OBJECTIVE:To provide reference for the sustainable development of pharmaceutical enterprises in Guizhou prov-ince. METHODS:A questionnaire was conducted for 55 pharmaceutical enterprises in Guizhou province,the basic situation of en-terprises,familiarity of related directors to Good Manufacture Practice of Drugs(GMP)and relevant policy,the current situation of implementing the new version GMP were investigated and statistically analyzed,problems were found,and corresponding coun-termeasures were put forward. RESULTS & CONCLUSIONS:Totally 55 questionnaires were sent out,49 valid ones were received with effectively recovery of 85.1%. The results showed 43 enterprises(87.8%)had passed the GMP authentication;only 13 enter-prises(26.5%)directors were very familiar with the new version GMP. In terms of personnel management,the head of production management and quality management and the authorized person of quality and personnel had not yet met related requirements of the new version GMP fully;in terms of equipment and production management,production area transformation(clean areas,lounges, warehouses,water use) and air purification system design in most enterprises met related requirements of the new version GMP, 23 enterprises (46.9%) still can not conduct fully inspection to products and materials;in terms of document management,there were still some enterprises not meeting the new version GMP standards fully,enterprises'documents(health area layout,air purifi-cation layout,management procedures,operating procedures,etc.) of production site were imperfect. According to the investiga-tion,the main existing problems included lack of funds in implementing the new version GMP reform,not enough understanding or familiarity with the new version GMP,relevant personnel management not reaching the designated position,equipment and pro-duction management needing to be strengthened,document management systemic being poor,risk management being not sound, etc. It is suggested that government should give all forms of capital policy and strengthen the training of the new version GMP;en-terprises should attach great importance to the relevant personnel management,strengthen the equipment and production manage-ment,set up perfect document management system and a sound system of risk management.

This paper is to report the study of the metabolism of lidamycin in vitro including in plasma and microsomes to guide clinical therapy. Lidamycin was quantified by detecting its active ingredient using HPLC-MS/MS. The metabolic stability of lidamycin in rat, Beagle dog, monkey and human plasma and liver microsomes, and its inhibition to cytochrome P450 isoforms in human liver microsomes were studied. Results showed that lidamycin was metabolized in the four species of plasma, and the sequence of metabolic rates in plasma were in rat > in dog > in human > in monkey. But among the four species of liver microsomes, lidamycin was metabolized only in monkey liver microsomes. There was almost no inhibition to cytochrome P450 isoforms at the concentrations of between 0.0005 and 10 ng x mL(-1). Therefore, the property of lidamycin metabolism in human is similar with that in dog, and metabolism of other drugs would not be decreased by cytochrome P450 as used along with lidamycin in clinic.

Objective To investigate the relationships between occupational coping self-efficacy, job stress and core competence of nurses. Methods A total of 493 registered nurses were recruited in the survey with the Chinese nurse job stressors scale, occupational coping self-efficacy scale for nurses and competency inventory for registered nurse (CIRN). The correlations were analyzed using Pearson correlation analysis. Results The total scores on occupational coping self-efficacy, job stress of nurses and core competence of nurses were (31.94 ± 6.39), (90.29 ± 17.41) and (159.93 ± 34.31), respectively. Nurses′occupational coping self-efficacy negatively correlated with (r=-0.267, P<0.01) and positively correlated with the core competence of nurses (r=0.355, P<0.01). Conclusions The occupational coping self-efficacy of the nurses can be improved by successful experiencing, verbal persuasion and positive feedback. In this way, nurses core competence can be enhanced and their job stress can be relieved and consequently the quality of nursing can be enhanced.

Aim To investigate the effects of cell pro-liferation and activation in HSC-T6 cells by inhibiting the expression of EZH2 , and its partial relevant mech-anism. Methods By introducing the inhibitor DZNep in activated HSC-T6 cells stimulated by TGF-β1 , the protein expression levels of EZH2, p-ERK, p-AKT andα-SMA were detected by Western blot. The siRNA targeting EZH2 was designed and synthesized according to its nucleotide sequence, and their corresponding ex-pression vectors were constructed and transfected into HSC-T6 cells with LipofectamineTM 2000. The prolifer-ation of HSC-T6 cells was determined by MTT. And the protein expression levels of EZH2, p-ERK, p-AKT and α-SMA were measured by Western blot. Results By introducing the inhibitor DZNep in activated HSC-T6 cells stimulated by TGF-β1 , it effectively de-creased the protein levels of EZH2 and also the protein levels of p-ERK, p-AKT and α-SMA. By introducing EZH2-siRNA in activated HSC-T6 cells, it effectively inhibited the cell proliferation, and also the protein levels of EZH2, p-ERK, p-AKT andα-SMA. Conclu-sion Silencing EZH2 expression inhibits HSC-T6 cell proliferation and activation, and EZH2 may be a poten-tial therapeutic target gene for hepatic fibrosis.

Objective To evaluate mono-and bi-exponential decay models in the diagnosis of hepatocellular carcinoma (HCC). Methods 28 patients with HCC who underwent conventional MRI imaging and diffusion-weighted imaging were collected,and all the HCC lesions were proved by operation pathology.The ADC values in mono-exponential decay model and ADCst ,ADCslow , ADCfast and ffast of the lesions in bi-exponential decay model were measured through the reconstruction of ADCmap ,ADCslow map, ADCfast map and fraction of fast ADC at a workstation.The relationships between the ADC values with low,medium and high b-val-ues and different differentiation degrees of HCC were analyzed.Moreover,the relationships between the ADCst ,ADCslow ,ADCfast , ffast values and HCC defferentiation grades were also explored.Results Significant differences in ADC value were found among differ-ent degrees of HCC differentiation in middle and high b-value groups (P <0.05).A positive correlation was found between the ADC value and the degree of HCC differentiation in middle (r=0.377,P <0.01)and high b-value group (r =0.81 5,P <0.01).There were no significant differences in ADC value among the different degrees of HCC differentiation in low b-value group.There were significant differences in the values of ADCst ,ADCslow and ADCfast among different degrees of HCC differentiation.Significant posi-tive correlations were found between the values of ADCst ,ADCslow and ADCfast and the degree of differentiation (P <0.01).There were no significant differences in the values of ffast among different degrees of HCC differentiation.Conclusion ADC value in mono-exponential decay model plays a potential role in the diagnosis of different differentiation degree of HCC with a b value ≥400 s/mm2 .Furthermore,the parameters in bi-exponential decay model,especially the values of ADCst ,ADCslow and ADCfast ,can provide new and unique information in the distinction of different degrees of HCC differentiation.

This paper is to report the study of the metabolism of forscolin in plasma and liver microsomes for guiding clinical therapy. Forscolin was quantified by HPLC-MS/MS. The metabolic stability of forscolin in rat, Beagle dog, monkey and human plasma and liver microsomes, mediated enzymes of forscolin and its inhibition on cytochrome P450 isoforms in human liver microsomes were studied. Results showed that forscolin was not metabolized in plasma of the four species but metabolized in liver microsomes of the four species. The t1/2 of forscolin in rat, Beagle dog, monkey and human liver microsomes were (52.0 +/- 15.0), (51.2 +/- 5.9), (6.0 +/- 0.2) and (11.9 +/- 1.8) min; CL(int) were (75.6 +/- 18.7), (60.9 +/- 6.8), (513.8 +/- 14.3) and (176.2 +/- 25.6) mL x min(-1) x kg(-1); CL were (34.8 +/- 4.5), (23.3 +/- 1.0), (40.3 +/- 0.5) and (17.9 +/- 0.3) mL x min(-1) x kg(-1), respectively. Forscolin was metabolized by CYP3A4 in human liver microsomes. There was definite inhibition on CYP3A4 at the concentrations of forscolin between 0.1 ng x mL(-1) and 5 microg x mL(-1). Therefore, forscolin is rapidly excreted from liver microsomes. Attention should be paid to the drug interaction when forscolin was used along with other drugs metabolized by CYP3A4 in clinics.

Objective To improve the diagnostic accuracy by analyzing the CT features of primary hepatic sarcoma.Methods The CT findings of 6 cases with primary hepatic sarcoma confirmed by histopathology were analyzed retrospectively,including primary hepatic angiosarcoma 2 cases,and epithelioid hemangioendothelioma,primary hepatic lymphoma,alveolar soft-part sarcoma,undif-ferentiated embryonal sarcoma,1 case each.Results Primary hepatic sarcoma appeared as multiple nodules with heterogeneous and progressive enhencement in one case,and a dominant mass with multiple satellite nodules in another case.Epithelioid hemangioendo-thelioma displayed as multifocal hepatic disease involving both liver lobes,more than half of the lesions were peripheral and extended to the liver margin.Primary hepatic lymphoma demonstrated as an ill-defined low-density lesion with irregular ring enhancement. Alveolar soft-part sarcoma presented as a well-defined low-density lesion with obviously heterogeneous enhancement in arterial phase.Undifferentiated embryonal sarcoma appeared as a huge cystic lesion with slightly margin enhancement.Conclusion The CT findings of primary hepatic sarcoma are associated with the pathological types,combining clinical symptoms with typical CT features are helpful to the diagnosis.The ultimate diagnosis relies on pathology and immune histochemistry.

Objective To investigate the familial incidence of multiple primary carcinoma in Chinese hereditary nonpolyposis colorectal cancer patients (HNPCC) in Northeast China.Methods By family line investigation,multiple primary carcinoma (MPC) spectrum' s characteristics of 509 patients in 85 families registered in strict conformity with the HNPCC Amsterdam criteria Ⅱ were analyzed retrospectively.Results Of the 85 HNPCC families,multiple primary carcinoma developed in 55 patients in 25 families,among them 45 patients had metachronous carcinoma in 17 families,16 patients had synchronous carcinoma occurred in 12 families,6 patients with both synchronous carcinoma and metachronous carcinoma in 4 families.Conclusions Multiple primary carcinoma developed in significantly high incidence in Northeast China in Chinese hereditary nonpolyposis colorectal cancer patients,the most common MPC are colorectal cancer and endometrial cancer.

A rapid, sensitive and simple liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for the simultaneous determination of yogliptin and its metabolite in Wistar rat plasma. Linagliptin and dexamethasone were chosen as the internal standards of yogliptin and its metabolite, (R)-8-(3-hydroxypiperidine- -yl)-7-(but-2-yn-1-yl)-1-((5-fluorobenzo[d]thiazol-2-yl)methyl)-3-methyl- H-purine-2, 6 (3H, 7H)-dione, respectively. After a simple protein precipitation using acetonitrile as the precipitating solvent, both analytes and ISs were separated on a Grace Altima HP C18 column (2.1 mm x 50 mm, 5 microm) with gradient elution using methanol (containing 0.1% formic acid, 4 mmol x L(-1) ammonium acetate)-0.1% formic acid (containing 4 mmol x L(-1) ammonium acetate) as the mobile phase. A chromatographic total run time of 4.4 min was achieved. Mass spectrometric detection was conducted with electrospray ionization under positive-ion and multiple-reaction monitoring modes. Linear calibration curves for yogliptin and its metabolite were over the concentration range of 0.5 to 500 ng x mL(-1) with a lower limit of quantification of 0.5 ng x mL(-1). The intra- and inter- assay precisions were all below 14%, the accuracies were all in standard ranges. The method was used to determine the concentration of yogliptin and M1 in Wistar rat plasma after a single oral administration of yogliptin (27 mg x kg(-1)). The method was proved to be selective, sensitive and suitable for pharmacokinetic study of yogliptin and M1 in Wistar rat plasma.

Objective To analyze the characteristics of dynamic contrast enhanced MR imaging (DCE-MRI)in prostate cancer (PCa)at 3.0T,and to evaluate the diagnostic value of DCE-MRI.Methods 85 patients with suepected PCa received conventional MRI and DCE-MRI.The signal intense-time (SI-T)curve was analyzed.Then the time to maximum (Tmax),the maximum degree of enhancement (STmax%),and the rate of enhancement (Rmax)were calculated.The differences of styles of SI-T curve and the parameters between the positive and negative group were compared respectively.Results 59 cases of PCa were proved by biopsy,and there was no evidence of tumor in 26 cases.507 zones had histopathological results with 250 zones in positive group and 257 zones in negative group .The most common style of SI-T curve in positive group was rapidly ascending followed with descending curve,the most common style of SI-T curve in negative group was persistent ascending curve and plateau curve.The mean values of Tmax,SImax%,Rmax were (69.49±22.53)s,1.74±0.43,7.83±3.80 in positive group respectively,while (175.61±52.64)s,1.05±0.35,1.86±1.10 in negative group respectively,there were statistically significant differences between the two groups(t =-24.24,1 6.34,1 7.75,P <0.01)respectively. The mean values of Tmax,SImax% ,Rmax were (8 9 .1 9 ± 3 1 .7 2 )s,1 .5 8 ± 0 .4 6 ,5 .2 1 ± 3 .3 4 in the low-risk group (Gleason score 2 - 6 )respectively,while (64.25±14.68)s,1.76±0.43,8.25±3.70 in the high-risk group (Gleason score 7-10)respectively, there were statistically significant differences between them(t = 7.09,-8.74,- 7.83,P <0.01).Conclusion 3.0T DCE-MRI has great value in the diagnosis of PCa.