Objective To establish an evaluation indicator system for pharmacovigilance(PV)work in medical institutions of Fujian province,and provide a reference for the PV work in healthcare facilities.Methods Based on literature analysis and interpretation of policies and regulations,combined with the practical pharmacovigilance work in Fujian province,a preliminary indicator system was constructed.Following this,three rounds of expert consultation were conducted,including two rounds of the Delphi method to determine the content of the index system,and one round of the Analytic Hierarchy Process(AHP)to determine the weights of each index.Results A total of 9 primary indicators,23 secondary indicators,and 59 tertiary indicators were selected for the evaluation of pharmacovigilance work in health facilities of Fujian province,including pharmacovigilance organizational structure,human resources,equipment resources,development and documentation of the quality management system's procedural documents,Performance indicators for monitoring and reporting,risk identification,assessment,control and research capabilities.The consensus coefficients for three rounds of consultation with experts were 100％,100％,and 100％.The average authority coefficient of the experts was 0.878,and the expert coordination coefficients for the two rounds of Delphi method were 0.081 and 0.343,respectively(P＜0.001).In the AHP,the weight vector for primary indicators ranged from 0.023 to 0.263,with a maximum eigenvalue of 9.195.The weight vector values of the secondary indicators were from 0.096 to 1.000,and the maximum eigenvalues were 3.018-4.061;The weight vectors of the tertiary indicators were 0.143 to 1.000,and the maximum eigenvalues were from 3.000 to 5.078.The consistency ratio(CR)of each judgment matrix was between 0 and 0.051.Conclusions The constructed indicator of capability assessment model,integrating regulatory functions and the practical situation of medical institutions,can be used by regulatory authorities to assess pharmacovigilance work in medical institutions.It provides a solid reference for improving the pharmacovigilance capabilities of medical institutions in Fujian province.

Objective To establish an evaluation indicator system for pharmacovigilance(PV)work in medical institutions of Fujian province,and provide a reference for the PV work in healthcare facilities.Methods Based on literature analysis and interpretation of policies and regulations,combined with the practical pharmacovigilance work in Fujian province,a preliminary indicator system was constructed.Following this,three rounds of expert consultation were conducted,including two rounds of the Delphi method to determine the content of the index system,and one round of the Analytic Hierarchy Process(AHP)to determine the weights of each index.Results A total of 9 primary indicators,23 secondary indicators,and 59 tertiary indicators were selected for the evaluation of pharmacovigilance work in health facilities of Fujian province,including pharmacovigilance organizational structure,human resources,equipment resources,development and documentation of the quality management system's procedural documents,Performance indicators for monitoring and reporting,risk identification,assessment,control and research capabilities.The consensus coefficients for three rounds of consultation with experts were 100％,100％,and 100％.The average authority coefficient of the experts was 0.878,and the expert coordination coefficients for the two rounds of Delphi method were 0.081 and 0.343,respectively(P＜0.001).In the AHP,the weight vector for primary indicators ranged from 0.023 to 0.263,with a maximum eigenvalue of 9.195.The weight vector values of the secondary indicators were from 0.096 to 1.000,and the maximum eigenvalues were 3.018-4.061;The weight vectors of the tertiary indicators were 0.143 to 1.000,and the maximum eigenvalues were from 3.000 to 5.078.The consistency ratio(CR)of each judgment matrix was between 0 and 0.051.Conclusions The constructed indicator of capability assessment model,integrating regulatory functions and the practical situation of medical institutions,can be used by regulatory authorities to assess pharmacovigilance work in medical institutions.It provides a solid reference for improving the pharmacovigilance capabilities of medical institutions in Fujian province.

Hepatic fibrosis （HF） is a pathological process of abnormal repair of liver tissue structure caused by chronic liver injury， and its pathogenesis has not been fully clarified. Related studies have shown that programmed cell death may be associated with the onset of HF， and traditional Chinese medicine （TCM） has a significant effect in regulating programmed cell death to intervene against HF. This article reviews the main mechanism of the influence of programmed cell death on HF and discusses the possible mechanism of TCM regulation of programmed cell death in improving HF， which provides new ideas for TCM prevention and treatment of HF.

ObjectiveTo investigate the role and possible mechanism of action of rhubarb decoction （RD） retention enema in improving inflammatory damage of brain tissue in a rat model of mild hepatic encephalopathy （MHE）. MethodsA total of 60 male Sprague-Dawley rats were divided into blank group （CON group with 6 rats） and chronic liver cirrhosis modeling group with 54 rats using the complete randomization method. After 12 weeks， 40 rats with successful modeling which were confirmed to meet the requirements for MHE model by the Morris water maze test were randomly divided into model group （MOD group）， lactulose group （LT group）， low-dose RD group （RD1 group）， middle-dose RD group （RD2 group）， and high-dose RD group （RD3 group）， with 8 rats in each group. The rats in the CON group and the MOD group were given retention enema with 2 mL of normal saline once a day； the rats in the LT group were given retention enema with 2 mL of lactulose at a dose of 22.5% once a day； the rats in the RD1， RD2， and RD3 groups were given retention enema with 2 mL RD at a dose of 2.5， 5.0， and 7.5 g/kg， respectively， once a day. After 10 days of treatment， the Morris water maze test was performed to analyze the spatial learning and memory abilities of rats. The rats were analyzed from the following aspects： behavioral status； the serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） and the level of blood ammonia； pathological changes of liver tissue and brain tissue； the mRNA and protein expression levels of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （AKT）， and mammalian target of rapamycin （mTOR） in brain tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the MOD group， the RD1， RD2， and RD3 groups had a significantly shorter escape latency （all P<0.01）， significant reductions in the levels of ALT， AST， IL-1β， IL-6， TNF-α， and blood ammonia （all P<0.05）， significant alleviation of the degeneration， necrosis， and inflammation of hepatocytes and brain cells， and significant reductions in the mRNA and protein expression levels of PI3K， AKT， and mTOR in brain tissue （all P<0.05）， and the RD3 group had a better treatment outcome than the RD1 and RD2 groups. ConclusionRetention enema with RD can improve cognitive function and inflammatory damage of brain tissue in MHE rats， possibly by regulating the PI3K/AKT/mTOR signaling pathway.

Liver failure is a syndrome of severe liver diseases commonly seen in clinical practice, and it has a high mortality rate and thus becomes one of the critical diseases in internal medicine. Massive hepatocyte death and the extent of hepatocyte death exceeding the liver’s regenerative capacity are considered the core events in the development and progression of liver failure, and direct injury and immune-mediated inflammatory injury are the two main factors in this process. An increasing number of evidence has shown that host immune response and inflammatory cascade play an important role in the pathogenesis of liver failure. This article reviews the mechanism of action of immunoregulation (congenital and adaptive) and inflammatory injury (inflammation inducers, receptor cells, and inflammatory mediators) in the process of hepatic failure, as well as the interactions between immune response and immune cells and between inflammatory response and inflammatory factors, in order to help understand the pathogenesis of liver failure and provide new ideas for the diagnosis and treatment of liver failure and drug research and development.

Objective: To investigate the distribution of bla_KPC gene in Lishui and to analyze the molecular epidemiological characteristics of Klebsiella pneumoniae (K.pneumoniae) bla_KPC gene. Methods: From 2010 to 2016, all of the non-repetitive K. pneumoniae carbapenemase (KPC)-producing isolates in Lishui Municipal Central Hospital were collected. They were identified with VITEK 2 Compact system and typed by multilocus sequence typing (MLST). Plasmids were classified based on the DNA sequences of replication initiators. Transposons were detected by PCR. Locations of bla_KPC gene were verified through complete sequencing of the plasmids by next-generation sequencing (NGS). Results: A total of 125 strains were collected. K. pneumoniae strains accounted for 88.8% (111) and among them, 103 were ST11 type. IncF plasmids were detected in 48.6% of K. pneumoniae strains and most of them carried mutant Tn1721/Tn4401 chimera (48/54 isolates). Untypable plasmids were discovered in 50.5% of isolated strains and most of them were positive for the wild-type chimera (54/56 isolates). IncF-positive strains isolated during the period of 2011 and 2013 accounted for 94.4%, followed by a dramatic decrease. However, 76.8% of the strains harboring untypable plasmids were isolated from 2014 to 2016 and the number increased year by year. Conclusion K. pneumoniae of ST11 type was the main cause of bla_KPC gene dissemination in Lishui area. Strains carrying the IncF plasmids integrated with the mutant Tn1721/Tn4401 chimera and the untypable plasmids with the wild-type chimera were prevalent before and after 2014, respectively.

Objective To explore the feasibility and effectiveness of otoacoustic emission (OAE) in hearing screening for preschool children .Methods A total of 616 preschool children aged 3～6 (mean age 4 .6 years old) were included in this study .All the subjects received transiently evoked otoacoustic emission (TEOAE) test by trained personnel .The children who failed the hearing screening received diagnostic examination in the hearing ex-amination center .Results Of 616 children ,66 (10 .71％ ) failed the hearing screening and 16 children received audi-ological assessment .In these 16 children ,8 had otitis media with effusion (5 with mild conductive hearing loss ) ,5 had impacted cerumen ,3 had normal hearing ,and none had sensorineural hearing loss .Conclusion OAE can be used effectively in the hearing screening for preschool children .But how to improve the referral rate of children who failed the hearing screening needs further discussion .

Objective To analyze the drug resistance phenotype and genetic background of New Delhi metallo-β-lactamase (NDM)-producing bacterial strains in Lishui area of Zhejiang province.Methods The imipenem-resistant Enterobacteriaceae strains were isolated from January 2012 to December 2016 in Lishui Municipal Central Hospital of Zhejiang Province.Mrieux Vitek 2 Compact system was used to identified strains and PCR was used to screen for blaNDMgene.Susceptibility was detected by K-B method and MICs were obtained by Vitek 2 with GN13 cards.Plasmids typing was carried out by DNA sequencing of the replication initiator with the transconjugates as templates.The blaNDMgenetic contexts were detected by PCR and complete genome sequencing.Results A total of 102 strains of carbapenem-resistant enterobacteria (CRE), mainly Escherichia coli and Enterobacter cloacae, were isolated, of which 15 were positive for blaNDMwith a positive detection rate of 14.7%.The resistance rate to β-lactam antibiotics was 100%, and the resistance rates to aztreonam, compound sulfamethoxazole , tobramycin and gentamicin were all ＞80%;and the resistance rate to quinolones was ＞50%.Among the 15 NDM-producing strains , 12 strains were positive for Hodge test, and 2 strains of Enterobacter cloacae and 1 strain of Escherichia coli were negative. There were 11 strains of blaNDM-1and 4 strains of blaNDM-1.A variety of plasmid types such as IncX 3, IncFIIγ and IncA/C were detected, and 4 blaNDM-5genes were located in the IncX3 plasmid.Four blaNDMsurrounding gene structures were found, of which 8 blaNDM-1genes were located in ISAb125-hyp-blaNDM-1-bleMBL-TrpF-DsbC-IS26, while blaNDM-5was located in IS3000-IS5-blaNDM-5-bleMBL-TrpF-DsbC-IS26 structure, and the former was reported for the first time in China.Conclusion NDM-producing bacterial strains in Lishui area are prevalent at a low level and have high sensitivity to fosfomycin and polymyxin .The blaNDMgene may have multiple sources, but IncX3 plasmid is still the main source for gene transfer.Some new types of blaNDM-1 gene structure have been also found in this study.

Objective To evaluate clinical efficacy and safety of loratadine combined with desloratadine in the treatment of chronic spontaneous urticaria(CSU)in children. Methods A total of 177 children with CSU were enrolled into this study, and randomly and equally divided into 3 groups:combination group treated with an age?based dose of desloratadine tablet every morning and a weight?based dose of loratadine tablet before sleep every night for consecutive 28 days, loratadine group treated with a half tablet of placebo(starch tablet)every morning and oral loratadine tablet before sleep every night for consecutive 28 days, and desloratadine group treated with a half tablet of placebo (starch tablet) every morning and oral desloratadine tablet before sleep every night for 28 consecutive days. Possible adverse reactions were observed and recorded after the start of treatment, and therapeutic effects were evaluated at the end of treatment. Results A total of 166 patients completed the trial, including 55 in the combination group, 56 in the loratadine group and 55 in the desloratadine group. After 28?day treatment, the total response rate was significantly higher in the combination group(90.9%, 50/55)than in the loratadine group (71.4%[40/56],χ2=6.865, P<0.05)and desloratadine group(74.5%[41/55],χ2=5.153, P<0.05). No significant difference in the incidence of adverse reactions was observed among the combination group (10.9%[6/55]), loratadine group (8.9%[5/56]) and desloratadine group (9.1%[5/55], P > 0.05). Conclusion Combination of loratadine and desloratadine was superior to loratadine or desloratadine alone in the treatment of childhood CSU, and there was no significant difference in the incidence of adverse reactions among the 3 treatment groups.

Objective To investigate the incidences, risk factors, genotypes and epidemiology of community-acquired blood stream infection caused by extended spectrum β-lactamases (ESBLs)-producing Escherichia coli and Klebsiella pneumonia strains and to analyze the sensitivity of those ESBLs producing strains to commonly used antibiotics. Methods Forty-two patients who were diagnosed with community-ac-quired blood stream infection caused by Escherichia coli or Klebsiella pneumonia strains in Sichuan Provincial People′s Hospital were recruited in this study. Disc diffusion method was used for the phenotypic confirmato-ry test of ESBLs. Agar dilution method was performed to measure the antimicrobial susceptibility of the ESBLs-producing strains to 13 clinically commonly used antibiotics. Genotypes of the ESBLs-producing strains were identified by polymerase chain reaction (PCR). Multilocus sequence typing (MLST) was used to analyze the epidemiology of ESBLs-producing strains. Logistic regression analysis was performed to analyze the risk factors for community-acquired blood stream infection. Results The ESBLs-producing Escherichia coli strains accounted for 56. 3% (18 / 32) and the ESBLs-producing Klebsiella pneumoniae strains accounted for 20% (2 / 10). All of the 20 ESBLs-producing strains were sensitive to imipenem, meropenem, ertapen-em, nitrofurantoin and moxalactam. The ESBLs-producing strains sensitive to amikacin, piperacillin-tazobactam and fosfomycin accounted for 95% , 90% and 85% , respectively. Drug resistance rates of the 20 strains to cefotaxime, levofloxacin, ciprofloxacin and cefepime were relatively high accounting for 100% , 80% , 80% and 75% , respectively. Among the 20 ESBLs-producing strains, 7 strains only carried the CTM gene, while the other 13 strains were all positive for two genotypes of ESBLs, mainly identified as TEM+CTM-M-14 and TEM+CTM-15 genotypes. The 18 Escherichia coli strains were classified into 10 ST types, most of which were ST131 type, followed by ST10 and ST38 types. This study indicated that malignant tumor might be a possible risk factor. Conclusion The prevalence of community-acquired blood stream infection caused by ESBLs-producing Escherichia coli strains was becoming increasingly serious. Malignant tumor might be the risk factor associated with the producing of ESBLs in Escherichia coli and Klebsiella pneumonia strains. TEM+CTX-M-14 was the predominant genotype of ESBLs-producing strains and the prevalent clone was ST131 type. Carbapenems and enzyme inhibitor compounds were ideal drugs for the treatment of commu-nity-acquired blood stream infection caused by ESBLs-producing Escherichia coli and Klebsiella pneumonia strains. This study was limited by the small sample size. Therefore, it is necessary to conduct further resear-ches based on a large number of samples.