1.CircRNA Circ_0120051 Inhibits the Fibrotic Phenotype of Myocardial Fibroblasts via Targeting miR-144-3p/IDH2 Axis
Yu LIANG ; Zhiqin HU ; Yihong WEN ; Huayan WU ; Ya WNAG ; Yupeng LIU ; Zhixin SHAN ; Xianhong FANG
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(2):196-205
		                        		
		                        			
		                        			ObjectiveTo investigate the regulatory effect of circular RNA circ_0120051 on the fibrotic phenotype of cardiac fibroblasts and the potential mechanism involved. MethodsThe expression of circ_0120051 and its host gene of solute carrier family 8 member A1(SLC8A1) mRNA in the myocardium of healthy organ donors (n=24) and heart failure (HF) patients (n=21) were assessed by real-time quantitative polymerase chain reaction (RT-qPCR) assay. RNA stability of circ_0120051 was identified by RNase R exonuclease digestion assay. The cytoplasmic and nuclear distribution of circ_0120051 in human cardiomyocyte AC16 was detected by RT-qPCR assay. The expression of fibrosis-related genes in mouse cardiac fibroblasts (mCFs) with adenovirus-mediated overexpression of circ_0120051 was detected by RT-qPCR and Western blot assay, respectively. The effect of overexpression of circ_0120051 on the migration activity of mCFs was evaluated by wound-healing assay. RNA co-immunoprecipitation (RIP) was conducted to detect the interaction between circ_0120051 and miR-144-3p. The binding site of miR-144-3p in the 3'-UTR of isocitrate dehydrogenase 2 (Idh2) mRNA was identified by the dual luciferase reporter gene assay. ResultsCirc_0120051 was significantly up-regulated in the myocardium of HF patients, while the mRNA expression of its host gene SLC8A1 was not changed. Circ_0120051 was mainly located in the cytoplasm of human AC16 cells. Results of RNase R exonuclease digestion revealed that circ_0120051 possesses the characteristic stability of circular RNA compared to the linear SLC8A1 mRNA. Overexpression of circ_0120051 could inhibit the expression of fibrosis-related gene in mCFs and mCFs migration. RIP assay confirmed the specific interaction between circ_0120051 and miR-144-3p. Transfection of miR-144-3p mimic could efficiently promote the expression of fibrosis-related genes in mCFs and reverse the inhibitory effect of circ_0120051 on the fibrotic phenotype of mCFs. Results of the dual luciferase reporter gene assay confirmed the interaction between miR-144-3p and the 3'-UTR of Idh2. Transfection of miR-144-3p transcriptionally inhibited Idh2 expression, and overexpression of circ_0120051 enhanced IDH2 expression in mCFs. MiR-144-3p mimic and Idh2 small interfering RNA (siRNA) could consistently reverse the inhibitory effects of circ_0120051 on fibrosis-related genes expression in mCFs and mCFs migration. ConclusionsCirc_0120051 inhibits the fibrotic phenotype of cardiac fibroblasts via sponging miR-144-3p to enhance the target gene of IDH2 expression. 
		                        		
		                        		
		                        		
		                        	
2.Comparison of the efficacy and safety of cisplatin, etoposide, and irinotecan combined with chemotherapy and topotecan monotherapy as second-line treatment for patients with sensitive relapsed SCLC
Liang ZHANG ; Xianhong LIU ; Ying LIU ; Lianwei BAI ; Ying CHENG
Chinese Journal of Clinical Oncology 2019;46(3):133-137
		                        		
		                        			
		                        			Objective: To investigate whether combination chemotherapy with cisplatin, etoposide, and irinotecan was better than topotecan alone as second-line chemotherapy in patients with sensitive relapsed small cell lung cancer (SCLC). Method: Between September, 2014 and September, 2017, the patients'data were collected in Jilin Province Cancer Hospital. All patients were diagnosed with sensitive relapsed SCLC. Thirty-six patients received combination chemotherapy containing cisplatin plus etoposide plus irinotecan, and 42 patients received topotecan alone. Combination chemotherapy consisted of five 2-week courses of intravenous cisplatin 25 mg/m2 on days 1 and 8, intravenous etoposide 60 mg/m2 on days 1-3, and intravenous irinotecan 90 mg/m2 on day 8. Topotecan therapy consisted of at least one course of intravenous topotecan 1.5 mg/m2 on days 1-5, every 3 weeks. The primary endpoints were progression-free survival (PFS) and overall survival (OS), and safety was assessed in all patients who received at least one dose of drugs. Results: PFS was significantly longer in the combination chemotherapy group [median 5.3 months, 95% confidence interval (CI) 4.3-5.8] than in the topotecan group (3.2 months, 95% CI: 2.7-4.0;P=0.0030); OS was also significantly increased in the combination chemotherapy group (median 16.3 months, 95% CI: 13.8-19.1) than in the topotecan group (13.1 months, 95% CI: 10.2-15.4; P=0.0097). The most common grade 3/4 adverse events were neutropenia [31 (86.1%) patients in the combination chemotherapy group vs. 28 (66.7%) patients in the topotecan group], anemia [26 (72.2%) vs. 10 (23.8%)], leucopenia [29 (80.6%) vs . 21 (50.0%)], and thrombocytopenia [13 (36.1%) vs . 11 (26.2%)]. One treatment-related death (febrile neutropenia with pulmonary infection) occurred in the combination chemotherapy group, and none occurred in the topotecan group. Conclusions:Combination chemotherapy with cisplatin plus etoposide plus irinotecan could be considered a treatment option in second-line che-motherapy for selected patients with sensitive relapsed SCLC. However, the combination chemotherapy group had a higher incidence of adverse events than the topotecan group, and appropriate drug dosages should be explored.
		                        		
		                        		
		                        		
		                        	
3.Mid and long-term outcomes of catheter ablation of recurrent atrial tachycardias post Mini-Maze surgery
Sulin ZHENG ; Xianzhang ZHAN ; Yumei XUE ; Xianhong FANG ; Hongtao LIAO ; Hai DENG ; Wei WEI ; Zili LIAO ; Fangzhou LIU ; Yang LIU ; Yuanhong LIANG ; Shulin WU
Chinese Journal of Interventional Cardiology 2017;25(7):372-378
		                        		
		                        			
		                        			Objective To analyze the clinical characteristics and follow-up data of catheter ablation of recurrent atrial tachycardias (ATs) after Mini-Maze surgery,and to explore prognostic factors for recurrence.Methods 59 patients in Guangdong General Hospital with ATs post Mini-Maze and concomitant open-heart surgery from April.2010 to June.2015 were included.According to high density precise mapping,activation mapping,voltage mapping and entrainment mapping,they underwent electrophysiological study and ablation which was guided by three-dimensional mapping system.All patients were followed up regularly.We explored the prognostic factors for recurrence by the Cox regression analysis.Results There were 88 types of ATs being mappedwith mean (1.49 ± 0.75) types of ATs identified per case.Most ATs were macro-reentry ATs(67/88,76.1%)and focal ATs (20/88,22.7%),respectively.56 patients (94.9%) achieved immediate ablation success.In a mean follow-up of (30.8 ± 17.7) months,recurrences were observed in 12 patients after the first time catheter ablation.Recurrent time was 3.5 (1.3,12.0) months and the overall ablation success rate was 74.6% (44/59).6 patients received second ablation and the achievement of freedom from arrhythmias reached 79.7% (47/59).Multivariate analysis showed that the LA diameter was the independent predictor for recurrence (HR 1.108,95% CI 1.002 to 1.226,P =0.045).Conclusion Catheter ablation of ATs post Mini-Maze with concomitant surgery is save and feasible.LA diameter is the independent predictor for recurrence.
		                        		
		                        		
		                        		
		                        	
4. Antagonism of lovastatin on oxidative stress and apoptosis in primary rat hippocampal neurons induced by β-amyloid peptide
Longchun TAN ; Liang ZHAO ; Xianhong LIU ; Chengmin DENG ; Zhizhong GUAN
Chinese Journal of Pathology 2017;46(7):491-496
		                        		
		                        			 Objective:
		                        			To investigate the effect of lovastatin on oxidative stress and apoptosis in neurons induced by β-amyloid peptide (Aβ).
		                        		
		                        			Methods:
		                        			Primary culture of rat hippocampal neuron was treated with Aβ oligomers alone or combined with lovastatin. The levels of OH-, H2O2, O2·-, malondialdehyde, superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities were measured by biochemical methods and protein expression of caspase-3 and bcl-2 was detected by Western blot.
		                        		
		                        			Results:
		                        			As compared with the control group, treatment of 0.5 μmol/L Aβ oligomers for 48 h led to significant increase of OH-, H2O2, O2·- and malondialdehyde content, inhibition of SOD and GSH-PX activities, enhanced caspase-3 expression and decreased bcl-2 expression. Interestingly, these neurotoxic modifications on the levels of OH-, H2O2, O2·- and malondialdehyde content, SOD and GSH-PX activities, and the protein expression of cleaved caspase-3 and bcl-2 were significantly attenuated when the cells were pretreated with 0.1 μmol/L lovastatin for 24 h before exposure of Aβ oligomers.
		                        		
		                        			Conclusion
		                        			Lovastatin may play an important role in antagonizing the neurotoxicity of Aβ through a mechanism likely related to the inhibition of oxidative stress. 
		                        		
		                        		
		                        		
		                        	
5.Hippocampal corticotropin releasing hormone mRNA expression and neuroprotective mechanism of adrenocorticotropic hormore in immature rats after N-methyl-D-aspartate induced spasm seizures
Lei WANG ; Baoqin GAO ; Liping ZOU ; Xianhong LIANG ; Chunmei YAO ; Yajie WANG
Chinese Journal of Neuromedicine 2017;16(4):325-328
		                        		
		                        			
		                        			Objective To study the hippocampal corticotropin releasing hormone (CRH) mRNA expression and neuroprotective mechanism of adrenocorticotropic hormore (ACTH) in immature rats after N-methyl-D-aspartate (NMDA)-induced spasm seizures.Methods Sixty 10-day-old Wistar rats were randomly divided into blank control group,NMDA-induced seizure group and ACTH treatment group (n=20).Rats in the blank control group did not give any treatment;rat models of infantile spasm in the NMDA-induced seizure group and ACTH treatment group were induced by intraperitoneal injection of NMDA (7 mg/kg) for a consecutive 7 d;3 h after NMDA injection,intraperitoneal injection of ACTH 0.5 mg/(kg· d) was performed in the rats of ACTH treatment group,and NMDA-induced seizure group was given an equal volume of saline.By in situ hybridization (ISH),the mean optical density of CRH mRNA-positive neurons in the hippocampus was measured.Results In the ACTH treatment group,the latencies of epileptic seizures one week after treatment were significantly prolonged as compared with those before treatment,and the scores of epileptic seizures one week after treatment were significantly decreased as compared with those before treatment (P<0.05);the latencies of epileptic seizures were significantly prolonged and the scores of epileptic seizures were significantly decreased in the ACTH treatment group as compared with those in the NMDA-induced seizure group (P<0.05).The CRH mRNA expression in NMDA-induced seizure group was significantly increased as compared with that in the blank control group (P<0.05),and the CRH mRNA expression in the ACTH treatment group was significantly decreased as compared with that in the NMDA-induced seizure group (P<0.05).Conclusion Systemic ACTH has neuroprotective effect via down-regulating the hippocampal CRH mRNA expression.
		                        		
		                        		
		                        		
		                        	
6.The equality of financing and compensation of New Rural Cooperative Medical Scheme:An empirical analysis in an eastern province in China
Xiaohe WANG ; Yu QIAN ; Xianhong HUANG ; Meng ZHANG ; Liang ZHANG
Chinese Journal of Health Policy 2014;(6):28-34
		                        		
		                        			
		                        			Objective:To analyse the degree of equality of New Rural Cooperative Medical Scheme (NRCMS) in different economic regions. We provide a reference for equal development of the NRCMS and the reform of the political system and mechanism under the provincial-controlled county fiscal system. Methods:A typical province was chosen with provincial-controlled county fiscal system was fully implemented several years. We collected data on coverage, financing and compensation for the NRCMS from 2005 to 2011. We used the variable coefficient, uniformity coefficient, Theil Index for comprehensive evaluation. Results:Per capita financing has not reached the bottom line. From 2005 to 2011, inter-re-gional and intra-regional variation coefficient, Theil index of service coverage, financing level and hospital actual compen-sation has declined year by year. The degree of inequality in economically developed regions was greater than in less eco-nomically developed regions and economic medium region. Conclusion:The degree of equalization of the NRCMS in the province continuously improved. Innovation of provincial-controlled county fiscal system and mechanism provides a favora-ble environment and forming conditions for equalizing the development of the NRCMS. The paper suggested exploring and building fiscal classification step transfer payment institution and dynamic prediction model of the NRCMS, further optimi-zing financing mechanism, promoting the provincial management system of the NRCMS as soon as possible in order to pro-mote the equalization development.
		                        		
		                        		
		                        		
		                        	
7.Strategy and effect of schistosomiasis emergency control after earthquake in Lushan County
Chaofu WANG ; Chengxiang WANG ; Lirong MOU ; Bo ZHONG ; Yang LIU ; Zisong WU ; Liang XU ; Xianhong MENG ; Zongcai YANG ; Yong CHENG ; Jinhua ZHU ; Qifu ZHOU
Chinese Journal of Schistosomiasis Control 2014;(5):557-558,572
		                        		
		                        			
		                        			Objective To evaluate the effects of measures on the schistosomiasis control after the earth quake in Lushan County so as to provide the experiences for post-disaster schistosomiasis control. Methods The measures taken in schistosomi-asis control after the earth quake were reviewed in Lushan County in 2013 and the epidemic situation of schistosomiasis was in-vestigated and the results were analyzed. Results The schistosomiasis control in floating population and the control of Oncome-lania hupensis snails were enhanced and no schistosome infections were found in both human and livestock. No infected snails and infested water were found. Conclusion The measures of schistosomiasis control after the disaster are effective in Lushan County and the goal to prevent major plague after the earth quake is achieved.
		                        		
		                        		
		                        		
		                        	
8.Study of early recovery of left ventricular rotation and torsion after percutaneous coronary intervention using two dimensional speckle tracking echocardiography
Zheng LI ; Cuizhen PAN ; Xianhong SHU ; Lili DONG ; Jie CUI ; Xianglin TANG ; Lilong LIANG
Chinese Journal of Ultrasonography 2013;(6):466-469
		                        		
		                        			
		                        			Objective To evaluate left ventricular rotation and torsion and its early recovery after percutaneous coronary intervention (PCI) in patients with coronary heart disease and normal left ventricular ejection fraction (LVEF) using two dimensional speckle tracking echocardiography.Methods Twenty three consecutive patients with coronary heart disease and normal LVEF were divided into group B (with coronary stenosis <70%) and group C (with coronary stenosis >70% and with PCI).Along with 11 healthy controls(group A),indices including basal rotation (BR),apical rotation (AR),left ventricular torsion (LVT) and normalized time to peak were compared among groups,correlative analysis was made between LVT and each indices mentioned above,indices of group C before and 24 hours after PCI were compared.Results AR,LVT in group B and C reduced relative to group A (P <0.05),meanwhile time to peak of BR in group C shortened relative to other groups.BR,AR and normalized time to peak of BR were correlated to LVT respectively.BR and LVT in group C increased after PCI(P <0.05).Conclusions AR was sensitive to ischemia,the reduction of time to peak of BR in group C might be restriction and compensation.Sensitive to early recovery of left ventricular function after reperfusion,BR could be a predictive index of early effect of percutaneous coronary intervention.
		                        		
		                        		
		                        		
		                        	
9.Developing the social evaluation strategy and the study framework for public hospitals as seen from the social governance perspective
Xiaohe WANG ; Xianhong HUANG ; Rui LI ; Hong ZHAO ; Jianmin GAO ; Qing GUO ; Liang ZHANG
Chinese Journal of Hospital Administration 2011;27(4):241-245
		                        		
		                        			
		                        			Social governance is a novel form of public administration made based on the analysis and judgment for the power pattern in the course of social administration, a model advocated in the premise of a clearly positioned relationship among the government, marketplace, society and citizens.Social evaluation is an effective carrier and means leveraging the social governance theory, which has found extensive and outstanding use in such issues as expression of public interests and responsibilities,and in tackling sharp social problems. The authors called into play the scenario analysis based on public hospital management reforms with the social governance theory. In addition, they explored social governance at home and abroad as well as the theories, meaning and progress of social evaluation, and analyzed the pathways and probes in social evaluation and governance in the fields in question. On such basis, the paper proposed to explore and develop the social evaluation strategies and study framework for public hospitals in terms of healthcare management, aiming at building the social governance system and policies for public hospitals.
		                        		
		                        		
		                        		
		                        	
10.Intravenous administration of rat bone marrow derived endothelia cells in rats after stroke
Chunxue WANG ; Yanfang LIU ; Shujing MAO ; Dejun LIANG ; Xianhong LIANG ; Yongjun WANG ; Hong WAN ; Liping LIU ; Junhua LI ; Jing ZHAI
Chinese Journal of Rehabilitation Theory and Practice 2005;11(9):689-692
		                        		
		                        			
		                        			ObjectiveTo observe the therapeutic benefit of administration of endothelial cells derived from rat bone marrow cells in ischemic stroke rats and to explore the related mechanism.MethodsPrepared endothelial cells from bone marrow stromal cells (BMSC) of rats, which were multiplied and differentiated in the medium with 400ng/ml rhGM-CSF in vivo. Rats were subjected to permanent cerebral middle artery occlusion (MCAO) models(n=45). Injected intravenously via tongue vein with 3×106 endothelial cells 24 h after stroke for test groups(n=15); injected same amount PBS for control group 1(n=15); control groups without any intervention after stroke (n=15). Neurologic functional behaviour tests (postural reflex test, limb use asymmetrical test and corner test) were performed before transplantation and 1,3,5,7,14 d after stroke. Meanwhile, immunohistochemistry staining was used to identify for vascular endothelial growth factor (VEGF) and its receptor FLK-1 expression in ischemic brain tissue.ResultsSignificant recovery of neurological function was detected in rats treated with endothelial cells on the 7th day and 14th day after stroke, compared with control group 1 and group 2(P<0.05);The number of positive cells of VEGF, FLK-1 were significant more in the peri-ischemic tissue and ipsilateral cortex, compared with non-ischemic hemisphere. The maximum number of positive cells was in the test group which was treated with endothelial cells(P<0.05);VEGF was mainly expressed at neurons, glial cells and part of endothelial cells; FLK-1 was mainly expressed at endothelial cells and part of neurons and glial cells;capillary hyperplasia was demonstrated more at the ischemic hemisphere in the rats treated with endothelial cells, compared with control group 1 or 2.ConclusionEndothelial cells derived from bone marrow cells in rats could improve neurological outcome in rats with ischemic stroke. The effect starts to be significant on the 7th day after transplantation and it shows more significant effect on the 14th day. Endothelial cells transplantation will enhance VEGF, FLK-1 expression at ischemic area and increases capillary hyperplasia formation, which may relate to the potential mechanism of neurological outcome improvement post stroke in rats.
		                        		
		                        		
		                        		
		                        	
            

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