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 investigate the expression level and application value of anti-carbamylated protein(CarP)antibody in rheumatoid arthritis(RA).Methods:Demographic data and laboratory test results of RA patients,non-RA patients and healthy controls in the physical examination center were re-viewed from December 2018 to June 2019 in the Rheumatology and Immunology Department of the Peo-ple's Hospital of Xinjiang Uygur Autonomous Region.The serum concentrations of anti-CarP antibodies in all the subjects were measured by ELISA and statistically analyzed.Results:A total of 259 subjects were included in this study,including 158 in the RA group(45 serum-negative RA patients),59 in the non-RA group and 42 in the healthy control group.The concentration of anti-CarP antibody in RA group[8.31(5.22,15.26)U/mL]was higher than that in non-RA group[4.50(3.35,5.89)U/mL]and healthy control group[3.46(2.76,4.92)U/mL].The concentration of anti-CarP antibody in non-RA group was not significantly different from that in healthy control group(P=0.10).Receiver operating characteristic(ROC)curve analysis showed that the sensitivity of anti-CarP antibody in the diagnosis of RA was 58.2％,and the specificity was 93.1％.The sensitivity of the combined detection of anti-CarP antibody,anti-cyclic peptide containing citrulline(CCP)antibody and rheumatoid factor(RF)was 82.3％,and the specificity was 96.5％.The positive rate of anti-CarP antibody in serum-negative RA patients was 44.4％(20/45).Univariate Logisitic regression analysis showed that age,C-reactive pro-tein(CRP),erythrocyte sedimentation rate(ESR),RF,glucose-6-phosphate isomerase(GPI),anti-CCP antibody and anti-CarP antibody were risk factors for RA.Multivariate Logisitic regression analysis showed that anti-CCP antibody and anti-CarP antibody were independent risk factors for RA.Spearman correlation analysis showed that there was no significant correlation between anti-CarP antibody and swol-len joint count(SJC),tenderness joints count(TJC),ESR,disease activity score for 28 joints(DAS28),clinical disease activity index(CDAI),simplified disease activity index(SDAI).The concentration of anti-CarP antibody in RA with bone erosion(n=88)was higher than that in RA without bone erosion(n=70),and there was significant difference between the two groups(P＜0.05).Conclusion:Anti-CarP antibody is an effective serological marker for the diagnosis of RA.The combined detection of RF,anti-CCP antibody and anti-CarP antibody can improve its diagnostic value,and anti-CarP antibody may be an effective assistant diagnostic tool for serum negative RA.The high serum concentration of anti-CarP antibody in patients with RA may indicate an increased risk of bone erosion and should be treated early,but further cohort studies are needed for follow-up observation.

Objective:To investigate the prevalence of hyperuricemia (HUA) in Bozidun Kirghiz township of Xinjiang Aksu region, and to explore the risk factors for the occurrence of HUA in the local area.Methods:A cross-sectional survey study was conducted by randomly selecting 9 villages in Bozidun Kirgiz Township by the whole-group sampling method and questionnaire were distributed to the households. The questionnaire included: demographic information, history of past illness, personal history, and all subjects were measured for height, weight, blood pressure, abdominal circumference, etc. The diagnostic of HUA if the serum uric acid (SUA) level >420 μmol/L in men or >360 μmol/L in women. The incidences of HUA in different age, sex, food type and life style behavior were analyzed. T test, non-parametric test and Chi-square test were used to analyze the differences among the groups, and logistic regression was used to analyze the risk factors. Results:①A total of 2 138 subjects were surveyed, among which 68 patients were with HUA, the prevalence of HUA in Bozidun Kirghiz township, Aksu region in the general population was 3.18%(68/2 138); the prevalence rate in men was 4.60%(45/978), 45 patients were identified; and the prevalence rate in women was 1.98%(23/1 160), 23 patients were identified. The peak age of HUA in male and female patients was 51~60 years old. ②The prevalence of HUA was lower in those who consumed dairy products ( χ2=6.91, P=0.017), nuts ( χ2=8.43, P=0.038) and eggs ( χ2=7.38, P=0.023), and lower in those who consumed more. Different intake of cereals ( χ2=0.87, P=0.647), meat( χ2=0.82, P=0.662), vegetables and fruits( χ2=5.22, P=0.073) had no effect on the prevalence of HUA.③In terms of different life behaviors, the prevalence of HUA in men who had been smoking was higher than those who had never smoked (57.78%, 28.89%, 13.33%, χ2=8.16, P=0.017). In the relationship between drinking and HUA, the prevalence rates of male always drinking, ever drinking and never drinking were 80.00%, 11.11% and 3.89%, respectively, the difference was statistically significant ( χ2=6.67, P=0.038). ④Multi-factor logistic regression analysis showed that high BMI, old age, high TG, increased Cr and increased WBC were risk factors for the occurrence of HUA [ OR(95% CI)=1.13(1.04, 1.23), 1.03(1.00,1.05),1.39(1.00, 1.93), 1.03(1.02, 1.05), 1.27(1.07, 1.49), all P<0.05]. Conclusion:The prevalence of HUA in Bozidun Kirgiz township in Aksu prefecture of Xinjiang is lower than that in other areas with continental climate. High BMI, old age, high TG, increased Cr and increased WBC count are risk factors for the development of HUA .

Objective:To investigate the positivity rate and high titer of antinuclear antibody (ANA) and anti-dsDNA antibody in healthy Tajik, Kirgiz, and Han Chinese populations in Xinjiang.Methods:A total of 3 687 cases of Tajik residents, 2 140 cases of Kyrgyz residents, and 2 034 cases of Han residents were selected as the study subjects, and ANA and anti-dsDNA antibodies were detected and comparatively analyzed. Data were analyzed using SPSS 22.0 software with χ2 test. Results:The positive rate of ANA in Tajik group was 15.1% [(555/3 687), 10.2%(147/1 445) male, 18.2%(408/2 242) female], of which high titers accounted for 25.8%(143/555). It was 16.7%(357/2 140) in the Kyrgyz group [10.3% male(101/980), 19.4%(256/1 160) female], with high titers accounting for 14.8%; and in the Han group, the positivity rate was 16.6% [9.8%(70/720) male, 19.1%(267/1 314) female], with high titers accounting for 18.4%(62/1 337). There was no significant difference in ANA positivity rate among the three ethnic groups( χ2=3.64, P=0.162), but there were differences in the percentage of high titer of ANA in Tajik ethnic group compared with Han and Kyrgyz ethnic groups(25.8% vs. 18.4%, χ2=6.02, P=0.014; 25.8% vs.14.8%, χ2=14.71, P=0.001), which accounted for a high percentage. The highest number of ANA high titers in all three groups was in the age group of 51~60 years. The ANA karyotype with the highest percentage of high titers in the Tajik and Kyrgyz populations was granular, while it was homogeneous and in the Han it was homogeneous.The positive rate of anti-dsDNA antibody in the Tajik group was 0.71%(26/3 687), of which high titer accounted for 23.1%(6/126); in the Kyrgyz group, it was 0.75%(16/2 034), and high titer accounted for 31.3%(4/14); and in the Han group, the positive rate was 0.69%(14/2 034), of which high titer accounted for 28.6%(4/64), and there was no statistical significance of in the difference in the positive rate of anti-dsDNA antibody and the proportion of high titer among the three groups( χ2=0.06, P=0.972; χ2=0.37, P=0.832). Conclusion:The percentage of ANA and anti-dsDNA antibodies and high titers varied vary among the three ethnic groups in this study, and long-term follow-up is needed to monitor keep an eye on the incidence of autoimmune diseases in people with high autoantibody titers.

Purpose/Significance To improve the performance of named entity recognition(NER)model of Chinese electronic medi-cal records(EMR)for better organization and mining of medical information.Method/Process The ERNIE-BiGRU-Attention-CRF NER model of Chinese EMR is constructed.Firstly,the ERNIE1.0 pre-training model is used to generate word vectors with semantic features,and then BiGRU is utilized to capture the global semantic features and grammatical structural features,which are fed into the Attention mechanism to further enhance the capture of the semantic features,and finally,the CRF decoding layer is connected to output the label sequences with the maximum global probability.Result/Conclusion Comparison experiments and ablation experiments are car-ried out on the publicly available medical text dataset CCKS2017,and examples analysis is conducted using the generated model.The model proposed in this paper achieves better recognition results.

OBJECTIVE: To explore the genetic etiology for a child with profound intellectual disabilities and obvious behavioral abnormalities. METHODS: A male child who had presented at the Zhongnan Hospital of Wuhan University on December 2, 2020 was selected as the study subject. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. Short tandem repeat (STR) analysis was carried out to determine its parental origin. The splicing variant was also validated in vitro with a minigene assay. RESULTS: WES results revealed that the child had harbored a novel splicing variant of c.176-2A>G in the PAK3 gene, which was inherited from his mother. The results of minigene assay have confirmed aberrant splicing of exon 2. According to the guidelines from the American College of Medical Genetics and Genomics, it was classified as a pathogenic variant (PVS1+PM2_Supporting+PP3). CONCLUSION The novel splicing variant c.176-2A>G of the PAK3 gene probably underlay the disorder in this child. Above finding has expanded the variation spectrum of the PAK3 gene and provided a basis for genetic counseling and prenatal diagnosis for this family.
Child ; Female ; Humans ; Male ; Pregnancy ; Exons ; Intellectual Disability/genetics* ; Mothers ; Mutation ; p21-Activated Kinases/genetics* ; Parents ; RNA Splicing

Objective To study the epidemiology of hand,foot,and mouth disease (HFMD) and the spectrum of serotypes in the other enterovirus (EV) (non-EV-A71 and non-Coxsaekievirus group A 16,CV-A 16) from 2016 to 2017 in Guangzhou,to provide the basis for its treatment,prevention and control.Methods Enteroviruses universal type,EV-A71 and CV-A16 were detected by real time reverse transeription-polymerase chain reaction in the specimens from HFMD suspected patients from 2016 to 2017.The positive specimens of non-EV-A71 and non-CV-A16 were amplified and sequenced based on 5'-untranslated region (UTR) region.The spectrum of serotypes was analyzed with BLAST in NCBI on the basis of 5'-UTR region.Results A total of 25779 specimens from HFMD patients were collected during 2016-2017,16 300 (63.23 ％) of which were positive.The positive rates of EV-A71,CV-A16,non-EV-A71 and non-CV-A16 were 4.57％ (1 178/25 779),12.70％ (3 274/25 779) and 45.96％ (11 848/25779),respectively.The average positive rate of non-EV-A71 and non-CV-A16 in 2017 was 55.68％,which was higher than that in 2016.Sequence analysis showed that there were 16 genotypes in 95 non-EV-A71 and non-CV-A16 positive specimen,including CV-A6,CV-A10,CV-A4,CV-A2,CV-A8,CV-A12,CV-A9,Coxsakievirus B5 (CV-B5),CV-B2,CV-B4,CV-B3,Echovirus 1 (E1),E16,E30,E2 and E18.CV-A6 (26.32％),and CV-A10 (15.79％) were the most common genotypes,followed by CV-A4 (6.32％)、CV-A8(4.21％),and CV-A2 (4.21％).Conclusions The infection rate of EV-A71 is very low during 2016-2017.From April to July 2016,there is a small peak of CV-A16 infection.The non-EV-A71 and non-CV-A16 enterovirus becomes the main causative agent of HFMD during 2016 to 2017.CV-A6 and CV-A10 are the most prevalent pathogens of non-EV-A71 and non-CV-A16 enterovirus.Research and monitoring of CV-A6,CV-A10 as the main non-EV-A71and non-CV-A16 virus should be strengthened.

PURPOSE: Numerous studies have assessed the association of SP110 gene variants with tuberculosis (TB), but the results were inconsistent. Through a comprehensive review and meta-analysis, our study aimed to clarify the nature of genetic risks contributed by 11 polymorphisms for the development of TB. MATERIALS AND METHODS: Through searching PubMed, web of science, China National Knowledge Infrastructure (CNKI) databases, a total of 11 articles including 13 independent studies were selected. The pooled odd ratios (ORs) along with their corresponding 95% confidence interval (CI) were estimated for allelic comparisons, additive model (homozygote comparisons; heterozygote comparisons), dominant model and recessive model. We also assessed the heterogeneity across the studies and publication bias. RESULTS: The results of combined analysis revealed a significantly increased risk of TB for single nucleotide polymorphism (SNP) rs9061 in all five comparisons (allelic comparisons: OR=1.28, 95% CI=1.14–1.44, p<0.0001; homozygote comparisons: OR=2.84, 95% CI=1.84–4.38, p<0.00001; heterozygote comparisons: OR=1.23, 95% CI=1.05–1.43, p=0.009; dominant model: OR=1.32, 95% CI=1.14–1.53, p=0.0003; recessive model: OR=2.26, 95% CI=1.18–4.34, p=0.01). In subgroup analysis, the risk of TB associated with SNP rs9061 appeared to be increased. Moreover, increased risk of TB was also found in Asian subgroup of SNP rs11556887, while decreased risk of TB appeared in large sample size subgroup of SNP rs1135791. No significant association was observed between other SNPs and the risk of TB. CONCLUSION: Our meta-analysis suggested that the variant of SNP rs9061 might be a risk factor for TB.
Alleles ; Asian Continental Ancestry Group/genetics ; China ; Confidence Intervals ; Genetic Predisposition to Disease ; Heterozygote ; Homozygote ; Humans ; Minor Histocompatibility Antigens/*genetics ; Nuclear Proteins/*genetics ; Odds Ratio ; *Polymorphism, Single Nucleotide ; Risk Factors ; Tuberculosis, Pulmonary/*genetics

OBJECTIVETo analyze relationships between the tumor deposits (TD) and clinicopathologic features of gastric cancer and investigate the value of TD in staging and prognosis in gastric cancer patients.

METHODSRetrospective cohort study was conducted to evaluate the clinicopathologic data of 388 gastric cancer patients who underwent surgical procedures in Chinese PLA General Hospital between November 2011 and December 2012. Relationships between TD and clinicopathologic features were analyzed by χor Fisher exact tests. Survival curves were also generated by Kaplan-Meier method. The univariate and multivariate analysis were performed with Log-rank and COX proportional hazard model to examine the association between prognosis and TD.

RESULTSTD were observed in 67 (17.3%) of 388 gastric cancer patients, including 48 male patients (48/289, 16.6%) and 19 female patients (19/99, 19.2%). There were 40 patients (40/198, 20.2%) whose age was above 64 years old. TNM staging of positive TD patients was as follows: for pathology, there were 5 patients (5/64, 7.8%) in stage II(b, 6 patients (6/58, 10.3%) in stage III(a, 14 patients (14/75, 18.7%) in stage III(b, 30 patients (30/135, 22.2%) in stage III(c, 12 patients (12/39, 30.8%) in stage IIII( and no one in stage I(b or II(a; for T-staging, there were 2 patients (2/18, 11.1%) in stage T2, 2 patients (2/27, 7.4%) in stage T3, 36 patients (36/259, 13.9%) in stage T4a and 27 patients (27/84, 32.1%) in stage T4b; for N-stage, there were 5 patients (5/72, 6.9%) in stage N0, 6 patients (6/72, 8.3%) in stage N1, 19 patients (19/82, 23.2%) in stage N2, 27 patients (27/100, 27.0%) in stage N3a and 10 patients(10/62, 16.1%) in stage N3b; for M-stage, there were 12 patients (12/40, 30.0%) in distal metastases; for vascular invasion, there were 29 patients (29/129, 22.5%). Among positive TD patients, the number of TD >3 was found in 38 of 67 cases(56.7%). TD was associated with pTNM-stage (χ=16.898, P=0.010), T-stage (χ=17.382, P=0.001), N-stage (χ=18.080, P=0.001), M-stage (χ=5.060, P=0.036) and vascular invasion(χ=3.675, P=0.039). The median survival time of positive TD patients was significantly shorter as compared to negative TD patients (22 months vs. 32 months, χ=23.391, P=0.012). Among positive TD patients, the median survival time of patients with TD number >3 was significantly shorter as compared to those with TD number <3 (17 months vs. 25 months, χ=5.157, P=0.023). Multivariate survival analysis showed that TD number >3 was the independent risk factor of prognosis (RR=2.350, 95%CI:1.345 to 4.106, P=0.003).

CONCLUSIONSTD state is closely associated with the staging of gastric cancer and TD number >3 indicates a poor prognosis.

Aged ; China ; Cohort Studies ; Female ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Invasiveness ; pathology ; Neoplasm Metastasis ; Neoplasm Staging ; methods ; statistics & numerical data ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Stomach Neoplasms ; classification ; diagnosis ; mortality ; pathology ; Survival Rate