Background and purpose:Tetrandrine is a natural compound whose role in retinoblastoma remains unclear. This study investigated the effects of tetrandrine (Tet) on human retinoblastoma cells.Methods:CCK-8 assays were performed to analyze the effects of Tet on viability of retinoblastoma cells. The apoptosis rate was determined by Annexin V/PI assays. After staining with 2′,7′-dichlorolfuorescin diacetate (DCFH-DA), cellular reactive oxygen species (ROS) was measured by lfow cytometry. Akt and p-Akt were detected by Western blot.Results:Tet inhibited cell viability of retinoblastoma cells. After treatment with Tet (4, 8, 10 and 20μmol/L) for 24h, cell viability inhibition rates of WERI-Rb-I were 5.7%, 25.0%, 55.1% and 84.9%, whereas inhibition rates of Y79 cells were 2.4%,2.9%, 23.8% and 54.2% (P<0.01). In cells treated with 10μmol/L of Tet for 12, 24 and 48 h, cell viability inhibition rates of WERI-Rb-I were 6.0%, 45.5% and 74.7%, whereas inhibition rates of Y79 cells were 2.9%, 19.4% and 43.3% (P<0.01). Tet induced retinoblastoma cell apoptosis. After treatment with Tet (10 μmol/L) for 24 and 48 h, apoptosis rates of WERI-Rb-I were (23.70±1.75)% and (34.83±3.15)%, respectively, whereas apoptosis rates of Y79 cells were (9.62±2.69)% and (14.97±1.50)%, respectively (P<0.01). Apoptosis inhibitor Z-VAD-FMK attenuated Tet-induced cell death (P<0.05). ROS levels were indeed increased in cells treated with Tet (10 μmol/L) for 6 and 12 h (P<0.01), while N-Acetyl-L-cysteine (NAC) decreased Tet-induced ROS (P<0.01). After ROS was inhibited by NAC, apoptosis rate was decreased compared with the control (P<0.01). Further study indicated that Tet inhibited PI3K/Akt pathway in retinoblastoma cells.Conclusion:Tet induces cell apoptosis via increasing ROS synthesis and inhibiting PI3K/Akt pathway.

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with congenital cataracts. METHODS: Clinical data and peripheral blood samples were collected for the pedigree. Following extraction of genomic DNA, whole exome sequencing was carried out to detect genetic variants. Candidate variants were verified by familial co-segregation analysis and Sanger sequencing. Bioinformatics analysis was carried out to predict the function of mutant genes. RESULTS: By comparing variants identified among affected and unaffected individuals, a heterozygous variant, c.110 G>C (p.R37P), was identified in exon 2 of the CRYGC gene among all patients, which also matched the criteria for potential disease-causing mutations. The result was confirmed by Sanger sequencing. CONCLUSION The c.110G>C variant of the CRYGC gene probably underlay the congenital cataracts in this pedigree.
Asian Continental Ancestry Group ; Cataract ; congenital ; genetics ; China ; Heterozygote ; Humans ; Mutation ; Pedigree ; gamma-Crystallins ; genetics

OBJECTIVE: To screen for mutations of fragile X mental retardation 1 (FMR1) gene during early and middle pregnancy and provide prenatal diagnosis for those carrying high-risk CGG trinucleotide expansions. METHODS: Peripheral blood samples of 2316 pregnant women at 12 to 21(+6) gestational weeks were collected for the extraction of genomic DNA. CGG repeats of the FMR1 gene were detected by fluorescence PCR and capillary electrophoresis. Genetic counseling and prenatal diagnosis were provided for 3 women carrying the premutations. RESULTS: The carrier rate of CGG repeats of the FMR1 gene was 1 in 178 for the intermediate type and 1 in 772 for the premutation types. The highest frequency allele of CGG was 29 repeats, which accounted for 49.29%, followed by 30 repeats (28.56%) and 36 repeats (8.83%). In case 1, the fetus had a karyotype of 45,X, in addition with premutation type of CGG expansion of the FMR1 gene. Following genetic counseling, the couple chose to terminate the pregnancy through induced labor. The numbers of CGG repeats were respectively 70/- and 29/30 for the husband and wife. In case 2, amniocentesis was performed at 20 weeks of gestation. The number of CGG repeats of the FMR1 gene was 29/-. No abnormality was found in the fetal karyotype and chromosomal copy number variations. The couple chose to continue with the pregnancy. Case 3 refused prenatal diagnosis after genetic counseling and gave birth to a girl at full term, who had a birth weight of 2440 g and no obvious abnormality found during follow-up. CONCLUSION Pregnant women should be screened for FMR1 gene mutations during early and middle pregnancy, and those with high-risk CGG expansions should undergo prenatal diagnosis, genetic counseling and family study.
DNA Copy Number Variations ; Female ; Fragile X Mental Retardation Protein/genetics* ; Fragile X Syndrome/genetics* ; Genetic Counseling ; Humans ; Mutation ; Pregnancy ; Trinucleotide Repeat Expansion ; Trinucleotide Repeats

Objective:To investigate the influencing factors of goiter in school-age children aged 8 to 10 in non-high iodine areas of Shijiazhuang City.Methods:In April 2018, 9 non-high iodine counties (cities) were selected as monitoring sites in Shijiazhuang City, and capacity proportional probability sampling (PPS) method was used. Each monitoring site was divided into five sampling areas according to five orientations: east, west, south, north, and middle, one township was selected from each area, one elementary school was selected from each township, and 40 school-age children aged 8 to 10 (balanced age, half males and half females) were selected from each school as respondents. Urine samples from any one time of children and drinking water samples from their village were collected, and urinary iodine and water iodine were detected by arsenic cerium catalytic spectrophotometry; the thyroid volume of children was measured by B ultrasound method; at the same time, the height and weight of children were measured and the body mass index was calculated. The influencing factors of goiter were analyzed by logistic regression analysis.Results:A total of 1 867 urine samples of school-age children were collected, and the median urinary iodine was 190.65 &mu;g/L, which was in the suitable level of iodine. A total of 1 046 drinking water samples were collected, water iodine ranged from 0.11 to 87.91 &mu;g/L, and the median water iodine was 3.01 &mu;g/L. A total of 1 867 school-age children were tested thyroid, the median thyroid volume was 3.01 ml. The medians thyroid volume of boys and girls (928 and 939 cases) were 2.90 and 3.13 ml, respectively, the difference was statistically significant between sex ( U = 2.09, P < 0.05); the medians thyroid volume of children aged 8, 9, and 10 years old (622, 629, 616 cases) were 2.47, 2.87, and 3.13 ml, respectively, the differences were statistically significant among ages ( H = 203.96, P < 0.01); the medians thyroid volume of normal, overweight and obese children (1 231, 300, 336 cases) were 2.61, 3.05 and 3.16 ml, respectively, the differences were statistically significant among body mass index ( H = 65.55, P < 0.01). The results of multifactorial logistic regression analysis showed that female and obesity were risk factors of goiter in school-age children [odds ratio ( OR) = 2.08, 2.86, 95% confidence interval ( CI): 1.05 - 4.12, 1.39 - 5.88, P < 0.05]. Conclusion:Female and obesity are risk factors of goiter in school-age children aged 8 to 10 in non-high iodine areas of Shijiazhuang City.

OBJECTIVETo analyze mutations of SLC26A4 gene and explore their origins for a patient with enlarge vestibuar aqueduct syndrome.

METHODSClinical data and peripheral venous blood samples were collected from the patient and her parents. Genome DNA was extracted from the peripheral blood. All of the 21 exons of the SLC26A4 gene were amplified with PCR and subjected to directly sequencing.

RESULTSThe patient was found to have carried two mutant alleles of the SLC26A4 gene, namely c.1522A to G and c.1229C to T, which were inherited from her father and mother, respectively.

CONCLUSIONSLC26A4 c.1522A to G is likely to be a pathogenic mutation. Above results may facilitate genetic counseling and prenatal diagnosis for this family.

Adult ; Amino Acid Sequence ; Child ; Exons ; Female ; Hearing Loss, Sensorineural ; genetics ; Humans ; Male ; Membrane Transport Proteins ; genetics ; Molecular Sequence Data ; Pedigree ; Vestibular Aqueduct ; abnormalities