Novel missense mutation in VPS33B is associated with isolated low gamma‐glutamyltransferase cholestasis: Attenuated,incomplete phenotype of arthrogryposis,renal dysfunction,and cholestasis syndrome

The typical phenotype of arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome involves three cardinal symptoms as the name describes, harboring biallelic mutations on VPS33B or VIPAS39. Except for ARC syndrome, low gamma‐glutamyltransferase (GGT) cholestasis often implies hereditary hepatopathy of different severity; however, some remain undiagnosed. Several monogenic defects typically with multiorgan manifestations may only present liver dysfunction at times, such as DGUOK defect and AGL defect. Previously, four VPS33B mutated cases were reported without arthrogryposis, or with less severe symptoms and longer lifespan, indicating the possibility of incomplete ARC phenotype of isolated hepatopathy. So we retrospectively reviewed all patients with confirmed VPS33B/VIPARS39 defect in our center and identified three presenting isolated low‐GGT cholestasis with intractable pruritus. Distinguished from others with typical ARC phenotype, these patients did not suffer the other two typical characteristics, survived much longer, and shared a novel missense VPS33B variation c.1726T>C, p.Cys576Arg, causing declined protein expression and abolished interaction with VIPAS39 in‐vitro. Serum bile acid profiles of our VPS33B/VIPAS39 mutated patients revealed similar changes to primary defect of bile salt export pump, among which those with isolated cholestasis phenotype had a higher level of total secondary bile acids than that with typical ARC phenotype, indicating the partial residual function of VPS33B.     

Graphene oxide regulates cox2 in human embryonic kidney 293T cells via epigenetic mechanisms: dynamic chromosomal interactions

To extend the applications of engineered nanomaterials, such as graphene oxide (GO), it is necessary to minimize cytotoxicity. However, the mechanisms underlying this cytotoxicity are unclear. Dynamic chromosomal interactions have been used to illustrate the molecular bases of gene expression, which offers a more sensitive and cutting-edge technology to elucidate complex biological processes associated with epigenetic regulations. In this study, the role of GO-triggered chromatin interactions in the activation of cox2, a hallmark of inflammation, was investigated in normal human cells. Using chromosome conformation capture technology, we showed that GO triggers physical interactions between the downstream enhancer and the cox2 promoter in human embryonic kidney 293T (293T) via p65 and p300 complex-mediated dynamic chromatin looping, which was required for high cox2 expression. Moreover, tumor necrosis factor-α (TNF-α), located upstream of the p65 signaling pathway, contributed to the regulation of cox2 activation through dynamic chromatin architecture. Compared with pristine GO and aminated GO (GO-NH₂), poly (acrylic acid)-functionalized GO (GO-PAA) induced a weaker inflammatory response and a weaker effect on chromatin architecture. Our results mechanistically link GO-mediated chromatin interactions with the regulation of cox2 and suggest that GO derivatives may minimize toxicity in practical applications.     

辅助用药临床使用情况的调查与研究

【摘要】 目的：调查我院2014-2016年辅助用药临床使用现状,为临床合理使用辅助用药提供参考。方法：结合我院近3年收集、上报的545例精神科药品不良反应的数据,对2014-2016年期间我院病区辅助用药的使用DDDs、金额排名及B/A值进行统计分析。结果：非注射剂辅助用药DDDs排名居前的是盐酸苯海索、盐酸普萘洛尔、二甲双胍等,主要用以对抗精神科用药引起的ADR为主;注射剂辅助用药金额排名居前的是奥拉西坦、参芎葡萄糖、赖氨酸等,主要以神经营养类、活血化瘀类为主。结论：我院病区非注射剂类辅助用药基本合理,但注射剂类辅助用药存在超适应症、过度治疗等现象,需进一步加强管理,确保患者用药的安全、有效、合理。     

Physical Activity Patterns and Correlates of 9-Month-Old Chinese Infants in the Macau Population

Objectives Many obesity-related chronic diseases originate from unhealthy childhood habits. The aim of this study was to describe 9-month-old infants’ physical activity levels and patterns and to examine the correlates. Understanding these factors is necessary for improving the effectiveness of physical activity intervention programs for infants. Methods In total, 143 infant–mother dyads from Macau, SAR China, participated in this study. Physical activity (PA) was assessed by using the Actigraph GT3X+ accelerometer and the demographic variables were collected by questionnaires. Results The most important findings were that: (1) infants had more screen time during weekdays (p?=?.044); (2) infants and mothers were least active at 8 a.m. (both weekdays and weekends) in the morning and most active at 7 p.m. (weekdays) and 8 p.m. (weekends) in the evening; (3) infants’ PA levels significantly correlated with their mothers’ PA intensities during the weekends (r?=?.192, p?=?.036), especially the mothers’ lower intensities in the mornings and evenings; (4) maternal BMI predicted the PA levels of the 9-month-old infants’ (R²?=?.06, β?=?29.188, p?=?.009). Conclusions for Practice Physical activity promotion programs for infants should be time-specific starting from early infancy. This study was one of the first to examine 9-month-old infants’ PA levels, patterns and correlates. The results may be helpful in improving the effectiveness of future healthy lifestyle intervention programs for infants in Macau and in the region in general.     

Peripheral blood leukocyte telomere length is associated with age but not renal function: A cross-sectional follow-up study

Objectives

We aimed to evaluate the relationship between baseline renal function and changes in telomere length in Han Chinese.

Methods

The telomere restriction fragment (TRF) length of leukocytes in the peripheral blood was measured in healthy volunteers recruited in 2014. The estimated glomerular filtration rate (eGFR) was calculated based on serum creatinine (Scr) and serum cystatin C (CysC)-eGFRcys and eGFRScr-cys through the Cockcroft-Gault formula (eGFRC-G) or the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI / eGFRCKD-EPI) equation. The correlation between telomere length changes over time and renal function was analyzed.

Results

Leukocyte TRF lengths were negatively correlated to age (r = -0.393, p < 0.001) and serum CysC (r = -0.180, p < 0.01), while positively associated with eGFRCKD-EPI, eGFRC-G, eGFRcys, and eGFRScr-cys (r = 0.182, 0.122, 0.290, and 0.254 respectively, p < 0.01). The 3-year change of telomere length was 46 bp/years. When adjusted for age, the associations between telomere length changes and baseline, subsequent TRF lengths, and serum CysC were no longer present. No association was observed between TRF length changes and renal function.

Conclusion

The rate of telomere length changes was affected by age and baseline telomere length. The telomere length changes might be important markers for aging.