The microRNAs is a kind of endogenous and non-coding small RNA ,which possesses biological function negatively regulating gene expression.Recent researches also found that artificial controlling some microRNAs ex-pressions can improve heart function via regulating skeletal myoblasts through multiple mechanisms,so may become a new breakthrough point in myocardial infarction treatment area.

Objective:To evaluate the benefit of autologous stem cell transplantation (ASCT) as a consolidation therapy in the survival of multiple myeloma (MM) patients at different risks. Methods:A total of 67 MM patients who received ASCT as consolida-tion therapy between August 2006 and July 2011 were enrolled in the retrospective study. The cases were divided into three risk groups on the basis of the International Staging System and fluorescence in situ hybridization. Another 67 patients who accepted consolidation chemotherapy at the same period were selected as case-paired controls matched in terms of age, sex, optimal response after induction, and risk stratifications. All the patients received bortezomib-and/or thalidomide-based induction therapies. Results:No statistical differ-ences in non-complete remission (nCR)/complete remission (CR) rate were observed between the ASCT and chemotherapy groups (44.8%vs. 37.3%, P=0.380) after the induction therapy. The progression-free survival (PFS) was longer in the ASCT group than in the chemotherapy group (32.4 months vs. 15.1 months, P<0.001). The overall survival (OS) was longer in the ASCT group than in the che-motherapy group (58.8 months vs. 42.1 months, P=0.009). both the PFS (median:30.5 months vs. 11.2 months, P<0.001) and the OS (median:85.5 months vs. 34 months, P=0.015) rates were significantly prolonged in the high-risk subgroup after ASCT. In the interme-diate-risk subgroup, neither PFS nor OS showed any significance after ASCT (P>0.05). In the low-risk subgroup, only PFS was extend-ed (median: 34.8 months vs. 17.6 months, P=0.012) after ASCT, without significant improvements in the OS (P>0.05). Conclusion:The MM patients obtained cytogenetic high-risk benefits mostly from ASCT consolidation after inductions based on novel agents.

Aim To investigate the effects of fluvastatin on epithelial-myofibroblast transdifferentiation and activation of ERK1/2 in HKC cells stimulated by AGEs. Methods HKC are divided into four groups: control group, AGEs group, AGEs plus fluvastatin group and AGEs plus ERK1/2 MAP kinase inhibitor PD98059 group. Immunocytochemistry staining was used to detect expression of ?-SMA. The protein expressions of ?-SMA, E-cadherin, Col I, ERK1/2 and p-ERK1/2 were observed by Western blot. The protein synthesis of TGF-?1 in the supernatants of the HKC was detected by enzyme-linked immunoadsorbent assay (ELISA).?-SMA and E-cadherin mRNA were measured by reverse transcription and polymerase chain reaction (RT-PCR). Results Compared with those of control group,the expressions of ?-SMA protein and mRNA,and Col I were significantly increased in HKC cells with AGEs stimulation and there was high concentration of TGF-?1 in the supernatants. However, the expressions of E-cadherin protein and mRNA were decreased with AGEs stimulation. AGEs induced ERK1/2 phosphorylation in HKC in a time-dependent manner, being significant at 15 minutes and peak occured at 1 h. PD98059 and fluvastatin inhibited AGEs-induced activation of ERK1/2 and high expression of Col I and ?-SMA protein and mRNA, and reversed the expression of E-cadherin protein and mRNA induced by AGEs. Meanwhile, fluvastatin and PD98059 reduced the concentration of TGF-?1 in the supernatants of HKC with AGEs stimulation. Conclusions Fluvastatin inhibited AGEs-induced HKC epithelial-myofibroblast transdifferentiation and collagen I synthesis might be partly through blocking activation of ERK1/2.

Objective To compare the dissolution curves of metronidazole tablets from 38 national manufactures and original drugs of Britain in four dissolution mediums,and provide the reference for the quality and clinical effect consistency evaluation of metronidazole tablets.Methods Paddle method was adopted at 50 r · min-1 in four dissolution mediums with the volume of 900 mL.The dissolution profiles were determined by ultraviolet spectrophotometry.The cumulative dissolution percentages were calculated and the dissolution curves were drawn.Similarity factor (f2)was used for comparing of the differences between dissolution curves.Results The dissolution profiles of 4 manufactures in pH 1.2 and 9 manufactures in pH 4.5 were similar (f2 ≥ 50)to that of original drugs,only 1 and 3 were similar to original drugs in water and pH 6.8,respectively.There are no companies whose dissolution curve were similar to that of original drugs in 4 dissolution mediums.Conclusion Great difference exists between domestic manufactures and pharmaceutical enterprises of origin in dissolution behaviors of metronidazole tablets.In order to ensure the consistency between the metronidazole tablets generics and original drugs of Britain in quality and clinical effect.It is advisable for the relevant companies to improve their product quality by improving the formulation and preparation.

Aim To investigate the effect of sphingo-sine kinase 1 (SphK1 )on unilateral ureteral obstruc-tion(UUO)-induced tubulointerstitial fibrosis and ex-plore the possible mechanism.Methods The CD-1 mice were randomly divided into four groups:sham-op-eration group(Sham),PF-543 treatment control group (Sham +PF-543),model group(UUO)and PF-543 treatment group(UUO +PF-543).On 1 ,3,7 and 1 4 d after operation,eight mice were selected randomly from each group and sacrificed.The protein expressions of SphK1 ,mature TGF-β1 ,FN,ColⅠ,LC3,Beclin1 ,Atg5 and Atg1 2 were observed by Western blot.The histo-logical changes were examined by Masson′s trichrome stain.Immunhistochemistry was performed to measure the levels of expression of SphK1 ,FN and Col Ⅰ. Transmission electron microscope was used to observe the autophagic body.Results SphK1 expression and autophagy were both upregulated in a mouse model of kidney fibrosis induced by UUO. Meanwhile, in-creased mature TGF-β1 and deposition of extracellular matrix(ECM)were observed in tubulointerstitial areas compared with sham-operated mice.After intraperito-neal injection with the SphK1 specific inhibitor PF-543 in UUO mice,enhanced expression of SphK1 and acti-vated autophagy were significantly abrogated.Howev-er,aggravation of renal fibrosis was detected when SphK1 inhibitor PF-543 was applied to suppress SphK1 expression in UUO mice.Conclusion SphK1 activa-tion is renoprotective through the induction of autoph-agy in the pathogenesis of kidney fibrosis.

Objective To investigate the effect of butylphthalide (NBP) on H2S content and the expression of NR2B in the hippocampus of alcohol dependence rats. Methods A total of 84 SD male rats were randomly divided into 6 groups. Except for the normal group, other groups were subjected to alcohol solution with concentration of 6% ( V/V) for 28 d. Drug intervention began at the 14th day,and rats in the low,medium,high dose group were treated with NBP with a different concentration. Erden abstinence scoring was used to evaluate the rats withdrawal symptom. H2S content was measured in one side of hippocampus and CBS activity was tested in the other side of hippocampus. Hippocampus of 3 rats from each group was used to investigate NR2B mRNA level. Results Withdrawal symptom score ( 12.27 ± 1. 19),H2S content(30. 25 ±8.82), CBS activity (72. 44 ±7. 46) and NR2B mRNA expression( 19. 47 ±0. 86) in medium dose NBP group rats were lower than withdrawal symptom score(14.09 ±2.21) ,H2S content(44. 50 ±6. 65) , CBS activity(79. 06 ±4. 57) and NR2B mRNA expression (29. 13 ±1.39) in experimental control group (P<0.05). Withdrawal symptom score(12. 18 ±1.08) ,H2S content(33.00 ±5.38) ,CBS activity(67. 81 ±9. 37) and NR2B mRNA expression(23. 12 ± 1. 86) in high dose NBP group rats were lower than experimental control group (P < 0. 05). Conclusion NBP can reduce withdrawal symptoms of alcohol dependence rats,may be related to decreased expression of H2S/CBS system, and NR2B mRNA expression.

Objective To evaluate the therapeutic effect and safety of tandospirone and buspirone in the treatment of generalized anxiety disorder.Methods The clinical control study oftandospirone and buspirone in the treatment of generalized anxiety disorder was earched by PubMed,CBM,CNKI,VIP,and Wanfang Data,with deadline from January 2000 to June 2016.Meta-analysis was carried out using RevMan5.0 software to each effect index.Results A total of seven RCTs were included involving 615 patients were identified.Meta-analysis showed that the significant efficiency rate[P=0.34,OR=1.19,95％CI (0.83～1.69)] and HAMA[P=0.80,MD=-0.08,95％CI (-0.72～0.56)] of tandospirone and buspirone had no significant difference.Two groups of adverse drug reactions,dizzy,dry,constipine,insomnia,anorexia,and nausea had no significant difference (P＞0.05).Conclusion The efficacy and adverse reaction oftandospirone and buspirone in the treatment of generalized anxiety disorder are fairly.

AIM:In order to investigate the molecular mechanism of alcoholism acting on learning and memory,the dysfunction of learning and memory function was observed and the content of nitric oxide(NO)and neuronal nitric oxide synthase(nNOS)were determined in rats with acute alcoholism.METHODS:The mature male Sprague-Dawley rats were randomly divided into two groups.The experimental group animals were intraperitoneally administered with ethanol.The control group animals were injected with saline in the same way.The tests of learning and memory were performed at Y-maze after 6 h.Then brains were removed and the content of NO in brain tissue and nNOS expression in hippocampus CA1,corpus striatum were determined,respectively.RESULTS:(1)The training times to reach qualifying standards of Y-maze in experimental group(34.33?13.04)were higher than those in control group(27.50?8.79,P

Objective To investigate the effect of suppressor of cytokine signaling-1 (SOCS-1)on expression of monocyte chemoattractant protein-1 (MCP-1)in human glomerular mesangial cells (HMCs) under high concentration of glucose. Methods Stable transfections of HMC with pCR3.1 vector and pCR3. 1-SOCS-1 were performed with hpofectamine 2000, and cells were selected with geneticin. Cells were stimulated with low glucose (LG, 5.5 mmol/L), high glucose (HG, 30 mmol/L), LG plus mannitol (24.5 mmol/L) and AG490 (10 μmol/L). The protein expression levels of SOCS-1, signal transducer and activators of transcription 1,3 (STAT1, STAT3),p-STAT1 and p-STAT3 were observed by Western blotting. The protein synthesis of MCP-1, FN and type Ⅳ collagen in the supernatants of the HMCs were detected by ELISA and radioimmunoassay. The expression level of SOCS-1 and MCP-1 mRNA was measured by BT-PCR.Results HG induced the expression of SOCS-1 protein and mRNA in HMCs in time-dependant manner, peaked at 4 h, and gradually decreased to baseline at 24 h. Compared with low glucose control group, the phosphorylation levels of STAT1 and STAT3 and the expression of MCP-1 mRNA [(0.39±0.05) vs (0.16±0.02)]were significantly increased in HMCs under high glucose medium (P ＜0.01 ). Exposure of HMCs to high glucose conditions showed high concentration of MCP-1 [(459±67) ng/L vs (241±19) ng/L], fibronectin [(5.84±0.61) mg/L vs (3.41±0.31) mg/L]and type Ⅳ collagen [(16.45±2.30) μg/L vs (9.56±1.52) μg/L]in the supernatants (all P＜0.01).Overexpression of SOCS-1 inhibited the phosphorylation levels of STAT1 and STAT3 and the expression of MCP-1 mRNA [(0.34±0.04) vs (0.42±0.05)]in HMCs under high glucose condition (all P＜0.05). Compared with vector control group, the concentration of MCP-1 [(387±47) ng/L vs (463±56) ng/L], fibronectin [(4.61±0.57) mg/L vs (5.76±0.74) mg/L]and type Ⅳ collagen [(13.4±2.32) μg/L vs (17.1±2.57) μg/L]was decreased in supernatants of HMCs with SOCS-1 overexpression (all P＜0.05). Compared with HG group, the expression of MCP-1 mRNA (0.31±0.04) and the concentration of MCP-1 [(361±53) ng/L], FN [(5.46±0.71) mg/L]and type Ⅳ collagen [(15.2±1.97) μg/L]in supernatants were decreased in HMCs treated with AG490.Conclusion Overexpression of SOCS-1 inhibits overproduction of MCP-1 and ECM proteins in HMCs under high glucose conditions, which may be partly by regulating the phosphoryhtion of STAT1 and STAT3.

ObjectiveTo observe the effect of alcohol exposure during pregnancy on learning and memory and content of hydrogen sulfide(H2S) in the hippocampus of infant rats.MethodsThe animal models of alcohol exposure during pregnancy were made,and the learning and memory were evaluated by Y-maze in adult offspring.Content of H2S and activity of cystathionine-beta-synthase(GBS) in the hippocampus of the brain were evaluated with spectrophotometry;and CBS protein expression in the hippocampus was detected by immunohistochemistry.ResultsThe learning and memory ( (43.00 ± 15.33 ) times) of alcohol exposure during pregnancy group was significantly decreased compared with that of control and drinking groups (( 25.13 ± 12.35 )times and (26.12 ±11.95 ) times,P ＜ 0.05 ) ; spectrophotometry results showed that the content of H2S ( ( 30.32 ± 5.84 ) nmoL/g) of alcohol exposure during pregnancy group was significantly increased compared with that of control ( ( 52.51 ±7.85 ) nmol/g) and drinking groups( (49.93 ± 4.29 ) nmol/g),and the activity of CBS( ( 55.13 ± 4.45 ) nmol/g)of alcohol exposure during pregnancy group was significantly increased (P ＜ 0.01 ) compared with that of control ( (71.06 ± 5.58 ) nmol/g) and drinking groups( (69.96 ± 6.13 ) nmol/g) ; immunohistochemistry showed that the expressionof CBSproteinofalcoholexposureduringpregnancygroupwassignificantlyincreased.ConclusionThe damage effect of alcohol exposure during pregnancy on nerve system of infant rats may interrelate with down-regulation of H2S/CBS in the hippocampus.