[Prospective observation of breakthrough cases and analysis of antibody dynamic changes after two doses of varicella].

Objective: To investigate the breakthrough rate and antibody level of children vaccinated two doses varicella vaccine in Tianjin city, and to compare them with those vaccinated one dose. Methods: A total of 1 112 children who were vaccinated two doses varicella vaccine were selected as the experimental group. According to the same street and township, children who had received only one dose within one year of age difference, and whose first injection time was less than one month from the first dose of varicella vaccine in the experimental group were selected as the control group. A three-year prospective observation was conducted on the incidence of varicella in the two groups. 108 pairs of children in the two groups were selected to collect antivaricella serum in the first to third year. The rate of breakthrough cases, antibody level and antibody positive rate were compared by χ2 test, t-test and variance analysis between and within the two groups in three years. Results: The cumulative breakthrough rate of the experimental group was 0.54%(6/1 112), which was lower than that of the control group 3.96% (44/1 112, χ²=29.544, P<0.001). The GMC level of antibody in the experimental group decreased year by year (F=18.291, P<0.001), and the GMC level in the control group also decreased year by year (F=91.383, P<0.001). There was significant difference in GMC level between the two groups (P<0.001). The difference of antibody positive rate in the experimental group was statistically significant in three years (χ²=11.107, P<0.01), there was significant difference in the positive rate between the first year and third year (P<0.01), there was no significant difference in the positive rate of the control group in three years (χ²=3.351, P>0.05). The positive rate of the experimental group was higher than that of the control group (P<0.001). Conclusion: Two doses varicella vaccine can significantly improve the antibody level and positive rate, but it still shows a downward trend with the extension of time. It is necessary to consider strengthening immunization according to the actual situation.

[Vincristine inhibits the proliferation of ovarian cancer cells by regulating the demethylation of RASSF2A].

Objective: To investigate the effect of vincristine on the proliferation of ovarian cancer cells by regulating RASSF2A demethylation. Methods: SKOV3 cells were infected with control (LV-NC) and RASSF2A lentivirus (LV-RASSF2A) and treated with or without vincristine. Cell counting kit-8 (CCK-8) was used to detect the activity of ovarian cancer cells (SKOV3) treated with different doses of vincristine. Colony formation assay was used to detect the proliferation of SKOV3 cells. Flow cytometry was used to detect the apoptosis of SKOV3 cells. Real time polymerase chain reaction (RT-PCR) was used to examine the mRNA expression of RASSF2A in IOSE-29 and SKOV3 cells. Western blot was used to examine the protein expression of RASSF2A in IOSE-29 and SKOV3 cells. Methylation-specific PCR was used to detect methylation and demethylation levels of RASSF2A gene in IOSE-29 and SKOV3 cells. Results: The cell viabilities of SKOV3 cell treated with 6.25 nmol/L, 12.5 nmol/L, 25 nmol/L, 50 nmol/L and 100 nmol/L vincristine were (87.19±4.49)%, (73.67±8.62)%, (66.35±6.04)%, (50.32±6.00)% and (34.92±6.11)%, respectively, lower than (100.46±4.69)% of control group (P<0.05). The half maximal inhibitory concentration of vincristine at 48 hours was 50.02 nmol/L. The proliferation abilities of SKOV3 cells in vincristine 12.5 nmol/L group, 25 nmol/L group and 50 nmol/L group were (41.70±2.21)%, (32.15±1.80)% and (23.00±2.01)%, respectively, significantly lower than (100.78±5.66)% in the control group (all P<0.05). The apoptotic rates of SKOV3 cells in vincristine 12.5 nmol/L group, 25 nmol/L group and 50 nmol/L group were (3.65±0.27)%, (5.21±0.76)% and (10.46±1.00)%, respectively, significantly higher than (2.12±0.23)% in the control group (all P<0.05). Compared with the IOSE-29 group (1.00±0.07 and 0.68±0.04), the mRNA expression (0.32±0.04) and protein expression (0.24±0.02) of RASSF2A were down-regulated in SKOV3 cells (P<0.05). Compared with the LV-NC group [(101.60±4.39)%, (100.73±3.29)%, (4.06±0.30)%], over-expression of RASSF2A down-requlated cell viability (68.92±3.94)%, inhibited proliferation (16.38±2.16)%, and promoted apoptosis (8.65±0.56)%, (P<0.05). Conclusion: Vincristine can increase RASSF2A expression and inhibit ovarian cancer cell proliferation by promoting the demethylation of RASSF2A promoter.

[Epidemiological characteristics of confirmed COVID-19 cases in Tianjin].

Objective: To investigate the clinical and epidemiological characteristics of 135 confirmed cases of COVID-19 in Tianjin. Methods: The clinical and epidemiological data of 135 cases of COVID-19 in Tianjin were collected, and the data were analyzed with descriptive method. The factors influencing the severity of the illness were analyzed. Results: Among the 135 COVID-19 cases, 72 were males and 63 were females, the age of the cases was (48.62±16.83) years, and the case fatality rate was 2.22%. Local transmission caused 74.81% of the cases. A total of 33 clusters occurred, involving 85.92% of all COVID-19 cases. The median of the incubation period of COVID-19 was 6.50 days, the average generation interval was 5 days, and the household secondary transmission rate was 20.46%. Fever was the main symptom (78.63%), followed by cough (56.48%). Multivariate regression analysis indicated that age (OR=1.038, 95%CI: 1.010-1.167) and the number of chronic underlying diseases (OR=1.709, 95%CI: 1.052-2.777) were the risk factors of severe illness. Conclusions: Fever was the main symptom at the early phase of COVID-19 in Tianjin, and the local cluster cases accounted for high proportion in confirmed COVID-19 cases reported in Tianjin. Severe illness was prone to occur in people with old age and multi underlying diseases. Strict isolation of close contacts and intensive care of high-risk groups are the main measures to reduce the morbidity and case fatality of COVID-19.

[Epidemiological investigation on a cluster epidemic of COVID-19 in a collective workplace in Tianjin].

Objective: To investigate and analysis the epidemiological characteristics of a cluster epidemic of COIVD-19 in a collective workplace in Tianjin, evduate the prevention and control measures based on limited evidence and experience in early period of COVID-19 epidemic. Methods: Descriptive research method was used to describe the distribution and other epidemiological characteristics of the cluster cases of COVID-19. Results: Since the onset of the first index case on January 15, ten confirmed COVID-19 cases had occurred in the workplace, and the epidemic had spread from the workplace to 4 families, infecting 7 family members. The median age of 17 cases was 55 (19-79) years. All the 10 employee cases were males, and in the family cases, 3 were males and 4 were females. Of the employee cases, 8 worked in CW workshop and 2 worked in administrative office building. The median exposure-onset interval of all the cases was 4 days, and the median exposure-onset interval was 4.5 days in the employee cases and 4 days in the family cases. The median onset-medical care seeking interval was 4 days in the non-isolated cases, 2.5 days in the cases with home isolation after onset, and 0.5 day in the cases with home isolation before onset. Conclusions: The clustering of COVID-19 cases was observed in this workplace in Tianjin, which affected 4 families. In the early stage of the epidemic, accurate and rapid blocking and control measures can completely prevent the large-scale spread of COVID-19.

[Analysis on cluster cases of COVID-19 in Tianjin].

Objective: To understand the characteristics of clusters of COVID-19 cases in Tianjin, and provide epidemiological evidence for the prevention and control of COVID-19. Methods: The data of all the COVID-19 cluster cases in Tianjin, reported by 22 February 2020, were collected to analyze the characteristics of different types of the clusters. Results: A total of 115 COVID-19 cases were reported in 33 clusters in Tianjin included 28 family clusters (71 cases), 1 work place cluster (10 cases), 3 transport vehicle clusters (8 cases) and 1 public place cluster (26 cases). Family clusters were caused by the cases from the working place or public place clusters. Numbers of secondary cases of family clusters was between 1 to 7, the median number was 2. The interval from onset to diagnosis for the first case was longer than those of other cases in the familial clusters (Z=-2.406, P=0.016). The median of incubation period of the public place clusters was 2 days. The intervals from onset to diagnosis were significant different among the family, working place and public place clusters (H=8.843, P=0.012), and also significant differences in onset time among the secondary cases (H=16.607, P=0.000). Conclusions: In the surveillance of COVID-19 epidemic, special attention should be paid to places where clustering are prone to occur, and the epidemiological investigation should be carried out timely to confirm the cluster. To prevent the transmission of COVID-19, the close contacts of the patients should be transferred to an assigned observation place on time for single room isolation. The awareness of COVID-19 prevention is low in some rural areas, reflected by many mass gathering activities and delayed medical care seeking after onset. It is necessary to strengthen the health education and take control measures in early period of epidemic.

[Etiological characteristics of Streptococcus pyogenes isolated from children with scarlet fever in Tianjin from 2012 to 2016].

Objective: To investigate the etiological characteristics of Streptococcus pyogenes that caused scarlet fever from 2012 to 2016 in Tianjin. Methods: The subjects were children diagnosed clinically as scarlet fever in Tianjin scarlet fever monitoring hospital from 2012 to 2016. The exclusion criteria were children with scarlet fever who were unable to cooperate with sampling. A total of 575 cases of children's swabs were collected. Biochemical methods were used to isolate and identify the bacteria of pharynx swab, and the PCR method was used to detect the emm genotyping and superantigen speA and speC, and the resistance of the strains to 10 antibiotics was measured by K-B paper method. We compared the carrying status of superantigen genes by different types of GAS and the resistance of all GAS to different antibiotics. Results: There were 5 emm types (emm1/11/12/22/89). The dominant types were emm12 (52.9%, 100 strains) and emm1 (44.4%, 84 strains). The carrying rates of speA and speC genes were 21.7% (41 strains) and 76.7% (145 strains), respectively. The speA gene carrying rate of emm1 type GAS was 33.3% (28 strains), which were higher than that of emm12 (12% (12 strains)) (χ(2)=12.21, P<0.001). The speA and speC gene simultaneous carrying rate of emm1 type GAS was 27.4% (23 strains), which was higher than that of emm12 type (12% (12 strains)) (χ(2)=7.01, P=0.008). The percentages of the strains that were resistant to Azithromycin, Erythromycin, Clarithromycin, Clindamycin, Tetracyclin, Levofloxacin and Chloramphenicol were 96.8% (183 strains), 96.3% (182 strains), 92.1% (174 strains), 92.1% (174 strains), 73.0%(138 strains), 2.1% (4 strains) and 1.6% (3 strains), respectively. All isolates were susceptible to Penicillin, Cefazolin and Vancomycin, and there were statistical significance (χ(2)=953.28, P<0.001). Conclusion: The dominant emm types causing scarlet fever are emm12 and emm1. The frequencies of speA and speC in emm1 and emm12 are different. S.pyrogenes in Tianjin were susceptible to penicillin, cefazolin and vancomycin, but highly resistant to the clindamycin, clarithromycin, erythromycin and azithromycin.

Virtual screening and rational drug design method using structure generation system based on 3D-QSAR and docking.

An efficient virtual and rational drug design method is presented. It combines virtual bioactive compound generation with 3D-QSAR model and docking. Using this method, it is possible to generate a lot of highly diverse molecules and find virtual active lead compounds. The method was validated by the study of a set of anti-tumor drugs. With the constraints of pharmacophore obtained by DISCO implemented in SYBYL 6.8, 97 virtual bioactive compounds were generated, and their anti-tumor activities were predicted by CoMFA. Eight structures with high activity were selected and screened by the 3D-QSAR model. The most active generated structure was further investigated by modifying its structure in order to increase the activity. A comparative docking study with telomeric receptor was carried out, and the results showed that the generated structures could form more stable complexes with receptor than the reference compound selected from experimental data. This investigation showed that the proposed method was a feasible way for rational drug design with high screening efficiency.