Leber hereditary optic neuropathy and dystonia overlapping mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes due to m.14459G>A mutation

Neurological Sciences - To report a Chinese family with combined m.14459G>A mutation and m.6064A>T mutation of which the female proband presenting unique Leber hereditary optic...     

Effects of intracerebral hemorrhage and subsequent minimally invasive hematoma aspiration on expression of apoptosisrelated genes in rats

This study was to investigate the effects of intracerebral hemorrhage (ICH) and subsequent minimally invasive hematoma aspiration on the expression of apoptosis-related genes in rats. IV-collagenase was injected to the caudate nucleus of the rats to make ICH models. In the control group, 30 Sprague-Dawley (SD) rats were mock treated with saline instead of collagenase. Thirty SD rats with successful modeling were designated as the ICH group. Twenty-five SD rats with successful modeling and subsequent minimally invasive hematoma aspiration were designated as the therapy group. Expression of heat shock protein 70 (Hsp70), B-cell leukemia/lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) in the brain tissues was detected by immunohistochemical assays. The expression of Hsp70, Bcl-2 and Bax in the control group was very low, and significantly increased in the ICH group and the therapy group. At each indicated time point, Hsp70 expression in the therapy group was significantly lower than that of the ICH group, Bax expression in the therapy group was significantly lower than that of the ICH group and Bcl-2 expression in the therapy group was significantly higher than that of the ICH group. These results suggest that ICH led to increased expression of apoptosis-related genes in the brain tissues. Hematoma aspiration up-regulated ICH induced Bcl-2 expression while down-regulated ICH induced Hsp70 and Bax expression.     

Vascular Risk Factor Burden,Atherosclerosis, and Functional Dependence in Old Age: A Population-Based Study

Background

Vascular risk factors such as hypertension and obesity have been associated with physical limitations among older adults.

Purpose

The purpose of this study is to examine whether individual and aggregated vascular risk factors (VRFs) are associated with functional dependence and to what extent carotid atherosclerosis (CAS) or peripheral artery disease (PAD) may mediate the possible associations of aggregated VRFs with functional dependence.

Method

This cross-sectional study included 1,451 community-living participants aged ≥60 years in the Confucius Hometown Aging Project of China. Data on demographic features, hypertension, high total cholesterol, obesity, smoking, physical inactivity, diabetes, CAS, PAD, and cardiovascular diseases (CVDs) were collected through an interview, a clinical examination, and laboratory tests. Functional dependence was defined as being dependent in at least one activity in the personal or instrumental activities of daily living. Data were analyzed using multiple logistic models controlling for potential confounders. We used the mediation model to explore the potential mediating effect of CAS and PAD on the associations of aggregated VRFs with functional dependence.

Results

Of the 1,451 participants, 222 (15.3 %) had functional dependence. The likelihood of functional dependence increased linearly with increasing number of VRFs (hypertension, high total cholesterol, abdominal obesity, and physical inactivity) (p for trend <0.002). Mediation analysis showed that controlling for demographics and CVDs up to 11 % of the total association of functional dependence with clustering VRFs was mediated by CAS and PAD.

Conclusion

Aggregation of multiple VRFs is associated with an increased likelihood of functional dependence among Chinese older adults; the association is partially mediated by carotid and peripheral artery atherosclerosis independently of CVDs.     

Novel PANK2 gene mutations in two Chinese siblings with atypical pantothenate kinase-associated neurodegeneration

Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal-recessive disorder characterized by neurodegeneration and iron accumulation in the brain. Classic and atypical PKAN are distinguished on the basis of age at onset and disease progression. PANK2, localized on chromosome20p13, is confirmed as the responsible gene. We report two Chinese siblings with atypical PKAN, who had a 26- and 24-year disease course, respectively. Brain MRI scans of the two siblings showed the specific “eye of the tiger” sign. Genetic analysis identified novel compound heterozygous mutations (IVS1-2 A>T, c.T1130C) in PANK2 gene, which were confirmed to be deleterious. We verify the clinical heterogeneity even in siblings with identical genotype and expand the gene mutation pool for PKAN.     

Anti-HMGCR myopathy overlaps with dermatomyositis-like rash: a distinct subtype of idiopathic inflammatory myopathy

Journal of Neurology - To characterize the clinical and pathological features of anti-HMGCR myopathy. The presence of anti-HMGCR antibody in the serum of 227 patients with idiopathic inflammatory...     

MERRF/MELAS overlap syndrome due to the m.3291T>C mutation

We report the case of a 19-year-old Chinese female harboring the m.3291T>C mutation in the MT-TL1 gene encoding the mitochondrial transfer RNA for leucine. She presented with a complex phenotype characterized by progressive cerebellar ataxia, frequent myoclonus seizures, recurrent stroke-like episodes, migraine-like headaches with nausea and vomiting, and elevated resting lactate blood level. It is known that the myoclonus epilepsy with ragged-red fibers (MERRF) is characterized by cerebellar ataxia and myoclonus epilepsy, while that the mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is characterized by recurrent stroke-like episodes, migraine-like headaches, and elevated resting lactate blood level. So the patient’s clinical manifestations suggest the presence of a MERRF/MELAS overlap syndrome. Muscle biopsy of the patient showed the presence of numerous scattered ragged-red fibers, some cytochrome c oxidase-deficient fibers, and several strongly succinate dehygrogenase-reactive vessels, suggestive of a mitochondrial disorder. Direct sequencing of the complete mitochondrial genome of the proband revealed no mutations other than the T-to-C transition at nucleotide position 3291. Restriction fragment length polymorphism analysis of the proband and her family revealed maternal inheritance of the mutation in a heteroplasmic manner. The analysis of aerobic respiration and glycolysis demonstrated that the fibroblasts from the patient had mitochondrial dysfunction. Our results suggest that the m.3291T>C is pathogenic. This study is the first to describe the m.3291T>C mutation in association with the MERRF/MELAS overlap syndrome.     

Residents’ Willingness to Maintain Contracts with Family Doctors: a Cross-sectional Study in China

BackgroundMost previous studies of the family doctor contract services (FDCS) evaluated its quality by using residents’ signing rates, awareness, and satisfaction. We hypothesize that renewal willingness could be another important indicator to examine the quality of FDCS.ObjectiveTo measure residents’ willingness to maintain contracts with family doctors and examine the influencing factors.DesignCross-sectional study.Participants11,250 residents in 31 provincial administrative regions across China.Main MethodsA multistage stratified random sampling method was used to recruit participants. Univariate analysis, mixed-effect regression model analysis, and stepwise multivariate logistic regression analysis were performed to determine the influencing factors of residents’ willingness to maintain contracts with family doctors.Key ResultsAbout 71.3% participants who contracted with and received healthcare services from family doctors were willing to maintain contracts with family doctors in China. Residents registering as local households (OR = 1.192, 95% CI = 1.039–1.368), enrolled in medical insurance (OR = 1.299, 95% CI = 1.011–1.668), reporting better health (OR = 1.246, 95% CI = 1.100–1.413), with shorter walking time to the nearest healthcare center (compared with > 30 min walking time, < 15 min: OR = 1.209, 95% CI = 1.003–1.458; 15–30 min: OR = 1.288, 95% CI = 1.124–1.475), and trusting in (OR = 4.403, 95% CI = 3.849–5.036) and satisfied with (OR = 18.514, 95% CI = 16.195–21.165) their family doctors had significantly higher willingness to maintain contracts with family doctors.ConclusionsResidents’ willingness to maintain contracts with family doctors could be another evaluation indicator of the quality of FDCS in China. Improving the accessibility and quality of healthcare services from family doctors may increase residents’ willingness to keep contracts with family doctors and promote the implementation of FDCS.Supplementary InformationThe online version of this article (10.1007/s11606-020-06306-y) contains supplementary material, which is available to authorized users.KEY WORDS: renewal willingness, family practice, family doctor contract service, influencing factors, Chinese     

Nicotine-induced chondrogenic differentiation of human bone marrow stromal cells in vitro

Purpose

Nicotine has been reported that it has a dose-dependent effect on matrix mineralization by human bone marrow cells. However, there is no relevant research concerning on chondrogenic differentiation potential of bone marrow stromal stem cells (BMSCs) treated with nicotine in vitro. The aims of the study were to examine the effects of nicotine (0, 10^?7, 10^?6 and 10^?5 M) on the proliferation and chondrogenic differentiation of BMSCs from three healthy donors in vitro.

Methods

BMSCs proliferation was analyzed by CCK8 assay and real-time polymerase chain reaction was used to assay the expression of type II collagen, aggrecan, type I collagen and type X collagen. The proteoglycan content was stained by Alcian blue, and the sulfated glycosaminoglycan (sGAG) content of BMSCs was quantified spectrofluorometrically using dimethylmethylene blue.

Results

The cell viability was not significantly impaired until up to a concentration of 10^?5 M nicotine. Nicotine promoted the proliferation and enhanced the expression of type II collagen at the level up to 10^?6 M (P < 0.05). The expression of aggrecan was reduced at the concentration of 10^?5 M nicotine at day 14 (P < 0.05), and there was no significant difference in aggrecan gene expression at 10^?7 and 10^?6 M nicotine levels compared to control group (n.s.). Also the fibroblastic and hypertrophic gene expressions were down-regulated in the chondrogenic medium with 10^?7–10^?5 M nicotine (P < 0.05).

Conclusion

It was implied that local application of nicotine at an appropriate concentration may be a promising approach for enhancing chondrogenic differentiation capacity of BMSCs in cell-based cartilage tissue engineering. Also these results indicate that nicotine maybe a potentially useful drug for the treatment of Osteoarthritis.     

遗传性成人近端型脊肌萎缩症（附3个家系分析及肌肉病理组化观察）

报告３个家系１８例成人近端型脊肌萎缩症，其中２个家系为常染色体显性遗传，另一家系的遗传方式无法确定。３个先证者肌活检病理组化观察发现，肌萎缩以Ⅱ型纤维为主，伴Ⅰ型纤维优势，同型肌群化及靶纤维少见，Ⅰ型纤维内肌膜下线粒体增多，这可能与肌纤维功能代偿时能量代谢活跃有关