OBJECTIVE:To study the effect of alcohol extract of Toddalia asiatica on the inflammation-associated cytokines of model rats with adjuvant arthritis(AA). METHODS:70 SD rats were randomly divided into a normal control group,a model con-trol group,a positive control chemical medicine group(Leflunomide tablets,0.012 g/kg),a positive control TCM group(Tripter-ygium glycosides tablets,0.012 g/kg)and the groups of low,medium and high-dose [1,4,6 g(crude drug)/kg] alcohol extract of T. asiatica,with 10 rats in each group. The rats in all groups except for the normal control group were given complete Freund’s complete adjuvant id for the establishment of AA models. At the same time,the rats in the drug administration groups were given corresponding drugs ig,while those in the normal control group and the model control group were given isometric normal saline ig,twice a day,for 28 consecutive days. The degree of toe swelling,arthritis index and the levels of interleukin(IL)-1β,IL-6, IL-10,tumor necrosis factor α(TNF-α)and prostaglandin E2(PGE2)in serum and synovial membranes of all groups of rats were determined. RESULTS:Compared to the normal control group,the model control group demonstrated higher degree of primary and secondary toe swelling,arthritis index and levels of IL-1β,IL-6,TNF-αand PGE2 in serum and joint synovial membrane,and low-er level of IL-10 therein(P<0.01). Compared to the model control group,all the above-mentioned indexes of the rats in drug ad-ministration groups significantly improved(P<0.05 or P<0.01). CONCLUSIONS:The alcohol extract of T. asiatica. has a preven-tive and therapeutic effect on the model rats with AA by regulating the expression of anti-inflammatory and proinflammatory cyto-kines in serum and synovial membrane.

Objective To investigate the relationship between eosinophil and in-stent restenosis in acute coronary syndrome patients. Methods One hundred and fifity-one ACS cases werenenrolled in this study. According to the results of coronary angiography (the stented segment lumen loss over 50% was judged to be ISR), patients were divided into the restenosis group and the non-restenosis group. Results Based on the logistic analysis, no significant association was found between eosinophil and ISR, and even after adjustment of related risk factors (P > 0.05). The stratification analysis showed that the high level of eosinophil might increase the risk of ISR in ACS patients with history of hypertension (P = 0.038) and myocardial infarction (P = 0.032). Conclusion Eosinophil may be associated with the risk of ISR in ACS patients with history of hypertension and myocardial infarction. The underlying mechanisms need to be elucidated in further study.

Objective:To investigate the correlation between interleukin-27(IL-27)polymorphisms and coronary heart disease(CHD)in the Guangxi Zhuang population.Methods:A total of 1 218 subjects were enrolled in this case-control study, and 571 cases were in the CHD group and 647 were in the control group.The Sequenom MassArray system was used to genotype IL-27 single nucleotide polymorphisms(SNPs), and other biochemical parameters were tested by using the standard protocol in the laboratory of our hospital.The correlation between IL-27 SNPs and CHD was evaluated by Logistic regression analysis, and risk factors including age, smoking, drinking, history of hypertension, history of diabetes mellitus and family history of CHD were adjusted in this model.Methods:Logistic regression analysis results indicated that the risk of CHD was elevated in subjects with the CC genotype of IL-27 rs428253, compared with those with the GG genotype( OR=2.18, 95% CI: 1.09-4.37, P<0.05). After adjustment for the related risk factors, the risk of CHD also increased in subjects with the CC genotype of IL-27 rs428253, compared with those with the GG genotype( R=2.82, 95% CI: 1.31-6.07, P<0.05). IL-27 rs4740, rs17855750, rs181206 and rs40837(all P>0.05)polymorphisms had no correlation with CHD in the Zhuang population, and there were no significant differences in C-reactive protein, total cholesterol, triglyceride or low-density lipoprotein cholesterol levels between CHD patients and controls with different genotypes of IL-27 rs428253(all P>0.05). Conclusions:IL-27 rs428253 polymorphism is correlated with the risk of CHD in the Guangxi Zhuang population.

Objective To investigate the correlation between plasma homocysteine(Hcy) and long term occurrence of main adverse cardiac events(MACE) in the patients with acute myocardial infarction(AMI).Methods A total of 326 inpatients with AMI in the cardiology department of this hospital from Mar.2012 to Dec.2014 were continuously included.The related laboratory biochemical indicators such as Hcy were detected according to the standard flow process by the hospital clinical laboratory department.The Hcy level and MACE occurrence rate were performed the receiver operating characteristic(ROC) curve analysis.The research subjects were divided into the Hcy(L) group and Hcy(H) group according to the cut-off value 11.69μmol/L.The base line data of all subjects were collected and the follow up was conducted for recording MACE.Results The plasma N-terminal pro-brain natriuretic peptide (NT-ProBNP) level in the Hcy(L) group was significantly lower than that in the Hcy(H) group[-(501.46-±-118.35)pg/mL vs.(1 324.11 ± 523.13) pg/mL,P =0.02],while the left ventricular ejection fraction(LVEF) was significantly higher than that in the Hcy(H) group[(55.23 ± 9.48) ％ vs.(50.79 ± 10.68) ％,P =0.03].After 1-year follow up,LVEF in the Hcy(H) group was significantly decreased compared with the base line [(45.32±10.18)％ vs.(50.79±10.68)％,P＜0.05],moreover the MACE occurrence risk in the Hcy(H) group was significantly higher than that in the Hcy(L) group,the difference after correcting the related confounding factors had statistical significance (P=0.048),but LVEF and minor axis shortening rate of left ventricle(FS) in the Hcy(L) group had no obvious difference compared with the base line data[(54.43 ± 10.68)％ vs.(55.23± 9.48) ％,(28.56±6.21) ％ vs.(29.22±5.30) ％,P＞0.05].Conclusion The risk of long term MACE occurrence in the patients with AMI complicating plasma high Hcy level is obviously increased compared with that in the patients with plasma low Hcy level and the prognosis is poor,prompting that plasma high Hcy level is one of possible independent predicting factors for poor prognosis in the patients with AML But its action mechanism and whether the Hcy interventional therapy improving prognosis of AMI patients still need to further study.

Objective:To investigate the effect of diabetes mellitus in the elderly on memory function in patients with mild cognitive impairment(MCI).Methods:Totally 449 community residents were selected for a 2-year follow-up survey.Montreal Cognitive Assessment(MoCA)and Mini-Mental State Examination(MMSE)were selected for overall cognitive function assessment.Fuld Object Memory(FOM)and Digital Span Test(DST)were used to evaluate delayed recall and instantaneous memory.Demographic data such as gender, age, education level, marital history, annual income, blood pressure, medical history etc.were collected.The glycosylated hemoglobin, fasting insulin, and carotid artery intima-media thickness were checked regularly.All subjects were grouped into non-diabetes mellitus normal cognitive group(NDM-NC group), non-diabetes mellitus mild cognitive impairment group(NDM-MCI group), diabetes mellitus normal cognitive group(DM-NC group)and diabetes mellitus mild cognitive impairment group(DM-MCI group).Results:In cross-sectional observation, the first, second, and last recall scores in the FOM showed a decreasing trend in the DM-MCI group, showed a word "U" -shaped fluctuation trend in the DM-NC group and the NDM-MCI group, and showed no significant change in the NDM-NC group.There were no significant differences in DST anterior-backward test scores between the DM-MCI group and NDM-MCI group(all P>0.05).Through longitudinal follow-up and two-by-two comparison with the other three groups, the average value of glycosylated hemoglobin in the DM-MCI group(6.78±0.60)% was the highest, and the differences were statistically significant( P<0.05).During follow-up, the average carotid intima-media thickness(CIMT)was higher in the DM-MCI group(1.03±0.20)mm than in NDM-NC group(0.89±0.20)mm( P<0.05), and the difference was statistically significant.Comparing with the other three longitudinal follow-up groups, the CIMT thickening speed in DM-MCI group was fastest. Conclusions:Elderly DM patient population have a higher prevalence of MCI, and their memory function fluctuates or declines significantly.Therefore, regular detection of memory function is conducive to delaying the progression of DM and MCI.

ObjectiveTo explore the association between triglyceride-glucose （TyG） index and major adverse cardiovascular events （MACEs） risk in coronary heart disease （CHD） patients with blood stasis syndrome after percutaneous coronary intervention （PCI）. MethodsA total of 857 CHD patients with blood stasis syndrome after PCI were enrolled and divided into four groups according to the baseline TyG index quartiles， Q1 （TyG ＜ 8.51）， Q2 （8.51 ≤ TyG ＜ 8.88）， Q3 （8.88 ≤ TyG ＜ 9.22）， and Q4 （TyG ≥ 9.22）. The clinical outcome was defined as a compound endpoint of cardiovascular events including cardiac death， non-fatal myocardial infarction， unplanned revascularization， in-stent restenosis and stroke. The machine learning Boruta algorithm was used for feature selection related to MACEs risk. Kaplan-Meier survival analysis and Cox proportional hazards regression model were used to compare the differences in MACEs risk among the four groups. Restricted cubic spline （RCS） and subgroup analysis were performed to determine the relationship between the TyG index and MACEs risk. The area under the receiver operating characteristic （ROC） curve （AUC）， calibration curve and Hosmer-Lemeshow test， and decision curve analysis （DCA） were plotted to evaluate the predictive value of the TyG index for MACEs risk. ResultsThe median follow-up time of the included patients was 2.45 years. During the follow-up period， 313 cases （36.52%） of new MACEs occurred. The incidence of MACEs in Q1， Q2， Q3， Q4 group was 28.17% （60/213）， 29.05% （61/210）， 39.45% （86/218） and 49.07% （106/216）， respectively. Kaplan-Meier survival analysis suggested statistically significant differences in MACEs risk among the four groups （P＜0.001）. Cox proportional hazards regression model analysis found that the risk of MACEs in patients with high TyG index increased by 60.1% （P＜0.01）. Using Q1 as the reference， the MACEs risk in Q2， Q3 and Q4 groups gradually increased， and the trend was statistically significant （P＜0.05）. RCS model suggested that the TyG index was nonlinearly associated with the MACEs risk （P＜0.001）. The TyG index had a good predictive performance for MACEs risk according to ROC analysis （AUC=0.758， 0.724-0.792） and Hosmer-Lemeshow test （χ² = 4.319， P = 0.827）. Additionally， DCA analysis also suggested a good clinical efficacy of the TyG index for predicting MACEs. Subgroup analysis showed that different baseline TyG index was positively correlated with the MACEs risk in the stratification of age， male， BMI， history of diabetes and hypertension， and low-density lipoprotein cholesterol （LDL-C）≥1.8 mmol·L^-1（P＜0.05）. ConclusionThe elevated TyG index is closely corrected with an increased risk of MACEs in CHD patients with blood stasis syndrome after PCI， indicating a guiding significance for early risk stratification and clinical decisions.

Objective    To summarize the reoperation experience for complete atrioventricular septal defect (CAVSD) with severe left atrioventricular valve regurgitation (LAVVR) by standardized mitral repair-oriented strategy. Methods    From 2016 to 2019, 11 CAVSD patients underwent reoperation for severe LAVVR by standardized mitral repair-oriented strategy at Fuwai Hospital, including 5 males and 6 females with a median age of 56 (22-152) months. The pathological characteristics of severe LAVVR, key points of repair technique and mid-term follow-up results were analyzed. Results    The interval time between the initial surgery and this surgery was 48 (8-149) months. The aortic cross-clamp time was 54.6±21.5 min and the cardiopulmonary bypass time was 107.4±38.1 min, ventilator assistance time was 16.4±16.3 h. All patients recovered smoothly with no early or late death. The patients were followed up for 29.0±12.8 months, and the echocardiograph showed trivial to little mitral regurgitation in 5 patients, little regurgitation in 5 patients and moderate regurgitation in 1 patient. The classification (NYHA) of cardiac function was class Ⅰ in all patients. Conclusion    Standardized mitral repair-oriented strategy is safe and effective in the treatment of severe LAVVR after CAVSD surgery, and the mid-term results are satisfied.

Objective    To report the short-term outcomes of a standardized, simplified and reproducible strategy of mitral valvuloplasty (MVP), which was focused on leaflet foldoplasty and anatomic anomalies of congenital mitral regurgitation (MR). Methods    Consecutive 74 patients who underwent MVP by our standardized strategy in our institution from 2016 to 2018 were included retrospectively. There were 30 males and 44 females with a median age of 18.5 (6-146) months and weight of 15.4 (7-51) kg. Results    Anatomic anomalies of MR included: (1) subvalvular apparatus: 72 (97.3%) patients with mal-connected chordae tendineae, 31 (41.9%) with absent chordae tendineae and 14 (18.9%) with fused or dysplastic papillary muscle; (2) leaflet: 10 (13.5%) patients with cleft of anterior leaflet, 61 (82.4%) with leaflet prolapse including 56 (91.8%) with anterior leaflet prolapse; (3) annulus: 71 (95.9%) patients with annular dilatation. Leaflet foldoplasty was performed in 61 (82.4%) patients with leaflet prolapse. All patients were successfully discharged and 4 (5.4%) patients were with moderate MR. The follow-up time was 22.0 (9.1-41.8) months. During the follow-up period, 3 patients had moderate MR and 1 patient had reoperation for severe MR. All patients were in normal cardiac function with a mean left ventricular ejection fraction of 66.0%±6.1%. In addition, the mean left ventricular end-diastolic dimension was 31.8±6.0 mm, which was significant smaller than that before the operation (t=6.090, P<0.000 1). Conclusion    The standardized leaflet foldoplasty with resection of mal-connected chordae tendineae and posterior annuloplasty technique is safe and feasible with favorable short-term outcomes in MR patients.

Objective    To summarize the clinical outcomes and experience of surgical treatment for patients with complete atrioventricular septal defect (CAVSD) above the optimal age for surgery. Methods    We retrospectively reviewed clinical data of 163 simple type CAVSD patients less than 7 years who underwent operations in Fuwai Hospital from 2002 to 2013. The patients were divided into a normal group (n=84, including 37 males and 16 females with an average age of 7.6±2.7 months) and an over-age group (n=79, including 30 males and 49 females with an average age of 34.6±19.6 months) according to whether the age was more than 1 year. Results    The average aortic cross clamp time (88.3±24.4 min vs. 106.1±35.4 min, P<0.001) and cardiopulmonary bypass time (123.6±31.1 min vs. 142.6±47.1 min, P=0.003) were statistically different between the two groups. During the follow-up period (the normal group 53.3±43.9 months, the over-age group 57.2±48.2 months), there was no statistical difference in all-cause mortality (10.7% vs. 8.9%, P=0.691), the incidence of moderate or severe left atrioventricular valve regurgitation (16.7% vs. 21.5%, P=0.430) and reintervention rate (3.6% vs. 0.0%, P=0.266) between the two groups. No left ventricular outflow tract obstruction and complete atrioventricular block occurred in both groups. Conclusion    For CAVSD children above the optimal age, rational surgical treatments can also achieve satisfying results.

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated proteins (Cas) system is a hotspot of gene editing and gene expression research, in which CRISPR/Cas13 system provides a new direction for RNA interference and editing. In this study, we designed and synthesized the corresponding gRNAs of CRISPR/Cas13a and CRISPR/Cas13b systems in non-homologous end joining (NHEJ) pathway, such as Ku70 and Lig4, and then detected the expression of ku70 and lig4 in HEK293T cells. The CRISPR/Cas13a system could efficiently knockdown the mRNA expression of ku70 and lig4 more than 50%, and CRISPR/Cas13b system also suppressed ku70 and lig4 about 92% and 76%, respectively. Also, CRISPR/Cas13a, b systems could down-regulate Ku70 and Lig4 proteins level to 68% and 53%, respectively. The study demonstrates that the CRISPR/Cas13 system could effectively knockdown the expression of RNA and protein in HEK293T cells, providing a new strategy for gene function and regulation research.
CRISPR-Cas Systems ; DNA Ligase ATP ; genetics ; Gene Expression Regulation ; genetics ; Gene Knockdown Techniques ; HEK293 Cells ; Humans ; Ku Autoantigen ; genetics