This paper presented the conventional methods for signal detection of adverse drug reactions (ADRs) and their applications, the research progress in ADRs signal mining based on healthcare big data, and briefed the methods and uses of ADRs prediction using machine learning technology in the era of healthcare big data.The conclusion was that deep learning, as a fast growing tool in machine learning, will become hotspot of research, expected to help with ADRs signal mining and rational clinical drug use.

Objective To explore the effects of tumor necrosis factor-α (TNF-α) on ventricular arrhythmias resulted from acute myocardial infarction (AMI) in rats. Method Two hundred and forty male Wistar rats were randomized (random number) into sham operation group, AMI group and recombinant human tumor necrosis factor receptor (rhTNFR) fusion protein (Fc) group. Acute anterior wall myocardial infarction was produced in rats of AMI group with ligating the left anterior descending coronary artery (LAD) , and the rats were just operated without ligation of LAD in sham group. The rats of Fc group were treated with rhTNFR-Fc (10 mg/kg), a TNF-α antagonist, 24 hours before LAD ligation. The original ECG was recorded 10 min before ligation and the ECGs of ventricular arrhythmias occurred spontaneously or induced by programmed electrical stimulation were recorded 10 min, 20 min, 30 min, 60 min, 3 h, 6 h and 12 hours after ligation. The protein levels and mRNA expressions of TNF-α in rats in different groups were detected with histochemistry and real-time fluorescent quantitative PCR. Results The expressions of TNF-α mRNA and levels of TNF-α protein markedly increased 10 min after infarction, reached the climax 20-30 min later, and then gradually returned to the original level in AMI group and Fc group. The time-windows of spontaneous and induced ventricular arrhythmias were consistent with the time-window of expressions of TNF-α mRNA and levels of TNF-α protein. Compared with AMI group, there were lower levels of TNF-α protein and lower incidence of ventricular arrhythmias in Fc group ( P < 0.05) , but there was no significant difference in TNF-α mRNA between two groups. There was no obvious change in TNF-α in rats of sham operation group. Conclusions The expressions of TNF-α mRNA and levels of TNF-α protein induced by AMI could contribute the initiation of ventricular arrhythmias.

OBJECTIVE:To improve the level of rational drug use,and to reduce the workload of clinical pharmacists. METH-ODS:Established“Intelligent Management and Solution for Clinical Rational Drug Use”of our hospital was introduced,including post-prescription review(all prescriptions review)system, self-maintenance system for rational drug use knowledge base,pre-pre-scription review (rational drug use real-time review) early warning system. The effects of intelligent system were evaluated. RE-SULTS & CONCLUSIONS:After the application of the system,the following aspects could be achieved,including“all prescrip-tions review”,“multi-prescriptions/longitudinal review”,system knowledge base real-time update and autonomous definition of re-view rules,effective communication and intervention between physicians and pharmacists before printing prescription by Yaozhidao instant messaging system. Through related trial evaluation,the proportion of false positive prescriptions decreased by 17.65% after 4 months of the application of the system;drug consultation prescriptions review average score of outpatient pharmacists increased from 81 to 94.85;the time of prescription review decreased by 4.72-5.46 times. Through mandatory interception of unqualified pre-scriptions,severe warning,timely prompt and pharmacists’intervention,the rate of unqualified prescriptions pre-reviewed by the system in respiration department decreased from 32% in Jan. 2015 and 21% in May to 4.62% in Dec. So,the application of the system promotes rational drug use in outpatient department,reduces the workload of pharmacists and ensures the safety of drug use comprehensively.

Objective To evaluate the effecof bilateral ovariectomy combined with hormone injection on the bone mineral density and biomechanical property of sheep proximal femu.Method16 healthy adulsheep were divided into the sham operation group (n=8) and the experimengroup (n=8) randomly .Bilateral ovariewere only exposed in the sham operation group .The ex-perimengroup waperformed bilateral ovariectomy (OVX) and began to conducthe intramusculainjection of methylprednisolone (0 .45 mg · kg -1 · d-1 ) aftepostoperative 1 month fo10 month.The bone density (BD) of all sheep proximal femuwameas-ured before OVX and in postoperative 1 yea.The compression tesand the axial pullouteswere performed to evaluate biome-chanical property of postoperative 1 yeaproximal femu.ResultBD of proximal femubefore surgery had no statistically signifi-candifference between the two group,and which in the sham operation group had no statistically significandifference between before and aftesurgery (P＞0 .05) .BD of proximal femuin postoperative 1 yeain the experimengroup wasignificantly de-creased and significantly lowethan thain the sham operation group (P＜0 .05) .The maximal compression stresand the energy absorption value in the experimengroup were significantly lowethan those in the sham operation group with statistically signifi-candifferences(P＜0 .05);the maximal axial pulling force and the energy absorption value in the experimengroup were signifi-cantly lowethan those in the sham operation group with statistically significandifference (P>0 .05) .Conclusion The method of bilateral ovariectomy combined with hormone injection can significantly decrease BD and biomechanical intensity of sheep proximal femu.

Objective To compare and explore the curative effects of elective operation and emergency operation in treating atlantoaxial vertebral segmental spinal canal space-occupying lesions.Methods Thirty-two patients suffering from atlanto-axial vertebral segmental spinal canal space-occupying lesions treated in our hospital from May 2010 to April 2015 were selected and divided into the emergency operation group (group A,n =14) and elective operation group (group B,n =18).The emergency and elective operations were adopted respectively.Then the operation time,intraoperative blood loss,JOA score,ODI index,VAS score,postoperative imaging(MRI) and effect satisfaction degree were compared between the two groups.Results After treatment,the JOA score in the group A was (25.23±4.47) points,which was higher than (22.10±3.56) points in the group B,and the difference was statistically significant (t=3.67,P＜0.05).The ODI index and VAS score of the two groups all were decreased.The ODI index in the group A was (18.56±3.10) points,which in the group B was (21.56±4.37) points,and there was statistically significant difference between the two groups (t=3.76,P＜0.05).The VAS score in the group A was (1.89 ±-0.53)points,which in the group B was (3.16±0.89)points,the difference was statistically significant between the two groups (t=3.76,P＜0.05).Before surgery and at postoperative 1 month,the spinal cord function classification(Frankel grade) of the two groups had no statistically significant difference between the two groups(Z=-0.18,P=0.85＞0.05,Z=-0.52,P=0.60＞0.05).The operation time had no statistical difference between the group A and B[(120.23±9.02)min vs.(126.25±12.12)min,P＞0.05].The intraoperative bleeding volume had had no statistical difference between the group A and B [(211.26±12.25)mL vs.(220.43±17.58)mL,P＞ 0.05].After one month of treatment,the satisfaction degree in the group A was 92.56 ％,which was higher than 72.22％ in the group B,and the difference was statistically significant (Z=-2.13,P＜0.05).Conclusion Emergency operation in treating atlantoaxial segment spinal space occupying lesions can effectively improve the therapeutic effect,and has higher patients satisfaction after treatment.Therefore which is worth promoting and applying.

Objective To observe effects of Naotaifang on MMP-9, NF-κB and TIMP-1 after focal cerebral ischemia in rats. Methods The rats were randomly divided into sham operation group, model group, and Naotaifang low- (3 g/kg), medium- (9 g/kg), high- dose (27 g/kg) group. After 3 days of corresponding therapy by intragastric administration once a day, the regional cerebral ischemia model was made by middle cerebral artery occlusion (MCAO) with suture method. Following 3 days, the rats were treated with previous method. On the third day, hippocampal C2 region of ischemic tissue was detected by HE dyeing. And the contents of MMP-9, NF-κB and TIMP1 proteins in hippocampal C2 region were measured by immunohistochemical method. Results The number of normal brain cells in high dose group of Naotaifang was more than that of the model group, and only a few cells appeared nucleus pycnosis. The MMP-9 expression of all dose groups of Naotaifang were significantly decreased than model group (P<0.05). The NF-κB expression of high and medium dose groups of Naotaifang were significantly decreased (P<0.05). The TIMP1 expression of all dose groups of Naotaifang were significantly increased compared with sham operation group (P<0.05). Conclusion The mechanism of Naotaifang protecting blood brain barrier against injury of cerebral ischemia may be involved in ameliorating MMP, NF-κB and increasing TIMP1 expression.

Objective To construct the murine allogeneic acute GVHD model.Methods C57BL/6 (H-2b) mice were used as the donors and Balb/c (H-2d) mice as the recipients in allogeneic bone marrow transplantation (BMT).Groups were set as total body radiation (TBI) control group (n =4),GVHD group (n =10),simple BM transplantation group (n =10) and normal control group (n =4).For TBI control group,mice were subjected to TBI but did not receive BMT after radiation.For GVHD group,5 days before TBI,gentamycin (320 mg/L) and erythromycin (250 mg/L) were added into the drinking water,and on the day of transplantation,mice received one total dose of 8.0 Gy 60Coγ TBI,and within 5 h,2 × 106 C57BL/6 BM cells and 1 × 107 C57BL/6 spleen cells were transfused per mouse via the tail vein.For simple BMT group,the pretreatment was the same as GVHD group,and mice received only 2 × 106 C57BL/6 BM cells per mouse via the tail vein.The mental status,activity,posture,fur,weight,and stool were observed after transplantation.Survival time of each mouse was recorded,survival rate was calculated,and survival curve was drawn.Pathological examination was done for the liver,skin,small intestine and BM on the brink of death.Results The median survival time (MST) in TBI control group,GVHD group and BMT group was (9.0 ± 0.7),(32.0 ± 3.2) and ( 17.5 ± 1.6) days respectively,and there was significant difference between every two groups (P ＜ 0.01 ).Pathological examination in TBI control group showedhematopoiesis exhaustion.GVHD group showed acute GVHD symptoms 10-13 days after allo-BMT,and the pathological changes of the skin,liver and small intestine corresponded to those of Ⅰ to Ⅱ degree of GVHD.Simple BMT group also showed acute GVHD symptoms 10-13 days after alloBMT,but their GVHD manifestation and histological changes were less serious and only 0 to Ⅰ degree of GVHD could be seen.ConclusionStable acute GVHD model can be constructed by transfusion of allogeneic BM cells and spleen cells into Balb/c mice after lethal TBI.

Objective To clone and identify the heat shock factors(HSFs)of Schistosoma japonicum and analyze its molec?ular structure and alternative splicing pattern. Methods The New Zealand rabbits were infected with the cercariae of Schistoso?ma japonicum and were killed and dissected 42 days post?infection,and the adult worms of S. japonicum and the livers of the rabbits were harvested. Then,the total RNA was extracted by using Trizol reagent. The Sj?hsf open reading frame(ORF)and the alternative splicing fragments were amplified by RT?PCR from the female,male and egg samples,then cloned and verified by enzyme digestion and sequencing. DNAMAN 8.0,InterPro,Mega 6 combined with the Internet databases were utilized to clarify the gene structure,functional domains,alternative splicing pattern,and the homology and phylogenetic tree of HSFs. Re?sults Sj?hsf ORF and the alternative splicing fragments were amplified from the female,male and egg samples of S. japonicum by RT?PCR. After cloning,the positive recombinant plasmids pBSjHSFf?F,pBSjHSFf?M,pBSjHSFf?E containing Sj?hsf ORF, pBSjHSFs?F,pBSjHSFs?M,pBSjHSFs?E with Sj?hsf alternative splicing fragments were identified by enzyme digestion and se?quencing. Three alternative splicing Sj?hsf isoforms were observed through sequence analysis:Sj?hsf?isoform1(2 050 bp),Sj?hsf ?isoform2(2 086 bp)and Sj?hsf?isoform3(2 111 bp);the GenBank accession numbers were KU954546,KX119143 and KX119144,respectively. All the three isoforms located in the same Contig SJC_S000780 of S. japonicum genome and all ex?pressed at female,male and egg stages,but Sj?hsf?isoform1 with a high?level expression. Sj?HSF?isoform1(671 aa)and Sj?HSF?isoform2(683 aa)had DBD(DNA binding domain),HR?A/B and HR?C domains,while Sj?HSF?isoform3(282 aa)stopped in advance without HR?C domain. Phylogenetic tree analysis of HSFs illustrated that Sj?HSFs belonged to HSF1 family,with a close phylogenetic relationship to Sm?HSFs. Conclusions There are three alternative splicing isoforms of Sj?HSF existing in the female,male and egg stages of S. japonicum,but Sj?HSF?isoform1 expresses in a high?level. This study lays the foundation for further study on molecular mechanisms of Sj?HSFs in regulating the heat shock response system.

Artemisnin is a novel sesquiterpene lactone with an internal peroxide bridge structure, which is extracted from traditional Chinese herb Artemisia annua L. (Qinghao). Recommended by World Health Organization, artemisinin is the first-line drug in the treatment of encephalic and chloroquine-resistant malaria. In the present study, transgenic A. annua plants were developed by overexpressing the key enzymes involved in the biosynthetic pathway of artemisinin. Based on Agrobacterium-mediated transformation methods, transgenic plants of A. annua with overexpression of both HDR and ADS were obtained through hygromycin screening. The genomic PCR analysis confirmed six transgenic lines in which both HDR and ADS were integrated into genome. The gene expression analysis given by real-time quantitative PCR showed that all the transgenic lines had higher expression levels of HDR and ADS than the non-transgenic control (except ah3 in which the expression level of ADS showed no significant difference compared with control); and the HPLC analysis of artemisinin demonstrated that transgenic A. annua plants produced artemisinin at significantly higher level than non-transgenic plants. Especially, the highest content of artemisinin was found in transgenic line ah70, in which the artemisinin content was 3.48 times compared with that in non-transgenic lines. In summary, overexpression of HDR and ADS facilitated artemisinin biosynthesis and this method could be applied to develop transgenic plants of A. annua with higher yield of artemisinin.
Artemisia annua ; genetics ; metabolism ; Artemisinins ; metabolism ; Biosynthetic Pathways ; Drugs, Chinese Herbal ; Mixed Function Oxygenases ; genetics ; Oxidoreductases ; genetics ; Plant Proteins ; genetics ; Plants, Genetically Modified ; genetics ; metabolism ; Plants, Medicinal ; genetics ; metabolism

Objective:To evaluate the efficacy and safety of recombinant human acidic fibroblast growth factor( rh-aFGF)and re-combinant human basic fibroblast growth factor( rh-bFGF)in the treatment of deep second degree burn. Methods:A multicenter,pro-spective,randomized and double-blind clinical trial was conducted. Totally 216 cases of deep second degree burn were selected from five research centers and given appropriate antibiotics and nutritional supplement therapy. The wound of 108 cases in the observation group were rinsing with rh-aFGF(one bottle / 5cm2)according to the wound area at the time of admission followed by rh-aFGF daily spraying,3-4 press/cm2 ,6-8 times a day. The 108 patients in the control group were treated with rh-bFGF with the same regimen as the observation group. After the 30-day follow-up,the wound healing was evaluated in the two groups. Results:The complete healing time,debridement time,complete healing rate in 12 days and 15 days in the observation group were all better than those in the control group(P<0. 05). After the 7-day treatment,the level of leukocyte and seepage score of the observation group were both lower than those of the control group(P<0. 01). The moderate rate showed significant difference between the two groups(P<0. 05). Conclu-sion:rh-aFGF shows better clinical efficacy than rh-bFGF in the treatment of deep second degree burn with the similar safety.