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Epilepsy is one of the most common disorders in children, with an incidence rate of approximately 5%. Although an increasing number of genes have been demonstrated to be pathogenic factors in epilepsy, evidence for a potential pathogenic role of ATP6V1A remains limited. Herein, the clinical and genetic data of a 5-year-old boy who experienced seizures at 9 months of age are collected. Genetic variants are screened using whole-exome sequencing (WES), and the effects of the candidate variants are further validated at both the RNA and protein levels. WES reveals a heterozygous variant [NM_001690.4: c .1132 C>T, p.Leu378Phe] of the ATP6V1A gene. This variant is not reported in the public database, but is predicted to be deleterious by multiple software packages, and classified as a variant of unknown significance following the American College of Medical Genetics and Genomics guidelines. Quantitative PCR and western blotting further confirm its down-regulatory role in both the RNA and protein expression of ATP6V1A. This case report confirms the pathogenicity of ATP6V1A in epilepsy with solid experimental evidence, thereby expanding the phenotype spectrum of ATP6V1A variants. More importantly, we show that seizures triggered by ATP6V1A variants could be controlled by Levetiracetam, crucially rescuing the development of the patient.
Subject(s)
Epilepsy , Vacuolar Proton-Translocating ATPases , Child, Preschool , Humans , Male , East Asian People , Epilepsy/genetics , Epilepsy/pathology , Mutation , Pedigree , RNA , Seizures , Vacuolar Proton-Translocating ATPases/genetics , InfantABSTRACT
Objective:To observe the recovery of exercise tolerance among stroke survivors using the cardiopulmonary exercise test (CPET) and analyze the factors influencing it.Methods:A total of 81 stroke survivors hospitalized in the Department of Rehabilitation Medicine of our hospital in year 2018 and 2019 were selected. The general clinical data of all patients were collected retrospectively and combined with the data from CPET to establish a data set. Version 25.0 of the SPSS software was used for multiple linear regressions analysis, with the peak oxygen uptake as the dependent variable, and the age, Brunnstrom stage, peak power, peak heart rate, peak respiratory exchange ratio, peak breathing reserve, peak ventilation per minute, the slope of the VE-VCO 2 curve (ΔVE/ΔVCO 2) and peak end tidal partial pressure of carbon dioxide as independent variables. Results:Stroke survivors at Brunnstrom stage III Ⅲ, Ⅳ and Ⅴ or higher decreased sequentially with their age, but their peak oxygen uptake increased gradually. The multiple linear regression model constructed by " stepwise method" showed that the fitted multiple linear regression equation was statistically significant ( F=100.228, P<0.001). Moreover, the average peak power, peak heart rate, peak ventilation per minute and the slope of the VE-VCO 2 curve were all found to be significant independent predictors of peak oxygen uptake in these stroke survivors. Conclusions:Skeletal muscle power, cardiac function, pulmonary ventilation and ventilation efficiency are useful independent predictors of the exercise tolerance of stroke survivors.
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BackgroundEffective therapies are urgently needed for the SARS-CoV-2 pandemic. Chloroquine has been proved to have antiviral effect against coronavirus in vitro. In this study, we aimed to assess the efficacy and safety of chloroquine with different doses in COVID-19. MethodIn this multicenter prospective observational study, we enrolled patients older than 18 years old with confirmed SARS-CoV-2 infection excluding critical cases from 12 hospitals in Guangdong and Hubei Provinces. Eligible patients received chloroquine phosphate 500mg, orally, once (half dose) or twice (full dose) daily. Patients treated with non-chloroquine therapy were included as historical controls. The primary endpoint is the time to undetectable viral RNA. Secondary outcomes include the proportion of patients with undetectable viral RNA by day 10 and 14, hospitalization time, duration of fever, and adverse events. ResultsA total of 197 patients completed chloroquine treatment, and 176 patients were included as historical controls. The median time to achieve an undetectable viral RNA was shorter in chloroquine than in non-chloroquine (absolute difference in medians -6.0 days; 95% CI -6.0 to -4.0). The duration of fever is shorter in chloroquine (geometric mean ratio 0.6; 95% CI 0.5 to 0.8). No serious adverse events were observed in the chloroquine group. Patients treated with half dose experienced lower rate of adverse events than with full dose. ConclusionsAlthough randomised trials are needed for further evaluation, this study provides evidence for safety and efficacy of chloroquine in COVID-19 and suggests that chloroquine can be a cost-effective therapy for combating 102 the COVID-19 pandemic.
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Objective To explore the proper and effective diagnostic strategies of diffuse sclerosing variant of papillary thyroid carcinoma.Methods Clinical data of 18 patients with diffuse sclerosing variant of papillary thyroid carcinoma who had been treated from September 2012 to September 2017 were analyzed retrospectively.Results The mean age of 18 patients was 28.5 years old,the ratio of man and woman was 1.0 to 3.5,and the neck mass (the thyroid gland diffusely enlarge) was the primary symptom of diffuse sclerosing variant of papillary thyroid carcinoma (89％,16/18);parts of patients with larger mass (3.2 to 4.5 cm) presented the sense of neck swelling (33％,6/18) or dysphagia (6％,1/18).Two patients (11％,2/18) presented hypothyroidism and hoarseness.The results of ultrasonography showed that the diffuse enlarged thyroid gland (89％,16/18),hypoechoic (78％,14/18),heterogeneous echogenicity (100％,18/18),diffuse microcalcification (89％,16/18),ill-defined tumor margin (100％,18/18) and the suspicious cervical lymph node (83％,15/18) were common features.CT scan showed that there were many suspicious cervical lymph nodes (100％,15/15).The results of fine needle aspiration cytology for the thyroid gland showed that all of the patients (100％,16/16) were diagnosed with papillary thyroid carcinoma,and cervical lymph node biopsy found lateral lymph node metastasis (100％,2/2).Postoperative pathological paraffin section indicated that most of the patients coexisted with Hashimoto thyroiditis (72％,13/18) and were found lymph node metastasis (central lymph node:89％,16/18;lateral lymph node:83％,15/18).Conclusions The young lady,the high rates of coexisting with Hashimoto thyroiditis,the diffuse enlarged thyroid gland,diffuse microcalcification and the suspicious cervical lymph node metastasis were the common features of ultrasonography in diffuse sclerosing variant of papillary thyroid carcinoma.The clinical features combined with the characteristics of ultrasonography and fine needle aspiration would be helpful for the early diagnosis and the surgery of diffuse sclerosing variant of papillary thyroid carcinoma.
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Objective To explore factors affecting diagnosis and treatment compliance in patients with gout leaving hospital,in order to provide a reference for late-stage clinical treatment.Methods 390 patients with gout treated in our hospital were selected from August 2012 to February 2016 for the study,all patients were followed up by telephone,their diagnosis and treatment compliance after discharge was investigated,and the factors affecting diagnosis and treatment compliance in gout patients after discharge investigated were,as well.Results The mean score of treatment adherence of 390 cases of gout patients after discharge was(3.93± 1.78) points.There were 117(30.00％) patients of which their score were ≥6 points for compliers,and 273 (70.00％) patients who do not comply with scores ＜6 points.Disease duration,education level,frequency of gout attacks,marital status and payment of medical expenses were closely related to diagnosis and treatment adherence(P＜0.05).Longer duration,low educational level,payment of medical expenses at their own expense were independent risk factors for poor adherence (P＜0.05).Conclusion We should strengthen the monitoring and follow-up of patients with gout who are with long duration of disease,low educational level,and pay medical expenses from their own pocke tinorder to improve patient diagnosis and treatment adherence,provide references for late-stage clinical treatment.
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Diffuse sclerosing variant papillary thyroid carcinoma,one of the variants of papillary thyroid carcinoma,nearly account for 0.7％ to 6.6％ of papillary thyroid carcinoma.It is an aggressive tumor that shows higher rates of recurrence,metastasis and persistent disease compares to classic papillary thyroid carcinoma,thus diffuse sclerosing variant papillary thyroid carcinoma needs stricter and more exhaustive operation.Since the incidence of diffuse sclerosing variant papillary thyroid carcinoma is low,many physicians lack of understanding of the disease,it's often missed diagnosis or misdiagnosed.Consequently.In order to let physicians understand more about diffuse sclerosing variant papillary thyroid carcinoma,this paper will elaborate the epidemiology,clinic and pathology features of it.
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Objective To explore the relationship between the level of serum Klotho with renal impairment in chronic kidney disease (CKD) patients. Methods 100 patients with CKD 1-5 stages (CKD group) and 30 non-CKD patients (control group) were enrolled. The serum of Klotho was detected by ELISA (enzyme-linked immunosorbent assay ) to investigate the correlation between the level of serum Klotho to progression of CKD. Results The levels of serum Klotho in CKD group 9.81 (7.45,12.2) ng/mL and control group 2.97 (1.75,5.23) ng/mL were significantly different (P < 0.01); The Klotho level declined as renal insufficiency progressed. Pearson correlation analysis showed that serum Klotho in CKD patients was positively correlated with eGFR (estimated glomerular filtration rate), blood calcium and hemoglobin,while was negatively correlated with phosphate, age, logserum creatinine, and logFGF-23. Multiple regression analysis showed age, logScr and logFGF-23 were independent factors for expression of serum Klotho in CKD patients. Conclusion Serum Klotho level in CKD patients decreased with the deterioration in renal function and serum Klotho maybe one of indicators to predict the progression of renal function in CKD patients.
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Hypoxia-inducible factor(HIF)is a pivotal transcription factor for hypoxic response.This article reviews the related characteristics of HIF-1 and its target genes vascular endothelial growth factor and the neuroprotective mechanisrms in cerebral ischemia.
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0.05).Compared with control group,the GK activity of liver cell,the expression of PEPCK and the expression of GLUT4 in model group decreased signifi cantly(P
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<p><b>OBJECTIVE</b>To establish a means for prenatal prediction of spinal muscular atrophy (SMA) through survival motor neuron (SMN) gene deletion analysis and genetic counseling in families with a child affected with SMA.</p><p><b>METHODS</b>Genetic analysis for prenatal prediction of Werdnig-Hoffmann disease was performed in a at risk Chinese family by polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) in SMN gene exons 7 and 8.</p><p><b>RESULTS</b>The pregnancy was positive for the homozygous deletion of the SMN gene, thus the fetus was diagnosed as being affected and the pregnancy was terminated.</p><p><b>CONCLUSION</b>This approach is fast and reliable for DNA-based prenatal diagnosis of Werdnig-Hoffmann disease.</p>