Changes in retinal and choroidal morphology after cerebrospinal fluid pressure reduction: a Beijing iCOP study

正Dear Editor,Glaucoma is a multifunctional neurodegenerative disease and is the leading cause of irreversible blindness. It is characterized by progressive loss of retinal ganglion cells and their axons leading to visual field defects. Two mechanisms of glaucomatous optic nerve damage have been     

Nanopore sequencing: a rapid solution for infectious disease epidemics

<正>Emerging and re-emerging infectious diseases have given rise to a large number of human infections, morbidity, and heavy economic burden, including the Middle East respiratory syndrome caused by a coronavirus in 2012, global influenza pandemic caused by the H7N9 influenza A virus in2013, Ebola epidemic in West Africa in 2014, and Lassa fever epidemic in Nigeria in 2019. The healthcare war against viruses deserves constant surveillance due to the continuous emergence of new viruses and rapid evolution of     

氰酸盐诱导氧化应激促进肾小管上皮细胞上皮–间充质转化

该研究探讨氰酸盐(cyanate)诱导肾小管上皮细胞氧化应激损伤和促进肾纤维化的作用。氰酸盐作用HK-2肾小管上皮细胞后, CCK8法检测其对细胞活力的影响;倒置显微镜观察细胞形态的改变; DCFH-DA法检测细胞ROS水平;细胞免疫荧光和Western blot分别检测E-cadherin、Fibronectin、α-SMA的表达; Western blot检测TGF-β的表达水平。结果显示, 2 mmol/L氰酸盐明显下调HK-2细胞的活力(P<0.05),细胞形态变为长梭形。氰酸盐作用24 h后, HK-2细胞内ROS水平呈浓度依赖性升高。免疫荧光和Western blot结果均显示,氰酸盐作用24 h后, HK-2的Fibronectin、α-SMA表达升高, E-cadherin表达下降; TGF-β的表达水平随氰酸盐浓度升高而上调(P<0.05)。以上结果表明,氰酸盐诱导肾小管上皮细胞产生过量ROS,上调TGF-β水平促进细胞上皮–间充质细胞转化(epithelia-mesenchymal transition, EMT)。     

Identification of a novel COL4A5 mutation in the proband initially diagnosed as IgAN from a Chinese family with X-linked Alport syndrome

Alport syndrome(AS) is a hereditary progressive nephropathy characterized by hematuria, ultrastructural lesions of the glomerular basement membrane, ocular lesions and sensorineural hearing loss. Germline mutations of COL4 A5 are associated with X-linked AS with an extreme phenotypic heterogeneity. Here, we investigated a Chinese family with Alport syndrome. The proband was a 9-year-old boy with hematuria and proteinuria. Based on the test results of renal biopsy and immunofluorescence,the proband was initially diagnosed as Ig A nephropathy and the treatment was recommended accordingly. Meanwhile, we found that the treatment outcome was poor. Therefore, for proper clinical diagnosis and appropriate treatment, targeted exome-based next-generation sequencing has been undertaken. We identified a novel hemizygous single nucleotide deletion c.1902 del A in COL4 A5 gene. Segregation analysis identified that this novel mutation is co-segregated among the affected family members but absent in unaffected family members. The clinical diagnosis of the proband was revised as AS accompanied by Ig A nephropathy,which has been rarely reported. Our findings demonstrated the significance of the application of Genetic screening, expanded the mutation spectrum of COL4 A5 associated AS patients with atypical renal phenotypes and provided a good lesson to be learned from our detour during the diagnosis.     

Doxorubicin‐induced cardiotoxicity is maturation dependent due to the shift from topoisomerase IIα to IIβ in human stem cell derived cardiomyocytes

Doxorubicin (DOX) is widely used to treat various cancers affecting adults and children; however, its clinical application is limited by its cardiotoxicity. Previous studies have shown that children are more susceptible to the cardiotoxic effects of DOX than adults, which may be related to different maturity levels of cardiomyocyte, but the underlying mechanisms are not fully understood. Moreover, researchers investigating DOX‐induced cardiotoxicity caused by human‐induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs) have shown that dexrazoxane, the recognized cardioprotective drug for treating DOX‐induced cardiotoxicity, does not alleviate the toxicity of DOX on hiPSC‐CMs cultured for 30 days. We have suggested that this may be ascribed to the immaturity of the 30 days hiPSC‐CMs. In this study, we investigated the mechanisms of DOX induced cardiotoxicity in cardiomyocytes of different maturity. We selected 30‐day‐old and 60‐day‐old hiPSC‐CMs (day 30 and day 60 groups), which we term ‘immature’ and ‘relatively mature’ hiPSC‐CMs, respectively. The day 30 CMs were found to be more susceptible to DOX than the day 60 CMs. DOX leads to more ROS (reactive oxygen species) production in the day 60 CMs than in the relatively immature group due to increased mitochondria number. Moreover, the day 60 CMs mainly expressed topoisomerase IIβ presented less severe DNA damage, whereas the day 30 CMs dominantly expressed topoisomerase IIα exhibited much more severe DNA damage. These results suggest that immature cardiomyocytes are more sensitive to DOX as a result of a higher concentration of topoisomerase IIα, which leads to more DNA damage.     

Circulating serum vitamin D levels and total body bone mineral density: A Mendelian randomization study

Until recently, randomized controlled trials have not demonstrated convincing evidence that vitamin D, or vitamin D in combination with calcium supplementation could improve bone mineral density (BMD), osteoporosis and fracture. It remains unclear whether vitamin D levels are causally associated with total body BMD. Here, we performed a Mendelian randomization study to investigate the association of vitamin D levels with total body BMD using a large‐scale vitamin D genome‐wide association study (GWAS) dataset (including 79 366 individuals) and a large‐scale total body BMD GWAS dataset (including 66,628 individuals). We selected three Mendelian randomization methods including inverse‐variance weighted meta‐analysis (IVW), weighted median regression and MR‐Egger regression. All these three methods did not show statistically significant association of genetically increased vitamin D levels with total body BMD. Importantly, our findings are consistent with recent randomized clinical trials and Mendelian randomization study. In summary, we provide genetic evidence that increased vitamin D levels could not improve BMD in the general population. Hence, vitamin D supplementation alone may not be associated with reduced fracture incidence among community‐dwelling adults without known vitamin D deficiency, osteoporosis, or prior fracture.