Objective To investigate the analgesia effect and the possible mechanism of intravenous administration with different concentrations of ozonized saline (OS) by observing changes in behavior,plasma tumor necrosis alpha (TNF-α),and interleukin-6 (IL-6) levels after rat plantar incision.Methods Fifty-four health adult male Sprague-Dawley rats were used in the investigation.Twenty four rats were randomly divided into four groups,6 in each group.The rats in group A1 were intravenously administered with 5ml/kg oxygen saline,10min before the incision.The rats in groups B1,C1,and D1 were intravenously administered with 20 μg/ml,30 μg/ml,and 40 μg/ml OS 5 ml/kg.An 1-cm incision was made in the right plantar surface from the heel to the toes according to the method described by Brennan under sevoflurane anesthesia.The 50％ paw withdrawal mechanical threshold (50％ PWMT) and cumulative pain score (CPS) at the times of 24 h before and 2,6,24,48 h after surgery were underwent.Thirty rats were randomly divided into five groups,6 in each group.Groups A2,B2,C2,and D2 processed as well as group 1.All groups except group E2 were made the model of incisional pain.2 ml blood was taken out of the right ventricular 2 h after the operation,then the levels of plasma TNF-α and IL-6 were detected by using enzyme linked immunosorbent assay (ELISA).Results There were no significant differences in the 50％PWMT between group A1 and group B1 at each time point after surgery (P ＞ 0.05).The 50％ PWMT in groups C1 and D1 were higher than those in group A1 at each time point after surgery (P ＜ 0.05).The CPS in groups B1,C1,and D1 were lower than those in group A1 after surgery (P ＜ 0.01).Compared to group E2,the levels of plasma TNF-α 2 h after the operation in group B2 and D2 were not statistically different (P ＞ 0.05).The levels of plasma TNF-α in groups C2 and A2 were higher than those in group E2 (P ＜ 0.05).The levels of plasma IL-6 2 h after the operation between group A2 and group E2 showed no difference (P ＞ 0.05).The levels of plasma IL-6 in groups B2,C2,and D2 were higher than those in group E2 (P ＜ 0.05).Concltsions Intravenous administration of ozonized saline can inhibit the incisional pain in rats.The analgesia effect of ozonized saline was dose-dependent.

Objective To explore the characteristics of clinical symptoms and serum brain-derived neurotrophic factor(BDNF)level between depressive patients with and without attempted suicide behavior.Methods Serum BDNF level in depressive patients with(n=36)and without(n=55)attempted suicide behavior were assayed by ELISA,the severity of depression was measured by Hamilton rating scale for depression(HAMD).Results HAMD24 total scores(t=3.632,P=0.000),cognitive disturbance(t=-2.339,P=0.019)and hopelessness factor scores(t=-2.812,P=0.005)in depressive patients with attempted suicide behavior were significantly higher than those in depressive patients without attempted suicide behavior.There were no significant differences of anxiety/somatization,body weight,diurnal variation,psychomotric inhibition and sleeping disturbance fator scores between two groups(P＞0.05).The serum BDNF level in depressive patients with attempted suicide behavior was significantly lower than that in depressive patients without attempted suicide behavior(t=-2.122,P=0.037).There was no significant difference of serum BDNF level between male and female patients(P＞0.05).Conclusion There were certain characteristics on clinical symptoms of depressive patients with attempted suicide behavior.The low serum BDNF level might play an important role in the risk of suicide in depressive patients.

Objective To observe the effectiveness and mechanism of Xiaoyao San (Xiaoyao Powder for Soothing Liver and Relieving Depression) in improving depression-like behavior of rats. Methods Male Wistar rats were randomized into normal group, model group, Xiaoyao San (1.9 g·kg-1·d-1) group, and fluoxetine (2 mg·kg-1·d-1) group. The rats were exposed to chronic unpredictable mild stress ( CUMS) to induce rat depression-like behavior. Field test was performed for the observation of effect of Xiaoyao San on rat depression-like behavior, Luminex liquid chip system was applied to detect the serum cytokines, and the amount and size of rat hepatic sinusoidal endothelial window were examined under electron microscope, and hepatic indoleamine 2, 3-dioxygenase ( IDO) and tryptophan 2, 3 -dioxygenaes ( TDO) expression levels were detected by immunohistochemical and Western blot methods. Results Xiaoyao San showed obvious effect on increasing sugar water consumption, the number of crossing the blocks and erection frequency in rats, decreasing serum levels of tumor necrosis factor alpha ( TNF-α) and interleukin 6 ( IL-6) , increasing the amount of hepatic sinusoidal endothelial window, promoting hepatic sinusoidal endothelial vascularization, and reducing TDO and IDO expression ( P<0.05 or P<0.01). Conclusion Xiaoyao San exerts obvious effect on improving rat depression-like behaviors, and the mechanism is probably related with the decrease of inflammatory factors, inhibition of IDO pathway, and improvement of hepatic sinusoidal endothelial function.

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.

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: 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.