Objective:To construct a recombinant retroviral vector carrying human inducible costimulator (ICOS) gene,screen for CHO cell line stably expressing ICOS protein and to study its biological activity.Methods: ICOS cDNA was obtained from human peripheral blood mononuclear cells (PBMC) through RT-PCR and was cloned into retroviral vector to construct retroviral recombinant pMSCV-ICOS; the latter was then packed and the high-titer virus producing cells were screened.Then CHO cell was infected by this high-titer virus and the stable cell line was screened.CHO-ICOS cells were co-cultured with PBMC (the ratio of CHO-ICOS to PBMC being 11,12,15, and 110) in presence of substimulating dose of anti-human CD3 antibody.The proliferation of PBMC and the CD25 expression on T cells were examined by 3H-TdR incorporation method and flow cytometry,respectively.CHO-pMSCV cells co-cultured with PBMC (11) served as the negative control and PBMC served as blank control.Results: We successfully constructed the retroviral recombinant pMSCV-ICOS and obtained CHO cell line stably expressing ICOS protein.3H-TdR incorporation method and flow cytometry showed that,compared with the negative control group and the blank control group,co-culture with CHO-ICOS cells significantly inhibited the anti-CD3 antibody-induced activation and proliferation of PBMC(P

Objective To analyze the current situation and developing trend of utilizaion of medical insurance drugs.Methods Data were collected from Suqian Hospital.Drug Utilization Analysis System and DDD were taken as the basic unit of measurement.Results The consumption of cost,DDDs and variety of type A medical insurance drugs were rising year by year,but the proportion in total was in declining trend.When analyzed according to DDDc,the type A,non medical insurance drugs and the type B ranked the first,the second and the third place during the 2009-2010,the DDDc of type A was lower than the non medical insurancedrugs and the type B.For example,the DDDc of type A was 3.32 yuan/day,the DDDc of the non medical insurance drugs and the type B was 15.04 and 15.97 yuan/day respectively.Conclusion Analyzed in respect to DDDs,the protortion of type A was in high level and the type B was in low.But analyzed in respect to the comsumption cost,the protortion of type B was in high level and the type A was in low.

Background and purpose:The quality of life and psychological status of the advanced cancer patients has been widely valued. This study aimed to analyze the psychological status of the advanced cancer patients and its influence factors.Methods:The patients who were hospitalized in the palliative care department of Fudan University Cancer Center from Sep. 2011 to Mar. 2013 were included in this study. Self-rating anxiety scale(SAS), self-rating depression scale (SDS), EORTC QLQ-C30, social support revalued scale and symptom checklist 90 (SCL-90) were recorded and analyzed.Results:Fifty-six patients were included in this study, 18 were depression and 24 were anxiety while 16 of them were depression together with anxiety. The patients were divided into 2 groups according to their psychological status. There’s no signiifcant difference between the age and the social support between the two groups, while the mental disorders group have lower scores on body function, role function, emotional function and social function. The mental disorders were positive correlated with the symptoms score while negative correlated with the quality of life.Conclusion:There’s a high ratio of mental disorders in advanced cancer patients, the symptom scores and quality of life are related to mental disorders. We should pay more attention to the patients who were suffered more from the illness or had lower QOL scores.

Objective Islet transplantation has been an effective method for diabetes mellitus. The quality of donor pancreas is important for successful islet isolation. In this study, we evaluated expanded criteria donor usability based on the warm ischemic time, fatty pancreas and perfusion injury. Methods The marginal pancreases include those from cardiac death donor, fatty pancreas and edema pancreas from perfusion injury. Islets were isolated and purified using a modified University of Minnesota method. Islet yield and purity was determined by Dithizone (DTZ) staining and microscopic examination. Islet viability was assessed by AO/EB staining, and islet function was assessed by static glucose stimulation test. Results In the cardiac death donor group, the islet quality, viability, and in vitro function were similar when the warm ischemic time within 15 min. The quality and viability was decreased when the warm ischemic time beyond 30 min, but the function remained well. With 45 min warm ischemic time, insulin release index was decreased significantly. The islet quality, viability, and in vitro function from severe obesity group and severe edema group were decreased obviously. Conclusion Donor factors play a vital role in pancreas transplant outcomes. We concluded that pancreas severe obesity, severe edema and pancreas from cardiac donors (warm ischemic time ＞30 min) are unsuitable for islet isolation.

Objective:To explore an ideal method for establishing a mouse model of chronic atrophic gastritis (CAG).Methods:CAG mouse models were established with five different modeling methods ( N-methyl- N′-nitro- N-nitrosoguanide (MNNG), sodium salicylate, sodium deoxycholate, Helicobacter pylori infection, and combinations of them) in BALB/c and C57 mice. The effect of each modeling method was evaluated by histological observation of gastric mucosa, plasma biochemical parameters, inflammatory response score, and the expression of anti-inflammatory factors. Results:The results of histological observation of gastric mucosa showed that all of the 5 methods could successfully establish CAG mouse models. In BALB/c mice, compared with the healthy control group, significant features of CAG accompanied with intestinal metaplasia was found in the model group established by combination of MNNG-free drinking, 2% sodium salicylate and 20 mmol sodium deoxycholate. From the results of serological detection, compared with the normal control group, the mRNA expression levels of related anti-inflammatory factors interleukin-2, interleukin-10, interleukin-13 and growth differentiation factor-15 of each model group decreased, which indicated that the mice of each CAG model group had different degrees of inflammation. The results of plasma biochemical parameters indicated that plasma gastrin of each group decreased and the ratio of pepsinogen Ⅰ and pepsinogen Ⅱ significantly dropped. The above results demonstrated that in BLAB/c mice, MNNG-free drinking, 2% sodium salicylate and 20 mmol sodium deoxycholate was better than other four modeling methods. For C57 mice, it was also found that simple chemical drug mutagenesis and Helicobacter pylori replication method both could successfully establish CAG models. No matter from pathological observation, relative expression of anti-inflammatory factors and analysis of plasma biochemical parameters, the effects of combination of the two methods was better. Conclusion:The CAG mouse model established by MNNG-free drinking, 2% sodium salicylate and 20 mmol sodium deoxycholate can provide a certain reference for the establishment and application of mouse model in CAG experiments in the future for pharmacological research.

Objective: This study was designed to evaluate the clinical value of seven combinedtumor-associated autoantibodies (7-TAAB) in the diagnosis of non-small cell lung cancer (NSCLC). Methods: This is a cross-sectional study. The 81 newly diagnosed patients with NSCLC were enrolled. 46 patients with benign pulmonary diseases (BLD) and 55 healthy subjects were selected as the BLD group and the healthy control (HC) group, respectively. ELISA was used to detect the concentration of seven TAABs of p53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGE A1 and CAGE in the serum of the NSCLC and the other two groups. The levels of lung cancer tumor markers CEA, NSE, SCC and CYFRA21-1 in serum were also detected in all enrolled subjects. Kruskal-wallis test was used for comparison among the three groups, Mann-Whitney test was used to evaluate the differences between the two groups, and positivity rates were analyzed by using standard χ² tests and Fisher exact tests. The receiver operating characteristic (ROC) analyses were performed to evaluate the diagnostic efficacy of 7-TAAB or combination of 7-TAAB and traditional tumor markers. Results: The serological levels of six TAABs (p53, SOX2, GAGE7, GBU4-5, MAGE A1, and CAGE) in the NSCLC group were higher than that in the BLD group (p53: Z=-4.370, P=0.000; SOX2: Z=-4.412, P=0.000; GAGE7: Z=-4.250, P=0.001; GBU4-5: Z=-2.678, P=0.025; MAGE A1: Z=-4.504, P=0.002; CAGE: Z=-4.646, P=0.001) and the HC group (p53: Z=-3.543, P=0.000; SOX2: Z=-3.383, P=0.002; GAGE7: Z=-4.893, P=0.001; GBU4-5: Z=-3.381, P=0.025; MAGE A1: Z=-3.369, P=0.001; CAGE: Z=-2.981, P=0.002),respectively. The differences were statistically significant. The comparison of PGP9.5 in NSCLC group with that in the BLD group was statistically significant (Z=-2.871, P=0.044), with that in the HC group was no difference (Z=-2.280, P=0.05). None of the seven TAABs showed a significant difference between the BLD group and the HC group (p53: Z=-1.917, P=0.917; PGP9.5: Z=-1.228, P=0.966; SOX2: Z=-1.789, P=0.325; GAGE7: Z=-0.563, P=1.000; GBU4-5: Z=-0.315, P=0.985; MAGE A1: Z=-2.310, P=0.857; CAGE: Z=-2.822, P=0.703). According to the criteria of cut-off value, the detection value of individual TAAB was judged as negative or positive. The specificity of every single TAAB to NSCLC was ≥89%, but the sensitivity was ≤39.5%. Positive in any of the single TAAB was considered as a positive result of 7-TAAB, the positive rate of 7-TAAB in NSCLC subgroups with early stages (stageⅠand stageⅡ) was considered higher than that of traditional biomarkers (7-TAAB:52.94%, CEA: 23.53%, NSE: 8.82%, CYFRA21-1∶20.59%, SCC:14.71%), and 7-TAAB was more sensitive to NSCLC patients with poor prognosis, such as advanced stages (stageⅢand stageⅣ) and moderately-poorly differentiation. The AUC of 7-TAAB was 0.734, with a sensitivity of 66.67% and a specificity of 80.20%. In coordination with 7-TAAB, CEA, NSE, CYFRA21-1 and SCC, the AUC was 0.917, with a sensitivity of 87.70% and a specificity of 81.20%. Conclusions 7-TAAB, regarded as a panel of serological markers, is helpful in NSCLC diagnosis and shows broad application prospect. The detection rate of 7-TAAB in patients with early NSCLC is superior to that of traditional serum tumor markers, and the combination of 7-TAAB with CEA, NSE CYFRA21-1 and SCC could improve the diagnosis sensitivity of patients with NSCLC.

Objective: To evaluate the effect of daily temperature on hand-foot-mouth disease (HFMD) in children under 5 years old in Jingzhou city. Methods: HFMD incidence data and meteorological data in Jingzhou city were obtained during 2010 and 2017. Distributed lag non-linear model (DLNM) was utilized to investigate the impact of daily temperature on HFMD incidence among children under 5 years old adjusting for potential confounders of other meteorological factors, secular trend, weekdays and holidays. Results: A total of 47 525 cases were reported during 2010 to 2017, of which the ratio of male to female was 1.52. Children under 1 year old, 1-<3 years old, 3-5 years old accounted for 9.72%, 62.10%, and 28.18% of the total cases, respectively. Children cared at home and children care in kindergarten accounted for 73.29% and 26.71% of the total cases, respectively. The relationship between the temperature and the daily cases of HFMD in children under five years old was a ‘M’ pattern. Compared with a reference temperature (the 50 th percentile of average temperature during the study period, P 50), the maximum value of effect at 8.21 ℃ and 25.81 ℃ were 1.53(95%CI=1.33-1.76) and 1.47(95%CI=1.31-1.65). Higher temperatures (such as 25.81 ℃ in this paper) showed a long lag effect on the HFMD incidence compared with lower temperatures (such as 8.21 ℃). Subgroup analyses indicated that children aged 3-5 years (children who attended daycare) were more vulnerable to the effects of temperature changes on HFMD than those under 1 year old and 1-<3-year-old (cared at home). Conclusion The temperature has a significant impact on the HFMD incidence among children under five years old in Jingzhou. Daycare centers is the key place for prevention and control of HFMD.

Objective To investigate the spatial correlation and spatial cluster pattern of hemorrhagic fever with renal syndrome (HFRS) in Jingzhou City,Hubei Province from 2013 to 2017.Methods The HFRS surveillance data during 2013-2017 were collected from China Disease Prevention and Control Information System.Software ArcGIS 10.3 was used to analyze the spatial distribution,and global autocorrelation analysis (Moran'sI) and hot spot analysis (Getis-Ord Gi) were used to analyze the spatial autocorrelation.Spatial cluster pattern was explored by trend surface analysis and directional distribution.Results In 2013-2017,the global Moran's I was 0.117 6 (P ＞ 0.05),0.349 8 (P ＜ 0.05),0.102 1 (P ＞ 0.05),0.276 3 (P ＜ 0.05),and 0.394 8 (P ＜ 0.05),respectively.The Getis-Ord Gi analysis showed that there were 7,8,8,8,15 hot areas with high incidence of HFRS during this period,respectively,which were part of townships in Jiangling County,Shashi District,Jianli County,and Honghu City.The cold spot area with low incidence of HFRS was only detected in 2015,and it was part of the township in Shashi District and Jingzhou District.The trend surface analysis showed that the inverted-U type curve could reflect the HFRS distribution from northern to southern,and it was also from eastern to western.The directional distribution showed that the HFRS cases were distributed in the north-central part of Jingzhou in 2013-2017,and they were inconsistent with the distribution of the Yangtze River system.Conclusions The incidence of HFRS has an obvious spatial clustering characteristic,and the areas at high risk are mainly in the north-central part of Jingzhou City.The spatial cluster pattern of HFRS has nothing to do with the Yangtze River system.

Objective:To analyze the effects of seasonal autoregressive integrated moving average model (SARIMA), generalized additive model (GAM), and long-short term memory model (LSTM) in fitting and predicting the incidence of hemorrhagic fever with renal syndrome (HFRS), so as to provide references for optimizing the HFRS prediction model.Methods:The monthly incidence data of HFRS from 2004 to 2017 of the whole country and the top 9 provinces with the highest incidence of HFRS (Heilongjiang, Shaanxi, Jilin, Liaoning, Shandong, Hebei, Jiangxi, Zhejiang and Hunan) were collected in the Public Health Science Data Center (https://www.phsciencedata.cn/), of which the data from 2004 to 2016 were used as training data, and the data from January to December 2017 were used as test data. The SARIMA, GAM, and LSTM of HFRS incidence in the whole country and 9 provinces were fitted with the training data; the fitted model was used to predict the incidence of HFRS from January to December 2017, and compared with the test data. The mean absolute percentage error ( MAPE) was used to evaluate the model fitting and prediction accuracy. When MAPE < 20%, the model fitting or prediction effect was good, 20%-50% was acceptable, and > 50% was poor. Results:From the perspective of overall fitting and prediction effect, the optimal model for the whole country and Heilongjiang, Shaanxi, Jilin, Liaoning and Jiangxi was SARIMA ( MAPE was 19.68%, 20.48%, 44.25%, 19.59%, 23.82% and 35.29%, respectively), among which the fitting and prediction effects of the whole country and Jilin were good, and the rest were acceptable. The optimal model for Shandong and Zhejiang was GAM ( MAPE was 18.29% and 21.25%, respectively), the fitting and prediction effect of Shandong was good, and Zhejiang was acceptable. The optimal model for Hebei and Hunan was LSTM ( MAPE was 26.52% and 22.69%, respectively), and the fitting and prediction effects were acceptable. From the perspective of fitting effect, GAM had the highest fitting accuracy in the whole country data, with MAPE = 10.44%. From the perspective of prediction effect, LSTM had the highest prediction accuracy in the whole country data, with MAPE = 12.23%. Conclusions:SARIMA, GAM, and LSTM can all be used as the optimal models for fitting the incidence of HFRS, but the optimal models fitted in different regions show great differences. In the future, in the establishment of HFRS prediction models, as many alternative models as possible should be included for screening to ensure higher fitting and prediction accuracy.

Objective:To analyze the epidemic characteristics and periodicity of hemorrhagic fever with renal syndrome (HFRS) in Jingzhou City, Hubei Province, and provide a basis for scientific prevention and control of HFRS in Jingzhou City.Methods:Retrospective analysis was used to collect HFRS case data and population data of Jingzhou City and 8 counties (cities, districts) within its jurisdiction, including Shashi District, Jingzhou District, Gongan County, Jianli City, Jiangling County, Shishou City, Honghu City, and Songzi City from 1962 to 2020, from the Archives of the Jingzhou Center for Disease Control and Prevention and the Infectious Disease Report Information Management System of the China Disease Control and Prevention Information System; and the epidemic characteristics of HFRS was analyzed in Jingzhou City and 8 counties (cities, districts) within its jurisdiction. The periodicity of HFRS onset was determined using wavelet analysis.Results:From 1962 to 2020, 18 936 HFRS cases were reported in Jingzhou City, with an average incidence rate of 5.95/100 000. There were a total of three epidemic peaks, namely from 1972 to 1973 (24.82/100 000, 24.84/100 000), 1983 (60.08/100 000), and 1995 (14.57/100 000). According to different regions, the high incidence areas of HFRS showed a phased transfer trend: from the 1960s to the 1970s, the Jiangbei area (Honghu City, Jianli City) was the highest incidence area; in the 1980s and 1990s, the high incidence areas were transferred to Jiangnan area (Songzi City, Shishou City, and Gongan County); after 2005, high incidence areas were relocated to Jiangbei area (Honghu City, Jianli City, Jiangling County). The wavelet analysis results showed that there were 12.30 and 21.77 years of HFRS epidemic cycles in Jingzhou City before 2000 ( P < 0.05); among them, the periodicity of Shashi District, Gongan County, Jiangling County, Shishou City, and Honghu City was relatively consistent with that of Jingzhou City, with epidemic cycles of about 12 or 22 years ( P < 0.05). Conclusions:Jingzhou City is currently at the peak of a 22-year epidemic cycle of HFRS, with Jiangbei area as the high incidence areas. The 12-year epidemic cycle in Jingzhou City has ended after 2000.