Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

Objective:To explore the effects of the γ-aminobutyric acid(GABA) neurons and melanin-concentrating hormone (MCH) neurons of the nucleus accumbens (NAc)-lateral hypothalamic area (LHA) neural pathway on the rewarding feeding(palatable food sweat condensed milk) in the obesity rats.Methods:Total 142 male Wistar rats of SPF grade were divided into normal diet (ND) group ( n=68) and high-fat diet induced obesity (DIO) group ( n=74) according to the principle of body mass matching. The rats in the two groups were given normal diet and high-fat diet for 8 weeks. Eight weeks later, 6 DIO rats were randomly selected to observe the nerve projection from GABA neurons in NAc to MCH neurons in LHA by fluorogold retrograde tracing combined fluorescence immunohistochemistry. And the expressions of c-Fos and MCH in LHA after ingestion of sweet condensed milk(rewarding feeding) were observed by fluorescence immunohistochemistry (6 rats in each group). GABA receptor agonist Musimol or GABA receptor antagonist Bicuculine was microinjected into the nucleus of LHA to observe the effect of GABA on rewarding food intake in ND and DIO rats ( n=8 in each group), and the changes of rewarding food intake after blocking MCH signal ( n=8 in each group). SPSS 17.0 was used for statistical analysis, two-way ANOVA and post hoc Bonferroni test were used for comparison among multiple groups, and t-test was used for comparison between two groups. Results:After 8 weeks of high-fat diet modeling, the intake of delicious food in DIO rats was significantly higher than that in ND rats((12.52±2.29) mL, (7.45±1.23) mL, t=4.778, P<0.01) after satiety.The results of fluorogold retrograde tracing combined with fluorescence immunohistochemistry showed that GABA neurons in NAc projected nerve fibers to neurons in LHA, and GABA A receptors in some neurons in LHA coexisted with MCH.The results of NAc-LHA pathway on delicious food intake showed that the interaction between rat group and drug intervention was significant( F=9.869, P<0.01). Simple effect analysis showed that the intake of delicious food after microinjection of Musimol into LHA nucleus of ND rats was significantly lower than that of microinjection normal saline ((4.25±1.38) mL, (7.29±1.49) mL, P<0.01), while the intake of delicious food after injection of Bicuculine was significantly higher than that of microinjection normal saline((10.72±2.11) mL, (7.29±1.49) mL, P<0.05). The intake of delicious food after microinjection of Musimol into LHA nucleus in DIO group was significantly lower than that of microinjection normal saline((3.51±1.77)mL, (13.68±2.95) mL, P<0.01), but there was no significant difference between microinjection Bicuculine and microinjection normal saline ((14.83±3.44) mL, (13.68±2.95) mL, P>0.05). The results of blocking MCH signal on delicious food intake showed that the interaction effect between SNAP-94847 and Bicuculine intervention was not significant ( F=1.468, P>0.05). The main effect of SNAP-94847 intervention was significant ( F=15.880, P<0.01)and the main effect of Bicuculine intervention was significant ( F=6.930, P<0.05). After intracerebroventricular injection of MCH receptor blocker SNAP-94847, the delicious food intake of ND rats was significantly less than that of injection normal saline((4.78±1.72) mL, (7.63±2.77) mL, P<0.05), and it was not affected by pre injection of Bicuculine in LHA ((6.24±2.18) mL, (4.78±1.72) mL, P>0.05). In the DIO rats, the interaction effect between SNAP-94847 and Bicuculine intervention was not significant( F=0.006, P>0.05). The main effect of SNAP-94847 intervention was significant ( F=18.46, P<0.01) and the main effect of Bicuculine intervention was not significant ( F=2.059, P>0.05). After intracerebroventricular injection of MCH receptor blocker SNAP-94847, the delicious food intake of DIO rats was significantly lower than that of injection normal saline((6.89±2.11) mL, (12.19±4.36) mL, P<0.05), and it was not affected by pre injection of Bicuculine in LHA ((8.72±2.26) mL, (6.89±2.11) mL, P>0.05). Conclusion:GABAergic signal in NAc can regulate the expression of MCH in neurons of LHA. In the DIO rats, the sensitivity of MCH neurons in LHA to satiety signal decreases and the hedonic feeding increases.

Objective To compare the diagnostic accuracy of magnifying chromoendoscopy (MCE) and endoscopic ultrasonography (EUS) for preoperative endoscopic assessment of the invasion depth of colorectal laterally spreading tumour(LST).Methods Data of 104 cases of colorectal LST were included.With the final pathological diagnosis as the golden standard,the accuracies of MCE and EUS for preoperative assessment of the invasion depth of colorectal LST were compared.Results The diagnostic accuracies of MCE and EUS for evaluating the invasion depth of LST were 89.4％ (93/104) and 73.1％ (76/104),respectively(P＜0.05).The lesion size and the endoscopist could affect the accuracy of the EUS evaluation (P=0.017,OR=3.561;P=0.035,OR =1.399).The accuracy of EUS seemed to show a downward trend for colorectal LST of larger diameters.Conclusion Both MCE and EUS are effective for evaluating the invasion depth of colorectal LST,but the accuracy of MCE may be higher than that of EUS.Large diameter of the lesion and the doctor's experience inadequacy may be the risk factors for the accuracy of EUS.

Objective: To compare the consistency of thyroid stimulating hormone (TSH) results from four chemiluminescence assays. Methods: A total of 102 fresh serum samples from Peking Union Medical College Hospital during March 2018 and April 2018 were collected for precision evaluation and methodological comparison referring to CLSI EP15-A2 and EP9-A2 protocols. The levels of serum TSH were detected by Abbott i2000 (system A), Beckman DXI800 (system B), Siemens ADVIA Centaur XP (system C) and Roche e601 (system D) automatic chemiluminescence analyzers and their matching reagents, respectively. The obtained results were compared with the passing-bablok and Bland Altman methods. Taking 0.27 μIU/mL and 5.33 μIU/mL as the medical decision level, the expected bias of each detection system was compared. Results: The precisions of systems A,B,C and D were 1.7%-3.3%， 2.3%- 3.9%，0.7%-2.3% and 0.6%-1.5%,respectively. The median (P 25,P 75) of TSH concentrations detected by systems A,B,C and D were 1.898 (0.518,4.809)μIU/mL, 2.819 (0.719,7.020)μIU/mL,2.502 (0.692,6.888)μIU/mL and 3.105 (0.886, 7.905)μIU/mL, respectively. The coefficients of determination (R 2 ) of regression equation were above 0.975 for 4 detection systems. The correlation coefficients (r), intercepts and slopes of 4 detection systems were 0.993 5-0.997 1, 0-0.06 and 0.59-1.15, respectively, and systems B and C had the best correlations with 1.02 of slope and 0 of intercept. The deviation plot showed that the bias% of 4 detection systems was between -48.1% and 17.3%. Among them, systems A and D had the largest bias, while systems B and C had the lowest bias. The expected bias of 4 detection systems at the medical decision level was -40.7%-37.2%. Conclusion The consistency between Beckman and Siemens TSH detection systems is good, while those of Roche and Abbott TSH detection systems are different from the other two.

Objective To investigate the prevalence and possible factors of hypouricemia in Peking Union Medical College Hospital.Methods A retrospective investigation.Serum uric acid, lipids, glucose and other chemistry tests were analyzed among 83176 outpatients(Male:30795,Female:52381), 15849 inpatients(Male:7402,Female:8447)and 24081 healthy subjects(Male:11859,Female:12222)in Peking Union Medical College Hospital from December 2015 to April 2016.Grouped by gender and age, the prevalence of hypouricemiawas analyzed in all subjects and the etiology and possible risk factors of hypouricemia were explored among all patients.Results The serum uric acid of outpatients,inpatients and healthy subjects were 286(235-348)μmol/L, 282(226-348)μmol/L and 298(244-358)μmol/L, respectively.And the prevalence were 0.6%(499/83176),2.5%(390/15849)and 0.2%(39/24081), respectively.The prevalence of hypouricemia ofwomen was significantly higher than that ofmen(outpatients:0.7%vs 0.4%,P<0.001;inpatients:2.8%vs 2.1%,P=0.004;healthy subjects:0.30%vs 0.04%, P<0.001).After analyzing 507 hypouricemia patients, the top three clinical diagnoses that related with hypouricemia were kidney diseases, tumor and rheumatic diseases.Compared with the control group, the prevalence of hypouricemia in hypertriglyceridemia group and group with eGFR higher than 90 ml/(min· 1.73 m2)were lower(OR:0.33, 95% CI:0.21-0.50; OR:0.16, 95% CI:0.09-0.29), and the prevalence of hypouricemia in hyperglycemia group was higher(OR:1.62, 95% CI:1.12-2.35). Conclusion The prevalence of hypouricemia of Chinese women was higher than that of men and may be related with TG,Glu and eGFR.

Objective To investigate the changes of prevalence of hyperuricemia ( HUA) and its correlations with blood glucose and lipid in healthy adults receiving physical examination at Peking Union Medical College Hospital (PUMCH) from 2012 to 2017. Meth-ods An observational approach was adopted for the data analysis.The test results of uric acid (UA),fasting blood glucose (FBG),to-tal cholesterol (TC),triacylglycerol (TG),low density lipoprotein cholesterol (LDL-C),high density lipoprotein cholesterol (HDL-C), creatinine (Cr) and Urea of 399 089 cases (206 881 males and 192 208 females) at PUMCH from January 2012 to December 2017 were collected and statistically analyzed.Results The total prevalence of HUA was 17.4% in which the prevalence of males was signif-icantly higher than that of females (25.6% vs 8.5%,χ2＝20 234.850,P＜0.01).During the years of 2012 to 2017,the prevalence of HUA was 26.5%,24.7%,28.6%,23.9%,24.8% and 24.5% in males,and 13.8%,6.3%,7.9%,6.1%,6.2% and 6.8% in females for each year respectively.The prevalence of HUA in males aged 18 to 64 years old was significantly higher than that in the age-matched fe-males (all P＜0.05).However, the prevalence of HUA in males aged≥65 years old was similar to the age-matched females.There was no statistically significant difference of HUA prevalence between males and females aged ≥65 in 2013,2015,2016 and 2017 ( χ2＝1.792,0.017,1.440 and 0.205 respectively;all P＞0.05).The percentages of hyperlipidemia in both males and females of HUA group were higher than those of non-HUA group respectively (all P＜0.01).The percentage of hyperglycemia in males of non-HUA group was higher than that of HUA group,but the percentage of hyperglycemia in females of non-HUA group was lower than that of HUA group ( all P＜0.01).High levels of TC,TG and FBG were risk factors of HUA with increased OR values in increased concentrations of TC,TG and FBG,respectively.Conclusion During the recent 6 years, in healthy adults receiving physiced examination at PVMCH, the preva-lence of male HUA diagnosed was at overall high level,but the prevalence of female HUA was in decreasing and relatively stable trend. Hyperlipidemia and hyperglycemia should be the risk factors of HUA.

Objective To validate the performance of six enzymatic glycated albumin reagents and evaluate their clinical application.Methods The performance of six enzymatic glycated albumin reagents(labled as A,B,C,D,E,F) from Beijing Jiuqiang Co, Beijing Lideman Co,Ningbomeikang Co, Beijing Haomai Co, Sichuan Maike Co and Asahi Kasei Co were assessed on Olympus AU5800 automatic biochemistry analyzer.According to the standard of CLSI,the precision,interference and linear correlation of these reagents were assessed.To assess the accuracy of GA% ,we used GA standard material whose value had been assigned using ID-LC/MS method provided by ReCCS.To do the method comparison and determine the consistency of assay, 50 fresh serum samples of T2DM outpatient and 80 fresh serum samples of apparently healthy people in Jan 2016 were tested using six kits.According to the EP28-A3C protocol, the reference range for GA%was validated in 122 apparently healthy individuals undertaking medical examination from January to February 2016 in PUMC.Results The precision,and the ability of anti-interference of the six reagents were good.The accuracy percentage deviation of six reagents was-19.3%-9.2%.The correlation coefficient of domestic reagents A to E and imported reagents F in the determination of GA% was 0.966-0.999, the average absolute bias was 7.0%-10.4%.The coincidence rate of A-E and F in determining abnormal GA% was between 88.5% and 96.9%.The coincidence rate was increased after switching to the reference range for preliminary clinical evaluation.Conclusion Six GA enzymatic kits used in automatic biochemical analyzer have high precision and strong anti-interference ability.Accuracy still needs to be improved.

Objective To explore achieving the consistent method of blood lipid examination by comparing the results of 5 dif-ferent blood lipid detection system commonly used in the use of refernce method to assign freach blood serum before and af-ter calibration.Methods Used the indoor quality control total variation (CV%)to evaluate the 5 blood lipid examination system of the imprecision.Referenced the United States Clinical and Laboratory Standardization Institution (CLSI)9A2 EP program,compared with 54 fresh blood serum in 5 commonly used examination system of Total Cholesterol (TC)and Tri-glyceride (TG),and then estimated the bias between the different detection systems and mean value.8 of the samples were determined by the reference method and estimate the bias of different system.The fresh frozen serum samples assigned by reference method were used to evaluate the above examination system,then compare and estimate the bias again with the same 54 fresh serum samples.Compared the variation of 54 samples in different detection system before and after calibra-tion.Results The TG imprecision of 5 examination system were between 3.76%~23.65%,the TC imprecision between 2.19%~23.43%,that mean the results were good,the r value of TG were between 0.996 7~0.999 6 and the TC were 0.956 2~0.996 7.But there were obvious differences between the results of the systems,and the biggest difference were 14.72%~34.21% in TG and 3.11%~14.57% in TC.After use the serum assignment by reference method,the variation of the systems has been significantly decreased.Conclusion Using the reference method to assign the fresh serum of different blood lipid detection system can effectively improve the consistency of the results.

Objective:To analyze the significance of equipment custodian routine maintenance work and then offer some suggestion of countermeasure.Methods: Twenty four cases of maintenance cassette sterilizer were divided into test group(12 cases), equipment custodian had been trained; control group (12 cases)has not received training. In addition, we analyzed separately the maintenance work with the risk theory and cost-benefit.Results: The total number of failures in the test group was 13, obviously lower than 32 in the control. The risk of all devices under control, the maintenance of the benefits far outweigh the cost.Conclusion:Training equipment custodian, can reduce the incidence of failure, are worthy of promotion.

Objective To assess the interference by calcium dobesilatein 7 peroxidase-baseduric acid assays and to determine its clinical significance.Methods In the in vitro experiments, uric acid in pooled serum with final concentrations of calcium dobesilate additions (0, 2, 4, 8, 16, 32, and 64μg/ml) were measured by 7 peroxidase-based assays.Percent Bias (%) was calculated relative to the drug-free specimen.In the in vivo experiments, changes in serum uric acid and calcium dobesilate concentrations were observed before and after calcium dobesilate administration ( baseline, 0 h, 1 h, 2 h, 3 h, 4 h, 6 h ) involunteers.The interference in different assays was assessed compared with LC-IDMS/MS method. Calcium dobesilate levels in 40 specimens from those taking calcium dobesilate were measured by HPLC method.Of the 40 specimens, 10 were selected to analyse the levels of uric acid by both peroxidase and UV measurement method to assess the impact in clinical status.Results In the in vitro study, concentrations of uric acid measured by 7 peroxidase-based assays were reduced by -6.3%to -21.2%compared with drug-free serum, when theconcentration of calcium dobesilate was16μg/ml.In the in vivo study, comparedto UA levels at 0 h, the biasesof serum uric acid determined by peroxidase method after calcium dobesilate administration(1 h, 2 h, 3 h, 4 h, 6 h) were of -3.33%, -6.79%, -7.49%, -6.07%, -4.09%, respectively.The observed uric acid concentrations for 8 participants measured by enzymatic assays were inhibited by -3.75% to -6.89% at 0 hour and by -16.9% to-22.22% at 2 hours relative to the concentrations measured by the LC-IDMS/MS method. Conclusions Calcium dobesilate produced a clinically significant negative interference with uric acid in all peroxidase-based uric acid assays,which may result in false evaluation of uric acid level in clinical status.Significant differences in the degree of interference were observed among the assays.