Objective:To explore the influence of bromodomain-containing protein 4 (BRD4) inhibitor on wild-type Kras differentiated thyroid carcinoma (DTC) and its mechanism.Methods:The DTC cell line Kras WT TPC-1 was selected and the mutant Kras G12D TPC-1 cells were constructed. CCK-8 assay was used to detect the effect of BRD4 inhibitor JQ-1 on the proliferation activity of Kras WT TPC-1 cells. Kras WT TPC-1 cells were treated with 0.2 μmol/L JQ-1 (JQ-1 group), and a negative control group (NC group) was set. Transwell invasion assay and flow cytometry were used to detect the effect of JQ-1 on the invasion and apoptosis of Kras WT TPC-1 cells. The effect of JQ-1 on the expressions of BRD4, miR-106b-5p and P21, and the effect of P21 inhibitor UC2288 on the expressions of P21 and BRD4 were detected. Kras WT TPC-1 cells were divided into JQ-1+ NC-OE group, JQ-1+ p21-OE group (overexpression of p21) and JQ-1+ p21-OE+ miR-106b-5p mimic group (overexpression of p21 and miR-106b-5 at the same time), and the proliferation, invasion and apoptosis of cells in each group were detected. TPC-1 cells were divided into Kras WT group, Kras WT+ JQ-1 group, Kras G12D group and Kras G12D+ JQ-1 group, and the cell proliferation, invasion and apoptosis of each group were detected. Results:JQ-1 inhibited the proliferation activity of Kras WT TPC-1 cells in a dose-dependent and time-dependent manner. In the NC group and JQ-1 group, the numbers of cell invasion were 124.67±9.61 and 82.67±8.02, and the apoptosis rates were (5.91±0.34)% and (10.33±1.10)%, respectively, with statistically significant differences ( t=5.812, P=0.004; t=6.653, P=0.003). JQ-1 significantly inhibited the expressions of BRD4 and miR-106b-5p, and promoted the expression of P21 in Kras WT TPC-1 cells. UC2288 significantly inhibited P21 expression, but had no significant effect on BRD4 expression. In the JQ-1+ NC-OE group, JQ-1+ p21-OE group and JQ-1+ p21-OE+ miR-106b-5p mimic group, the proliferation activities at 24 h of Kras WT TPC-1 cells was 0.46±0.03, 0.35±0.04 and 0.44±0.03 ( F=8.720, P=0.017), and the proliferation activity of JQ-1+ p21-OE group was significantly lower than that of the JQ-1+ NC-OE group ( P<0.05). The numbers of cell invasion in the three groups were 83.00±9.17, 56.67±6.03 and 79.67±10.07 ( F=8.347, P=0.018), and the number of cell invasion in the JQ-1+ p21-OE group was significantly lower than that in the JQ-1+ NC-OE group ( P=0.009). The apoptosis rates of the three groups were (10.00±0.49)%, (15.39±1.14)% and (10.32±0.80)% ( F=37.764, P<0.001), and the apoptosis rate of the JQ-1+ p21-OE group was significantly higher than that in the JQ-1+ NC-OE group ( P<0.001). There were no significant differences in cell proliferation activity, invasion number and apoptosis rate between JQ-1+ p21-OE+ miR-106b-5p mimic group and JQ-1+ NC-OE group (all P>0.05). In Kras WT group, Kras WT+ JQ-1 group, Kras G12D group and Kras G12D+ JQ-1 group, the cell proliferation activities at 24 h were 0.50±0.05, 0.39±0.04, 0.68±0.08 and 0.64±0.05 ( F=17.776, P<0.001). Compared with the Kras WT group, cell proliferation activity in the Kras WT+ JQ-1 group was significantly decreased, while that in the Kras G12D group was significantly increased (both P<0.05). The numbers of cell invasion in the four groups were 129.33±11.50, 86.00±9.54, 161.67±13.01 and 146.33±13.20 ( F=22.598, P<0.001). Compared with the Kras WT group, the number of cell invasion in the Kras WT+ JQ-1 group was significantly decreased ( P=0.002), and that in the Kras G12D group was significantly increased ( P=0.010). The apoptosis rates in the four groups were (6.17±0.50)%, (10.42±0.73)%, (3.43±0.47)% and (3.41±0.32)% ( F=119.170, P<0.001). Compared with the Kras WT group, the apoptosis rate in the Kras WT+ JQ-1 group was significantly increased ( P<0.001), and that in the Kras G12D group was significantly decreased ( P<0.001). There were no significant differences in cell proliferation activity, invasion number and apoptosis rate between Kras G12D+ JQ-1 group and Kras G12D group (all P>0.05). Conclusion:BRD4 inhibitor can specifically inhibit the development of wild-type Kras DTC via regulating the molecular axis of BRD4/miR-106b-5p/P21, but has no significant effect on the proliferation, invasion and apoptosis of mutant Kras DTC tumor cells.

Objective:To describe the regional and demographic differences on passive non-smokers from 10 regions involved in the China Kadoorie Biobank (CKB) study.Methods:Detailed information regarding passive smoking behaviors related to 317 486 non-smokers who were 30-79 years old from the 10 study regions were gathered and analyzed.Results:Following the standardization of the 2010 China national population, the prevalence rate of passive smoking was 56.7 %, and the prevalence rate of living with smokers was 66.5 % among the Chinese adults. Both of the aforementioned rates were higher in rural than in urban areas. Meanwhile, the regional distribution of weekly passive smoking frequency and cumulative duration of passive smoking per week and cumulative duration of passive smoking per day were significantly different. The cumulative passive smoking duration per week increased along with the weekly frequency in people living in urban areas. Among women, the weekly passive smoking frequency was the highest, and the cumulative durations per week and per day appeared the lowest in Hunan, opposite to the situation in Henan. The prevalence of passive smoking among participants living with smokers was 2.27 times (95 %CI: 2.24 -2.29) of those who were not and the association appeared stronger in women ( OR=2.61, 95 %CI: 2.58-2.64) but not in men ( OR=1.01, 95 %CI: 0.95-1.06). Almost all the indicators seemed higher in women than those in men, except for the cumulative duration per day. Furthermore, these indicators appeared higher among those who were at younger age or with less education. The prevalence rates of passive smoking and living with smokers were lower but the cumulative duration per day was higher among those with lower household income. And the two rates were higher in married women and lower in married men, as compared to their counterparts. Conclusion:Regional and demographic differences in passive smoking were noticed among study population of CKB in the 10 regions.

Objective:To explore effects of clinical learning environment on occupational values of nursing students in higher vocational colleges under the background of industry-education integration so as to provide the basis for improving the clinical learning environment and improving the quality of nursing personnel training.Methods:From May to June 2019, 3 colleges were selected from the higher vocational colleges in Jiangsu Province that carried out medical and educational cooperative nursing personnel training and 200 nursing students in the second grade (2017 grade) of nursing majors from each of 3 colleges were selected as research objects by the convenient sampling method.Results:The total score of the nursing occupational value scale for 85 nursing students was (90.70±10.88) , and the total score of the clinical learning environment assessment scale was (152.72±14.84) . The results of multiple linear regression analysis showed that interpersonal relationship, working atmosphere and team spirit, task positioning in the clinical learning environment assessment scale were the influencing factors of occupational values of nursing students ( P<0.05) . Conclusions:Under the medical and educational cooperation talent training model, occupational values of nursing students are at a medium level, and clinical learning environment has positive effects on occupational values. It is necessary for schools and teaching hospitals to further improve the clinical learning environment so as to improve occupational values of nursing students.

Objective: The objective of this study was to analyze the disease burden of influenza in schools and child care settings in rural areas of Hangzhou. Methods: Hospital visit influenza cases aged 3-17 years in hospitals that reported based on influenza surveillance system from 2016 to 2018 in Chun′an county, Hangzhou city were selected as study subjects and a total of 294 confirmed cases of influenza were selected using system sampling method. Questionnaires were designed to investigate the basic information and data on inpatients and outpatients among, health care and life quality, etc.. Direct and indirect economic burden and disability adjusted life year (DALY) were analyzed and compared among different age groups. Results: The mean age of investigated subjects was (8.88±3.92) years. A total of 143 (48.64%) investigated cases were male. In total of 283 (96.26%) cases were outpatients. The total economic burden was 124 743.95 CNY. The mean economic burden was 424.30 CNY per person. The mean direct and indirect economic burden was 361.33 and 62.97 CNY per person respectively. The difference of the mean direct, indirect and total economic burden per person between different age group was statistically significant (P<0.001). The 3-5 years age group showed the highest economic burden with the median value of direct, indirect and total economic burden per person being 276.24, 50.98 and 321.26 CNY, respectively, while the 12-17 years age group showed the lowest values with 175.30, 26.54, 201.79 CNY, respectively. The DALY of 294 influenza cases was 1.18, and the median of burden strength was 3.21 DALY/thousand. The difference of the burden of strength between different age group influenza case was statistically significant (P<0.001), of which the 12-17 years age group showed the highest value with 4.25 DALYs/thousand while the 3-5 years age group showed the lowest value with 2.60 DALY/thousand. Conclusion The disease burden of influenza was heavy in schools and kindergartens in rural areas of Hangzhou city, with the cases aged from 3 to 5 years showing higher economic burden and cases aged from 12 to 17 years showing greater burden strength.

Objective: To evaluate the post-marketing safety profiles of the inactivated enterovirus type 71 (EV-A71) vaccine (Vero cell) after routine inoculation. Methods: Eleven cities of Zhejiang Province, Fengtai district of Beijing, Qinnan district, two counties as Pingle and Pingguo of Guangxi Zhuang Autonomous Region, and Dongtai city of Jiangsu Province were selected as the field sites. A total of 45 239 subjects were enrolled in this study from children who seeked the vaccination of EV-A71 vaccine during the period from July, 2016 to June, 2018. Different sampling method were adopted in different sites. All vaccinated children were invited to participate in the study in Fengtai and Dongtai, however, systematic sampling method were adopted in other sites. Active surveillance was conducted and information about adverse reactions (ARs) occurred in 30 min, 3 d and 30 d following each dose of EV-A71 immunization was collected by field observation, phone-call or face-to-face interview. The incidence of ARs in different types, symptoms and grades were described. Results: In total, there were 45 239 children who received 71 243 doses EV-A71 vaccine. The overall incidence of ARs was 1.079% (769 doses), with the highest incidence of 1.182% (177/14 973) in 5-11 month group and the lowest incidence of 0.849% (18/2 119) in ≥ 36 month group among different age groups. There was a higher incidence in solicited ARs, which was 1.047% (746 doses). The incidences of grade 1 and grade 2 ARs were also higher, which were 0.404% (288 doses) and 0.554% (395 doses), respectively. No grade 4 ARs occurred. The doses of the first and the second vaccination was 40 736 and 30 507, respectively, and the incidences of ARs were 1.281% (522 doses) and 0.810% (247 doses). Also, the incidences of ARs were 0.091% (37 doses) and 0.043% (13 doses) in local, and 1.168% (476 doses) and 0.760% (232 doses) in system. The symptoms of ARs after the two doses of vaccination were basically the same. Redness at the injection site was the most common local ARs after each dose vaccination, with doses of 24 and 11, while fever was the most common systemic ARs, with doses of 362 and 190. Moreover, ARs mainly occurred in 30 min to 3 d after each dose vaccination, with incidence of 1.016% (414 doses) and 0.698% (213 doses) in the first and second dose, respectively. Conclusion The ARs had a low incidence after vaccination in children and most were mild or moderate. EV-A71 vaccine with good safety is suitable for inoculation in a large scale.

Objectives: To evaluate the safety of inactivated enterovirus A71(EV-A71) vaccines after large-scale immunization in the community. Methods: We selected EV-A71 susceptible people (healthy children) aged 6-59 months in vaccination clinics from 89 counties in Zhejiang Province between April 2016 and March 2018. All local and systematic adverse actions were collected by 30 min on-site inspection, within 3 days and 4-30 days follow-up. Chi-square test and Fisher′s exact test were used to compare the difference of AEs incidence in various characteristics among two groups. Results: A total of 71 663 doses of vaccines were included for active safety analysis, which included 37 331 doses in boys and 34 332 doses in girls. Among all the doses, children aged 6 to 11 months, 12 to 23 months and 24 to 59 months were received 13 707, 32 639 and 25 317 doses respectively. The incidence of adverse reactions within 30 min, 3 days and 4-30 days were 0.33% (239 doses), 1.58% (1 133 doses) and 0.34% (244 doses) respectively. Adverse reactions within 3 days were 1 372 doses, with a incidence of 1.91%; among all the cases, 539 doses (0.75%) were grade 1, 677 doses (0.94%) were grade 2 and 156 doses (0.22%) were grade 3, no grade-4 adverse reaction was reported. The common local adverse reactions were redness, swelling and pruritus, with the incidence rates were 0.05% (39 doses), 0.02% (16 doses) and 0.02% (12 doses), respectively, while the most common systemic adverse reaction was pyrexia with an incidence of 1.19% (856 doses), followed by diarrhea and anorexia with the incidence rates were 0.15% (104 doses) and 0.13% (90 doses) respectively. Conclusion Most adverse actions of EV-A71 vaccines were mild and moderate and majority of them were common adverse actions. No new adverse reactions were found in the study.

Objective The objective of this study was to analyze the disease burden of influenza in schools and child care settings in rural areas of Hangzhou. Methods Hospital visit influenza cases aged 3-17 years in hospitals that reported based on influenza surveillance system from 2016 to 2018 in Chun′an county, Hangzhou city were selected as study subjects and a total of 294 confirmed cases of influenza were selected using system sampling method. Questionnaires were designed to investigate the basic information and data on inpatients and outpatients among, health care and life quality, etc.. Direct and indirect economic burden and disability adjusted life year (DALY) were analyzed and compared among different age groups. Results The mean age of investigated subjects was (8.88±3.92) years. A total of 143 (48.64%) investigated cases were male. In total of 283 (96.26%) cases were outpatients. The total economic burden was 124 743.95 CNY. The mean economic burden was 424.30 CNY per person. The mean direct and indirect economic burden was 361.33 and 62.97 CNY per person respectively. The difference of the mean direct, indirect and total economic burden per person between different age group was statistically significant (P<0.001). The 3-5 years age group showed the highest economic burden with the median value of direct, indirect and total economic burden per person being 276.24, 50.98 and 321.26 CNY, respectively, while the 12-17 years age group showed the lowest values with 175.30, 26.54, 201.79 CNY, respectively. The DALY of 294 influenza cases was 1.18, and the median of burden strength was 3.21 DALY/thousand. The difference of the burden of strength between different age group influenza case was statistically significant (P<0.001), of which the 12-17 years age group showed the highest value with 4.25 DALYs/thousand while the 3-5 years age group showed the lowest value with 2.60 DALY/thousand. Conclusion The disease burden of influenza was heavy in schools and kindergartens in rural areas of Hangzhou city, with the cases aged from 3 to 5 years showing higher economic burden and cases aged from 12 to 17 years showing greater burden strength.

Objective The objective of this study was to analyze the disease burden of influenza in schools and child care settings in rural areas of Hangzhou. Methods Hospital visit influenza cases aged 3-17 years in hospitals that reported based on influenza surveillance system from 2016 to 2018 in Chun′an county, Hangzhou city were selected as study subjects and a total of 294 confirmed cases of influenza were selected using system sampling method. Questionnaires were designed to investigate the basic information and data on inpatients and outpatients among, health care and life quality, etc.. Direct and indirect economic burden and disability adjusted life year (DALY) were analyzed and compared among different age groups. Results The mean age of investigated subjects was (8.88±3.92) years. A total of 143 (48.64%) investigated cases were male. In total of 283 (96.26%) cases were outpatients. The total economic burden was 124 743.95 CNY. The mean economic burden was 424.30 CNY per person. The mean direct and indirect economic burden was 361.33 and 62.97 CNY per person respectively. The difference of the mean direct, indirect and total economic burden per person between different age group was statistically significant (P<0.001). The 3-5 years age group showed the highest economic burden with the median value of direct, indirect and total economic burden per person being 276.24, 50.98 and 321.26 CNY, respectively, while the 12-17 years age group showed the lowest values with 175.30, 26.54, 201.79 CNY, respectively. The DALY of 294 influenza cases was 1.18, and the median of burden strength was 3.21 DALY/thousand. The difference of the burden of strength between different age group influenza case was statistically significant (P<0.001), of which the 12-17 years age group showed the highest value with 4.25 DALYs/thousand while the 3-5 years age group showed the lowest value with 2.60 DALY/thousand. Conclusion The disease burden of influenza was heavy in schools and kindergartens in rural areas of Hangzhou city, with the cases aged from 3 to 5 years showing higher economic burden and cases aged from 12 to 17 years showing greater burden strength.

Objective To explore the effects of humanistic concern teaching model on quality and ability in humanistic concern among nursing students. Methods The "Fundamental Nursing" was selected as experimental curriculum. From October 2015 to June 2016, two classes of 2015 with nursing speciality were divided into the observation group (n=44) and the control group (n=46). Nursing students of the observation group accepted humanistic concern teaching model. Nursing students of the control group were taught with the traditional teaching model. The teaching effectiveness was evaluated with the Humane Care Quality Scale and the Caring Ability Inventory (CAI). Results The total scores of the Humane Care Quality Scale and CAI of nursing students in the observation group were (175.98±9.74) and (201.41±16.09) respectively higher than those [(157.02±12.98), (185.76±14.42)] in the control group with significant differences (t=7.811, 4.864;P< 0.01). Conclusions The nursing humanistic concern teaching model is conducive to cultivating quality and ability of humanistic concern of nursing students.

OBJECTIVE:To provide reference for reducing the occurrence of chemotherapy-induced constipation and optimizing constipation therapy.METHODS:Medical records of malignant lung tumor inpatients meeting inclusion criteria were collected from respiration department of our hospital,and then investigated and analyzed statistically in respects of patient's gender,age,constipation history,tumor types and phases,physical status score,living habit change,chemotherapy plan (including adjuvant drug),constipation occurrence,prevention and treatment,etc.The related factors of chemotherapy-induced constipation were investigated.RESULTS:A total of 135 patients were enrolled in the investigation.Of 135 patients,66 patients had constipation with incidence of 48.89％,among which 96.97％ were grade 1 and grade 2 constipation.The onset of constipation were independent from age,gender and living habit change (P＞0.05).The patients with history of constipation,advanced tumor stage,the period of treatment≥ 3 days,the use of palonosetron and combined with aprepitant had higher prevalence of constipation (P＜0.05).The clinical symptoms were improved spontaneously in 21.21％ patients,33.33％ after diet adjustment and 45.45％ by drug treatment as suppositories glycerol,lactulose;24.24％ patients used lactulose to prevent constipation at rehospitalization.CONCLUSIONS:Chemotherapy-induced constipation was commonly occurred and related to serval factors and had not got enough attention yet.The clinical pharmacists should assist the physicians to make individual chemotherapy regimen as well as the prevention of adverse drug reactions.