1.Effect of dichloroacetate on expression of Kv1.5 in a rat model of pulmonary arterial hypertension
Chinese Journal of Anesthesiology 2011;31(6):735-738
Objective To investigate the effect of dichloroacetate on the expression of Kv1.5 in a rat model of pulmonary arterial hypertension (PAH) .Methods Thirty-two male SD rats weighing 200-250 g were randomly divided into 4 groups ( n = 8 each): normal control group (group C), dichloroacetate control group (group D),PAH group, and PAH + dichloroacetate group (group PD). PAH was induced by left lung resection combined with subcutaneous injection of monocrotaline 60 mg/kg in PAH and PD groups. In group PD, dichloroacetate 80 mg/kg was given through a gastric tube into stomach once a day for 28 consecutive days after monocrotaline injection,while the equal volume of normal saline was given instead of dichloroacetate in group PAH. Group D only received dichloroacetate 80 mg/kg through a gastric tube into stomach once a day for 28 consecutive days. Pulmonary arterial pressure (PAP) was measured at day 28 after monocrotaline injection. The rats were then sacrificed and lung tissues were removed to calculate the percentage of thickness of the tunica media of pulmonary artery and right venicular hypertrophy index and to determine the proliferating cell nuclear antigen (PCNA) and Kv1.5 protein expression (by Western blot) and Kv1.5 mRNA expression (by RT-PCR).Results Compared with group C, the PAP,percentage of thickness of the tunica media, right ventricular hypertrophy index were significantly increased, Kv1.5 mRNA and protein expression was down-regulated and PCNA expression was up-regulated in groups PAH and PD ( P < 0.05). Compared with group PAH, the PAP, percentage of thickness of the tunica media, right ventricular hypertrophy index were significantly decreased, Kv1.5 mRNA and protein expression was up-regulated and PCNA expression was down-regulated in group PD (P < 0.05). There was no significant difference in the indexes mentioned above between group C and group D ( P > 0.05). Conclusion Dichloroacetat alleviates PAH through upregulating Kv1.5 expression in lung tissues and inhibiting pulmonary vascular remodeling in rats.
2.The potential role of sildenafil in serotonin-induced pulmonary arterial SMCs proliferation is mediated via upregualtion of ERK1/ERK2 phosphorylation
Bingbing LI ; Zhen JIANG ; Jianying SHEN
Fudan University Journal of Medical Sciences 2009;36(6):687-691
Objective To explore the underlying mechanism of potential effect of sildenafil on porcine pulmonary artery smooth muscle cells (SMCs) proliferation induced by serotonin. Methods Porcine pulmonary artery SMCs at 3-5 passages were randomly divided into 4 groups: control group (CON), 5-HT group (HT), sildenafil group (SIL) and sildenfil-5HT combined group (S-HT). Pulmonary artery SMCs at exponential growth phase were serum starved with 0.2% FBS for 72 h, followed by sterile PBS, serotonin (10 μmol/L) and sildenafil (1 μmol/L) incubation in CON group, HT group and SIL group, respectively. In combined group (S-HT): pulmonary artery SMCs were serum starved and then exposed to sildenafil for 20 min, followed by serotonin incubation for indicated time. The phosphorylation of extracellular signal regulated kinase (ERK1/ERK2) was measured by Western blot at indicated time points. Flow active cell sorting (FACS) was used to evaluate the ratio of S phase cells in the cell cycle after 24 h of treatment. MTT color metric method was used to analyze SMCs proliferative index after 72 h of treatment. Results Compared with CON group, the phosphorylation of ERK1/ERK2, the percentage of cells in S phase, and the cell proliferation index increased remarkably after incubation with 5-HT (P<0.05). Preincubation with sildenafil followed by serotonin enhanced the phosphorylation of ERK1/ERK2 (p-ERK1/ERK2) and further elevated the percentage of cells in S phase and the cell proliferation index compared with that of HT group. While the total ERK1/ERK2 (t-ERK1/ERK2) was not statistically different among these groups. Conclusions Sildenafil potentiates the proliferative effect of serotonin on pulmonary arterial SMCs via upregulating phosphorylation of ERK1/ERK2.
3.Observation on the Ratio of Apoptosis and Proliferating Cell Nuclear Antigen in Gastric Carcinoma
Shanling GAO ; Bingbing SHEN ; Hui XING
Journal of Chinese Physician 2001;0(07):-
Objective To investigate the ratio of apoptosis to proliferating cell nuclear antigen(PCNA) in gastric carcinoma(GC) and elucidate the possible role of apoptosis and proliferation in the development of GC.Methods Apoptosis and PCNA were examined in 24 cases with gastric carcinoma and in 24 cases of the surrounding non-cancerous tissue embedded in paraffin by TUNEL and immunohistochemical staining technique respectively.Results The study indicated that the proliferation labeling indices(PIs) in GC(51 2) was significantly higher than that in the surrounding non-cancerous tissue(27 4),and the apoptotic indices(AIs) in GC(3 1) was significantly lower than that in the surrounding non-cancerous tissue(5 4)(P
4.Discussion on Medical Information Management Talents Cultivation under Population Health Informatization Background
Lining SHEN ; Bingbing TUO ; Biao XU
Journal of Medical Informatics 2015;(8):2-7
The paper introduces American health informatization talents cultivation scheme, combining the current situation and ex-isting problems of medical information management talents cultivation in China, it proposes medical information management undergradu-ate talents cultivation strategies under the strategic background of population health informatization from three perspectives: curriculum system, teaching staff and teaching mode.
5.The clinical characteristics of etiologies, diagnoses and treatment of emergency gastrointestinal hemorrhage
Ru ZHANG ; Bingbing SHEN ; Jiaming QIAN ; Shubin GUO
Chinese Journal of Internal Medicine 2010;49(1):38-41
Objective To investigate the causes, clinical features, treatment and prognosis of gastrointestinal bleeding (GIB) patients in emergency department.Methods To analyze prospectively the clinical data of 168 GIB patients admitted to the emergency department of Peking Union Medical College Hospital during 2006.1-2006.12.Results (1) General data; male: female = 1.75:1 ( 107: 61) , mean age 13-87(56.5 ±17.8) years with a peak in 60-69 years.The percentage of old patients was significantly higher than that of young and middle age ( 52.4% vs 19.6% and 28.0% , P = 0.000 ).( 2 ) The incidence of acute gastric mucosal lesion in patients taking non-steroidal antiinflammatory drugs ( NSAIDs) ( 18.5% ) was significantly higher than that in patients not taking( 0.7% , P = 0.000 ).( 3 ) 86.9% ( 146/168 ) of the patients had anemia.(4) More patients who took emergency gastroscopy could be diagnosed than those patients who did not (89.4% vs 58.5% , P =0.000), while no significant difference could be seen between patients who took emergency enteroscopy and patients who had non-emergency gastroscopy (20.0% vs 57.9% , P =0.315).(5)The hemostatic ratio in GIB patients due to peptic ulcer was obviously higher than that in GIB patients due to other causes (86.0% vs 40.7% ,P =0.000).The rate of emergency operation for GIB patients was 1.8%.Conclusions Most of the GIB patients admitted to tertiary general hospitals are elderly males.NSAIDs administration is one of the most important causes of upper GIB.Upper GIB patients should have gastroscopy as soon as possible, while emergency coloscopy is of little significance in cases with lower gastrointestinal hemorrhage.
6.Changes m expression of hypoxia-inducible factor 1alpha in proliferated intima of pulmonary arterioles in rats with pulmonary hypertension
Qing SUN ; Yan SHEN ; Jie YAN ; Bingbing LI
Chinese Journal of Anesthesiology 2014;34(12):1471-1474
Objective To evaluate the changes in the expression of hypoxia-inducible factor 1 alpha (HIF-1α) in the proliferated intima of pulmonary arterioles in rats with pulmonary hypertension.Methods Thirty-two pathogen-free male Sprague-Dawley rats,aged 2 months,weighing 200-230 g,were used in the study.Thirty-two rats were randomly divided into 4 groups with 8 animals in each group using a random number table:shamoperation group (group S),left pneumonectomy group (group P),monocrotaline group (group M),and left pneumonectomy combined with monocrotaline group (group PM).The rats underwent left pneumonectomy in P and PM groups.In M and PM groups,monocrotaline 60 mg/kg was injected subcutaneously at 7 days after operation.On day 35 after operation,mean pulmonary artery pressure (mPAP) and right ventricle systolic pressure (RVSP)were measured via direct puncture of right ventricle outflow tract with gauge 24 iv catheter connected to pressure transducer.At the end of experiment,the hearts and right lobes of the lung were excised for measurement of right ventricle hypertrophy index (RVHI) and the thickness of the medial layer (tunica media) of pulmonary arterioles (MT).Vascular occlusion score (VOS) was performed.The expression of HIF-1α,α-smooth muscle actin (α-SMA),and proliferating cell nuclear antigen (PCNA) in the pulmonary arterioles was determined.Results Compared with S group,MT was significandy increased,and the expression of α-SMA was up-regulated in P group,mPAP,RVSP,RVHI and MT were increased in M group,mPAP,RVSP,RVHI,MT and VOS were increased in PM group,and the expression of HIF-1α,α-SMA,and PCNA was up-regulated in M and PM groups.Compared with P group,mPAP,RVSP,RVHI and MT were significantly increased,and the expression of HIF1α,α-SMA,and PCNA was up-regulated in M and PM groups.Compared with M group,RVSP,RVHI,MT and VOS were si gnificantly increased,and the expression of HIF-1α,α-SMA,and PCNA was up-regulated in PM group.Conclusion The mechanism of pulmonary arteriole intimal proliferation is related to up-regulated HIF-1α expression and promoted proliferation of vascular smooth muscle cells in rats with pulmonary hypertension.
7.Resveratrol reduces electrical remodeling in atrial fibrillation by down-regulating microRNA-21 in neonatal rat atrial myocytes
Song ZHANG ; Bingbing SHEN ; Fei LI ; Qiren ZHU ; Zhirong WANG ; Zhuoqi ZHANG
Chinese Journal of Pathophysiology 2017;33(8):1353-1358
AIM: To detect the effects of resveratrol (RSV) on the expression of microRNA-21 (miR-21) in primarily cultured neonatal rat atrial myocytes with electric remodeling induced by rapid electrical stimulation (RES).Furthermore, to find out the possible mechanism of miR-21 regulating electrical remodeling.METHODS: The neonatal rat atrial myocytes were isolated by double-enzyme (trypsin and collagenase I) digestion and differential adhesion method.The atrial fibrillation (AF) model was induced by RES.Atrial myocytes were randomly divided into 4 groups: control group, RSV group, RES group, and RSV+RES group.To further detect whether RSV regulated electric remodeling by miR-21, except the 4 groups, we add miR-21 over-expression group and miR-21 inhibitor group: RES+negative control (NC) group, RES+miR-21 mimics group, RES+miR-21 mimics+RSV group, RES+miR-21 inhibitor group, and RES+miR-21 inhibitor+RSV group.The optimal concentration and pretreatment time of resveratrol were determined by CCK-8 assay.The expression of miR-21 and the mRNA expression of L-type calcium channels CACNA1C and CACNB2 in atrial myocytes were detected by qPCR.The protein expression of L-type calcium channels Cav1.2 and Cavβ2 in the atrial myocytes was analyzed by Western blot.RESULTS: The expression of miR-21 in RES group was significantly increased compared with control group, while preconditioning with RSV decreased the expression of miR-21.Compared with RES+miR-21 mimics group, the expression of miR-21 in RES+miR-21 mimics+RSV group was significantly decreased.Meanwhile, the mRNA expression of CACNA1C and CACNB2, and the protein levels of Cav1.2 and Cavβ2 were increased (P<0.05).Compared with RES group, the expression of miR-21 in RES+miR-21 inhibitor group and RES+miR-21 inhibitor+RSV group was decreased, while the mRNA expression of CACNA1C and CACNB2, and the protein levels of Cav1.2 and Cavβ2 were increased.However, no difference of the expression of miR-21, the mRNA expression of CACNA1C and CACNB2, and the protein levels of Cav1.2 and Cavβ2 among RSV+RES, RES+miR-21 inhibitor and RES+miR-21 inhibitor+RSV groups was observed (P<0.05).CONCLUSION: In AF model induced by RES, RSV may reduce electric remodeling by inhibiting the expression of miR-21 and regulating the downstream target genes.
8.Application of enteral nutrition in patients with ulcerative colitis
Bingbing SHEN ; Jiaming QIAN ; Dongsheng WU ; Feng ZHU ; Hong LU ; Ru ZHANG
Parenteral & Enteral Nutrition 1997;0(03):-
0.05).After the EN,the level of blood total protein,albumin and prealbumin significantly increased(P
9.gene polymorphism and Crohn′s disease in Han population Correlation between interferon regulatory factor 5 ,vitamin D receptor ,beta-defensin 1 ,Toll-like receptor 4
Pan LI ; Bingbing SHEN ; Hong LU ; Hong YANG ; Xiaoou YANG ; Jiaming QIAN
Chinese Journal of Digestion 2015;35(10):659-664
ObjectiveTo investigate the correlation between interferon regulatory factor 5 (IRF5) ,vitamin D receptor (VDR ) ,beta-defensin 1 (DEFB1 ) ,Toll-like receptor 4 (TLR4 ) gene polymorphismand Crohn′s disease (CD) in Chinese Han population .MethodsFrom January 2007 to May 2011 ,thedata and serum samples of 158 CD patients and 246 healthy controls were collected .The genotype of 14tag single-nucleotide polymorphisms (SNP) of IRF5 ,VDR ,DEFB1 and TLR4 were detected .Chi-squaretest was performed for rate comparison between CD group and healthy control group . Multifactordimensionality reduction (MDR) was used to analyze the combined effects of above candidate genes and therelation with susceptibility of CD .ResultsAccording to allele or genotype correlation analysis ,there wasno correlation between IRF5 ,VDR ,DEFB1 ,TLR4 and susceptibility of CD (all P> 0 .05) .The resultsof haplotype correlation analysis indicated that the frequency of GTACC haplotype in IRF5 of CD groupand healthy control group was 0 .046 and 0 .089 ,respectively ,the difference was statistically significant (χ2 = 5 .223 ,P= 0 .022 3) .The results of genotype and clinical type analysis indicated that the genotypesof rs2978880 of DEFB1 in CD patients were C/C ,C/T ,T/T ,the frequency of patients with surgery was0 .235 ,0 .603 and 0 .162 ,respectively ,and the frequency of patients without surgery was 0 .482 ,0 .388and 0 .129 ,respectively .The risk of intestinal surgery in patients with C /C genotype was lower (χ2 =10 .065 ,P= 0 .006 ) .The results of MDR analysis indicated that no interactions were detected betweenabove genes and susceptibility of CD (all P > 0 .05) .ConclusionsThe GTACC haplotype in IRF5 wascorrelated with the susceptibility of CD ,and the C/C genotype of rs2978880 of DEFB1 was correlatedwith CD clinical phenotype in Chinese Han population .
10.Phenotype analysis of 9 cases with mutations in PKHD1 gene
Guomin LI ; Qian SHEN ; Li SUN ; Qi CAO ; Yihui ZHAI ; Xiaoyan FANG ; Bingbing WU ; Hong XU
Chinese Journal of Nephrology 2017;33(11):831-837
Objective To summarize the clinical features of 9 cases with mutations in PKHD1 gene for a better understanding of its phenotype.Methods Clinical data of nine cases with mutations in PKHD1 gene were summarized from January 2011 to December 2016 in our center,including clinical manifestations,laboratory findings,imaging data and family investigation.Next generation sequencing was used to screen 4000 genes in case 1 to 4 and whole exons in case 5 to 9.Significant variants detected by next generation sequencing were confirmed by conventional Sanger sequencing.Segregation analysis was performed using parental DNA samples.Relevant literature was reviewed.Results Among these 9 cases,5 are male,4 are female.The average age of onset was 2.6 years old (ranging from 0.5-5.2 years).Renal ultrasound revealed that all 9 cases had cysts in bilateral kidney,7 cases with enlarged kidney,1 case with normal size kidney,1 case with normal size kidney,and 1 case with bilateral renal atrophy.Two cases with renal artery stenosis,1 case with focal narrowing in left main branch and 1 case with vesico-ureteral reflux were found.Among the 9 cases,3 cases had homozygous mutations,and 6 cases had compound heterozygous mutations,including 1 nonsense mutation,1 frameshift mutation and 15 missense mutations.There were 2 cases with 3 heterozygous mutations,2 c.5935C > T mutations and 2 eases with C.5869G > A mutations.A total of 10 new mutations were identified.Conclusion Patients with mutations in the PKHD1 gene had normal size kidney,or even atrophic kidney.Renal artery stenosis,vesicoureteral reflux and bronchial stenosis were all first reported in patients with mutations in PKHD1 gene.The novel mutations,c.274C > T,c.9059T > C,c.8996delG,c.281C > T,c.10424T > A,c.7092T > G,c.4949T > C,c.5869G > A,c.6197A > G and c.1877A > G further expanded the mutation spectrum of PKHD1 gene.