Next generation sequencing of RB1gene for the molecular diagnosis of ethnic minority with retinoblastoma in Yunnan.

BACKGROUND: Retinoblastoma is a rare intraocular malignancy and typically initiated by inactivating biallelic mutations of RB1 gene. Each year, ~ 8000 children worldwide are diagnosed for retinoblastoma. In high-income countries, patient survival is over 95% while low-income countries is ~ 30%.If disease is diagnosed early and treated in centers specializing in retinoblastoma, the survival might exceed 95% and many eyes could be safely treated and support a lifetime of good vision. In China, approximate 1100 newly diagnosed cases are expected annually and 28 hospitals covering 25 provinces established centers classified by expertise and resources for better treatment options and follow-up. Comparing with other province of eastern China, Yunnan province is remote geographically. This might result that healthcare staff have low awareness of the role of genetic testing in management and screening in families. METHODS: The patients with retinoblastoma were selected in Yunnan. DNA from blood was used for targeted gene sequencing. Then, an in-house bioinformatics pipeline was done to detect both single nucleotide variants and small insertions/deletions. The pathogenic mutations were identified and further confirmed by conventional methods and cosegregation in families. RESULTS: Using our approach, targeted next generation sequencing was used to detect the mutation of these 12 probands. Bioinformatic predictions showed that nine mutations were found in our study and four were novel pathogenic variants in these nine mutations. CONCLUSIONS: It's the first report to describe RB1 mutations in Yunnan children with retinoblastoma. This study would improve role of genetic testing for management and family screening.

Applicability of a filter paper method to measure blood lead levels in large populations of Chinese children.

BACKGROUND: Capillary filter paper can be useful for screening blood lead concentrations in large populations of geographically dispersed Chinese children. METHODS: A total of 159 at 0-6 years of age were enrolled in the study when they came for routine pediatric care. Paired venous and capillary filter paper samples were collected from all subjects. Graphite furnace atomic absorption spectrophotometry was used to measure blood lead concentrations. Comparability of the lead assay methods was assessed. The concordance coefficient between these two methods was 0.87 (p < 0.01). The values of blood lead concentrations measured by the different methods were comparable statistically. The sensitivity of the filter paper method was 85%, 73% and 75%; specificity was 92%, 99% and 100%; the positive predictive value was 86%, 89% and 100%, and negative predictive value was 91%, 98% and 99% at cut-offs of 10, 15 and 20 microg/dl, respectively. The Youden's index was 77, 71 and 75 at those cut-offs. Values obtained via the filter paper method appeared to be relatively stable up to 4 weeks post-collection. CONCLUSIONS: The filter paper method for lead determinations has a sufficiently high sensitivity and specificity and correlates well with venous sampling. The ease with which this technique can be performed and screened samples can be sent to a centralized laboratory by regular mail indicates that it is a promising and attractive reference method, particularly in large populations of widely dispersed young children in China and other countries.

5,7,3'-Triacetyl hesperetin suppresses adjuvant-induced arthritis in rats through modulating JAK2/STAT3 pathway.

This work was designed to identify the effect of 5,7,3'-triacetyl hesperetin (TAHP) on rat adjuvant arthritis (AA) and further clarify the possible role of TAHP on modulating Janus kinase signal transducers and activators (JAK/STAT in this process. Freund's complete adjuvant was used to induce AA in rats. TAHP (33, 66, 132 mg/kg) was administered intragastrically. Secondary paw swelling, polyarthritis index, index of immune organs and histopathological assessment were used to evaluate the effects of TAHP on AA in rats. IL-6 in serum and in synovial tissues was examined with ELISA and RT-PCR. In addition, JAK2/STAT3 pathway-related key molecules mRNA expression in synovial tissues of AA rats were detected by RT-PCR and western blot respectively. It was found that TAHP (66, 132 mg/kg) could significantly inhibit secondary paw swelling, restore the index of immune organs and reduce polyarthritis index. Results of histopathological assessment showed that TAHP clearly ameliorated the pathological changes in AA rats. TAHP could downregulate the level of IL-6 in serum and in synovial tissues of AA rats. Besides, treatment with TAHP could decrease mRNA expressions of STAT3 and JAK2, as well as the ratio of p-JAK2/JAK2 protein and p-STAT3/STAT3 protein from synovial tissues. Thus, the paper demonstrated that TAHP had a therapeutic effect on AA in rats and the mechanisms were partly associated with modulating proinflammatory cytokine IL-6 production in serum and in synovial tissues and inhibiting excessive activation of JAK2/STAT3 signaling pathway which might play a crucial role in the pathogenesis of AA.