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.

BACKGROUND: Evidence on the relations of the American Heart Association's ideal cardiovascular health (ICH) with mortality in Asians is sparse, and the interaction between behavioral and medical metrics remained unclear. We aimed to fill the gaps. METHODS: A total of 198,164 participants without cancer and cardiovascular disease (CVD) were included from the China Kadoorie Biobank study (2004-2018), Dongfeng-Tongji cohort (2008-2018), and Kailuan study (2006-2019). Four behaviors (i.e., smoking, physical activity, diet, body mass index) and three medical factors (i.e., blood pressure, blood glucose, and blood lipid) were classified into poor, intermediate, and ideal levels (0, 1, and 2 points), which constituted 8-point behavioral, 6-point medical, and 14-point ICH scores. Results of Cox regression from three cohorts were pooled using random-effects models of meta-analysis. RESULTS: During about 2 million person-years, 20,176 deaths were recorded. After controlling for demographic characteristics and alcohol drinking, hazard ratios (95% confidence intervals) comparing ICH scores of 10-14 vs. 0-6 were 0.52 (0.41-0.67), 0.44 (0.37-0.53), 0.54 (0.45-0.66), and 0.86 (0.64-1.14) for all-cause, CVD, respiratory, and cancer mortality. A higher behavioral or medical score was independently associated with lower all-cause and CVD mortality among the total population and populations with different levels of behavioral or medical health equally, and no interaction was observed. CONCLUSIONS ICH was associated with lower all-cause, CVD, and respiratory mortality among Chinese adults. Both behavioral and medical health should be improved to prevent premature deaths.
Adult ; Humans ; Cardiovascular Diseases/prevention & control* ; East Asian People ; Prospective Studies ; Risk Factors ; Smoking

With the advance of the economy and population aging, the acceleration of urbanization and the change of people's lifestyles, the prevalence of chronic diseases has become very serious. However, the etiologies and pathogeneses of the diseases are not yet clear, and the evidence of effective prevention and treatment strategies is lacking. Cohort study is an important method for exploring etiology and pathogenesis. Therefore, based on the support of the Ministry of Science and Technology for precision medicine in 2016, we launched a prospective cohort study of common chronic and non-communicable diseases in three provinces (Hubei, Hunan and Henan) in central China. Three independent and integratable sub-cohorts consisting of 115 424 participants at baseline survey and 107 252 participants in follow up were established, including dynamic measurements in 39 000 subjects in Dongfeng-Tongji prospective cohort. Each participant was asked to complete a questionnaire survey, an anthropometric measurement, a laboratory measurement, and blood and urine samples were collected from them. The cohort study contributes greatly to elucidating the etiologies and pathogeneses of common chronic and non-communicable disease in Chinese population and the development of precision medicine in China. This paper briefly introduces the design concept, basic information, major achievements and progress, and challenges of the prospective cohort study of common chronic and non-communicable diseases in central China.

The bile acid-responsive G-protein-coupled receptor TGR5 is expressed in monocytes and macrophages, and plays a critical role in regulating inflammatory response. Our previous work has shown its role in promoting the progression of non-small cell lung cancer (NSCLC), yet the mechanism remains unclear. Here, using Tgr5-knockout mice, we show that TGR5 is required for M2 polarization of tumor-associated macrophages (TAMs) and suppresses antitumor immunity in NSCLC via involving TAMs-mediated CD8⁺ T cell suppression. Mechanistically, we demonstrate that TGR5 promotes TAMs into protumorigenic M2-like phenotypes via activating cAMP-STAT3/STAT6 signaling. Induction of cAMP production restores M2-like phenotypes in TGR5-deficient macrophages. In NSCLC tissues from human patients, the expression of TGR5 is associated with the infiltration of TAMs. The co-expression of TGR5 and high TAMs infiltration are associated with the prognosis and overall survival of NSCLC patients. Together, this study provides molecular mechanisms for the protumor function of TGR5 in NSCLC, highlighting its potential as a target for TAMs-centric immunotherapy in NSCLC.

Objective:To investigate the influencing factors for postoperative venous thromboembolism (VTE) of inguinal hernia.Methods:The retrospective case-control study was conducted. The clinical data of 350 patients undergoing surgical treatment of inguinal hernia who were admitted to Affiliated Hospital of Zunyi Medical University from January to December 2017 were collected. There were 287 males and 63 females, aged from 15 to 89 years, with a median age of 57 years. Observation indicators: (1) surgical and postoperative situations; (2) follow-up; (3) analysis of influencing factors for postoperative VTE of inguinal hernia. Follow-up using outpatient examination and telephone interview was performed to detect recurrence and complications of inguinal hernia after patients being discharged from hospital. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test.Measurement data with skewed distribution were represented as M (range), and comparison between groups was analyzed using the nonparametric rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Multivariate analysis was conducted using the binary Logistic regression model. Results:(1) Surgical and postoperative situations: of the 350 patients, 173 underwent open inguinal hernia surgery including 66 cases with plain patch repair, 54 cases with Lichtenstein repair, 30 cases with mesh plug plain patch repair, 23 cases with Bassini repair, and 177 underwent laparoscopic inguinal hernia surgery including 134 cases with laparoscopic transabdominal preperitoneal prothetic repair, 43 cases with laparoscopic totally extraperitoneal prothetic repair. There were 335 of the 350 patients negative for postoperative VTE while 15 patients positive for postoperative VTE. Of the 15 patients who were diagnosed with postoperative VTE, 13 cases underwent open surgery while 2 cases underwent laparoscopic surgery including 1 died; 12 cases were diagnosed with deep vein thrombosis and 3 cases were diagnosed with pulmonary thromboembolism including 1 died. (2) Follow-up: 349 of the 350 patients were followed up for one year after operation. Of the 349 patients, 2 had recurrence of inguinal hernia and 18 had seroma in the operation area within one year. None of the 349 patients had postoperative patch-related infection or incision infection in the operation area. Of the 14 patients who were diagnosed with postoperative VTE, recurrence of inguinal hernia was not observed within one year. (3) Analysis of influencing factors for VTE of inguinal hernia. Results of univariate showed that age, body mass index (BMI), hypertension, type of operation, the compression time of operative area, time to first out-of-bed activities, duration of hospital stay, postoperative Caprini score were influencing factors for postoperative VTE of inguinal hernia ( χ2=13.217, 9.183, 4.388, 8.694, Z=-4.690, -5.265, -4.281, -4.883, P<0.05), and age, cases with chronic bronchitis, the stable stage of chronic obstructive pulmonary disease (COPD) were influencing factors for postoperative VTE of inguinal hernia ( P<0.05). Results of multivariate analysis showed that age≥65 years, BMI≥25.0 kg/m 2, chronic bronchitis, the stable stage of COPD, open surgery, the compression time of operative area≥42 hours, time to first out-of-bed activities≥60 hours, postoperative Caprini score>5 were independent risk factors for postoperative VTE of inguinal hernia ( odds ratio=1.085, 1.320, 0.256, 0.013, 7.874, 1.112, 1.027, 6.909, 95% confidence interval: 1.031-1.141, 1.024-1.702, 0.071-0.929, 0.016-0.800, 1.489-41.630, 1.061-1.165, 1.008-1.047, 3.045-15.678, P<0.05). Conclusions:Age≥65 years, BMI≥25.0 kg/m 2, cases with chronic bronchitis preoperatively, the stable stage of COPD, open surgery, the compression time of operative area≥42 hours, time to first out-of-bed activities≥60 hours, postoperative Caprini score>5 are independent risk factors for postoperative VTE of inguinal hernia.

Objective: To explore the relationship between anthropometric indices and the incident risk of hypertension, compare novel anthropometric indices with traditional indices in hypertension prediction and establish hypertension prediction models among elderly Chinese. Methods: A total of 27 009 retirees from the Dongfeng Motor Corporation were recruited at baseline in 2008 and the first follow-up was conducted in 2013. After the exclusion of participants less than 60 years old, participants with hypertension, coronary heart disease, stroke, cancer, and those with missing data, a total of 6 784 elderly participants were enrolled in this study. A multivariate logistic regression model was used to analyze the relationship between traditional anthropometric indices, body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), novel anthropometric indices, visceral adiposity index (VAI), body shape index (ABSI), body roundness index (BRI), and the incident risk of hypertension. Meanwhile, a multivariate logistic regression model was used to establish hypertension prediction models. Receiver operating characteristic (ROC) curve was applied to compare the prediction ability of different models. Results: A total of 1 787 incident cases of hypertension were identified, with the incidence of hypertension about 27.59%. Significant positive associations were detected between BMI, WC, WHtR, VAI, BRI and the incident risk of hypertension after adjusting for potential confounders (all P values<0.05). In men, the OR (95%CI) (upper tertile vs lower tertile) was 1.45 (1.22-1.73) for VAI, and 1.86 (1.55-2.23) for BRI. In women, the OR (95% CI) (upper tertile vs lower tertile) was 1.55 (1.22-1.96) for VAI, and 1.60 (1.27-2.01) for BRI. For ABSI, no significant association was observed in either men (OR (95%CI): 1.07 (0.90-1.28)) or women (OR (95%CI): 1.03 (0.82-1.29), both P values >0.05). The basic hypertension prediction model included age, drinking (only in men), education status (only in men), systolic blood pressure (SBP), diastolic blood pressure (DBP), and fasting blood glucose levels. Based on the basic prediction model, BMI (in men: AUC=0.697) and BRI (only in men: AUC=0.696) improved area under ROC curve (AUC) significantly (P<0.05). BMI was the strongest predictor in both men (AUC=0.697) and women (AUC=0.685) in the extended model. Conclusion Significant positive associations were detected between BMI, WC, WHtR, VAI, BRI and the incident risk of hypertension among elderly Chinese. BMI was the strongest predictor in hypertension prediction model compared with other anthropometric indices.

Objective To investigate the effectiveness and safety of endovascular embolization for the treatment of middle cerebral artery aneurysms. Methods From March 2007 to May 2015,the clinical data of 170 patients with 173 middle cerebral artery aneurysms treated with endovascular embolization at the Department of Neurosurgery,Nanjing Jinling Hospital were analyzed retrospectively,including 120 (69.4%)ruptured aneurysms and 53 (30. 6%)unruptured aneurysms. The incidence of complications and prognosis were compared between the 2 groups. Results (1)A total of 170 patients who could perform endovascular embolization after preoperative evaluation successfully completed the interventional procedure. None of the patients died. (2)18 patients (10. 6%)had intraoperative and postoperative complications,including 4 (7. 5%,4/53)in the unruptured aneurysm group and 14 (11. 7%,14/120)in the ruptured aneurysm group. There was no significant difference in the incidence of complications between the two groups. (3)101 patients were followed up for 3-48 months. No new nervous system symptoms and reruptured aneurysm were observed. One patient had recurrence in the unruptured aneurysm group and 4 had recurrence in the ruptured aneurysm group. Conclusion Endovascular treatment of middle cerebral artery aneurysms is a safe,effective,and feasible technique.

Objective To investigate the preoperative and intraoperative assessed values of the color-coded digital subtraction angiography (DSA ) for intracranial arteriovenous malformation (AVM). Methods Fifteen patients with AVM performed preoperative routine whole brain DSA were analyzed retrospectively,and the iFlow software was used to perform color-coded DSA of image post-processing. A comprehensive analysis such as the range of lesions,vascular architecture and hemodynamics of AVM was conducted on the two-dimensional DSA images and color-coded DSA. Results Of the 15 patients with AVM,9 were small-sized (including 4 nidi showed diffuse type),3 were medium-sized,and 3 were large-sized;8 patients had single feeding artery,and 7 had multiple feeding arteries;11 had single draining vein,and 4 had multiple draining veins. When showing the size of AVM nidus,particularly diffuse type nidus, the color-coded DSA was clearer than the two-dimensional image. The color-coded DSA could visually display the traveling of the superficial and deep draining veins,at the same time,the primary and secondary draining veins could be identified according to the size of the area under the curve and the full width at half maximum,and intuitively reflected the complete cycle of cerebral blood flow. Conclusion The color-coded DSA can quickly and accurately depict the range of AVM,angioarchitecture features and intraoperative hemodynamic changes.

The development of translational medicine requires knowledgeable and capable talents.In this study, by systematic analysis on scientific literatures published openly during 2010 till 2014, we comprehensively described basic circumstances pertinent to talent cultivation during global translational medicine development, and analyzed diathesis requirements for qualified talents, as well as cultivation strategies from employers perspectives, in terms of knowledge, skill, social roles, values, self-concept, trait and motive characteristics, with the aim to explore the premium cultivation paths for such talents.

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.