Bile acids(BAs)are synthesized by the liver from cholesterol through several complementary pathways and aberrant cholesterol metabolism plays pivotal roles in the pathogeneses of cholesterol gallbladder polyps(CGP)and cholesterol gallstones(CGS).To date,there is neither systematic study on BAs profile of CGP or CGS,nor the relationship between them.To explore the metabolomics profile of plasma BAs in healthy volunteers,CGP and CGS patients,an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method was developed and validated for simultaneous determination of 42 free and conjugated BAs in human plasma.The developed method was sensitive and reproducible to be applied for the quantification of BAs in the investigation of plasma samples.The results show that,compared to healthy volunteers,CGP and CGS were both characterized by the significant decrease in plasma BAs pool size,furthermore CGP and CGS shared aberrant BAs metabolic characteristics.Cheno-deoxycholic acid,glycochenodeoxycholic acid,λ-muricholic acid,deoxycholic acid,and 7-ketolithocholic acid were shared potential markers of these two cholesterol gallbladder diseases.Subsequent analysis showed that clinical characteristics including cysteine,ornithine and body mass index might be closely related to metabolisms of certain BA modules.This work provides metabolomic information for the study of gallbladder diseases and analytical methodologies for clinical target analysis and efficacy evaluation related to BAs in medical institutions.

Objective: To investigate the effects of miRNA on the expression of paraoxonase 1 (PON1) and its clinical application in the patients with nonalcoholic steatohepatitis (NASH). Methods: Bioinformatics methods were used to analyze and predict PON1 related regulation on miRNA. PON1 luciferase reporter gene vectors were constructed and the activity of dual luciferase was analyzed. The up/down-regulated levels of miRNA in HepG2 cells of different groups were detected by real-time fluorescence quantitative PCR (qRT-PCR), and the levels of PON1 protein in HepG2 cells were detected by western blot. The levels of miR140-5p in the serum of healthy people and NASH patients were also analyzed by qRT-PCR. Results: According to the prediction of TargetScan database, miR140-5p may bind complementarily to the end of PON13′-UTR. The analysis for the activity of dual luciferase reporter gene showed that miR-140-5p mimic significantly downregulated the fluorescence of wild type PON1 vector (P＜0.01). The results of qRT-PCR demonstrated that miR-140-5p mimic group showed high overexpression (P＜0.01) compared with the normal cell control group and the negative mimic control group, while miR-140-5p inhibitor group appeared corresponding low expression (P＜0.05). western blot results suggested that the transfection of miR140-5p mimic significantly down-regulated the expression of PON1 (P＜0.01) while miR140-5p inhibitor up-regulated this expression (P＜0.01). Compared with the healthy control group, the level of miR140-5p was decreased in the serum of NASH patients, and the difference was statistically significant (P＜0.01). Conclusion miR140-5p may be involved in the progression of nonalcoholic steatohepatitis through regulation for the posttranscriptional gene expression of PON1.

Pyrrolizidine alkaloids(PAs)are among the most hepatotoxic natural compounds that are widely distributed throughout the world.Most PAs are metabolically activated to trigger toxicity.Exposure to herbal medicine containing PAs and food supplements contaminated by PAs is considered to be one of the two main causes of hepatic sinusoidal obstruction syndrome(HSOS),which is a rare hepatic vascular disease with a high mortality rate.PAs-induced HSOS cases have been reported worldwide.However,there is no clinically effective therapy for PAs-induced HSOS,which is partially because the toxic mechanism is not fully understood.This review focuses on updating the information on the metabolism and the molecular mechanisms of PAs hepatotoxicity,including oxidative stress,apoptosis,and dysfunction of bile acid metabolism,and their interactions.

Objective:To explore the application value of transcranial magnetic stimulation combined with language training for children with language retardation.Methods:100 children with language retardation who were treated in our hospital from March 2015 to March 2016 were selected as the research object.They were divided into control group and observation group according to the random number table method,50 cases in each group.The control group was treated with routine language training,while the observation group was treated with transcranial magnetic stimulation combined with language training.The treatment of the two groups were 3 months.The therapeutic effects were evaluated by the language development in Chinese children assessment method and the changes of developmental quotient before and after treatment were evaluated by the neuropsychological development test for children.Results:The effective rate of the observation group was 98.0％,which was significantly higher than 87.0％ of the control group (P＜0.05).Compared with before treatment,the language development quotient and development quotient of the two groups after treatment for 1,2 and 3 months were significantly improved,and the observation group was significantly better than the control group (P＜0.05).The normal rate of the observation group was 80.0％,which was significantly higher than 66.0％ of the control group (P＜0.05).Conclusion:The effect oftranscranial magnetic stimulation combined with language training is ideal,which can effectively improve the developmental quotient of children with language retardation,and it is worth promoting in clinical practice.

OBJECTIVE:To explore the role of clinical pharmacists participating in the individualized treatment for purulent meningitis. METHODS:Clinical pharmacists participated in the therapy for a patient with purulent meningitis complicated with Staphylococcus aureus infection. According to patient's condition,clinical pharmacists assisted physicians to formulate preliminary therapeutic plan. Reviewing relevant guidelines,domestic and foreign literatures,clinical pharmacists suggested to combine with dexamethasone so as to relieve inflammatory reaction. According to the results of drug sensitivity test,based on vancomycin plasma concentration monitoring and population pharmacokinetics model fitting,clinical pharmacists suggested to reduce the dose of vanco-mycin to 0.5 g,ivgtt,q12 h. The pharmaceutical care were conducted throughout the therapy,including efficacy evaluation of an-ti-infective therapy,ADR monitoring,renal function monitoring,etc. RESULTS:Physicians adopted some suggestions of clinical pharmacists. The disease condition of the patient was recovred,and no ADR related to vancomycin was found. On the 16th day, the patient was discharged from the hospital. CONCLUSIONS:Clinical pharmacists participate in treatment of purulent meningitis, assist physicians to optimize therapy plan based on relevant guideline,literature,etiological examination,blood concentration moni-toring and pharmacokinetics model fitting results. It not only guarantee therapeutic efficacy of anti-infective therapy,but also pre-vent and reduce the occurrence of ADR.

Objective To summarize the main nursing points of toxic epidermal necrolysis. Methods On the foundation of conventional therapy, an overall assessment was carried out among 10 patients with toxic epidermal necrolysis. On loose skin with erythema, a combination of zinc oxide and talcum powder was externally applied to skin lesions where blisters were not broken in order to promote dry-style exfoliation of the skin lesion. After infrared irradiation, gauze containing MEBO was applied externally to skin lesions with eroded secretions to moisturize them, thus facilitating healing of the skin lesion. Meanwhile, mucosa of special part of patient's body was well nursed. Protective isolation was enhanced in order to reduce secondary infection. The patient's conditions were observed closely. Diet guidance was also done. Results All the patients were dry-style exfoliated with treatment ranges reaching up to 30%to 60%of the affected area. Dry-style exfoliation time was between 5 to 10 days, with an average of 7.20 ±1.69 days. The area of skin lesion erosion ranged from 10% to 60%. Following the external application of MEBO gauze to moisturize and heal, skin lesion healing time ranged from 7 to 18 days with an average of 13.70 ±3.40 days. Conclusion According to the specific situation of toxic epidermal necrolysis, targeted nursing and treatment can promote the dry-style exfoliation of skin lesions, reduce the area of skin erosions, alleviate the suffering of patients and promote healing of the skin lesion.

BACKGROUND: In recent years, the immunoregulatory effects of mesenchymal stem cells (MSCs) can be used to induce immune tolerance. OBJECTIVE: To evaluate the safety and feasibility of human umbilical cord-derived MSCs (hUC-MSCs) in liver transplantation patients. METHODS: hUC-MSCs were cultured and identified. After approved by the Medical Ethics Committee, a total of 50 patients were randomly divided into experimental group and control group according to the proportion of 1:1. In the experimental group, hUC-MSCs were perfused by the portal vein during the operation and infused into the jugular vein on the 3rd day after the operation. The injection dose was 1×106/kg (prepared as 50 mL of cell suspension). Both groups received standard immunosuppressive regimens. Blood biochemistry and immune function indicators were detected preoperatively and at postoperative days 3, 7, months 1, 2, 3, 6, 12. Acute and chronic rejection rates, incidence of infection, and incidence of transplantation-related complications were recorded. RESULTS AND CONCLUSION: (1) At 3 and 7 days after the operation, the percentage of peripheral blood CD4+CD25+ cells (regulatory T cells) in the experimental group was significantly higher than that in the control group (P < 0.05). The percentage of CD4+ cells (helper/inducer T cells) and ratio of CD4+/CD8+ T lymphocytes were significantly lower in the experimental group than the control group (P < 0.05). (2) There was no significant difference in postoperative alanine aminotransferase and total bilirubin levels between the two groups (P > 0.05). (3) The incidence of abnormal liver function in the experimental group was significantly lower than that in the control group (P < 0.05). (4) The incidence of transplantation-related complications and the rate of infection showed no significant difference between the two groups (P > 0.05). Overall, the intravenous infusion of hUC-MSCs is safe and feasible in liver transplantation patients, which in early stage can promote the the proliferation and activation of CD4+CD25+ cells (regulatory T cells), reduce the percentage of CD4+ cells (helper/inducer T cells) and lower the ratio of CD4+/CD8+ T cells, thereby improving the immune status in liver transplantation patients.

Objective Bevacizumab ( BM ) is an angiogenesis inhibitor widely used in cancer therapy, but its off-target effect of proteinuria may lead to discontinuation of treatment.This study was to explore the mechanisms of BM inducing proteinuria in mice. Methods Twenty-four healthy mice were randomly divided into four groups, saline control, low-dose BM, medium-dose BM, and high-dose BM, treated by injection of normal saline and BM at 10, 35, and 60 mg per kg of the body weight, respectively, though the tail vein.At 4 weeks after injection, 24-hour urine was collected to determine the total urine protein and blood obtained from the eyeballs for biochemical analysis.Then all the mice were sacrificed and the kidneys harvested for observation of pathologic changes in the glomeruli as well as for immunohistochemistry, Western blotting, and real-time PCR analysis. Results Compared with normal saline,BM obviously elevated the level of 24-hour urine protein, with statistically significant differences between the control and the medium-and high-dose BM groups (0.23 ±0.02 vs 1.14 ±0.13 and 1.43 ±0.10, P<0.01), but not between the control and the low-dose BM (0.23 ±0.02 vs 0.29 ±0.07, P>0.05).No significant differences were observed among the four groups in the levels of Cr, BUN, AST and ALT (P>0.05).Under the optical microscope, the kidneys showed normal structures in the control group, no signifi-cant pathologic changes in the low-dose BM, and vacuolus-like alteration with atrophic glomerular endothelial cells in the medium-and high-dose BM groups.Immunohistochemical analysis demonstrated the expressions of VEGF and podocin were moderately or strongly positive in the control and low-dose BM groups, by weakly positive or negative in the medium-and high-dose BM groups.Compared with the control group, the expression of the VEGF protein in the renal tissue was significantly decreased in the high-dose BM group (0.76 ±0.09 vs 0.39 ±0.05, P<0.01) but had no remarkable difference from that in the low-dose (0.81 ±0.10) or medium-dose BM (0.64 ±0.08) group (P>0.05), and the expression of the podocin protein was significantly reduced in the medium-dose BM (0.67 ±0.07 vs 0.43 ±0.10, P<0.05) and high-dose BM (0.67 ±0.07 vs 0.19 ±0.04, P<0.01), but not in the low-dose BM group (0.67 ±0.03) (P>0.05).The mRNA expressions of VEGF and podocin were not significantly changed in the low-dose BM group as compared with the control (1.07 ±0.61 and 1.12 ±0.09 vs 1.23 ±0.25 and 1.17 ±0.19, P>0.05) but remarkably de-creased in the medium-dose (0.82 ±0.38 and 0.71 ±0.18) and high-dose BM groups and (0.47 ±0.64 and 0.42 ±0.09) groups (P<0.01). Conclusion Bevacizumab damages glomerular filtration membrane and induce proteinuria partially by down-regulating the protein and mRNA expressions of VEGF and podocin.

Objective To establish a rat model of nonalcoholic steatohepatitis (NASH),and to investigate the preventative and therapeutic effects of compound ginkgo extract against NASH.Methods A total of 60 male Sprague-Dawley rats were fed with high-fat feed and 10％ fructose water for 24 weeks to establish the rat model of NASH.The general behaviors of the rats were observed,and the body weight was recorded.Blood samples from the inferior vena cava and the liver were collected after the last administration to measure serum total cholesterol (TC),triglyceride (TG),high-density lipoprotein cholesterol (HDL-C),and low-density lipoprotein cholesterol (LDL-C),as well as liver function parameters.The liver index was calculated,HE staining was performed to observe liver histopathological changes,and the total lipase activity and the levels of TC,TG,and free fatty acid (FFA) in liver tissue were measured.Results After 24 weeks,compared with the normal group,the model group had a significantly faster increase in body weight,significant increases in serum levels of TC (2.20±0.52 mmol/L),TG (0.87±0.22 mmol/L),LDL-C (1.22±0.50 mmol/L),alanine aminotransferase (ALT) (129.4±44.7 U/L),and aspartate aminotransferase (AST) (209.3±42.8 U/L),liver index (3.62％±0.28％),and the levels of TC (4.42±1.39 mmol/mg.prot),TG (0.85±0.11 mmol/mg.prot),and FFA (644.78±36.65 μmol/L) in liver tissue,and significant reductions in serum HDL-C level (0.58±0.11 mmol/L) and the activity of lipoprotein lipase (LPL) (9.95±1.64 U/mg.prot)and hepatic lipase (HL) (9.91±1.03 U/mg.prot) (all P ＜ 0.01).In addition,the pathological results showed severe hepatocyte steatosis,varying degrees of inflammatory cell infiltration,exudation in the portal area,and necrosis of liver cells in the model group.After the intervention with compound ginkgo extract,there were significant reductions in serum levels ofTC (1.78±0.21 mmol/L),TG (0.58±0.07 mmol/L),LDL-C (0.84±0.19mmol/L),and ALT (84.1±17.1 U/L),AST (155.4±20.9 U/L),liver index (2.71 ％±0.15％),and the levels of TC (2.24±1.02 mmol/mg.prot),TG (0.46±0.11 mmol/mg.prot),and FFA (580.56±50.63 μmol/L) in liver tissue,as well as significant increases in serum HDL-C level (0.68±0.10 mmol/L) and the activities of LPL (15.54±2.21U/mg.prot) and HL (11.92± 1.87 U/mg.prot) (P ＜ 0.05 or P ＜ 0.01).At the same time,it significantly reduced hepatomegaly in rats and improved fatty degeneration and degree of inflammation in liver cells.Conclusion Compound ginkgo extract can prevent and treat NASH by correcting dyslipidemia,improving liver function and fatty degeneration in hepatocytes,and reducing the degree of inflammation,and its mechanism of action may be associated with increasing total lipase activity,reducing FFA in the liver,increasing the decomposition of TG,and reducing the synthesis of TG.

Objective To understand the demanding situation for professionals in Zhejiang Province;To improve the relevance of professional training and effectiveness of education. Methods Interviews and questionnaires were used for the six aspects of research:traditional Chinese medicine industry and its needs for professionals, the school-enterprise cooperative education and staff training needs, Chinese professional competence, medicine curriculum system, personnel positioning and analysis of knowledge, ability and quality requirements, and follow-up survey for graduates. This survey was opened to 12 pharmaceutical companies in 5 areas in Zhejiang Province, with a purpose to analyze the demands and requirements for Chinese medicine professionals in Zhejinag Province. Results and Conclusion The Chinese medicine market of Zhejiang Province demands for structured and diversified professionals in large quantities, especially for skilled professionals of high-quality of vocational level, which provides a good environment for Chinese medicine professional training.