Background: There are few studies investigating the relationship between serum vitamin B6 and mortality risk in the elderly. This study hereby evaluated the associations between biomarkers of serum vitamin B6 status and cardiovascular, cancer, and all-cause mortality risks in the elderly.Methods: Our study included a total of 4,881 participants aged 60 years or older from the National Health and Nutrition Examination Survey (NHANES) 2005-2010. Serum vitamin B6 status was estimated based on levels of pyridoxal 5’-phosphate (PLP), 4-pyridoxic acid (4-PA), and vitamin B6 turnover rate (4-PA/PLP) detected by high-performance liquid chromatography. Survival status and corresponding causes of death were matched through the National Death Index records through December 31, 2019. Multivariate Cox regression model was adopted to assess the relationships between serum vitamin B6 status and the risk of mortality.Results: During a median follow-up period of 10.33 years, 507 cardiovascular deaths, 426 cancer deaths, and 1995 all-cause deaths were recorded, respectively. In the multivariate-adjusted Cox model, the hazard ratios (HRs) and 95% confidence intervals (CIs) for the highest versus the lowest quartiles of PLP, 4-PA, and 4-PA/PLP were 0.70(0.54-0.90), 1.33(0.88-2.02), and 2.01(1.41-2.79) for cardiovascular mortality, 0.73(0.52-1.02), 1.05(0.71-1.57), and 1.95(1.25-3.05) for cancer mortality, and 0.62(0.53-0.74), 1.05(0.82-1.34), and 2.29(1.87-2.79) for all-cause mortality, respectively.Conclusion: Our study found that lower serum PLP levels were associated with increased risks of cardiovascular and all-cause mortality among the elderly population. And higher vitamin B6 turnover rate was associated with increased risks of cardiovascular, cancer, and all-cause mortality.

Environmental pollutants significantly impact health and quality of life. High levels of harmful metals in drinking water, vegetables, and soil can accumulate in the body, leading to serious health issues. In Gilgit-Baltistan, Pakistan, the prevalence of cancer is notably high, and heavy metals are considered among the possible risk factors. In this study, the distribution of heavy metals, e.g., Cd, Mn, Cu, Cr, and Ni, in the drinking water, vegetables, and soil in the Gilgit and Skardu Districts was assessed. A geo-accumulation index was combined with a deterministic technique to examine potential carcinogenic and non-carcinogenic impacts on human health. Cr and Ni levels in drinking water exceeded the permissible limits from both districts. Drinking water had a HQ > 1 for Cd, Cr, Ni, and Mn, posing significant non-carcinogenic health effects. The lifetime cancer risk (LCR) by drinking water for Cd, Cr, and Ni in Gilgit (0.0087, 0.55, and 0.0048) and Skardu (0.071, 0.21, and 0.014) indicated a considerable cancer risk (>1 × 10⁻⁴) for adults. The cancer risk for vegetable intake was observed within the safe limit, while LCR_ingetsion > LCR_dermal and LCR_inhalation for the soil samples in both regions. These findings highlight the need for regular monitoring, enhanced waste management, and advanced purification methods to reduce cancer risk, lower heavy metal contamination, and safeguard public health in the region.

Background: The congenital stationary night blindness (CSNB) affects the patients' dim light vision or dark adaption by impairing the normal function of retina. It is a clinically and genetically heterogeneous disorder and can be inherited in an X‐linked, autosomal dominant or autosomal recessive pattern. Several genetic alterations to the genes involved in visual signal transduction of photoreceptors and/or bipolar cells underlie its pathogenesis.Methods: In this study, we used Sanger sequencing and next‐generation sequencing (NGS)‐based gene panel screening to investigate a family of three patients with CSNB inherited in an apparent autosomal dominant pattern. We expected to find out the disease‐causing gene defects carried by this family.Results: We found that the patients in this family did not carry the RHO, GNAT1, or PDE6B mutation, but carried compound heterozygotes mutations of GRM6. Three deleterious GRM6 variants, p.Arg621Ter, p.Gly51Val, and p.Gly464Arg, were found to be co‐segregating with the disease, causing a pseudodominant inheritance of GRM6‐related autosomal recessive complete CSNB.Conclusion: This study presents a rare case of autosomal recessive CSNB (arCSNB) pseudodominant inheritance, which potentially leads us to expand our gene candidate list in future genetic testing for apparent dominant pedigrees. The discovery of the two novel likely pathogenic variants p.Gly51Val and p.Gly464Arg could broaden our knowledge about the genetics of CSNB and provide insights into the structure and function of the GRM6 protein.

Background: Hao-fountain syndrome (HAFOUS) is a neurodevelopmental syndrome characterized by global developmental and severe language delays, behavioral abnormalities (including autism), and mild dysmorphic impairment of intellectual development. It is a dominant genetic disease caused by USP7 gene (*602519) mutations on chromosome 16p13.2. So far, only 15 cases with 14 deleterious variants in the USP7 gene have been reported.Materials and methods: This study describes three unrelated patients with USP7 variants. Besides, we identified novel de novo heterozygous USP7 variants using trio-whole exome sequencing and verified by Sanger sequencing. Furthermore, clinical characteristics were evaluated by reviewing the medical records.Results: The three identified variants, i.e., one frameshift variant (c.247_250del, p.Glu83Argfs × 18) and two missense variants (c.992A > G, p.Tyr331Cys; c.835T > G, p.Leu279Val) are unreported. The predominant clinical manifestations of the three patients included: DD/ID; language impairment; abnormal behavior; abnormal brain magnetic resonance (dilation of lateral ventricles, dilation of Virchow-Robin spaces, dilated the third ventricle, abnormal cerebral white matter morphology in bilateral occipital lobes, hypodysplasia of the corpus callosum, arachnoid cyst, delayed myelination, and widened subarachnoid space); some also had facial abnormalities.Conclusion: In summary, DD/ID is the most prevalent clinical phenotype of HAFOUS, although some patients also exhibit language and behavioral abnormalities. For the first time in China, we identified three variants of the USP7 gene using whole-genome sequence data. This work expands the USP7 gene mutation spectrum and provides additional clinical data on the clinical phenotype of HAFOUS.