Objective:To identify and observe disease-causing gene variants and clinical phenotypes in a Han Chinese family with Leber congenital amaurosis (LCA).Methods:A retrospective study. A patient with LCA10 and his parents who had presented at Department of Ophthalmology of Henan Provincial People's Hospital on May 2022 were selected as the study subject. Detailed medical and family histories were recorded, fundus photography and flash electroretinogram (F-ERG) were performed. Peripheral venous blood samples (3 ml) of the proband and his parents were collected to extract whole genomic DNA, then whole exome sequencing (WES) and mitochondrial DNA (mtDNA) sequencing were carried out for the proband to determine the disease-causing gene and variants. All variants were annotated by bioinformatics analysis. According to the American College of Medical Genetics and Genomics (ACMG) guidelines, the pathogenicity of all detected variants were evaluated. Candidate variants were verified by Sanger sequencing, and in vitro minigene assay were performed to evaluate the impact of the missense variant with insufficient evidence on mRNA splicing.Results:The proband, male, 7-month-old, presented with an inability to follow light or objects, eye poking, photophobia, nystagmus, partial loss of retinal pigment epithelium around the fovea of the macula. At the age of 2 years old, F-ERG revealed severe reduction, elongation, or even no waveform of a-wave and b-wave in both eyes. No obvious abnormality was found in the clinical phenotype of his parents. The result of WES revealed that the proband carried two variants in exon 40 and exon 2 of CEP290, a frameshift variant c.5515_5518del (p.Glu1839Lysfs*11) (V1) and a novel missense variant c.74C>T (p.Ala25Val) (V2), respectively. The result of mitochondrial DNA sequencing was negative. Sanger sequencing confirmed that the heterozygous frameshift variant was inherited from his father and the heterozygous novel missense variant was inherited from his mother, which constituted compound heterozygous variants. In vitro minigene splicing assay confirmed that V2 created a new splicing donor at exon 2, leading to the in-frame deletion of 30bp fragment during transcription and loss of 10 amino acid residues in the protein. The two variants were pathogenic (V1) and likely pathogenic (V2) based on ACMG guidelines, respectively. Conclusions:The c.5515_5518del and novel c.74C>T compound heterozygous variants of the CEP290 gene probably are the cause of LCA10 in this family, which lead to the production of a truncated protein and aberrant splicing of pre-mRNA, respectively. LCA is characterized by early onset, severe impairment of visual function, and a wide range of disease-causing variations.

Objective:To investigate the clinical features, diagnostic methods and treatments of left ventricular apical fibroma.Methods:The clinical manifestations, ECG, imaging features and treatment plans of 2 patients with giant fibroma of left ventricular apex diagnosed in September 2020 and May 2022 were analyzed retrospectively, and the related literature was reviewed.Results:Both patients had slight chest distress and discomfort after activities. The ECG showed T-wave inversion of different degrees, which were misdiagnosed as “myocarditis” and “coronary heart disease” respectively. The cardiac magnetic resonance imaging and echocardiography showed left ventricular apical mass. Coronary artery stenosis was not found in coronary angiography. One patient required conservative treatment, and there was no significant change in clinical symptoms and tumor size in the follow-up for half a year; Another patient underwent cardiac mass removal, and the pathological examination after operation confirmed that it was cardiac fibroma, and there was no recurrence in the follow-up 2 years.Conclusion:Fibroma of left ventricular apex is a rare cardiac tumor, which is easy to be missed and misdiagnosed, and is one of the rare causes of T-wave inversion. Cardiac magnetic resonance imaging, CT and echocardiography are commonly used imaging methods to diagnose cardiac fibroma, and surgical resection is an effective treatment.

Objective:To compare the safety and efficacy of domestic Firebird2 TM rapamycin eluting stent and imported Endeavor Resolute stent in the treatment of coronary heart disease patients. Methods:The clinical data of 889 patients with coronary heart disease who underwent percutaneous coronary intervention (PCI) in Wuhan Asian heart hospital from 2010 to 2015 were analyzed retrospectively A case-control study was conducted. According to the type of stent used, 550 cases were divided into domestic Firebird 2TM group and 325 cases were divided into imported endeavor resolve group The incidence of major adverse cardiovascular events (MACE) was compared between the two groups. All patients was followed up for 1 year.Results:There was no significant difference in gender, age, body mass index, medical diseases, whether it was emergency PCI, previous PCI history, coronary artery bypass grafting history and left ventricular between the two groups (all P>0.05). The success rate of PCI in the two groups was 100%. The TIMI blood flow of target vessels in the two groups was grade 3. There was no stent unloading during the operation, and balloon pretreatment and post-treatment were performed. The results of one-year follow-up showed that there was no significant difference in the incidence of mace (3.1% (17/550) and 2.2%(7/325)) and the incidence of independent end points between domestic Firebird 2 TM group and endeavor group (all P>0.05); There was no significant difference in survival without mac between the two groups ( P>0.05). Conclusion:The domestic Firebird2 TM rapamycin eluting stent has the same clinical efficacy as the imported Endeavor Resolute drug eluting stent.

Objective: To investigate the efficacy and safety of cuboid stereotactic aspiration of necrotic brain tissue for treating malignant middle cerebral artery infarction in the elderly patients. Methods: Sixteen elderly patients with malignant middle cerebral artery infarction were selected from June 2017 to January 2019 in our hospital. Patients were followed up for 6 months to evaluate the efficacy of stereotactic aspiration of necrotic brain tissue using the modified Rankin Scale (mRS). Results: The 30-day mortality was 18.75%. Among the 16 elderly patients, 6 (37.5%) had an mRS score of 3 (defined as moderate disability), 6 (37.5%) had an mRS score of 4 (defined as moderate to severe disability), 1 (6.25%) had an mRS score of 5 (defined as severe disability), and 3 (18.75%) had an mRS score of 6. The probability of 6-month favorable outcome, defined as an mRS score of ≤3, was 37.5%, and the 6-month mortality was 18.75%. Conclusions It is a simple, minimally invasive, effective and safe method to treat malignant middle cerebral artery infarction in the elderly patients with cuboid stereotactic aspiration of necrotic brain tissue, which needs to be confirmed by further randomized controlled studies.

Objective To compare the prognosis of vascular in situ and bridge vessel percutaneous coronary intervention ( PCI) therapy strategies in patients with recurrent angina after coronary artery bypass grafting ( CABG) . Methods A total of one hundred and two patients with recurrent angina after CABG from January 2008 to January 2016 were involved in this study and were divided into two groups according to interventional therapy strategy:74 patients in the vascular in situ PCI group ( in situ group,74 cases) and 28 patients for bridge vessel PCI group ( bridge vessel group,28 cases) . The patients have been followed up for (33. 6± 10. 2) months. The major adverse cardiovascular events ( MACE) of the two groups were recorded, including non?fatal acute myocardial infarction ( AMI) ,target vessel revascularization ( TVR) and cardiac death, and multivariate logistic regression analysis was used to analyze the related factors of MACE. Results Compared with the bridge vessel group,the non?MACE survival rate,non?AMI survival rate and non?TVR survival rate of the in situ group were significantly increased ( ( 71. 6% ( 53/74 ) vs. 57. 1% ( 16/28 ) , 93. 2% ( 69/74 ) vs. 82. 1% (23/28),81. 1% (60/74) vs. 67. 9% (19/28) ),the differences were statistically significant (χ2=8. 141,4. 219,5. 436, P<0. 05) . Multivariable logistic regression analysis showed that age of bridge ( OR=1. 023,95%CI 1. 005-1. 026,P=0. 019) ,diabetes mellitus ( OR=2. 386,95%CI 1. 425-3. 991,P=0. 003) and bridge vessel PCI (OR=1. 884,95%CI 1. 093-3. 220,P=0. 025) were factors that affect the clinical prognosis in patients with recurrent angina pectoris after CABG. Conclusion The clinical prognosis of the in situ PCI is better than bridge vascular PCI in patients with recurrent angina after CABG,while the age of bridge, diabetes mellitus, vascular interventional treatment are factors for the effect of interventional therapy patients prognosis. The clinical prognosis is much better in native vessel PCI than that of bridge vessel PCI in patients with recurrent angina after CABG. The age of bridge,diabetes mellitus and bridge vessel PCI are the factors that affect the clinical prognosis in the patients.

Objective Nrf2 is an important neuroprotective factor and the ubiquitin proteasome system ( UPS) , as a highly specific intracellular protein degradation pathway, plays an important role in maintaining gene and protein functions.This paper pres-ents a preliminary study on the relationship between Nrf2 and the ubiquitin proteasome system in the mouse model of traumatic brain in-jury ( TBI) . Methods Forty-two healthy male ICR mice were randomly divided into three groups: control, TBI +sulforaphane ( SFN) and TBI+vehicle, and 12 Nrf2-knockout mice were included in the TBI+Nrf2 -/-group.The animals of the TBI+SFN group were treated with SFN while those of the TBI+vehicle group with the same volume of 10%corn oil at 5 minutes after TBI.At 24 hours after TBI, brain samples were collected from the mice for determining the Nrf2 expression and ubiquitinated protein content by Western blot and the changes in the Nrf2 and ubiquitinated proteins were observed by immunohistochemistry and electron microscopy. Results Compared with the controls, the mice in the TBI+vehicle group showed significantly increased expressions of Nrf2 ( 0.09 ± 0.02 vs 0.66 ±0.09, P<0.05) and ubiquitinated proteins (3.27 ± 0.21 vs 10.58 ±0.75, P<0.05).In comparison with animals in the TBI+vehicle group, those in the TBI+SFN group exhibited a signifi-cant increase in the Nrf2 protein level (0.66 ±0.09 vs 1.22 ±0.14, P<0.05) but a decrease in the ubiquitinated protein level (10.58 ±0.75 vs 6.97 ±0.86, P<0.05), and those in the TBI+Nrf2 -/-group showed a markedly decreased expression of the Nrf2 protein (0.66 ±0.09 vs 0.17 ±0.02, P<0.05) but increased expression of the ubiquitinated protein (10.58 ±0.75 vs 14.35 ± 0.65, P<0.05).Similar results were observed by immunohistochemistry and electron microscopy. Conclusion Nrf2 played a neu-roprotective role in the mouse model of traumatic brain injury by regulating the ubiquitin proteasome system.

Objective To evaluate the potential involvement of melatonin in the activation of nuclear factor-E2-related factor 2-antioxidant response element (Nrf2-ARE) signaling pathway and anti-oxidative stress in an experimental model of traumatic brain injury (TBI).Methods One hundred and sixteen ICR male mice,aged 6-8 weeks,were randomly divided into sham-operated group,model group,vehicle group and melatonin treatment group (n=29);mice in the later three groups were established TBI models by Flierl improved free-fall method;0,1,2,3 and 4 h after that,mice in the melatonin treatment group were performed intraperitoneal injection of melatonin (10 mg/kg,3 mg/mL diluted in normal saline),and those in the vehicle group were given the same volume of normal saline.Twenty-four h after TBI,the neuronal degeneration was investigated by Fluoro-Jade C (FJC) staining and brain water content was measured by wet-to-dry weight ratio method;colorimetric method was employed to detect the malondialdehyde (MDA),superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels;Western blotting was engaged to analyze the protein content of nuclear Nrf2,cytoplasmic Nrf2,NADPH quinine oxidoreductase-1 (NQO1) and heme oxidase-1 (HO-1);real-time quantitative-PCR was employed to evaluate the mRNA content of HO-1 and NQO-1;electrophoresis mobility shift assay (EMSA) was performed to measure the Nrf2 DNA binding activity.Results As compared with the sham-operated group,the other three groups had significantly increased number of cortical degenerative neurons,water content,MDA content,nuclear Nrf2 expression,and nuclear HO-1 and NQO-1 protein and mRNA expressions,and had significantly lower levels of cytoplasmic Nrf2 and GPx.As compared with the model group and vehicle group,the melatonin treatment group had significantly decreased number of cortical degenerative neurons,water content,MDA content and nuclear Nrf2 expression,and had significantly increased cytoplasmic Nrf2 level,GPx content and nuclear HO-1 and NQO-1 protein and mRNA expressions (P＜0.05).The SOD content in the sham-operated group and melatonin treatment group was significantly higher than that in the model group and vehicle group (P＜0.05).EMSA showed that the Nrf2 DNA binding activity increased accordingly in the order of sham-operated group,model group,vehicle group and melatonin treatment group.Conclusion The melatonin can improve the anti-oxidative stress neuroprotection following TBI,which may be associated with the activation of Nrf2-ARE signaling pathway.

Objective To compare different Nrf2 expressions in glioblastoma cell lines and glioma stem cells (GSCs) from xenografts and to study the concentration of Nrf2 in nuclear. Methods GSCs were analyzed by immunofluorescence and different expressions of Nrf2 in glioblastoma cell lines and GSCs from xenografts were detected with real-time RCR and Western. Results GSCs were successfully isolated from xenografts of U251 and U87 cell lines. The percentage of tumor stem cells in total cells was 1.24%, and that was 1.63% in xenografts. Immunofluorescence indicated that Nrf2 was overexpressed in GSCs as compared with that in glioblastoma cell lines. Conclusion Nrf2 may be a potential biomarker and rational therapeutic target for GSCs.

Objective To study the lesion patterns of hemorrhagic type of moyamoya disease (MMD) in adults. Methods Seventy-two consecutive cases of hemorrhagic type of MMD, confirmed by digital cerebral angiography in Jinling hospital between January 2004 and February 2010, were retrieved from the Nanjing Stroke Registry Program. MMD patients were classified according to the hemorrhagic sites into 4 types: non-thalamic parenchymal, thalamic, primary ventricular and subarachnoid. The ipsilateral anterior choroidal artery and posterior communicating artery (AChA-PComA) were evaluated by the modified Morioka's 3-points grading system: normal or mild to moderate dilation, severe dilation with abnormal extension and non-visualization. The relationship between lesion patterns and the angiographic findings was analyzed. Results In the stage of normal or mild to moderate dilation of AChA-PComA, non-thalamic parenchymal hemorrhage was the more frequent type (51.6%, 16/31 ;Z = -3.266,P =0.001 ), and there was a high incidence of intrastriatal hemorrhage occurred (22.6%, 7/31 ). In the stage of severe dilation with abnormal extension, intraventricular hemorrhage was most common ( 58.8%, 20/34 ;Z = -2.696 ,P =0.008). In addition, posterior circulation subarachnoid hemorrhage (SAH) was associated with a higher grade of AChA-PComA than anterior circulation SAH (Z = -4.655 ,P ＜ 0.01 ). Furthermore, posterior circulation SAH was the only type of SAH in the stage of non-visualization(9.7% ,7/72; x2 =42.999,P ＜0.01 ). Conclusion In adult patients with MMD, different subtypes of hemorrhagic stroke were associated with angiographic changes of AChA-PComA, and the angiographic characteristics may predict the location of hemorrhage.

It is purposed to analyze therapeutic effectiveness at community and designated hospitals for extensive influenza A H1N1 outbreaks at five universities in Qingdao,Shandong,east China during September 1 to 30,2009,including 28 confirmed cases,182 suspected cases and 136 close contacts treated at community health-care facilities,and 56 confirmed cases treated at designated hospitals.There was no significant difference in therapeutic effectiveness between community health-care facilities and designated hospitals (P ＞ 0.05).No new cases occurred seven days after their isolation was lifted for suspected cases and close contacts at community,indicating influenza A H1N1 could be prevented,controlled and cured and its mild cases could be treated at community health-care facilities.