Spectrum of SLC20A2, PDGFRB, PDGFB, and XPR1 mutations in a large cohort of patients with primary familial brain calcification.

Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder with four causative genes (SLC20A2, PDGFRB, PDGFB, and XPR1) that have been identified. Here, we aim to describe the mutational spectrum of four causative genes in a series of 226 unrelated Chinese PFBC patients. Mutations in four causative genes were detected in 16.8% (38/226) of PFBC patients. SLC20A2 mutations accounted for 14.2% (32/226) of all patients. Mutations in the other three genes were relatively rare, accounting for 0.9% (2/226) of all patients, respectively. Clinically, 44.8% of genetically confirmed patients (probands and relatives) were considered symptomatic. The most frequent symptoms were chronic headache, followed by movement disorders and vertigo. Moreover, the total calcification score was significantly higher in the symptomatic group compared to the asymptomatic group. Functionally, we observed impaired phosphate transport induced by seven novel missense mutations in SLC20A2 and two novel mutations in XPR1. The mutation p.D164Y in XPR1 might result in low protein expression through an enhanced proteasome pathway. In conclusion, our study further confirms that mutations in SLC20A2 are the major cause of PFBC and provides additional evidence for the crucial roles of phosphate transport impairment in the pathogenies of PFBC.

Association of Apolipoprotein A1, B with Stenosis of Intracranial and Extracranial Arteries in Patients with Cerebral Infarction.

BACKGROUND: To investigate the distribution of stenosis of intracranial and extracranial arteries of Han population patients suffering from cerebral infarction in the city of Quanzhou in Fujian and to determine the correlation of apolipoprotein A1 and apolipoprotein B with intracranial and extracranial atherosclerosis stenosis. METHODS: For this study, we enrolled patients with cerebral infarction between December 2009 and October 2012 at the Neurology Department of The Second Affiliated Hospital of Fujian Medical University. All patients were examined by computed tomography angiography (CTA). Past medical history, demographic data, and biochemical markers were collected. Multiple logistic regression analysis was used to study the association between apo A1, apo B, and cerebral atherosclerosis stenosis. RESULTS: A total of 412 patients were included in this study. 137 cases (33.3%) were classified as the intracranial atherosclerosis stenosis (ICAS) group, 74 cases (18.0%) as the combined intracranial and extracranial atherosclerosis stenosis (COAS) group, 44 cases (0.7%) as the extracranial atherosclerosis stenosis (ECAS) group, and 157 cases (38.1%) as the non-cerebral atherosclerosis stenosis (NCAS) group. Middle cerebral arteries (43.8%) were the most common lesions of intracranial arterial atherosclerosis stenosis. Extracranial carotid stenosis (30.7%) were more likely to be stenoses in the extracranial internal carotid arteries. Compared with the NCAS group, apo B was significantly higher (p < 0.001), apo A1 was significantly lower in the ICAS group and COAS group (p = 0.02 and p = 0.030). Compared with the mild atherosclerosis stenosis group, apo B was higher in the severe extracranial atherosclerosis stenosis group (p = 0.03), apo A1 was lower in the severe intracranial atherosclerosis stenosis group (p < 0.001). The multiple logistic regression analyses showed that when apo A1 > 1.28 g/L, it was an independent protective factor of intracranial stenosis (OR, 0.39), apo B was an independent risk factor of the cerebral atherosclerosis stenosis group, and when apo B > 1.16, it is significantly associated with the cerebral atherosclerosis stenosis group (ICAS: OR, 6.41) (ECAS: OR, 5.15). CONCLUSIONS: 1. The occurrence of atherosclerosis stenosis in intracranial arteries is more frequent than that in extracranial arteries in population with cerebral infarction; 2. Apo B is an independent risk factor of intracranial and extracranial arterial stenosis, apo A1 is associated with the degree of intracranial stenosis and an independent protector of intracranial stenosis.

Exhausting T Cells During HIV Infection May Improve the Prognosis of Patients with COVID-19.

T-cell reduction is an important characteristic of coronavirus disease 2019 (COVID-19), and its immunopathology is a subject of debate. It may be due to the direct effect of the virus on T-cell exhaustion or indirectly due to T cells redistributing to the lungs. HIV/AIDS naturally served as a T-cell exhaustion disease model for recognizing how the immune system works in the course of COVID-19. In this study, we collected the clinical charts, T-lymphocyte analysis, and chest CT of HIV patients with laboratory-confirmed COVID-19 infection who were admitted to Jin Yin-tan Hospital (Wuhan, China). The median age of the 21 patients was 47 years [interquartile range (IQR) = 40-50 years] and the median CD4 T-cell count was 183 cells/µl (IQR = 96-289 cells/µl). Eleven HIV patients were in the non-AIDS stage and 10 were in the AIDS stage. Nine patients received antiretroviral treatment (ART) and 12 patients did not receive any treatment. Compared to the reported mortality rate (nearly 4%-10%) and severity rate (up to 20%-40%) among COVID-19 patients in hospital, a benign duration with 0% severity and mortality rates was shown by 21 HIV/AIDS patients. The severity rates of COVID-19 were comparable between non-AIDS (median CD4 = 287 cells/µl) and AIDS (median CD4 = 97 cells/µl) patients, despite some of the AIDS patients having baseline lung injury stimulated by HIV: 7 patients (33%) were mild (five in the non-AIDS group and two in the AIDS group) and 14 patients (67%) were moderate (six in the non-AIDS group and eight in the AIDS group). More importantly, we found that a reduction in T-cell number positively correlates with the serum levels of interleukin 6 (IL-6) and C-reactive protein (CRP), which is contrary to the reported findings on the immune response of COVID-19 patients (lower CD4 T-cell counts with higher levels of IL-6 and CRP). In HIV/AIDS, a compromised immune system with lower CD4 T-cell counts might waive the clinical symptoms and inflammatory responses, which suggests lymphocyte redistribution as an immunopathology leading to lymphopenia in COVID-19.

Effect of soil-rock system on speleothems weathering in Bailong Cave, Yunnan Province, China / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Bailong Cave with its well-developed Middle Triassic calcareous dolomite's system was opened as a show cave for visitors in 1988. The speleothem scenery has been strongly weathered as white powder on the outer layers. Study of the cave winds, permeability of soil-rock system and the chemical compositions of the dripping water indicated: (1) The cave dimension structure distinctively affects the cave winds, which were stronger at narrow places. (2) Based on the different soil grain size distribution, clay was the highest in composition in the soil. The response sense of dripping water to the rainwater percolation was slow. The density of joints and other openings in dolomite make the dolomite as mesh seepage body forming piles of thin and high columns and stalactites. (3) Study of 9 dripping water samples by HYDROWIN computer program showed that the major mineral in the water was dolomite.