Objective To investigate the NOTCH3 gene mutation and clinical features in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) families.Methods The clinical features of 4 CADASIL probands in Henan,China were analyzed retrospectively,and the incidences of other members in their families were investigated.The NOTCH3 gene mutations in the 3rd,4th,llth,and 18th exons were detected and the results were analyzed in the patients and some family members.Results Gene sequencing showed that 6 patients in 4 families and 1 mutant carrier had NOTCH3 gene R607C mutation in exon llth,they all met the clinical features of CADASIL.Three patients accompanied with vascular risk factors.The clinical stroke patients had unilateral limb weakness.All 5 patients with complete head MRIdata had thalamic infarction.Conclusions In the 4 CADASIL families of R607C mutation,the clinical features of 6 patients with CADASIL were similar,but there were individual differences in different family members.Imaging examination has important role in the diagnosis of CADASIL.The vascular risk factors,such as hyperte.

Objective To analyze the clinical, imaging characteristics and NOTCH3 mutations of cerebral autosomal dominant arteriopathy with the subcortical infarcts and leukoencephalopathy (CADASIL) in Henan, China.Methods CADASIL patients diagnosed by gene or biopsy in People′s Hospital of Zhengzhou University between 2012-2016 were recruited.Clinical and imaging features of these patients were analyzed retrospectively.The distribution of NOTCH3 gene mutations hotspots was described in Henan region at the same time.Results There were 37 patients from 19 families who were diagnosed as CADASIL by genetic testing or biopsy, 27 of whom had symptoms of CADASIL.Two families were confirmed by pathological examination and 17 by genetic testing.Of these 17 families, 13 mutations were found.Mutations in exon 11 were found in eight families, in exon 4 were detected in four families, and in exon 13 were found in two families.Mutation in exons 3, 8 and 20 was detected in one family respectively.Most patients presented with stroke and several presented with cognitive decline.Twelve patients had been attacked by risk factors.Magnetic resonance imaging (MRI) was performed on 22 patients.White-matter lesions were distributed in brain stem, basal ganglia, subcortical, temporal pole, external capsule.There were 19 patients with white-matter lesions in temporal pole and seven in capsula externa, showed as a high signal in T2WI.Conclusions CADASIL patients can be associated with risk factors.T2WI hyperintensities in the anterior temporal lobe were more common than that in the capsular external.Exon 11 and exon 4 were the hotspots for the NOTCH3 mutation in Henan patients.

Objective: To analyze the clinical data of a family with early-onset familial Alzheimer′s disease and to analyze the mutation of the pathogenic gene in the family. Methods: The clinical data of a proband who was clinically diagnosed as early-onset Alzheimer′s disease in the Department of Neurology, People′s Hospital of Zhengzhou University in October 2018 and her family members were collected. Moreover, whole exome sequencing was performed on blood sample from the proband, then its deleterious effects were assessed according to the Standards and guidelines for the interpretation of sequence variants, a joint consensus recommendation of the American College of Medical Genomics. Subsequently, the strong pathogenic mutation was validated by Sanger sequencing in the some members of the family and 50 sporadic Alzheimer′s disease and 50 normal individuals of the family. Apolipoprotein E (APOE) typing of 10 family members was all epsilon 3/epsilon 3. Results: The proband in this family showed decreased memory, visual space disorder, verbal repetition, personality change and abnormal mental behavior. The mutation at codon 717 of exon 17 of the proband amyloid precursor protein gene was detected by gene detection. The mutation at codon 717 of exon 17 of the proband beta-amyloid precursor protein gene was also found in the other five members of the family. The mutation was not found in 50 sporadic Alzheimer′s disease patients and 50 normal individuals outside the family. The proband′s head magnetic resonance imaging (MRI) showed bilateral hippocampal atrophy on plain scan, especially on the left side. No obvious abnormality was found in the head magnetic resonance angiography. The head MRI of the proband′s sister showed brain atrophy and bilateral hippocampal atrophy. Conclusions The study identified the pathogenic mutation of the beta-amyloid precursor protein gene p.V717I in six patients of a family with early-onset familial Alzheimer′s disease, and the mutation showed a phenomenon of family segregation. This finding is of great significance to the study of early-onset Alzheimer′s disease in Chinese population.

Objective To investigate the clinical manifestations,imaging features,molecular genetic characteristics and possible pathogenic mechanisms of hereditary cerebral small vessel disease (CSVD) caused by heterozygous mutation of HtrA serine protease-1 (HTRA1) gene.Methods The clinical data of a Chinese Han family with CSVD carrying a heterozygous mutation of HTRA 1 gene,which came from the Department of Neurology,Henan Provincial People's Hospital in March 2018,were analyzed retrospectively.The clinical and radiographic features were summarized.Several high-throughput whole exon high-throughput sequencing was used to capture the mutation sites and the Sanger sequencing was used to validate the results.The family diagram was drawn and the 3D model construction and mutation function prediction were performed using silico tools.The relevant literature was reviewed and the pathogenesis was explored.Results The pedigree map showed that the family had an autosomal dominant inheritance pattern.Three generations of the family were investigated,and three family members in the same generation suffered from the disease.The first symptom of the proband was diplopia at the age of 39,accompanied by recurrent stroke,cognitive impairment and mood disorders,without alopecia.Head magnetic resonance imaging revealed bilateral diffuse,symmetric lesions,multiple lacunar infarcts,perivascular space,and microbleeds.The elder sister of the proband developed symptoms of left limb weakness at the age of 46,whose other clinical and imaging features were similar to those of the proband.The proband's mother died at the age of 59 due to repeated strokes.Whole exon sequencing indicated heterozygous missense mutation at c.821G＞A locus of HTRA1 gene in the proband and her 4th elder sibling,which was a new pathogenic mutation after consulting several mutation sites of databases.Function prediction suggested pathogenicity.Conclusions The heterozygous mutation of c.821G＞A in HTRA1 gene may lead to autosomal dominant CVSD.This genetic type should be given clinical attention.

Objective:To evaluate the performance of three antibody kits for novel coronavirus (SARS-CoV-2) and to investigate the feasibility and advantages of them in clinical application.Methods:A total of 104 patients who were admitted to Guangzhou Eighth People′s Hospital with COVID-19 from January to February 2020 were selected as research group. Fifty-one healthy subjects were selected during the same period as negative control group. Serum antibodies (IgM/IgG) against SARS-CoV-2 were detected using two kinds of colloidal gold kits (A and B kits) and one chemiluminescence kit (C kit). The positive rates of SARS-CoV-2 nucleic acid in different samples from patients with COVID-19 were retrospectively analyzed.Results:The clinical sensitivity of A kit to detect SARS-CoV-2-specific IgM and IgG was 77.88% (81/104) and 65.38% (68/104), respectively, and the clinical specificity was 70.59% (36/51) and 100.00% (51/51). However, the false positive rate in IgM detection was as high as 29.41% (15/51). The sensitivity of B kit to test total antibodies to SARS-CoV-2 was 63.46% (66/104), and the clinical specificity was 94.12% (48/51). The clinical sensitivity of C kit to detect SARS-CoV-2-specific IgM and IgG were respectively 31.73% (33/104) and 64.42% (67/104), and the clinical specificity were both 98.04% (50/51). There was a moderate correlation between the detection results of two colloidal gold kits and the chemiluminescence kit with the Kappa values of 0.462 and 0.587 ( Z=6.157, P<0.01; Z=7.345, P<0.01). C kit had the highest positive detection rate for IgG, and would be more reliable to be used for IgG detection in COVID-19 patients 14 d after onset. The total positive detection rate of nucleic acid in all types of samples was 63.46% (66/104). The highest positive detection rate was in throat swabs or sputum samples, followed by those in blood samples and anal swabs. No viral nucleic acid was detected in urine samples for the time being. Conclusions:SARS-CoV-2-specific antibodies could be detected in the early or late stage of COVID-19. The method of antibody detection has the advantages of shorter detection time, simple operation and high biological safety, indicating that it could be used as a supplementary or auxiliary detection for the diagnosis of suspected COVID-19 cases with negative nucleic acid test results. The chemiluminescence kit has good sensitivity and specificity, and is well recommended for clinical laboratories.

Objective To observe the effects of Jianpi Liqi Huashi Prescription on hepatocyte injury,oxidative stress and nitrative stress in mice with non-alcoholic steatohepatitis(NASH);To explore its mechanism in the treatment of NASH.Methods Totally 32 male C57BL/6J mice were randomly divided into control group,model group and TCM low-and high-dosage groups,with 8 mice in each group.The control group was fed with ordinary diet,and the other groups were fed with high-fat diet,for consecutive 16 weeks.Starting from the 13th week,the control group and model group were given 0.4%CMC-Na solution by intragastric administration and the TCM groups were given corresponding doses of drugs by intragastric administration,respectively.Biochemical instrument was used to detect serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)contents,HE staining and oil red O staining were used to detect liver histopathology,triglyceride(TG)content and myeloperoxidase(MPO)activity in liver tissue were detected through test kit.immunofluorescence staining was used to detect positive expression of CD11b in liver tissue,the mRNA expressions of NOX1 and NCF1 were detected by RT-PCR,and the protein expressions of inducible nitric oxide synthase(iNOS)and 3-nitrotyrosine(3-NT)in liver tissue were detected by Western blot.Results Compared with the control group,the hepatocytes in the model group showed diffuse steatosis,hepatocyte swelling and inflammatory cell infiltration;a large number of fat droplets were formed by oil red O staining;serum ALT and AST contents significantly increased(P<0.05),the TG content and MPO activity in liver tissue significantly increased(P<0.05);the positive expression of CD11b in liver tissue increased;the mRNA expressions of NOX1 and NCF1 in liver tissue significantly increased(P<0.05);the expressions of iNOS and 3-NT protein in liver tissue significantly increased(P<0.05).Compared with the model group,the degree of liver steatosis,the level of inflammatory cell infiltration and the number of lipid droplets in TCM groups decreased significantly;serum ALT and AST contents significantly decreased(P<0.05);the TG contents and MPO activity in liver tissue significantly decreased(P<0.05);the positive expression of CD11b in liver tissue decreased;the mRNA expressions of NOX1 and NCF1 in liver tissue significantly decreased(P<0.05);the expression of 3-NT protein in liver tissue significantly decreased(P<0.05);the expression of iNOS protein in liver tissue of mice in TCM high-dosage group significantly decreased(P<0.05).Conclusion Jianpi Liqi Huashi Prescription may relieve liver cell damage,lipid deposition and inflammation in NASH mice by alleviating oxidative stress and nitrative stress in the liver,and play a role in the treatment of NASH.

OBJECTIVETo investigate a cerebral autosomal dominant arteriopathy with the subcortical infarcts and leukoencephalopathy (CADASIL) case with clinical manifestations of baldness, lumbago and Parkinson's symptoms.

METHODSClinical and imaging data of the patient were analyzed. The patient and his family members were also subjected to genetic testing.

RESULTSThe symptoms of the patient included recurrent stroke, dementia, and mood disturbance, in addition with lumbago, baldness and Parkinson's symptoms but no migraine. Cranial MRI of the patient showed bilateral symmetric leukoencephalopathy and multiple small subcortical lacunar infarcts. A point mutation in exon 11 of the NOTCH3 gene (R558C) was discovered in the proband and four asymptomatic relatives.

CONCLUSIONCADASIL is characterized by recurrent subcortical ischemic stroke, dementia, pseudobulbar palsy, and mood disturbance. Baldness, lumbago and Parkinson's symptoms may also be seen in such patients.

Alopecia ; etiology ; CADASIL ; complications ; diagnostic imaging ; genetics ; Humans ; Low Back Pain ; etiology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Mutation ; Parkinsonian Disorders ; etiology ; Receptor, Notch3 ; genetics

Objective To analyze the clinical characteristics,imaging manifestations and prognoses of anti-GABAB receptor antibodies encephalitis.Methods The clinical manifestations,laboratory findings and radiological data of 13 patients with anti-GABAB receptor encephalitis,admitted to our hospital from September 2015 to March 2017,were retrospectively analyzed.Modified Rankin scale (mRs) was performed to evaluate the prognoses (good prognosis:mRs scores ＜ 2;poor prognosis mRs scores≥3).Results These 13 patients had an average age of 58 years (ranged 49-76 years) with a male to female ratio of 12:1.The major clinical features,including epileptic seizure,were found in 12 patients,psychiatric symptoms in 11 patients,cognitive disorder in 7 patients,and disturbance of consciousness in 4 patients.Brain MR imaging showed abnormal signal in 5 patients:4 were located in the hippocampus and amygdaloid,and one in the pons and left temporal lobe.Five patients showed abnormalities in PET-CT,including 4 with temporal hypermetabolism and 1 with cortical hypometabolism.Chest CT showed lung occupying lesions in 4 patients,of which 2 patients were diagnosed as having small cell lung cancer (SCLC) by pathological examination.Ten patients received immunomodulatory therapy,and three were with supportive care.After the average of 8 months of follow-up,7 patients had good prognosis,5 patients had poor prognosis and one patient lost of follow up.Conclusions Anti-GABAB receptor encephalitis frequently occurs in elderly male subjects and the main characteristic includes prominent refractory epilepsy and shows neurological improvement on immunotherapy.It can accompany by SCLC and have a relatively poor prognosis.

Objective To investigate the frequency and location of cerebral microbleeds in cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL) to understand the imaging and clinical features of the disease.Methods Cranial magnetic resonance imaging and susceptibility-weighted imaging were assessed in seven symptomatic CADASIL patients in People's Hospital of Zhengzhou University from 2014 to 2017.Imaging features and clinical significance of these patients were analyzed retrospectively.Results The seven patients were diagnosed by Notch3 gene detection.Mutations were found in exon 11 in four cases,and in exon 4 in three cases.All the seven patients with CADASIL had cerebral microbleeds,the number of which was 108 (4-36).The number of cerebral microbleeds was found to be higher in cortico-subcortical region than in any other regions.One of CADASIL patients with cerebral microbleeds had intracerebral hemorrhage located in external capsule.The patient with intracerebral hemorrhage had hypertension and multiple cerebral microbleeds.Conclusions Cerebral microbleeds are common imaging characteristics in symptomatic CADASIL,most of which locate in cortico-subcortical region.Cerebral hemorrhage is one of the clinical manifestations of CADASIL patients.

Objective To explore the clinical features,auxiliary examinations,therapies and prognoses of patients with antibodies against contactin-associated protein-like 2 (CASPR2).Methods The clinical data of 11 anti-CASPR2 encephalitis patients who were admited to the People's Hospital of Zhengzhou University from March 2015 to April 2018 were retrospectively analyzed.Results The age of these 11 cases was (35.6± 19.4) years (ranged 20-74 years),and eight cases were females.There were seven cases with limbic encephalitis which included six cases of epilepsy,four cases of memory impairment,two cases of mental and behavioral abnormalities.Four cases had peripheral nerve hyperexcitability.Four cases had neuropathic pain.There were six cases with autonomic dysfunction including five cases of constipation,three cases of tachycardia,two cases of hyperhidrosis,two cases of urinary disorder.Seven cases had sleep disorder.Four cases had weight loss.Two cases showed cerebellar symptoms and two cases had hyponatremia.Magnetic resonance imaging scan of the brain showed abnormal signal in two cases,mainly involved medial temporal lobe and the hippocampus.Six cases underwent 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) examination,and three cases showed abnormalities,including two with temporal hypermetabolism and one with cortical hypermetabolism.Chest enhanced CT and PET-CT showed thymoma in one case.All cases received immunotherapy,and after treatment their symptoms were improved.Long-term follow-up was performed in nine cases,and three cases relapsed.Conclusions The major clinical manifestations of anti-CASPR2 encephalitis were limbic encephalitis,peripheral nerve hyperexcitability,neuropathic pain,autonomic dysfunction,insomnia and so on.Immunotherapy was effective and some patients may have recurrence.