With the development of information technology, the massive growth of pharmaceutical electronic data and the significant increase in the reports of drug adverse event reports have brought great challenges to pharmacovigilance research. Data mining techniques can automatically extract the risk signals of adverse drug reaction from real-world data. Therefore, efficient data mining of massive adverse event reporting is a necessary measure to realize the automatic detection of adverse drug reactions. By introducing the current major large-scale adverse drug event reporting databases and related data mining methods, this study reviews the application and limitations of adverse drug reaction data mining technology in pharmacovigilance, which provides reference for pharmacovigilance-related institutions and researchers.

Objective To compare the differences in the intestinal microflora of WHBE rabbit and JW rabbit models of diarrhea-predominant irritable bowel syndrome(IBS). Methods 16 WHBE rabbits and 16 JW rabbits were randomly divided into normal control(NC)group and IBS model group, respectively(n=8). The diarrhea-predominant IBS model was established by wet-heat stress combined with intragastric gavage of senna decoction. The abdominal circumference index,water content of feces and colonic transit function were observed. After sacrifice,colon tissue samples were taken for histopathological examination and colon contents for intestinal flora diversity analysis. Results Compared with the NC group,the IBS model rabbits showed an increased abdominal circumference index and fecal water content,and a shortened colon transit time, but no obvious pathological changes were observed in the colon tissues. Meanwhile, the Shannon index and Chao1 index of IBS model rabbits were significantly decreased(P<0.05). According to the result of OTU classification analysis,Firmicutes and Bacteroidetes are the dominant bacteria in the intestinal microflora of rabbits. Compared with the NC group, the Firmicutes, Verrucomicrobia, Chloroflexi, Akkermansia, and Streptococcus in the WHBE rabbit IBS model group were significantly reduced(P < 0.05, P < 0.01), while Bacteroidetes and rc4-4 significantly increased(P < 0.05, P < 0.01). However, in the JW rabbit IBS model group, Eubacterium and Subdoligranulum were significantly increased(P< 0.05),while Lactobacillus,Coprobacter,Veillonella and Streptococcus were markedly decreased(P<0.05). Compared with the JW rabbit NC group,the abundance of Firmicutes,Odoribacter, Veillonella,Streptococcus,Oscillospira and Pseudoflavonifractor were significantly decreased(P<0.05, P<0.01), but Bacteroidetes,Verrucomicrobia,Eubacterium,Akkermansia and Coprobacter were significantly increased(P<0.05,P<0.01)in the WHBE rabbit NC group. Compared with the JW rabbit IBS model group, the abundance of rc4-4, Bacteroidetes,Coprobacter and Clostridium were significantly higher(P < 0.05, P < 0.01), while the Firmicutes, Dorea, Coprococcus and Subdoligranulum were significantly lower(P <0.05)in the WHBE rabbit IBS model group. Conclusions There is an intestinal microflora imbalance in rabbits with IBS, resulting in a decrease of microflora diversity. The changes of intestinal microflora in the WHBE rabbits and JW rabbits with IBS have their own characteristics, and have apparent differences.

Objective To establish a Wuzhishan minipig model of atherosclerosis(AS) induced by high fat/cholesterol diet,and observe the changes of expression of lipoprotein associated phospholipase A2(Lp-PLA2) in plasma and plaques.Methods 10 Wuzhishan minipigs were randomly divided into 2 groups:The normal control(Ctr,n=4) group was fed with normal diet,and AS model(n=6) group fed with high fat/cholesterol diet for 24 weeks.After the modeling for 24 weeks,the changes of total cholesterol(TC),low density lipoprotein(LDL-C),high density lipoprotein(HDL-C),triglyceride(TG),C-reactive protein(CRP),Lp-PLA2 activity and composition were detected.The changes of vascular lipid deposition and plaques were assessed by pathology using oil red O staining and HE staining,respectively,and immunohistochemical staining for IL-6 protein expression.Moreover,the expression of Lp-PLA2 mRNA determined by RT-PCR and protein by Western blot were observed in the abdominal aortic tissues.Results Compared with the control group,the body weight,body mass index(BMI),TC,LDL-C,HDL-C,CRP,Lp-PLA2 activity and composition and aortic lipid deposition were significantly increased,and AS plaque formation was observed in the AS model group(P<0.05,P<0.01).The expression of Lp-PLA2mRNA and protein and IL-6 protein in abdominal aortic tissues were also significantly increased(P<0.05).Conclusions Long-term high fat/cholesterol diet feeding for 24 weeks can induce atherosclerosis in Wuzhishan minipigs,and Lp-PLA2 plays a key role in the vascular inflammation and plaque formation.

Objective To explore ICSI treatment process in the different proportion of oocytes maturation and dosage of gonadotropin affecting embryo quality and clinical outcome. Methods From Jan. to Dec. 2015,we retrospectively analyzed the patients from the center line of ICSI cycle ,divided them into three groups according to the maturity of oocytes. The 3 groups were due to maturity rate of oocytes in 50% in group A(n = 19),50% 0.05). Group A had the best egg rate,high quality embryo rate,clinical pregnancy rate than the other two groups (P < 0.05). In pregnancy and non-pregnancy groups ,the dosage of gonadotropin in the non-pregnancy group was obviously higher than that in the pregnancy group in oocyte maturation in the same proportion interval(P<0.05). Conclusion In ICSI treatment process,the high dose of gonadotropin and rising rates of oocytes maturation are not conducive to the development potential of the egg and clinical outcome,so the dose of gonadotropin and oocyte maturation ratio should be controlled in a certain range to collect and protect the best dominant egg which matches to the state of the patient.

Objective To investigate the toxic reaction,toxic organs or target tissues of protamine recombinant human insulin (Insulin NPH),and provide basis for clinical trials by single dose toxicity test in mice,repeated toxicity and immunogenicity of Beagle's dogs,and systemic active allergy in guinea pig.Methods ① Using maximum dose method,mice in single dose toxicity test were sc injected with normal saline (NS),vehicle,and Insulin NPH (2092-2488 IU/kg),the toxic reactions after injection were monitored.② In repeated toxicity study,Beagle's dogs were sc administrated with vehicle,the original (Humulin NPH,1.5 IU/kg)and different doses of Insulin NPH (0.5,1.0 and 1.5 IU/kg) for 30 d continuously,followed by a 14-d recovery.During the administration and recovery period,general observation,local irritation,body weight,anus temperature,blood glucose,and electrocardiogram (ECG) were checked,moreover,hematology,serum biochemistry and urine were detected.Also,organic weights and histopathological examination were conducted.Binding antibodies in dog serum were measured by indirect ELISA method in immunogenicity test.③ In systemic active allergy study,cavies were sc injected with low-and high-dose (4 and 12 IU/kg) Insulin NPH,normal saline and vehicle.Besides,ova as positive control was also included.After five times of sensitization test with above doses,the excitation reactions of iv injection with tripled sensitizing doses were observed.Results No obvious toxicity was observed in mice after injected with 165 times of usual clinical dose of Insulin NPH.Repeated toxicity study of Beagle's dogs revealed that 1.0 IU/kg was the no-toxic-effect dose (NOAEL) for Insulin NPH,which was equivalent to 2 times of clinical dose.No bindingantibodies were found in immunogenicity test.There was no obvious allergic symptom in the active systemic allergy study of guinea pig.Conclusion Under the experimental conditions,no serious toxicity of Insulin NPH is found.

In this cross-sectional study, consecutive Chinese Han ethnic inpatients in the Division of Cardiology, the First Affiliated Hospital of Soochow University from January 1, 2010 to December 31, 2013 were included. According to the exclusion criteria, 9 587 patients [1 604 with type 2 diabetes mellitus (T2DM) and 7 983 without T2DM]were obtained for final analysis. Logistic regression model was used to analyze the association of ApoB/A-1 ratio with T2DM and the possible interactions between ApoB/A-1 ratio and other risk factors. The results showed that the distribution of ApoB/A-1 ratio was positively skewed in Chinese Han ethic population. The median of ApoB/A-1 ratio of female was lower than that of male (0.68 vs 0.73,P<0.01). In all groups, the proportion of T2DM was increased with the raised ApoB/A-1 ratio. By the stratification analyses of sex, age, coronary artery disease, and the use of statins, ApoB/A-1 ratio was still correlated with T2DM. There existed significant interactions between ApoB/A-1 ratio and the smoking status or creatinine in T2DM.

In order to establish the minipig model of chronic myocardial ischemia and apply non-invasive telemetry technique, the minipig model of chronic myocardial ischemia was made induced by Vitamin D3, isoproterenol and combined with high fat diet, and the non-invasive telemetry technique was used to detect and evaluate the symptoms of minipig model of chronic myocardial ischemia.Moreover, the effects of transport stress and the risk factors of atherosclerosis (AS) induced by high fat diet among Wuzhishan minipigs, Bama minipigs and Tibetan minipigs were also evaluated.Our study has successful established the Bama minipig model of chronic myocardial ischemia and the technical specification for evaluation,.The non-invasive telemetry technique can be used to detect and evaluate the symptoms of chronic myocardial ischemia model, and defines minipigs at least need to keep for more than 4 weeks after transport stress to adaptive recovery period.In addition, the different characteristics of AS risk factors such as hyperlipidemia, hypertension and hyperinsulinemia were observed in Wuzhishan minipigs, Bama minipigs and Tibetan minipigs in high fat environment, and this provides a reference for the selection and application of minipigs in the research of cardiovascular diseases.

Objective To observe the morphological structures of WHBE rabbit brain in vivo based on 3.0 T magnetic resonance imaging system (MRI), accumulate the basic biological data of WHBE rabbit brain imaging, and provide a background information to further expand the WHBE rabbit application.Methods Nine healthy adult male WHBE rabbits were intravenously anesthetized with 3% pentobarbital sodium.3.0 T MRI plus rabbit brain dedicated coil was used to perform routine transverse and sagittal scans, and the size of brain structures were measured.Results MRI scanning can be successfully performed to obtain sagittal and transverse T2WI or T1WI images of WHBE rabbit brain in vivo, and can be clearly observed the basic structures of WHBE rabbit brains in vivo, such as olfactory bulb, cerebrum, cerebellum and pituitary gland.In addition, high signal was found in the hippocampus of the left and right temporal lobes in 4 rabbits with T2WI, but also low signal appeared in the corresponding regions in T1WI, and the others were not abnormal.Meanwhile, the reference data of frontal lobe, hippocampus, cerebrum, lateral ventricles, pituitary gland and other related anatomical structures were also obtained.Conclusions Using the 3.0 T magnetic resonance imaging system and rabbit brain coil,the morphological and anatomical structures of rabbit brain can be clearly observed, and the basic imaging data of WHBE rabbits brain have been established preliminarily.

Objective To explore risk factors for healthcare-associated infection (HAI)in patients undergoing craniocerebral operation,and provide guidance for the prevention of HAI in patients in department of neurosurgery. Methods 200 patients who underwent craniocerebral operation in a department of neurosurgery from November 2013 to November 2014 were surveyed,risk factors for HAI were analyzed.Results Among 200 patients undergo-ing craniocerebral operation,81 patients developed 99 cases of HAI,HAI rate was 40.50%,HAI case rate was 49.50%;the top five HAI sites were lower respiratory tract,urinary tract,intracranial site,bloodstream,and in-testinal tract.Univariate analysis showed that patients’age ≥60,Glasgow Coma Scale (GCS)<15,intraoperative blood loss ≥800 mL,staying in intensive care unit(ICU),indwelling gastric tube,ventricular drainage,using ventilator,tracheotomy,and using H2 receptor antagonists were important risk factors for HAI in patients undergo-ing craniocerebral operation (all P <0.05).Multivariate logistic regression analysis showed that patients’age ≥60, GCS<15,staying in ICU,and using H2 receptor antagonists were independent risk factors for HAI in patients un-dergoing craniocerebral operation.Conclusion Strengthening the surveillance of HAI patients undergoing cranioce-rebral operation and realizing risk factors for HAI are helpful for taking comprehensive prevention measures and re-ducing the incidence of HAI.

It is difficult to select the appropriate ventilation mode in clinical mechanical ventilation. This paper presents a nonlinear multi-compartment lung model to solve the difficulty. The purpose is to optimize respiratory airflow patterns and get the minimum of the work of inspiratory phrase and lung volume acceleration, minimum of the elastic potential energy and rapidity of airflow rate changes of expiratory phrase. Sigmoidal function is used to smooth the respiratory function of nonlinear equations. The equations are established to solve nonlinear boundary conditions BVP, and finally the problem was solved with gradient descent method. Experimental results showed that lung volume and the rate of airflow after optimization had good sensitivity and convergence speed. The results provide a theoretical basis for the development of multivariable controller monitoring critically ill mechanically ventilated patients.
Exhalation ; Humans ; Lung ; physiology ; Models, Biological ; Nonlinear Dynamics ; Pulmonary Ventilation ; Respiration ; Respiration, Artificial ; Tidal Volume