1.The status and prospects of niacin and its combination therapy with statins
Chenlu WU ; Shuiping ZHAO ; Danhua ZHANG
Chinese Pharmacological Bulletin 2010;26(3):414-415
Niacin, a broad-spectrum lipid-regulating agent, can significantly lower plasma triglyceride and raise the high density lipoprotein-cholesterol.Extended-release niacin added to statins monotherapy could further modify the lipid profile and reduce residual cardiovascular risk.This combination therapy provides a safe, effective and economical treatment for clinicians and may be superior to other drugs combined with statins.
2.Clinical analysis of 24 patients with POEMS syndrome
Chenlu ZHANG ; Dali CAI ; Juan HE
Journal of Leukemia & Lymphoma 2012;21(2):101-104
ObjectiveTo analyze the characters of POEMS syndrome, raise physician awareness of diagnosis and therapy,and explore the optimal treatment strategies.MethodsThe clinical features,laboratory examination and therapy of 24 patients with POEMS syndrome were analyzed,and relative literatures were reviewed. ResultsA strong predominance of male over female was found, 18 vs 6. All patients were over 40 years old,with a mean age 56.5 years old,indicating a common adult involvement.All presented with polyneuropathy,which was also the most common complaints when admitted,which reminded neurologists of underlying possibility of a rare plasma cell disorder.Organomegaly was found,including 19 cases with hepatomegaly,17 patients with splenomegaly.Endocrinal abnormalities were also found in 15 cases.18 patients were M protein positive. Skin pigmentation was recognized in 21 cases. Melphalan in combination with prednisone was applied and 100 % response was observed. One of the patients received peripheral blood stem cell transplantation(PBSCT)2 years ago and a durable response was observed with a continuous complete remission of polyneuropathy and the absence of M protein following 2 years post PBSCT.ConclusionPOEMS syndrome is a rare multisystem disorder, the combination of symptoms and signs is highly complex,which is easy to misdiagnose or missed diagnose.A polyneuropathy with either organomegaly,endocrinal abnormalities, skin disorder or serositis is required a further investigation of clonal M protein and bone marrow.Melphalan and prednisone probable are the optimal regimens.PBSCT provides a new choice for therapy and research of POEMS syndrome.
3.Activation of rat hepatic stellate cells and changes of DNA methyltransferase 1, 3a mRNA expression levels induced by sodium arsenite
Shunhua WU ; Lulu ZHANG ; Chenlu WANG ; Jing LI
Chinese Journal of Endemiology 2017;36(1):32-36
Objective To observe the activation of rat hepatic stellate cells (HSC-T6) and the changes of methyltransferase (DNMT)1,DNMT3a mRNA expression with different doses of sodium arsenite stimulation.Methods HSC-T6 cells were exposed to a final concentration of 0 (control),5 (low dose),15 (medium dose) and 25 (high dose) μmol/L sodium arsenite in culture medium for 24,48 and 72 h,cells and cell culture supernatant were harvested.Enzyme-linked immunosorbent assay (ELISA) kit was used to measure fibrosis factors contents of type Ⅰ collagen (COL-1),type 11Ⅲ collagen (COL-3) and alpha smooth muscle actin (α-SMA) and quantitative real-time PCR was used to detect the expression levels of DNMT1 and DNMT3a mRNA.Results Different arsenic exposure time (24,48,72 h) had a significant effect on COL-1,COL-3 and α-SMA contents in HSC-T6 cells (F =249.574,328.493,3 157.436,all P < 0.01);Different arsenic exposure content (low,medium,high dose groups) had a significant effect on COL-1,COL-3 and α-SMA contents in HSC-T6 cells (F =3 946.521,1 006.399,13 025.770,all P < 0.01).After arsenic exposure for 24 and 48 h,the expression levels of DNMT1 mRNA in high dose group (4.33 ± 0.24,2.34 ± 0.43) were higher than those of control group (1.00 ± 0.00,1.00 ± 0.00,all P < 0.05).At the same arsenic exposure levels (low,medium or high dose),the expression level of DNMT1 mRNA was declined with prolongation of sodium arsenite stimulation time (all P < 0.05).After arsenic exposure for 48 and 72 h,the expression levels of DNMT3a mRNA in high dose group (2.23 ± 0.50,5.02 ± 0.23) were higher than those of control group (1.00 ± 0.00,1.00 ± 0.00,all P < 0.05).The expression levels of DNMT3a mRNA in medium and high dose groups at 72 h (3.80 ± 0.14,5.02 ± 0.23) were higher than those of 24 h (3.03 ± 0.12,0.42 ± 0.15,all P < 0.05).Conclusion HSC-T6 cells are obviously activated with pro-fibrotic effect;the expression levels of DNMT1 and DNMT3a mRNA are both up regulated in HSC-T6 cells after being exposed to sodium arsenite.
4.Proteomics analysis of rat liver fibrosis caused by sodium arsenite
Shunhua WU ; Jing LI ; Lulu ZHANG ; Chenlu WANG ; Xiaoying LIU
Chinese Journal of Endemiology 2016;35(3):182-188
Objective To study the mechanism of liver fibrosis in rats caused by chronic exposure through drinking water containing sodium arsenite,to identify the differential proteins via proteomics technique.Methods Totally 40 healthy 8-week-old male Sprague Dawley (SD) rats of specific pathogen free (SPF) grade were randomly divided into 4 groups,which were control group (deionized water),0.68,1.36 and 2.73 mg/kg sodium arsenite (iAs3+) treated groups,respectively.The rats were fed with iAs-treated drinking water freely for 24 consecutive weeks.Twenty-four hour urine sample,blood and liver samples were collected.Hepatic fibrosis indices,specifically,type Ⅲ precollagen (PC Ⅲ),type Ⅳ collagen (Ⅳ-C),hyaluronic acid (HA) and laminin (LN) were detected by enzymelinked immunoassay (ELISA).Based on the isobaric tags for relative and absolute quantitation (iTRAQ) reagent 8-plex experiment,combined with 2DLC-MS/MS,the proteins in rats liver tissue of the medium dose group and the high dose group were compared with the those of control groups.Results ①The serum HA contents in the C (control) group,the L (low dose) group,the M (medium dose) group and the H (high dose) group were (198.51 ± 16.64),(218.39 ± 34.98),(261.72 ± 30.56) and (297.31 ± 35.72) ng/L;the serum PCⅢ contents in C,L,M and H groups were (15.32 ± 2.15),(16.78 ± 2.64),(19.51 ± 0.85) and (21.42 ± 1.63) μg/L;the serum LN contents in C,L,M and H groups were (734.57 ± 86.00),(792.65 ± 94.15),(916.83 ± 84.40) and (1 008.09 ± 64.17) μg/L;the serum Ⅳ-C contents in C,L,M and H groups were (52.34 ± 14.65),(59.72 ± 12.84),(74.38 ± 4.83) and (78.46 ± 4.30) μ.g/L,respectively.The differences in serological indices of liver fibrosis between-groups were statistically significant (F =21.136,19.957,22.007,14.288,all P < 0.05).In multiple comparison of serum HA,PCⅢ and LN,there were no statistical significant differences between L group and C group.M and H groups were higher than L group and C group,significant statistical difference was found between H group and M group (all P < 0.05).②Combining iTRAQ with 2DLC-MS/MS,based on the confidence threshold of protein (unused protScore) > 1.3 and at least 1 matched peptides within the 95% confidence interval,2 948 proteins were identified.Totally 2 162 proteins were detected in three groups compared with Venn diagram,after removing significant different proteins in C group,687 up-regulated proteins and 548 down-regulated proteins were identified in M group;633 up-regulated proteins and 519 downregulated were found in H group;the differences of protein expression between M and H groups were not statistically significant (P > 0.05).③Up-regulated proteins related to the metabolism including AS3MT,MAT,SHMT,CHDH,CTH,CSAD and BHMT in M and H groups;of the two kinds of proteins of MTR,METK1 was up-regulated and F1LRB8 was down-regulated.Proteins associated with GSH including Gsta1,Gsta4,Gsta5,Gstt1,Gstt2,Gstk1,Gstp1,Gstm1,Gstm2,Gstm3,Gss,Gpx1,Gpx4,Esd,Hagh,Glo1,Mgst1 and B6DYQ5 which were all up-regulated.Proteins associated with liver fibrosis were Hic-5,Gss and six kinds of Tpm,and six kinds of Tpm subunits including two kinds of Tpm1,three kinds of Tpm2 and one kind of Tpm3 which were all up-regulated.Conclusions There is liver accumulation of arsenic after chronic arsenic exposure and resulting in liver fibrosis and decline of liver function.Expressions of AS3MT,MTR,MAT,SHMT,BHMT,CHDH,CTH and CSAD are up-regulated;arsenic meta bolism methionine cycle,folic acid cycle and sulfur transfer pathways are closely related.GSH plays an important role in arsenic metabolism and liver fibrosis,Hic-5,GSS and TPM may be associated with the occurrence of liver fibrosis.
5.Clinical application of the evidence-based clinical nursing guideline for nasogastric tube feeding
Chenlu LI ; Yun CHENG ; Lirong ZHAO ; Ying ZHANG
Chinese Journal of Nursing 2017;52(8):905-910
Objective To explore the effectiveness,feasibility and suitability of the guideline for nasogastric tube feeding in adult patients.Methods Based on the Ottawa Model of Research Use as framework,we screened relevant evidence from guidelines,and developed new nasogastric tube feeding nursing procedure.Nursing knowledge,the rate of compliance to new procedure and the incidence of complications of nasogastric tube feeding were used to evaluate the clinical effects of the guideline.Results Nurses' knowledge increased significantly(P<0.05).Nurses had a high degree of implementation of the new procedure,with the rate of over 85%.Compared with the control group,the rate of complications of nasogastric tube feeing in the experimental group was lower than that in the control group.Especially,the rates of reflux and aspiration were significantly lower(P<0.05).Both rates of tube shedding and skin damage in the intervention group were decreased significantly(P<0.05).Conclusion The nasal feeding nursing guideline in our clinical scenarios has its effectiveness,feasibility and suitability.
6.Nutritional Status and Intervention for Children with Cerebral Palsy
Meirui LI ; Jianmin WU ; Honghong ZHANG ; Jie YAN ; Qiaoyu CHEN ; Chenlu XIONG
Chinese Journal of Rehabilitation Theory and Practice 2014;20(12):1150-1152
Objective To investigate the condition of nutrition in child with cerebral palsy (CP) and the effect of nutritional intervention. Methods 49 CP children and other 60 health children (controls) were measured their bodies, hemoglobin, serum trace elements, and bone mineral density (with ultrasonic), and the feeding behavior was also investigated. Results The incidence of malnutrition was 48.97%, in which 26.53% for low weight. The levels of serum iron and zinc were poor in the CP children, and the incidence of iron deficiency anemia was 34.67% in the CP children, different from the controls (P<0.05), while the incidence of low bone mineral density was 30.61%, not significantly different from the controls (P>0.05). Feeding problems were found in 44.9% of CP children. About 50% of malnutrition was corrected, especially the body weight after 4 months of Intervention, with anemia corrected in 88.2%, and bone mineral density recovered in 50%. Conclusion It is a problem for many CP children with malnutrition and nutritional disorders, and need nutrition intervention as the content of the rehabilitation.
7.Retrospective cohort study for the impact on readmission of patients with ischemic stroke after treatment of aspirin plus clopidogrel or aspirin mono-therapy
Cheng YANG ; Yuqi ZHANG ; Xun TANG ; Pei GAO ; Chenlu WEI ; Yonghua HU
Journal of Peking University(Health Sciences) 2016;48(3):442-447
Objective:To see the influence of different antiplatelet therapies on stroke patients’ readmission by performing a deep data-mining into Beijing Healthcare Insuring Database,based on a large sample size.Methods:Aretrospective cohort study,was adopted to extract patients primarily diag-nosed as ischemic stroke from healthcare database.The first hospital records were considered as the pa-tient’s baseline in this study,who were divided into MAPT (aspirin)and DAPT (aspirin and clopi-dogrel)according to the patient’s baseline medications.A follow-up was conducted to see whether the patients would have rehospitalization record because of major result events after medication.The major re-sult events,included:(1 )recurrence of ischemic stroke;(2)hemorrhagic transformation of ischemic stroke;(3)myocardial infarction;(4)the digestive hemorrhage.The Kaplan-Meier figure was used to compare the survival situations between these two groups,the log-rank test was used to test the difference of the survival curve,and 1 ∶1 propensity score matching was calculated from the patients’baseline da-ta.Cox proportional hazards model was used to calculate the hazard ratio (HR).Results:A total of 27 695 patients From January 201 0 to September 201 3 were included,4 047 with DAPT,and 23 648 with MAPT.Because the baseline characteristics of the patients was disequilibrium,so we used 1 ∶1 pro-pensity score matching,after which,the number of the two groups was 4 046 each.Adjusted for the gen-eral demographic characteristics such as age,sex,nationality,complication and drug combination,no statistical significance was observed between the survival curves of the two groups (P =0.06).HR value of major result events between the groups was 0.91 (0.82 -1 .01 ,P =0.07),which was not statistically significant.The covariate gender HR =1 .36 (1 .20 -1 .55,P <0.05),accompanied by diabetes HR =1 .36 (1 .20 -1 .54,P <0.05 ),dyslipidemia HR =1 .1 3 (1 .00 -1 .27,P =1 .1 3),heart disease HR =1 .39 (1 .22 -1 .58,P <0.05)was statistically significant.Drug combination with other antiplate-let agents HR =1 .05 (0.95 -1 .1 7,P >1 .05)did not increase the risk of readmission.Conclusion:There was no difference in prevention of readmission between patients with DAPT and MAPT.Patients with complications should actively treat the complications at the same time as they prevent recurrence after first attack.
8.Effect of alpha-lipoic acid on cardiomyocyte apoptosis following renal ischemia-reperfusion injury in rats
Yan LIU ; Leiqiang LI ; Yunlu LI ; Chenlu DU ; Yuntao SHAO ; Xinchun ZHENG ; Cuiying ZHANG
Chinese Journal of Anesthesiology 2011;31(11):1374-1376
ObjectiveTo evaluate the effect of alpha-lipoic acid (ALA) on cardiomyocyte apoptosis following renal ischemia-reperfusion injury(RIRI) in rats.MethodsThirty-six male SD rats weighing 250-280 g were randomly divided into 3 groups ( n =12 each): group sham operation (group S) ; group I/R and group I/R + ALA ( group L).The model of RIRI was produced by occlusion of renal artery and vein for 45 min followed by 24 h reperfusion,in group S the renal pedicles were exposed but not occluded.In group L ALA infusion (30 mg/kg) was given via tail vein at 20 mln before ischemia and at 20 min before reperfusion,while in group I/R the equal volume of solution (35% polyethylene glycol + 60% physiological saline + 5% ethanol) was infused instead of ALA.The animals were saerificed at the end of 24 h of reperfusion,blood samples were taken for detecting concentrations of serum creatinine (Cr) and malondialdehyde (MDA).Then the hearts were immediately removed for determination of SOD activity,MDA content,cardiomyocyte apoptosis (flow cytometry) and Bcl-2/Bax ratio (immunohistology).ResultsSerum Cr concentration,serum and myocardium MDA levels and cardiomyocyte apoptosis were significantly increased after RIRI in groups I/R and L as compared with group S ( P < 0.05).ALA treatment significantly decreased serum Cr concentration,serum and myocardium MDA levels,cardiomyocyte apoptosis and increased SOD activity and Bcl-2/Bax ratio ( P < 0.05).ConclusionALA can attenuate myocardium injury by inhibiting cardiomyocyte apoptosis following RIRI in rats.
9.Effects of bromodomain containing protein 4 specific inhibitor JQ-1 on human hypertropic scar
Yange HU ; Jian HAO ; Di ZHANG ; Chuanfeng YANG ; Chenlu SONG ; Yong FANG
Journal of Shanghai Jiaotong University(Medical Science) 2017;37(7):924-929
Objective·To investigate effect and the possible molecular mechanism of JQ1,a specific inhibitor of bromodomain containing protein 4,on human hypertropic scar.Methods·Primary fibroblasts were isolated from human hypertrophic scars and treated with JQ-1 of different concentrations (0.1,0.5,1.0,2.0,2.5,and 12.5μmol/L) for 48 h.Then CCK-8 kit and wound healing assay were used to measure proliferation and migration of the fibroblasts.ELISA was adopted to detect the levels of collagen type Ⅰ (COL Ⅰ) and TGF-β1 after JQ-1 treatment for 24 h.Thirty-six nude mice were used for hypertrophic scar models.Human hypertrophic scars (1.0 cm× 1.0 cm×0.5 cm) were grafted subcutaneously at the backs of nude mice to establish scar animal models.After 4 weeks,the nude mice were averagely divided into two groups,i.e.JQ-1 group and DMSO group,which were respectively injected with 0.5 μmol/L JQ-1 and 0.1% DMSO each mouse every day.COL Ⅰ / Ⅲ and α-smooth muscle actin (α-SMA) were examined by immunohistochemical method and sirius red staining.Results·Cell experiments showed that JQ-1 with the concentration of 0.5 μmol/L and above significantly inhibited proliferation of fibroblasts (P<0.01).JQ-1 inhibited migration of fibroblast (P<0.01).JQ-1 inhibited secretion of COL Ⅰ and TGF-β1 of fibroblasts (P<0.01).Animal experiments showed that concentration and proportion of COL Ⅰ / Ⅲ in JQ-1 group decreased compared to DMSO group (P<0.05).α-SMA protein expression in JQ-1 group also decreased (P<0.05).Conclusion·JQ-1 can inhibit proliferation,migration,secretion of COL Ⅰ,and production of TGF-β1 of human sear fibroblasts in vitro;it can also inhibit secretion of COL Ⅰ /Ⅲ and fibroblast-myofibroblast differentiation in the human hypertrophic scars in nude mice.
10.Inhibitory effect of decorinon invasion of colorectal adenocarcinoma cell line HCT116 in vitro
Chenlu FENG ; Min ZHANG ; Jixia WANG ; Xiangli MENG ; Xiufeng CHU ; Ping LU
Basic & Clinical Medicine 2017;37(6):849-854
Objective To investigate the effect and mechanism of decorin (DCN) on invasion of colorectal cancer cell line HCT116 in vitro.Methods Transwell assay was employed to detect the invasion of HCT116 cells;Real-time PCR was used to detect the expression of CD133 and TIMP-2 mRNA of HCT116 cells;Western blot method was used to detect the expression of HIF-1α, CD133 and TIMP-2 protein of HCT116 cells.Results 1) When the concentrations of DCN was 0, 1 and 3 mg/L, under the conditions of normal oxygen and hypoxia, the numbers of invasive cells were (241±46), (168±46), (51±17) fields in each well (P<0.01) and (207±61), (213±64), (156±54), (44±17) fields in each well (P<0.01).2) Under the normoxic conditions, the TIMP-2 mRNA and protein in HCT116 cells were increased by DCN (3 mg/L) (P<0.01), but that of CD133 were not affected.3) DCN (3 mg/L) significantly decreased the expression of HIF-1α/CD133/TIMP-2 protein in HCT116 cells under hypoxia (P<0.01), but had no significant effect on the expression of CD133 mRNA.ConclusionsUnder the conditions of hypoxia and normal oxygen, DCN may function through different mechanisms to inhibit the invasion of colorectal adenocarcinoma cell line HCT116 in vitro.