocular pressure (accounting for 62%), iris atrophy (accounting for 46%), and posterior corneal embryotoxon (accounting for 31%). Conclusions:For this Chinese family diagnosed with ARS, a novel pathogenic 4q25 microdeletion variant encompassing the PITX2 gene was found in the proband, which is associated with characteristic phenotypes including microcornea, congenital iris dysplasia, polycoria, tooth loss, and a protruding umbilicus.

Objective:To identify the ABO blood group in a family with ABO forward/reverse typing discrepancies using serological methods and third-generation sequencing technology.Methods:In January 2024, samples with ABO blood group forward/reverse typing discrepancies were referred to Dalian Blood Center for blood group identification. Standard serological techniques were used to identify the ABO blood group. For the samples of the proband with a serological phenotype of AB weak and his father, full-length haplotype sequencing of the ABO gene was performed using third-generation sequencing. The impact of amino acid mutations on protein structure was also predicted. Results:Sequencing revealed that, compared to the reference sequence ABO*B.01, both the proband and his father had a haplotype with a mutation c.278C>T in Exon 7, resulting in p.Pro93Leu. This is consistent with the ABO*BW.12 genotype. The spatial structure of the ABO*BW.12 protein was altered, leading to reduced stability and impaired function of the B glycosyltransferase (GTB).Conclusion:For the identification of AB weak blood group, the combination of serological methods and third-generation sequencing technology enables accurate and efficient detection of haplotype mutations and identification of ABO subtypes, thus ensuring clinical transfusion safety.

Objective: To explore the results of comprehensive geriatric assessment (CGA) among convalescent elderly population, so as to provide the basis for strengthening the health management service level for convalescent elderly population. Methods: A total of 200 elderly people who convalesced at Hangzhou Wuyunshan Hospital from January 2021 to December 2023 were selected as the research subjects. The basic information, physical condition, psychological status, functional status, and social environment of the elderly were investigated using the CGA protocol. The basic characteristics of the elderly, physical conditions such as medication adherence, pain, malnutrition and frailty, psychological conditions such as cognitive function, anxiety symptoms and depression symptoms, functional conditions such as fall risk and social support level and social environment assessment results were analyzed. Results: Among the 200 elderly individuals, 58.00% were male, 44.50% were aged 70 to <80 years, 58.00% had an education level of high school or above, 55.00% were unmarried, 61.50% were childless, and 60.50% had basic medical insurance for employees. In terms of physical condition, 59.00% had comorbid chronic diseases, 40.50% used multiple medications, and the incidences of poor medication adherence, pain, malnutrition, and frailty were 22.50%, 10.00%, 54.00%, and 36.00%, respectively. Regarding psychological status, the incidences of impaired cognitive function, anxiety symptoms, and depressive symptoms were 57.00%, 89.50%, and 91.00%, respectively. In terms of functional status and social environment, 90.00% had a risk of falling, and 31.00% had a high level of social support. Univariable analysis showed that elderly individuals aged ≥80 years and those with an education level of primary school or below had higher incidences of poor medication adherence during convalescence; elderly individuals with poor medication adherence had a higher incidence of pain; and elderly individuals with impaired cognitive function, anxiety symptoms, and depressive symptoms had higher incidences of malnutrition (all P<0.05). Conclusions The physical condition and psychological status of convalescent elderly individuals are relatively poor, with a high risk of falling and insufficient levels of social support. Poor medication adherence is associated with advanced age and lower education levels, while malnutrition is associated with impaired cognitive function, anxiety symptoms, and depressive symptoms. Comprehensive health management for convalescent elderly population should be strengthened, and personalized health management services should be provided to improve their quality of life and sense of well-being.

Objective To investigate the expression of kinesin family member 23(KIF23)in rectal cancer and its association with prognosis.Methods This study included 90 patients with rectal cancer who underwent surgical treatment at the First Central Hospital of Baoding from May 2017 to October 2019.Immunohistochemical staining was used to detect KIF23 expression,and the results were analyzed in combination with clinical and pathological data.Survival analysis was conducted using Kaplan-Meier methods and Cox proportional hazards models to assess the association between KIF23 expression and patient prognosis.Results Compared with adjacent non-tumor tis-sues,the expression level of KIF23 protein was significantly higher in rectal cancer tissues.Positive expression of KIF23 was significantly correlated with TNM stage,lymph node metastasis and distant metastasis in rectal cancer patients(P＜0.05).Kaplan-Meier analysis revealed that individuals expressing high levels of KIF23 experienced notably diminished disease-free survival(DFS)and overall survival(OS)relative to those with low KIF23 expression(P＜0.05).Cox regression analysis revealed that advanced TNM stage,lymph node metastasis,distant metastasis,and elevated KIF23 expression served as an independent predictor of adverse outcomes in pa-tients with rectal cancer(P＜0.05).Conclusions The expression level of KIF23 is closely related to the prognosis of rectal cancer.

OBJECTIVES: To investigate the effect of moslosooflavone (MOS) for ameliorating dextran sulfate sodium (DSS)-induced colitis in mice and the underlying molecular mechanism. METHODS: C57BL/6J mice with or without DSS exposure in the drinking water were both randomized into two groups for treatment with intraperitoneal injections with MOS (200 mg/kg) or normal saline for 7 days (n=6). Disease severity of the mice was assessed by observing changes in body weight, colon length, histopathology (HE staining), intestinal barrier function, and TUNEL staining. In the in vitro studies, lipopolysaccharide (LPS)-stimulated mouse colon organoids were treated with MOS (120 μmol/L) for 24 h, and the changes in barrier dysfunction and inflammation were analyzed. Network pharmacology and Western blotting were employed to identify functional pathways and apoptotic protein regulation associated with the therapeutic effect of MOS on colitis. RESULTS: In the mouse models of DSS-indcued colitis, MOS treatment significantly reduced body weight loss, disease activity index (DAI) scores and colon shortening, ameliorated colonic histopathological changes and inflammation, and lowered pro-inflammatory cytokine levels (TNF-α, IL-1β, IL-6, and IFN-γ). MOS effectively restored intestinal barrier integrity in the mice by reducing serum FITC-dextran and I-FABP concentrations while enhancing the tight junction proteins (ZO-1 and claudin-1). In the colon organoids, MOS significantly suppressed LPS-induced inflammatory responses and epithelial barrier disruption. Western blotting revealed that MOS downregulated C-caspase-3 and BAX and upregulated Bcl-2 expressions in both models. Mechanistically, MOS suppressed PI3K and AKT phosphorylation in both DSS-treated mouse colonic tissues and LPS-stimulated organoids. CONCLUSIONS MOS alleviates experimental colitis in mice by inhibiting intestinal epithelial apoptosis via inhibiting the PI3K/AKT pathway, thereby restoring intestinal barrier integrity and reducing inflammation.
Animals ; Dextran Sulfate ; Mice, Inbred C57BL ; Colitis/metabolism* ; Mice ; Signal Transduction/drug effects* ; Intestinal Mucosa/metabolism* ; Apoptosis/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Flavones/pharmacology* ; Male

OBJECTIVES: To study the impact of SURF4 expression level on long-term prognosis of gastric cancer (GC) and biological behaviors of GC cells. METHODS: SURF4 expression level in GC and its association with long-term patient prognosis were analyzed using publicly available databases and in 155 GC patients with low and high SURF4 expressions detected immunohistochemically. The Cox proportional hazard model and Kaplan-Meier survival curves were used to analyze independent prognostic predictors of GC and the 5-year survival rate of the patients with different SURF4 expression levels. Informatics analyses were conducted to explore the correlation of SURF4 expression level with immune cell infiltration in GC, SURF4-related differential genes and their associated pathways. In cultured GC cell line HGC-27, the effects of SURF4 knockdown and overexpression on proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) were investigated. RESULTS: Analysis of GEPIA dataset and immunohistochemical results suggested significant SURF4 overexpression in GC (P<0.05), which was associated with shortened 5-year survival time of the patients (χ²=38.749, P<0.001). The prognosis of GC was closely related to tumor stage T3-4, N2-3, CEA≥5 μg/L and CA19-9≥37 kU/L (P<0.05). SURF4 expression level was negatively correlated with activated B cells, NK cells and CD8⁺ effector memory T cells (P<0.05) and positively correlated with CD4⁺ T cells (P<0.05). GO and KEGG enrichment analysis suggested that SUFR4 may participate in GC carcinogenesis by promoting EMT through the tight junction pathway. In HGC-27 cells, SURF4 overexpression significantly decreased E-cadherin expression, increased N-cadherin expression, inhibited ZO-1 and claudin-1 expressions, and promoted cell proliferation, migration and invasion. CONCLUSIONS SURF4 is highly expressed in GC, and its overexpression is associated with a shortened 5-year survival of the patients possibly by enhancing tumor cell proliferation, migration and invasion via inhibiting tight junction proteins and promoting EMT.
Humans ; Stomach Neoplasms/metabolism* ; Cell Proliferation ; Cell Movement ; Epithelial-Mesenchymal Transition ; Cell Line, Tumor ; Neoplasm Invasiveness ; Prognosis ; Tight Junction Proteins/metabolism* ; Membrane Proteins/metabolism* ; Female ; Male