This paper analyzes the influence of modern enterprise system on managerial mechanism and industrial management of pharmaceutical enterprise, and the countermeasure that should be adopted by enterprise are discussed as well.

Objective To assess the usefulness of contrast echocardiography in differential diagnosing space-occupying lesions of the heart.Methods Contrast echocardiography was assessed for 38 patients of space-occupying lesion of the heart (SOLH).Contrast enhancement of SOLH was assessed visually,comparing with that in the adjacent myocardium:significant contrast enhancement,intensity higher than or equal to the adjacent myocardium; mild or partial contrast enhancement,intensity lower than the adjacent myocardium,or no contrast enhancement.Respectively,malignant tumors,benign tumors,and thrombus were diagnosed.Twenty-eight patients among the 38 cases had gold standard diagnosis.The consistency between visual assessment diagnosis and gold standards were compared with Kappa statistic.Results Visual semi-quantitative diagnosis of contrast echocardiography:thrombus,benign tumors and malignant tumors were diagnosed for 8,8 and 12 cases,separately.Except two highly vascular benign tumors (1rhabdomyoma and 1 paraganglioma) were misdiagnosed as malignant tumors,the rest 26 cases matched gold standard diagnosis.Quantitative analysis of contrast echocardiography,16 cases were suitable for quantitative an alysis,10 cases were diagnosed as benign tumors or thrombus (quantitative analysis could not differentiate the two),the rest 6 cases were diagnosed as malignant tumors.Quantitative analysis got the same 2 misdiagnosis as visual semi-quantitative diagnosis.Kappa value on visual semi-quantitative diagnosis of contrast echocardiography comparing with gold standard diagnosis was 0.892.Conclusions The characteristics of vascularity of SOLH can be accurately determined by the contrast enhancement level in diseased region through visual semi-quantitative analysis with contrast echocardiography.Contrast echocardiography can be mainly used in SOLH except thrombus that has been clearly diagnosed,especially for patients with on going or fore-past malignancy in other organs.

Objective To investigate the expression of 4-hydroxynonenal (4-HNE) in the kidney of diabetic rats and the effect of probucol.Methods The rats were being intraperitoneal injected with STZ (60 mg/kg) to establish diabetic models.Then diabetic rats were randomly divided into diabetic group (group D,n =24),probucol treated group (group P,n =24).Normal rats were taken as control group (group C,n =24).Rats in group P were treated by probucol (110 mg·kg-1·d-1); rats in group D and group C were given equal volume water instead.Scr,BUN,triglyceride (TG),total cholesterol (TC) and 24-hour urinary proteinin were measured at the 4th,8th and 12th week.PAS staining and HE staining were used to evaluate the pathological changes of the kidney.The immunohistochemistry and Western blotting were used to detect the expression of 4-HNE in renal tissue.Results Levels of Scr,BUN,TG,TC and 24-hour urinary protein in group D were higher than those in group C at the 4th,8th and 12th week(all P ＜ 0.05); Levels of Scr,BUN,TG,TC and 24-huor urinary protein in group P were lower than those in group D at 4th,8th and 12th week (all P ＜ 0.05).The pathological changes of the kidney in group D were more serious than that in group P.The expression of 4-HNE in group D were higher than group C at the 4th,8th and 12th week (all P ＜ 0.05);The expression of 4-HNE in the kidneys of group P decreased significantly compared to that of group D at the same time (P ＜ 0.05).Conclusions As an indicator of lipid peroxidation,the expression of 4-HNE significantly increases in the kidney of diabetic rat.Probucol may protect the diabetic kidney through decreasing the expression of 4-HNE and the level of lipid peroxidation.

Objective To investigate the expression of glucose-regulated protein 78(GRP78)and cysteine aspartic acid protease 12(Caspase-12) and evaluate the endoplasmic reticulum stress (ERS) in rats with contrast-induced nephropathy (CIN),and observe the protective effects of hydroxytyrosol on CIN rats.Methods Eighty-four Wistar rats,(220±20) g,were randomly divided into control group,CIN group,hydroxytyrosol treated group (group C+H).At 12th,24th,48th,72th day after the rats model were established,BUN and Scr were detected.ELISA were used to detect the expression of methane dicarboxylic aldehyde (MDA),superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px).HE staining were used to evaluate the pathological change of kidney.TUNEL were used to detect the apoptosis of tubular ceils.Real-time PCR were used to detect the expression of GRP78 mRNA and Caspase-12 mRNA in tubular cells.Immunohistochemistry and Western blotting were used to detect the expression of GRP78 and Caspase-12 protein in tubular cells.Results BUN,Scr,the mRNA and protein expression of GRP78,Caspase-12 in hydroxytyrosol treated group were higher than that in control group(P ＜ 0.05),but were significantly lower than that in CIN group (P ＜ 0.05).Pathological changes and the apoptosis of tubular cells in CIN group were more serious than that in hydroxytyrosol treated group (P ＜ 0.05).Conclusions Endoplasmic reticulum stress may be associated with contrast-induced nephropathy.Hydroxytyrosol can protect kidney from contrast medium via reducing the endoplasmic reticulum stress.

Objective To evaluate left ventricular function in the way of intracavitary vortex by vector flow mapping(VFM),and to demonstrate the formation and variation of the vortex. Methods Twenty-six patients with dilated cardiomyopathy(DCM) and 44 healthy controls were involved. The velocity distribution imagings on the section plane of the flow in the left ventricle were obtained by VFM, the location of the vortex and its variation in every phase of cardiac cycle were focused,and series parameters were measured,such as the diameter of the vortex (transverse diameter, vertical diameter), number of the vertex. Results relaxation(e) period. Vortices were observed mostly during diastolic period, nearby the anterior leaflet of mitral valve,middle upper 1/3 of left ventricle,and their shapes changed 2 - 3 times. The diameters of the vortex (transverse diameter,vertical diameter) , number of the vertices in one cardiac cycle during 7 phases mostly nearby the cardiac apex, middle lower 2/3 of left ventricle, and their shapes changed 4 - 5 times.Compared with control group,the diameters of the vortex (transverse diameter, vertical diameter) during 7 phases in DCM group were bigger,and number of the vertices were more ( P ＜0.01 ). The diameters of the vortex (transverse diameter, vertical diameter), number of the vertices within DCM group in one cardiac cycle during 7 phases were significantly different ( P ＜ 0.01 ). Conclusions VFM can demonstrate the variation of intracavitary vortex. Vortex in DCM group were significantly bigger than those of control group.

Objective To investigate the roles of a epoprostenol(PGI2) analog (Iloprost) in regulating the differentiation of CD4+ T cells to Treg cells and the possible mechanism.Methods Naǐve CD4+ T cells were isolated from human peripheral blood samples by using the magnetic-activated cell sorting (MACS) and then cultured under Treg-polarizing condition.The percentages of Treg cells and the expression of Foxp3 at mRNA level were respectively measured by using flow cytometry and RT-PCR for evaluation the effects of Iloprost on the differentiation of CD4+ T cells to Treg cells.The cAMP accumulation assay was used to detect the level of intracellular cAMP.Flow cytometry analysis was performed to detect the phosphorylation of signal transducer and activator of transcription 5 (STAT5).Results lloprost decreased the percentage of Treg cells and inhibited the expression of Foxp3 at mRNA level in a dose dependent manner (P＜0.05).However,the inhibitory effects of Iloprost were weakened when IP receptors were blocked by IP antagonist (CAY10449).A six-fold increase in the levels of intracellular cAMP in Treg cells was induced by Iloprost (P＜0.05) and a similar effect could be achieved by using a cAMP agonist,db-cAMP (P＞0.05).H-89,a protein kinase A inhibitor,inhibited the Iloprost-induced expression of cAMP in Treg cells.Moreover,Iloprost inhibited the IL-2 mediated phosphorylation of STAT5 (P＜0.05) and a similar effect could be achieved by using db-cAMP (P＞0.05).The Iloprost-mediated down-regulation of pSTAT5 was blocked by using H-89.Conclusion PGI2 could activate the cAMP-PKA signaling pathway by binding to the IP receptor,resulting in inhibited phosphorylation of STAT5 and suppressed differentiation of naǐve CD4+ T cells to Treg cells.

Objective To construct a eukaryotic expression system of IFN-λ,examine the expression of IFN-λand evaluate its bio-functions including anti-proliferation and anti-viral activity.Methods The genes of human IFN-λ1 /2 (hIFN-λ1 /2)were cloned from the mRNA of poly I∶C treated HuH-7 cells.The PCR product was examined with DNA sequencing.The genes of IFN-λ1 /2 were sub-cloned into pcDNA3 vector.The correct insertion of the gene IFN-λ1 /2 was identified with enzyme digestion.The constructed pcDNA3-IFN-λ1 /2 plasmids were transfected into COS-7 cells and IFN-λ1 /2 protein was checked in the supernatant and lysis of transfected cells using Western blotting analysis.The human esophageal carcinoma YES5 and T.Tn cells were treated with the IFN-λ1 /2 from the transfected cells and the proliferation of carcinoma cells were measured with CCK-8 kit.In the treated carcinoma cells,the apoptosis and antivirus related molecules such as caspase-3,ISG15 and MxA was analyzed with Western blotting or Quantitative real time PCR.Results The sequence of hIFN-λ1 /2 fragment matched that of the gene bank and the gene of the cytokines was inserted into pcDNA3 vector correctly.With Western blotting analysis,IFN-λ1 /2 protein was detected in the pcDNA3-IFN-λ1 /2 transfected COS-7 cells.The IFN-λ1 /2 from the transfected COS-7 cells inhibited the growth of YES5 and T.Tn cells, activated apoptosis related caspase-3,and up-regulated the anti-virus gene expression of ISG15 and MxA.Conclusion COS-7 cells can express IFN-λ1 /2 after transfection with pcDNA3-IFN-λ1 /2,suggesting that eukaryotic expression system of IFN-λis established.IFN-λ1 /2 from the system can perform bio-functions,such as proliferation inhibition,apoptosis induction and anti-viral gene up-regulation,which indicates that the system can contribute to further investigations of IFN-λbio-activity and its clinical application.

Objective To explore the predictive effect of depression and impulsivity on suicidal ideation in violent criminals.methods 423 violent criminals were assessed by Self-rating Idea of Suicide Scale(SIOSS),Patient Health Questionnaire (PHQ-9) and Barratt Impulsiveness Scale(BIS-11).Result sPeople with suicidal ideation accounted for 17.04% of the total number of violent criminals.The scores of the group with suicidal ideation (respectively (4.95±4.82),(56.79±8.68),(12.95±2.29),(19.03±3.91),(28.81±4.95)) were higher than those without suicidal ideation group (respectively (4.95±4.82),(56.79±8.68),(12.95±2.29),(19.03±3.91),(28.81±4.95)) in depression and every dimension of impulsivity(attentional impulsivity,motor impulsivity and non-planning impulsivity) (t=9.49,t=4.61,t=4.04,t=3.88,t=3.08) (all P<0.01).Positive correlation was observed between suicidal ideation,depression and impulsivity(r=0.156-0.628,P<0.01),while sleeping factor was not associated with non-planning impulsivity.According to the multi-factoral regression module,depression and nonplanning impulsivity scores had positive prediction on suicidal ideation(R2=0.419,SIOSS=-2.471+ 0.192× depression+ 0.149× nonplanning impulsivity).Conclusion There is a close relationship in suicidal ideation,depression and impulsivity,meanwhile depression and nonplanning impulsivity can predict the suicidal ideation.

OBJECTIVETo investigate α-toxin-induced apoptosis of umbilical vein endothelial cells and explore its role in vertical infection of Staphylococcus aureus L-form.

METHODSHUV-EC-C cells exposed to different concentrations (0, 10, 30, 90, and 270 ng/ml) of α-toxin for different time lengths (0, 2, 4, 6, and 8 h) were examined for apoptosis using flow cytometry with Annexin V-PI staining. The levels of tumor necrosis factor-α (TNF-α) and the activities of, caspase-3 and caspase-8 in the cell culture were detected by ELISA and colorimetric method, respectively. α-Toxin-induced cell apoptosis was also analyzed in HUV-EC-C cells treated with a neutralizing antibody of TNF-α or with the inhibitory peptides of caspase-3 (zDEVD-FMK) and caspase-8 (zIETD-fmk).

RESULTSα-Toxin induced apoptosis of HUV-EC-C cells in a dose- and time-dependent manner and caused significantly enhanced expression of TNF-α and the activation of both caspase-3 and caspase-8. Inhibition of TNF-α with its neutralizing antibody and the inhibitory peptides of caspase-3 or -8 all significantly decreased α-toxin-induced cell apoptosis, and the caspase-3 inhibitor completely blocked α-toxin-induced cell apoptosis.

CONCLUSIONα-Toxin-induced apoptosis is partially mediated by the extrinsic cell death pathway of TNF-α and caspase-8 and plays an important role in the vertical infection of S. aureus L-form to affect fetal growth and development.

Apoptosis ; Bacterial Toxins ; toxicity ; Caspase 3 ; metabolism ; Caspase 8 ; metabolism ; Cells, Cultured ; Human Umbilical Vein Endothelial Cells ; cytology ; Humans ; L Forms ; Staphylococcal Infections ; Staphylococcus aureus ; Tumor Necrosis Factor-alpha ; metabolism

Through consulting related literatures on modern medicine pathogenesis and treatment status of chronic pain,new clinical treatment methods were revealed and summarized.Literatures on modern medicine pathogenesis and treatment of chronic pain were retrieved from the CNKI,Wanfang Data,VIP,and Pubmed database from January 2000 to December 2016.Literatures with big influence,strong representation and new treatment method were screened.All methods were classified to summarize the pathogenesis and clinical application situation.This paper discussed the pathogenesis of peripheral sensitization,central sensitization,psychological mechanism and clinical medication.Through nearly 15 years of literature analysis,the pathogenesis of modern medicine and treatment status of chronic pain were summarized.