Objective To explore the protective effect in a model of nicotinamide riboside(NR)against carbonyl cyanide m-chlorophenylhydrazone(CCCP)-induced oxidative stress in R28 cells.Methods 4 μmol/L CCCP was used to induce oxidative stress in R28 cells,and 400 nmol/L NR was used to intervene.The cell viability was quantified by CCK-8 assay.The apoptosis was detected by Annexin-V/PI double staining and flow cytometry.Western blotting was used to examine the levels of Cytochrome C,Caspase-3,and Caspase-9 to evaluate the apoptosis.Tetramethylrhodamine ethyl ester was used to detect the mitochondrial membrane potential(MMP),MitoSOX was used to detect the mitochondrial reactive oxygen species(mtROS)levels,and adenosine triphosphate(ATP)assay kit was used to assess ATP generation ability to evaluate mitochondrial function.Results After CCCP treatment of R28 cells,the cell viability decreased,the apoptotic protein levels and apoptosis rates increased,the MMP decreased,and the mtROS generation increased(P＜0.05).After NR pretreatment,the cell viability increased,the apoptotic protein levels and apoptosis rates decreased,the MMP increased,and the mtROS generation decreased(P＜0.05).Conclusion:NR enhances the cell viability,reduces the expression of apoptotic proteins,and ultimately reduces the apoptosis of retinal ganglion cell by inhibiting oxidative stress response and protecting mitochondrial function.

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Objective: To develop and validate a deep learning model based on fundus photos for the identification of coronary heart disease (CHD) and associated risk factors. Methods: Subjects aged>18 years with complete clinical examination data from 149 hospitals and medical examination centers in China were included in this retrospective study. Two radiologists, who were not aware of the study design, independently evaluated the coronary angiography images of each subject to make CHD diagnosis. A deep learning model using convolutional neural networks (CNN) was used to label the fundus images according to the presence or absence of CHD, and the model was proportionally divided into training and test sets for model training. The prediction performance of the model was evaluated in the test set using monocular and binocular fundus images respectively. Prediction efficacy of the algorithm for cardiovascular risk factors (e.g., age, systolic blood pressure, gender) and coronary events were evaluated by regression analysis using the area under the receiver operating characteristic curve (AUC) and R² correlation coefficient. Results: The study retrospectively collected 51 765 fundus images from 25 222 subjects, including 10 255 patients with CHD, and there were 14 419 male subjects in this cohort. Of these, 46 603 fundus images from 22 701 subjects were included in the training set and 5 162 fundus images from 2 521 subjects were included in the test set. In the test set, the deep learning model could accurately predict patients' age with an R² value of 0.931 (95%CI 0.929-0.933) for monocular photos and 0.938 (95%CI 0.936-0.940) for binocular photos. The AUC values for sex identification from single eye and binocular retinal fundus images were 0.983 (95%CI 0.982-0.984) and 0.988 (95%CI 0.987-0.989), respectively. The AUC value of the model was 0.876 (95%CI 0.874-0.877) with either monocular fundus photographs and AUC value was 0.885 (95%CI 0.884-0.888) with binocular fundus photographs to predict CHD, the sensitivity of the model was 0.894 and specificity was 0.755 with accuracy of 0.714 using binocular fundus photographs for the prediction of CHD. Conclusion: The deep learning model based on fundus photographs performs well in identifying coronary heart disease and assessing related risk factors such as age and sex.
Humans ; Male ; Retrospective Studies ; Deep Learning ; Fundus Oculi ; ROC Curve ; Algorithms ; Risk Factors ; Coronary Disease/diagnostic imaging*

Objective To explore the expression and role of bromodomain-containing protein 4(BRD4) in spinal cord of mice which suffered inflammatory pain induced by formaldelryde solution. Methods Thirty-two ICR mice were randomly divided into normal saline group and formaldehyde injection 5 minutes, 30 minutes and 60 minutes groups, with 8 mice in each group. The expression of BRD4 protein and mRNA in spinal cord of mice in each group were detected by Western blotting (n = 4/group) and Real-time PCR (n = 4/group); 66 mice were randomly divided into formaldelryde injection group, vehicle (DMSO) plus formaldelryde injection group and 6. 25, 12. 5, 25 and 50 mg/kg JQl injection plus formaldelryde solution group, with 11 mice in each group. The effect of BRD4 inhibitor JQl on spontaneous pain in each group was observed (n= 11/group); Immunohistochemistry (n= 3/group), Real-time PCR (n = 4/group) or Western blotting (n= 4/group) were used to detect the effects of 25 mg/kg JQ1 on the expression of c-fos and glutamate receptor 2 (GluR2) in the spinal cord of model mice. Results The result showed that levels of BRD4 protein (P<0. 01) and mRNA in spinal cord increased significantly 30 min and 60 min after formaldehyde solution injection (P<0. 05). The behavioral test showed that both 25 mg/kg and 50 mg/kg JQf administration could reduce the second phase spontaneous pain compared with the solvent (DMSO) group (P < 0 . 05). Furthennore, immunohistochemistry and Real-time PCR result showed that 25 mg/kg JQf injection could significantly reduce positive numbers (P<0. 01) and high mRNA expression of c-fos in mouse spinal cord induced by formaldehyde solution (P < 0 . 05), and the Western blotting result showed that 25 mg/kg JQf administration could significantly reduce the expression of glutamate receptor GluR2 (P < 0. OOf). Conclusion BRD4 may play an important role in the induction of central sensitization of inflammatory pain, and JQf may alleviate inflammatory pain behavior by inhibiting the formation of central sensitization of pain.

OBJECTIVE: To test the effect of Banxia Xiexin Decoction (, BXD) on the contraction and relaxation of gastric smooth muscle (SM) in diabetic gastroparesis (DGP) model rats, and to explore the mechanism of BXD in the prevention and treatment of DGP through experiments of signal pathway both in vivo and in vitro. METHODS: Sixty Sprague-Dawley rats were divided into 6 groups according to a random number table: control group, model group, high-, medium- and low-dose BXD groups (9.2, 4.6 and 1.8 g/(kg·d), respectively), and domperidone group (10 mg/(kg·d)), 10 rats per group. DGP model was established initially by a single intraperitoneal injection of streptozotocin (STZ), and was confirmed by recording gastric emptying, intestinal transport velocity and gastric myoelectric activity of rats after 2 months. Each group was treated with a corresponding drug for 4 weeks. The mRNA and protein expressions of phospholipase C (PLC), inositol triphosphate (IP RESULTS: Compared with the model group, high- and medium-dose BXD and domperidone significantly increased the expressions of PLC, IP CONCLUSIONS Treatment with high- and medium-dose BXD significantly attenuated STZ-induced experimental DGP in rats. The therapeutic effect of BXD on DGP rats might be associated with the PLC-IP

Objective:To explore the expression and clinical significance of ubiquitin-like with PHID and ring finger domains 2 (UHRF2) in intrahepatic cholangiocarcinoma (ICC).Methods:The expression of UHRF2 in 138 ICC was determined by immunohistochemistry,and the relationships between UHRF2 expression with prognosis and clinicopathological features of ICC were analyzed:Results:UHRF2 was highly expressed in ICC compared with paratumorous tissues.Level of UHRF2 was associated with high AFP level (P=0.010),poor tunor differentiation (P=0.026),lymph node metastasis (P=0.001),and advanced TNM stage (P=0.019).Hevated UHRF2 expression was suggested to be associated with poor prognosis and high recurrence rate in ICC patients (P＜ 0.001),and multivariable analysis indicated that UHRF2 was of theprognostic indicators of ICC (P＜0.05).Conclusions:High level of UHRF2 is related to the malignant phenotype of ICC,and can be a prognostic and recurrent indicator of postoperative patients.

Objective    To evaluate the outcomes and summarize the clinical experience of totally endoscopic mitral valve repair with artificial chordae implantation. Methods    From May 2013 to June 2016, 71 patients with mitral valve insufficiency were admitted to our hospital who underwent totally endoscopic mitral valve repair with artificial chordae implantation. There were 47 males and 24 females with the age of 46.0±14.4 years ranging from 13-78 years. The pathogenesis included degenerative valvular diseases in 63 patients, congenital valvular diseases in 4, infectious endocarditis in 2, rheumatic disease in 1 and cardiomyopathy in 1. Prolapse of anterior, posterior, or both leaflets was present in 26 (36.6%), 19 (26.8%), and 25 (35.2%) patients, respectively; one patient (1.4%) presented valve annulus enlargement and thirteen were associated with commissure lesion. The mitral regurgitation area ranged from 4.2 to 26.3 cm2 (mean, 12.2±5.6 cm2). All the procedures were performed by total endoscopy under cardiac arrest. 5-0 Gore-tex sutures were used as the material of artificial chordae which was implanted one by one. Results    There was no in-hospital death. One patient was transferred to mitral valve replacement, and one median sternotomy due to bleeding. The mean cardiopulmonary bypass time was 156.0±31.6 min and aortic cross-clamp time 110.0±20.1 min. We finally had 39 isolated mitral valve repair, 28 mitral valve repair combined tricuspid valve repair, 3 mitral valve repair combined atrial septal  defect closure, and 1 mitral valve repair combined correction of partial anomalous pulmonary vein connection. Each patient was implanted artificial chordae of 2.5±1.7 (ranging from 1 to 7), and 65 patients received mitral annulus (full ring). The intraoperative transoesophageal echocardiography found no mitral regurgitation in 44 patients, the area of mitral regurgitation was 0-2 cm2 in 24, and 3 patients with mitral regurgitation>2 cm2 experienced serious systolic anterior motion. Of the 3 patients with systolic anterior motion (SAM), one transferred to mitral valve replacement, one underwent mitral re-repair, and one took conservative treatment. The mean follow-up was 12.7±10.5 months (range: 1 to 36 months), while 2 patients were lost to follow up with the follow-up rate of 97.2%. Recurrent severe regurgitation occured in 3 patients, moderate in 5, mild or trivial in 27 and no regurgitation in 36. During the follow-up, 1 patient died of myocardiopathy-induced heart failure post discharge, 1 suffered from cerebral infarction, and no patient underwent reoperation. Conclusion    The totally endoscopic surgical treatment of mitral valvuloplasty with artificial chordae is reliable for patients with mitral valve prolapse, which provides favorable clinical efficacy and outcomes. The difficulty lies in how to determine the appropriate length of the chordae and keep the stability of length.

BACKGROUND: Recent studies have demonstrated that sterol regulatory element binding protein-2 (SREBP-2) plays a key role in osteoarthritis, but its exact pathogenesis remains incompletely understood yet. OBJECTIVE:To investigate the expression of SREBP-2 in the process of interleukin-1β-induced articular chondrocyte degenerationin vitro. METHODS: Articular chondrocytes obtained from C57BL/6J mice were culturedin vitro. After the second passage, cels were randomly divided into four groups: control group, and three experimental groups treated with 10 μg/L interleukin-1β for 24, 48 and 72 hours, respectively. RESULTS AND CONCLUSION:The cels became hypertrophic after being stimulated by interleukin-1β, and the staining of colagen X was positive at 72 hours. MTT assay demonstrated that the cel activity after stimulation with interleukin-1β decreased with time. Results of RT-PCR showed that the expression of SREBP-2 and SREBP cleavage activating protein mRNA was significantly increased after stimulation with interleukin-1βas compared with the control group and increased with time. On the contrary, the expression of aggrecan and colagen II mRNA was decreased with time. It is revealed that interleukin-1β could inhibit the proliferation of regular chondrocytes and the expression of its extracelular matrix, and furthermore, induce chondrocyte hypertrophy. The expression of SREBP-2 showed a negative relationship with key cartilage genes during this interleukin-1β-induced degeneration.

OBJECTIVETo determine whether elevated serum uric acid (UA) levels are associated with type 2 diabetes diagnosed using HbA1c levels among Chinese adults.

METHODSWe conducted two population-based cross-sectional studies in Qingdao in China in 2006 and 2009. A total of 6894 (39.4% men) subjects aged 35-74 years were included in the data analysis. Newly diagnosed diabetes was defined as HbA1c level of ⋝6.5%, and prediabetes was classified as HbA1c level between 5.7% and 6.4% according to the International Diabetes Federation criteria. Multivariate logistic regression was employed to assess the association between UA and prevalence of type 2 diabetes defined using Glycated hemoglobin A1c (HbA1c) levels.

RESULTSSubjects with prediabetes had higher UA levels than those with normal glucose tolerance, newly diagnosed diabetes, and known diabetes, with corresponding values of 325.1 (82.5) µmol/L, 310.9 (84.2) µmol/L, 291.3 (81.7) µmol/L, 305.2 (83.6) µmol/L, respectively (P<0.001 for all comparisons). Binary logistic regression analysis showed that UA was a possible predictor for the prevalence of type 2 diabetes diagnosed using HbA1c levels, and the second quartile of UA levels had a higher odds ratio (OR: 4.088; 95% CI: 2.900-5.765) for HbA1c than the other quartiles after adjusting for age, body mass index, sex, marital status, education, income, alcohol consumption, smoking, and cardiometabolic parameters.

CONCLUSIONSerum UA is significantly associated with type 2 diabetes diagnosed using HbA1c levels, independent of other cardiometabolic parameters.

Adult ; Aged ; Asian Continental Ancestry Group ; statistics & numerical data ; China ; epidemiology ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2 ; blood ; epidemiology ; Female ; Glycated Hemoglobin A ; metabolism ; Humans ; Male ; Middle Aged ; Prevalence ; Uric Acid ; blood