Objective: To explore the importance of selecting appropriate human antiserum for absorption and elution tests by analyzing two cases in which weak A antigens were detected using this method. Methods: The microcolumn agglutination and tube methods were used to perform ABO blood group typing of the patients. Absorption and elution tests were conducted to detect weak A antigens on red blood cells. Molecular biological methods were employed for genotyping. Results: Serological tests showed that the forward typing results of the two patients were O and B, respectively, and weak anti-A1 antibodies were present in their sera. When O-type human high-titer (anti-A≥256) serum was used for absorption and elution tests, patient 1 eluted anti-A, confirming the presence of weak A antigens on their red blood cells; patient 2 eluted anti-A and anti-AB simultaneously. When B-type human antiserum was used for absorption and elution, patient 2 eluted anti-A, confirming the presence of weak A antigens on their red blood cells as well. Gene sequencing results showed that the genotypes of the two patients were ABO Aw. 04/ABO O. 01. 02 and ABO AEL (c. 410C>T)/ABO B.01, respectively. Conclusion: When absorption and elution tests are needed for weak A/B antigens alone on red blood cells, O-type human high-titer serum can be prioritized. However, when both A and B antigens are present, the human antiserum selected for absorption and elution tests should only react with the weak antigen and not with the normally expressed antigen.

Efferocytosis refers to the process of phagocytes engulfing and clearing the cells after programmed cell death. In recent years, an increasing number of studies have shown that the mechanisms of efferocytosis are closely related to drug-induced liver injury, hepatic ischemia-reperfusion injury, viral hepatitis, cholestatic liver diseases, metabolic-associated fatty liver disease, alcoholic liver disease, and other liver disorders. This review summarized the research progress on the role of efferocytosis in liver diseases, with the hope of providing new targets for the prevention and treatment of liver diseases.
Humans ; Liver Diseases/metabolism* ; Animals ; Phagocytosis/physiology* ; Phagocytes ; Efferocytosis

Objective:To investigate the effect of mild moxibustion on transient receptor potential vanilloid type 1(TRPV1)channel expression in primary dysmenorrhea(PD)rats and explore its mechanism in alleviating central pain sensitization.Methods:Thirty-two female non-pregnant Wistar rats were randomized into a blank group,a model group,a mild moxibustion group,and a capsazepine group,with 8 rats in each group.Except for the blank group,the other three groups used estradiol benzoate,ice-water bath,and oxytocin to establish the rat PD model of cold-dampness stagnation pattern.The interventions began on day 1 of modeling,once a day,and lasted 10 d.The mild moxibustion group received mild moxibustion at Shenque(CV8)and Guanyuan(CV4),20 min/time;in the capsazepine group,capsazepine was injected at a dose of 2 mg/(kg·bw).The abdominal pain threshold was measured 10-30 min after oxytocin injection on day 11;enzyme-linked immunosorbent assay was used to detect serum prostaglandin F2α(PGF2α)level;the expression of TRPV1,cluster of differentiation 11B(CD11B),and proto-oncogene c-Fos in the spinal dorsal horn and hypothalamus was detected by immunofluorescence and Western blotting.Results:Compared to the blank group,the model group showed a decreased pain threshold(P<0.05)and an increased serum PGF2α level with elevated TRPV1,CD11B,and c-Fos protein expression in the spinal dorsal horn and hypothalamus(P<0.05).Compared to the model group,both the mild moxibustion group and capsazepine group showed significantly increased pain thresholds(P<0.05),along with decreased serum PGF2α levels and reduced protein expression levels of TRPV1,CD11B,and c-Fos in the spinal dorsal horn and hypothalamus(P<0.05).Rat pain threshold in the capsazepine group was higher than that in the mild moxibustion group(P<0.05).Serum PGF2α level,the expression levels of CD11B and c-Fos proteins in the spinal dorsal horn,as well as TRPV1,CD11B,and c-Fos proteins in the hypothalamus of the capsazepine group were lower than those in the mild moxibustion group(P<0.05).Conclusion:Mild moxibustion at Shenque(CV8)and Guanyuan(CV4)may alleviate the central pain sensitization in PD rats by down-regulating TRPV1 channel expression in the spinal dorsal horn and hypothalamus,thus playing an analgesic effect.

Objective:To explore the genetic etiology of a child with Spastic paraplegia and psychomotor retardation with or without seizures (SPPRS).Methods:A child who was admitted to the Children′s Hospital Affiliated to Nanjing Medical University in April 2022 for motor developmental delay, intellectual disability, and hypertonia was selected as the study subject. Relevant clinical data were retrospectively analyzed. Whole exome sequencing (WES) was carried out for the child and his parents. Candidate variants were searched in the Single Nucleotide Polymorphism Database (dbSNP) and Online Mendelian Inheritance in Man (OMIM) database. Pathogenicity of the variants was assessed based on guidelines from the American College of Medical Genetics and Genomics (ACMG). Using key words such as " HACE1 gene" " Spastic paraplegia and psychomotor retardation with or without seizures" and " SPPRS", previous reports on SPPRS patients due to HACE1 gene variants were retrieved from the CNKI, Wanfang Data Knowledge Service Platform, CQVIP, and PubMed databases, with the time set from January 1, 2000 to April 7, 2024. A mutation map for the HACE1 protein in the patients was created. This study was approved by the Ethics Committee of the Children′s Hospital Affiliated to Nanjing Medical University (Ethics No. 202404008-1). Results:The clinical manifestations of the child had included motor developmental delay, intellectual disability and hypertonia. Magnetic resonance imaging revealed hypoplasia of posterior corpus callosum and splenium, with slight enlargement of lateral ventricles. WES revealed that the child has harbored compound heterozygous variants of the HACE1 gene, namely c. 535(exon7)_c.538(exon7)delACAG (p.T179fs*5) and c. 1678+ 2(IVS15)T>C, which were respectively inherited from his parents. Based on the guidelines from the ACMG, the variants were respectively rated as likely pathogenic (PVS1 + PM2_Supporting) and pathogenic (PVS1 + PM2_Supporting + PM3). Literature search has identified 8 papers, which reported 23 SPPRS cases due to HACE1 gene variants. All patients exhibited psychomotor developmental delay, among whom 18 HACE1 gene variants were identified. Conclusion:The c. 535(exon7)_c.538(exon7)delACAG (p.T179fs*5) and c. 1678+ 2(IVS15)T>C compound heterozygous variants of the HACE1 gene probably underlay the pathogenesis of SPPRS in this child. Above discovery has enriched the mutational and phenotypic spectrum of the HACE1 gene and provided a reference for clinical diagnosis and genetic counseling.

Objective:To explore the clinical phenotype and variants of KIF4A gene associated with X-linked intellectual disability type 100 (XLID100) in a child by whole-exome sequencing (WES). Methods:A child presented at the Children′s Hospital Affiliated to Nanjing Medical University in September 2023 was selected as the study subject. Clinical data of the child was retrospectively analyzed. Peripheral blood samples were collected from the child and his family members for WES analysis. Candidate variant was verified by Sanger sequencing. Pathogenicity of the candidate variant was rated based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). The variant was also searched in dbSNP, OMIM, HGMD, ClinVar and gnomAD databases. Amino acid sequences of the KIF4A protein across various species were retrieved from the Ensembl Genome Browser Database and analyzed using Clustal Omega software. Relevant literature on KIF4A gene mutations associated with XLID100 was reviewed. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No. 202402022-1). Results:The child, a 3-year-6-month-old male, had manifested intellectual impairment, language delay, autism, and choroid cyst revealed by cranial magnetic resonance imaging. No facial dysmorphism, tooth anomaly, gross motor development delay or regression, and history of seizure and febrile convulsion was noted. WES revealed that he has harbored a c. 3385delinsTATC (p.Thr1129delinsTyrPro) variant of the KIF4A gene. Sanger sequencing confirmed that his mother and sister have harbored the same variant, whilst his father was of the wild type. Both of his parents had a normal phenotype. The variant was classified as of uncertain significance based on the guidelines from the ACMG. It was not recorded by the dbSNP, OMIM, HGMD, ClinVar and the gnomAD database. Conservative analysis suggested that the variant site, which normally encodes a cysteine, is highly conserved among various species. A review of the literature had retrieved 6 relevant articles documenting a total of 27 cases of KIF4A gene mutations, with only one case from China. Conclusion:The c. 3385delinsTATC (p.Thr1129delinsTyrPro) variant of the KIF4A gene probably underlay the XLID100 in this child. Above finding has provided a reference for the clinical diagnosis and genetic counseling and enriched the mutation spectrum of the KIF4A gene.

Objective:To explore the association between single nucleotide polymorphism (SNP) rs2073618 and rs3102735 of the TNFRSF11B gene and the susceptibility to gastric cancer. Methods:A case-control study was conducted. A total of 577 patients with primary gastric cancer treated at Zhenjiang First People′s Hospital from May 2013 to June 2017 were selected as the case group, and 678 healthy individuals who underwent physical examinations at the same hospital during the same period were enrolled as the control group. Blood samples were collected from both groups, and genomic DNA was extracted. The target gene fragments were amplified using PCR, and genotyping was performed using the Snapshot technique. Statistical analysis was conducted using SPSS v2.0 software. This study was approved by the Medical Ethics Committee of the Zhenjiang First People′s Hospital (Ethics No. 20150083). Results:① The smoking rate was significantly higher in the case group than in the control group ( P=0.006). ② The T > C polymorphism at the rs3102735 locus of the TNFRSF11B gene was significantly associated with an increased risk of gastric cancer (CC vs. TT: OR=2.164, 95% CI=1.063~4.406, P=0.030). In contrast, the rs2073618 polymorphism did not show a significant association with gastric cancer susceptibility ( P>0.05). ③ Stratified analysis by age, gender, smoking status, and drinking status revealed no significant association between the rs2073618 polymorphism and gastric cancer susceptibility ( P>0.05). However, the rs3102735 polymorphism showed a significant association with gastric cancer risk in individuals over 62 years of age (CC vs. TT: OR=5.44, 95% CI=1.54~19.21, P=0.003). Conclusion:The rs3102735 polymorphism of the TNFRSF11B gene may be associated with susceptibility to gastric cancer, particularly in older populations. This polymorphism could serve as a potential indicator for identifying high-risk groups for gastric cancer.

Objective:To explore the genetic etiology of Pontocerebellar Hypoplasia Type 2D (PCH2D) due to compound heterozygous variants of the SEPSECS gene and to conduct a literature review. Methods:A child with PCH2D diagnosed at the Children′s Hospital of Nanjing Medical University due to " motor and cognitive retardation" in June 2022 was selected as the study subject. Clinical and imaging data were collected. Genomic DNA was extracted from the peripheral blood samples of the child and her parents. Whole-exome sequencing (WES) was conducted using capture-based high-throughput sequencing technology. Candidate variants were confirmed by Sanger sequencing and bioinformatics analysis. The pathogenicity of variant was rated according to the Standards and Guidelines for the Interpretation of Sequence Variants released by American College of Medical Genetics and Genomics (ACMG). Additionally, relevant literature on PCH2D caused by SEPSECS gene variants was reviewed to assess the genotype-phenotype correlation. This study was approved by the Medical Ethics Committee of the Children′s Hospital of Nanjing Medical University (Ethical No.: 202402022-1). Results:The child, a 1-year-and-3-month-old girl, had presented with global developmental delay, progressive microcephaly, hypotonia, elevated blood lactic acid, feeding difficulties, and absent tendon reflexes. Cranial MRI indicated thinning of the splenium of the corpus callosum. Electromyography suggested peripheral neurogenic changes primarily affecting sensory nerves. WES revealed the she has harbored compound heterozygous variants of the SEPSECS gene, namely c. 194A>G (p.N65S) and c. 896_c.897insA (p.N299fs*2) (NM_016955), which were inherited from her father and mother, respectively. Neither of her parents had related clinical manifestations. According to the ACMG guidelines, the c. 194A>G (p.N65S) variant was classified as pathogenic (PM1+ PM2_Supporting+ PM3+ PP3), and the c. 896_c.897insA (p.N299fs*2) variant was as likely pathogenic (PVS1+ PM2_Supporting). A total of 18 relevant literature were retrieved, which have involved 32 patients (including this case). The p. N65S variant has been reported previously, while the p. N299fs*2 variant is novel. Conclusion:Compound heterozygous variants in the SEPSECS gene probably underlay the pathogenesis of PCH2D in this child. Above finding has expanded the mutational and phenotypic spectrum of the SEPSECS gene.

OBJECTIVE: To explore the genetic etiology of a child with Spastic paraplegia and psychomotor retardation with or without seizures (SPPRS). METHODS: A child who was admitted to the Children's Hospital Affiliated to Nanjing Medical University in April 2022 for motor developmental delay, intellectual disability, and hypertonia was selected as the study subject. Relevant clinical data were retrospectively analyzed. Whole exome sequencing (WES) was carried out for the child and his parents. Candidate variants were searched in the Single Nucleotide Polymorphism Database (dbSNP) and Online Mendelian Inheritance in Man (OMIM) database. Pathogenicity of the variants was assessed based on guidelines from the American College of Medical Genetics and Genomics (ACMG). Using key words such as "HACE1 gene" "Spastic paraplegia and psychomotor retardation with or without seizures" and "SPPRS", previous reports on SPPRS patients due to HACE1 gene variants were retrieved from the CNKI, Wanfang Data Knowledge Service Platform, CQVIP, and PubMed databases, with the time set from January 1, 2000 to April 7, 2024. A mutation map for the HACE1 protein in the patients was created. This study was approved by the Ethics Committee of the Children's Hospital Affiliated to Nanjing Medical University (Ethics No. 202404008-1). RESULTS: The clinical manifestations of the child had included motor developmental delay, intellectual disability and hypertonia. Magnetic resonance imaging revealed hypoplasia of posterior corpus callosum and splenium, with slight enlargement of lateral ventricles. WES revealed that the child has harbored compound heterozygous variants of the HACE1 gene, namely c.535(exon7)_c.538(exon7)delACAG (p.T179fs*5) and c.1678+2(IVS15)T>C, which were respectively inherited from his parents. Based on the guidelines from the ACMG, the variants were respectively rated as likely pathogenic (PVS1 + PM2_Supporting) and pathogenic (PVS1 + PM2_Supporting + PM3). Literature search has identified 8 papers, which reported 23 SPPRS cases due to HACE1 gene variants. All patients exhibited psychomotor developmental delay, among whom 18 HACE1 gene variants were identified. CONCLUSION The c.535(exon7)_c.538(exon7)delACAG (p.T179fs*5) and c.1678+2(IVS15)T>C compound heterozygous variants of the HACE1 gene probably underlay the pathogenesis of SPPRS in this child. Above discovery has enriched the mutational and phenotypic spectrum of the HACE1 gene and provided a reference for clinical diagnosis and genetic counseling.
Humans ; Male ; Seizures/genetics* ; Ubiquitin-Protein Ligases/genetics* ; Heterozygote ; Mutation ; Child ; Child, Preschool ; Paraplegia/genetics* ; Intellectual Disability/genetics* ; Polymorphism, Single Nucleotide ; Exome Sequencing ; Psychomotor Disorders/genetics*

OBJECTIVE: To explore the clinical phenotype and variants of KIF4A gene associated with X-linked intellectual disability type 100 (XLID100) in a child by whole-exome sequencing (WES). METHODS: A child presented at the Children's Hospital Affiliated to Nanjing Medical University in September 2023 was selected as the study subject. Clinical data of the child was retrospectively analyzed. Peripheral blood samples were collected from the child and his family members for WES analysis. Candidate variant was verified by Sanger sequencing. Pathogenicity of the candidate variant was rated based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). The variant was also searched in dbSNP, OMIM, HGMD, ClinVar and gnomAD databases. Amino acid sequences of the KIF4A protein across various species were retrieved from the Ensembl Genome Browser Database and analyzed using Clustal Omega software. Relevant literature on KIF4A gene mutations associated with XLID100 was reviewed. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No. 202402022-1). RESULTS: The child, a 3-year-6-month-old male, had manifested intellectual impairment, language delay, autism, and choroid cyst revealed by cranial magnetic resonance imaging. No facial dysmorphism, tooth anomaly, gross motor development delay or regression, and history of seizure and febrile convulsion was noted. WES revealed that he has harbored a c.3385delinsTATC (p.Thr1129delinsTyrPro) variant of the KIF4A gene. Sanger sequencing confirmed that his mother and sister have harbored the same variant, whilst his father was of the wild type. Both of his parents had a normal phenotype. The variant was classified as of uncertain significance based on the guidelines from the ACMG. It was not recorded by the dbSNP, OMIM, HGMD, ClinVar and the gnomAD database. Conservative analysis suggested that the variant site, which normally encodes a cysteine, is highly conserved among various species. A review of the literature had retrieved 6 relevant articles documenting a total of 27 cases of KIF4A gene mutations, with only one case from China. CONCLUSION The c.3385delinsTATC (p.Thr1129delinsTyrPro) variant of the KIF4A gene probably underlay the XLID100 in this child. Above finding has provided a reference for the clinical diagnosis and genetic counseling and enriched the mutation spectrum of the KIF4A gene.
Humans ; Kinesins/genetics* ; Male ; Child, Preschool ; Intellectual Disability/genetics* ; Mutation ; Exome Sequencing ; X-Linked Intellectual Disability/genetics* ; Phenotype

OBJECTIVE: To explore the association between single nucleotide polymorphism (SNP) rs2073618 and rs3102735 of the TNFRSF11B gene and the susceptibility to gastric cancer. METHODS: A case-control study was conducted. A total of 577 patients with primary gastric cancer treated at Zhenjiang First People's Hospital from May 2013 to June 2017 were selected as the case group, and 678 healthy individuals who underwent physical examinations at the same hospital during the same period were enrolled as the control group. Blood samples were collected from both groups, and genomic DNA was extracted. The target gene fragments were amplified using PCR, and genotyping was performed using the Snapshot technique. Statistical analysis was conducted using SPSS v2.0 software. This study was approved by the Medical Ethics Committee of the Zhenjiang First People's Hospital (Ethics No. 20150083). RESULTS: The smoking rate was significantly higher in the case group than in the control group (P = 0.006). The T>C polymorphism at the rs3102735 locus of the TNFRSF11B gene was significantly associated with an increased risk of gastric cancer (CC vs. TT: OR = 2.164, 95%CI = 1.063~4.406, P = 0.030). In contrast, the rs2073618 polymorphism did not show a significant association with gastric cancer susceptibility (P > 0.05). Stratified analysis by age, gender, smoking status, and drinking status revealed no significant association between the rs2073618 polymorphism and gastric cancer susceptibility (P > 0.05). However, the rs3102735 polymorphism showed a significant association with gastric cancer risk in individuals over 62 years of age (CC vs. TT: OR = 5.44, 95%CI = 1.54~19.21, P = 0.003). CONCLUSION The rs3102735 polymorphism of the TNFRSF11B gene may be associated with susceptibility to gastric cancer, particularly in older populations. This polymorphism could serve as a potential indicator for identifying high-risk groups for gastric cancer.
Humans ; Stomach Neoplasms/genetics* ; Polymorphism, Single Nucleotide ; Male ; Female ; Genetic Predisposition to Disease ; Middle Aged ; Case-Control Studies ; Osteoprotegerin/genetics* ; Aged ; Adult ; Genotype