OBJECTIVETo investigate the association of polymorphisms in the apolipoprotein B gene (APOB) 3'variable number of tandem repeat with natural longevity in the Xinjiang Uighur nationality people.

METHODSTotally 191 healthy individuals over 90 years and 53 individuals aged 65-70 years were recruited among Xinjiang Uighur population, the nationality, gender and living area were matched. Genotyping was performed using polymerase chain reaction-sequence specific primer(PCR-SSP) and PCR-sequencing.

RESULTSFourteen alleles were found in the Xinjiang Uighur nationality population. The frequency of HVE36 and HVE42 in the natural longevity group were significantly higher than that in the control group (both P<0.05) and HVE44, HVE46, HVE48 and HVE58 were only found in the natural longevity group. However, the frequency of HVE26, HVE30 and HVE34 were markedly lower in the natural longevity group compared to the control group. Logistic regression analyses revealed that allele L and the genotypes LL were positively associated with age, whereas the allele S and genotype SS were negatively associated with age (both P<0.05). Each allele consists of 15 bp tandem repeats with rich-AT by PCR-sequencing.

CONCLUSIONThese results indicate that the S allele, and SS genotype are frail factors in China Uighur natural longevity people, whereas allele L and genotypes LL are protective factors.

Aged ; Aged, 80 and over ; Apolipoproteins B ; genetics ; Base Sequence ; China ; Female ; Gene Frequency ; Genotype ; Humans ; Longevity ; genetics ; Male ; Middle Aged ; Minisatellite Repeats ; genetics ; Molecular Sequence Data ; Polymerase Chain Reaction ; Polymorphism, Genetic ; genetics

OBJECTIVETo investigate the effects of caspase-3 siRNA on the neurobehavior of mice exposed to aluminum.

METHODSMale KunMing mice (3 months old) were randomly divided into 4 groups by weight:blank control group (4 microl normal saline), Al group (4 microl 0.5% AlCl3), Al plus empty vector group(3 microl 0.5% AlCl3 plus control siRNA expression vector)and Al plus RNAi group (3 microl 0.5% AlCl3 plus targeted siRNA expression vector). All groups were treated by lateral cerebral ventricle micro-injection for 5 days. The neurobehavior was tested by the Morris water maze test, Open-field and Step-down tests for all treated mice. Pathological changes in hippocampus was observed by electron microscopy, the caspase-3 gene expression levels were detected using RT-PCR.

RESULTSThe results of Step-down test indicated that as compared with control group, the latent time [LT, (44.67 +/- 10.60) s] in A1 group decreased significantly, the error number (3.63 +/- 0.52) in Al group increased significantly and the LT [(68.00 +/- 14.70) s] in Al plus empty vector group decreased significantly (P<0.05). the LT [(239.50 +/- 19.36) s] in Al plus RNAi group increased significantly and the error number in Al plus RNAi group decreased significantly, as compared with Al group (P<0.05). The results of Morris water maze test showed that as compared with control group, the LT in Al group increased significantly, and residence time in the former platform quadrant decreased significantly and the LT in Al plus empty vector group increased significantly (P<0.05). The LT in Al plus RNAi group was significantly longer than that in Al group (P<0.05). The results of open-field test demonstrated that as compared with control group, the time in the central grid in Al group and Al plus empty vector group increased significantly, the rearing number and the modification number in Al group and Al plus empty vector group decreased significantly (P< 0.05). As compared with Al group, the time in the central grid in Al plus RNAi group decreased, the inter-cell number, the rearing number and the modification number increased significantly (P<0.05). The results of electron microscopic examination exhibited that a slight change of hippocampal cells appeared in control group, the obvious pathological changes of hippocampal cells appeared in Al group and Al plus empty vector group, but the pathological changes of hippocampal cells in Al plus RNAi group significantly reduced as compared with Al group. The results of thionin staining indicated that the layers of neural cells of hippocampal CA3 were more clear and there was not obvious denatured injury of neural cells of hippocampal CA3 in control group. The number and Nissl body color of neural cells of hippocampal CA3 in Al group and Al plus empty vector group decreased significantly. After RNA interference, the number and Nissl body color of neural cells of hippocampal CA3 increased obviously. The expression levels of caspase-3 gene in Al group and Al plus empty vector group were 2.24 +/- 0.57 and 2.28 +/- 0.33, respectively, which were significantly higher than that (1.00 +/- 0.00) in control group (P<0.05). The expression level of caspase-3 gene in Al plus RNAi group was 0.44 +/- 0.08, which was significantly lower than those in Al group and control group (P<0.05).

CONCLUSIONAluminum can decrease the learning and memorizing ability, and inhibited the activity or exploration function of mice. It is suggested that Caspase-3 siRNA may reduce the neurotoxicity induced by aluminum to a certain extent.

Aluminum ; toxicity ; Animals ; Caspase 3 ; genetics ; Male ; Maze Learning ; Mice ; Mice, Inbred Strains ; Neurons ; RNA Interference ; RNA, Small Interfering ; genetics

OBJECTIVETo explore the relationship between genetic polymorphisms of C-344T in the promoter region and K173R in the exon 3 of aldosterone synthase gene (CYP11B2) and the incidence of essential hypertension in a northern Chinese Han population.

METHODSWe conducted a case-control study including 182 hypertensive patients and 189 healthy controls in Harbin newspaper office and assayed the genotypes of C-344T and K173R using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing technology.

RESULTSThe distributions of C-344T and K173R genotype frequencies in men and women were in accordance with the Hardy-Weinberg equilibrium. The differences of C-344T allele and genotype as well as K173R allele frequency distributions between hypertensive patients and healthy controls were not statistically significant in men and women and pooled population (P > or = 0.05). The difference of K173R genotype frequency distribution reached borderline significance (P = 0.0500) and was more pronounced in women (P = 0.0038) according to the dominant mode of inheritance. Moreover, the magnitude of this mode of inheritance was more remarkable after the confounding factors were adjusted. K173R statistically correlated with the systolic hypertension in women.

CONCLUSIONThe CYP11B2 K173R polymorphism correlates with the susceptibility of essential hypertension in the northern Chinese Han population.

Asian Continental Ancestry Group ; Case-Control Studies ; Cytochrome P-450 CYP11B2 ; genetics ; Female ; Genetic Association Studies ; Genetic Predisposition to Disease ; Humans ; Hypertension ; genetics ; Male ; Polymorphism, Genetic

Objective To evaluate the bias of creatinine testing by external quality assessment (EQA) and analyze the effects of calibration on the bias of tested values using Jaffe assay.Methods The EQA data from The Clinical Laboratory Centre of Chongqing City were utilized to investigate the frozen pooled-human serum in which the value of creatinine was determined by reference method.The differences between Jaffe assay and creatine oxidase method were analyzed and the bias was evaluated.After the routine measurement systems were calibrated using the frozen pooled-human sera with double levels,the EQA samples were tested.Results The number of the laboratories using Jaffe method for creatinine measurement reduced significantly in Chongqing from 2012 to 2016.The robust average values of Jaffe assay were different from enzymatic assay significantly and the difference of the values were correlated with the concentration of creatinine (r =0.774 6).The results of the investigation using frozen pooled human serum and the trueness verification program of National Center for Clinical Laboratories indicated the positive bias of Jaffe assay was observed in low levels of creatinine with maximum of 10.39％ and 13.31％ and the bias correlated with the concentration of creatinine (r =0.988 9),by contrast the bias was low in enzymatic assay with maximum of 1.04％ and 1.49％ only.After the measurement systems were calibrated by frozen pooled human sera with double-levels,the positive bias of Jaffe assay in the low concentration of creatinine could be corrected.Conclusion There may be a positive bias of Jaffe assay for the samples with low concentration of creatinine,which could be corrected by using the calibrators with double-levels.

Acupuncture Therapy ; Humans ; Medicine, Chinese Traditional ; Moxibustion ; Osteoporosis ; diagnosis ; pathology ; therapy ; Practice Guidelines as Topic

OBJECTIVETo examine whether the polymorphisms of endothelial nitric oxide synthase (eNOS) gene are associated with the susceptibility to high altitude pulmonary edema (HAPE) in Chinese railway construction workers at Qinghai-Tibet where the altitude is over 4 500 m above sea level.

METHODSA case-control study was conducted including 149 HAPE patients in the construction workers and 160 healthy controls randomly recruited from their co-workers, matching the patients in ethnicity, age, sex, lifestyle, and working conditions. Three polymorphisms of eNOS gene, T-786C in promoter, 894G/T in exon 7, and 27bp variable number tandem repeat (VNTR) in intron 4, were genotyped using polymerase chain reaction (PCR) and confirmed with DNA sequencing.

RESULTSThe frequencies of 894T allele and heterozygous G/T of the 894G/T variant were significantly higher in HAPE patients group than in the control group (P=0.0028 and P=0.0047, respectively). However, the frequencies of the T-786C in promoter and the 27bp VNTR in intron 4 were not significantly different between the two groups. Haplotypic analysis revealed that the frequencies of two haplotypes (H3,T-T-b, b indicates 5 repeats of 27 bp VNTR; H6, C-G-a, a indicates 4 repeats of 27 bp VNTR) were significantly higher in HAPE patients (both Pü0.0001). On the contrary, the frequencies of H1 (T-G-b) and H2 (T-G-a) were lower in HAPE patients than in healthy controls (both Pü0.001).

CONCLUSIONSTwo haplotypes (T-T-b and C-G-a) may be strongly associated with susceptibility to HAPE. Compared with the individual alleles of eNOS gene, the interaction of multiple genetic markers within a haplotype may be a major determinant for the susceptibility to HAPE.

Adolescent ; Adult ; Altitude ; Base Sequence ; Case-Control Studies ; DNA Primers ; Genotype ; Haplotypes ; Humans ; Male ; Middle Aged ; Nitric Oxide ; blood ; Nitric Oxide Synthase Type III ; genetics ; Occupational Diseases ; enzymology ; genetics ; Polymorphism, Genetic ; Pulmonary Edema ; enzymology ; genetics ; Tibet ; Young Adult

Background: Decision-making concerning the treatment of choroid plexus tumor (CPT) in pediatric patients remains a topic of considerable debate. The aim of this work was to describe clinical features and prognostic risk factors of CPT in the pediatric population and to provide theoretical opinions regarding clinical decisions for CPT. Methods: The data of 96 patients with CPT and younger than 14 years were retrospectively analyzed. Clinical characteristics such as pathological type of CPTs, rate and severity of hydrocephalus, treatment and outcome, and recurrence were investigated. For categorical variables, the Pearson's Chi-square test was performed. The Mann-Whitney U-test was used for comparisons between nonnormally distributed parameters. Log-rank test was used for progression-free survival (PFS). Results: The study included 70 choroid plexus papilloma (CPP) cases, 17 atypical choroid plexus papilloma (aCPP) cases, and 9 choroid plexus carcinoma (CPC) cases. Compared with patients with CPP or aCPP, patients with CPC had a shorter disease course (median: CPP, 4 months; aCPP, 2 months; CPC, 1 month; H: 23.5, P < 0.001), higher rate of acute hydrocephalus (CPP, 27.1%; aCPP, 52.9%; CPC, 77.8%; χ = 10.9, P < 0.05), and lower incidence of cure rate (CPP, 85.7%; aCPP, 70.5%; CPC, 33.3%; χ = 13.5, P < 0.05). The severity of hydrocephalus with tumor in the lateral or third ventricle was significantly higher than that with tumors in the fourth ventricle (severe hydrocephalus: lateral ventricle, 51.7%; third ventricle, 47.0%; fourth ventricle, 11.1%; χ = 26.0, P < 0.001). Patients with gross total surgical resection had no better PFS than those with partial resection because of the use of adjuvant therapy in the latter (χ = 4.0, P > 0.05). Patients with CPC experienced shorter time for recurrence than those with CPP or aCPP (χ = 40.1, P < 0.0001). Conclusions Our results indicated that CPP in the fourth ventricle could trigger serious clinical symptoms at an early stage, requiring early intervention. Adjuvant treatment might be necessary for patients with partially resected CPP, aCPP, and CPC to achieve a favorable outcome.
Child ; Child, Preschool ; Choroid Plexus Neoplasms ; mortality ; pathology ; surgery ; Female ; Humans ; Hydrocephalus ; etiology ; Infant ; Male ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Prognosis ; Risk Factors

Objective: To analyze the clinical and molecular diagnostic status of Fanconi anemia (FA) in China. Methods: The General situation, clinical manifestations and chromosome breakage test and genetic test results of 107 pediatric FA cases registered in the Chinese Blood and Marrow Transplantation Registry Group (CBMTRG) and the Chinese Children Blood and Marrow Transplantation Registry Group (CCBMTRG) from August 2009 to January 2022 were analyzed retrospectively. Children with FANCA gene variants were divided into mild and severe groups based on the type of variant, and Wilcoxon-test was used to compare the phenotypic differences between groups. Results: Of the 176 registered FA patients, 69 (39.2%) cases were excluded due to lack of definitive genetic diagnosis results, and the remaining 107 children from 15 hospitals were included in the study, including 70 males and 37 females. The age at transplantation treatment were 6 (4, 9) years. The enrolled children were involved in 10 pathogenic genes, including 89 cases of FANCA gene, 7 cases of FANCG gene, 3 cases of FANCB gene, 2 cases of FANCE gene and 1 case each of FANCC, FANCD1, FANCD2, FANCF, FANCJ, and FANCN gene. Compound heterozygous or homozygous of loss-of-function variants account for 69.2% (72/104). Loss-of-function variants account for 79.2% (141/178) in FANCA gene variants, and 20.8% (37/178) were large exon deletions. Fifty-five children (51.4%) had chromosome breakage test records, with a positive rate of 81.8% (45/55). There were 172 congenital malformations in 80 children.Café-au-Lait spots (16.3%, 28/172), thumb deformities (16.3%,28/172), polydactyly (13.9%, 24/172), and short stature (12.2%, 21/172) were the most common congenital malformations in Chinese children with FA. No significant difference was found in the number of congenital malformations between children with severe (50 cases) and mild FANCA variants (26 cases) (Z=-1.33, P=0.185). Conclusions: FANCA gene is the main pathogenic gene in children with FA, where the detection of its exon deletion should be strengthened clinically. There were no phenotypic differences among children with different types of FANCA variants. Chromosome break test is helpful to determine the pathogenicity of variants, but its accuracy needs to be improved.
Male ; Female ; Humans ; Child ; Fanconi Anemia/genetics* ; Chromosome Breakage ; Retrospective Studies ; Exons ; China/epidemiology*