OBJECTIVE To investigate the mechanisms of rutin in alleviating depressive symptoms associated with premenstrual dysphoric disorder （PMDD） characterized by liver qi stagnation syndrome. METHODS Network pharmacology was employed to identify the intersecting targets of action between PMDD and rutin. A protein-protein interaction network was constructed to screen core targets， followed by gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis. Molecular docking simulations validated rutin’s binding affinity to core targets. The bilateral ovaries of female Wistar rats were removed， followed by artificial hormone induction. The rats were then randomly divided into normal group （10 rats） and modeling group （50 rats）. PMDD rat model with liver qi stagnation syndrome was established via restraint stress. The successfully modeled rats were further divided into model group， fluoxetine group （positive control） and rutin group， with 12 rats in each group. The corresponding drug solutions or water were administered by gavage at 9：00 a.m. every day， continuing for two estrous cycles. The open-field test， forced swimming test and Y-maze test were utilized to evaluate the effects of rutin on the behavioral indexes of model rats. Additionally， the density of neuronal dendritic spines in the hippocampal tissues of the rats was observed. Serum brain-derived neurotrophic factor （BDNF） levels and the expressions of BDNF， tyrosine kinase receptor type B （TrkB）， synuclein （Syn）， and postsynaptic density protein 95 （PSD95） in hippocampal tissues were quantified， respectively. RESULTS Network pharmacology and molecular docking revealed the core targets through which rutin ameliorated PMDD characterized by liver qi stagnation syndrome included BDNF， TrkB， PSD65， Syn， etc. The results of experimental validation demonstrated that rutin significantly increased the spontaneous alternation behavior scores of PMDD model rats with liver qi stagnation syndrome during the non-receptive phase， shortened their immobility time during the forced swimming test， and enhanced the density of neuronal dendritic spines in the hippocampal tissues. Additionally， rutin upregulated the levels of serum BDNF and the protein expressions of BDNF， TrkB and Syn in the hippocampal tissues （P＜0.05）. However， it had no significant effect on the above indexes in model rats during the receptive phase （P＞0.05）. CONCLUSIONS Rutin ameliorates depressive symptoms， enhances spatial memory capabilities， and reduces neuronal damage in PMDD model rats with liver qi stagnation syndrome. These effects may be associated with the activation of BDNF/TrkB signaling pathway and upregulation of Syn protein expression.

Objective:By analyzing epidemic characteristics and prevention and control measures of Corona virus disease 2019 (COVID-19) in South Korea and Japan, to provide reference for prevention and control of the epidemic.Methods:Information on COVID-19 from official websites of the South Korea Central Disaster Safety Management Headquarters and the Ministry of Health, Labor and Welfare of Japan as well as authoritative media in South Korea and Japan, were collected and used to analyze the epidemic characteristics and prevention and control measures.Results:The first confirmed case of COVID-19 was reported in South Korea on January 20, 2020. The epidemic peak occurred early in South Korea at the end of February. The South Korean government controlled the epidemic in early April by active searching, quarantine, testing and treating every case and traced every contacted person. In Japan, the first confirmed case was reported on January 16, 2020. The epidemic peak occurred late in Japan in early April. The Japanese government controlled the epidemic in early May by adopting containment measures that issued a "Declaration of Emergency" to the whole country, calling on the public to avoid unnecessary and urgent travel, staying at home, and asking businesses to close down. But at the end of June, the epidemic of Japan rebounded.Conclusion:The epidemic situation in South Korea and Japan is generally at a low level, and some prevention and control experiences are worth study and absorption, especially the prevention and control mode in South Korea needs further follow-up observation and study.

Objective:To describe the COVID-19 epidemic and its characteristics in Heilongjiang province, and provide evidence for the further prevention and control of COVID-19 in the province.Methods:The information of COVID-19 cases and clusters were collected from national notifiable disease report system and management information system for reporting public health emergencies of China CDC. The Software’s of Excel 2010 and SPSS 23.0 were applied for data cleaning and statistical analysis on the population, time and area distributions of COVID-19 cases.Results:On January 22, 2020, the first confirmed case of COVID-19 was reported in Heilongjiang. By March 11, 2020, a total of 482 cases domestic case of COVID-19, The incidence rate was 1.28/100 000, the mortality rate was 2.70% (13/482) in 13 municipalities in Heilongjiang. There were 81 clusters of COVID-19, The number of confirmed cases accounted for 79.25% (382/482) of the total confirmed cases and 12 cases of deaths. The family clusters accounted for 86.42% (70/81). Compared with the sporadic cases, the mortality rate, proportion of elderly cases aged 60 or above and severe or critical cases of clinical classification were all higher in the clusters especially the family clusters, but the differences were not significant ( P>0.05). There were 34 clusters involving more than 5 confirmed cases accounted for 41.98% (34/81) of the total clusters, the involved cases accounted for 68.31% (261/382) of the total cases of clusters. There were significant differences in age distribution of the cases among the case clusters with different case numbers. In the clusters involving 6-9 cases, the proportion of cases aged 65 years or above was more (26.53%, 39/147). Conclusions:The incidence rate of COVID-19 was relatively high and the early epidemic was serious in Heilongjiang, The number of cases was large in clusters especially family clusters.

Objective The objective of this study was to investigate and understand the life quality and its influencing factors in breast cancer patients with chemotherapy. Methods Based on the European Research and Treatment Association,the EORTC-BR53 scale consisting of QLQ-C30 and QLQ-BR23 was used as the main basis to design a questionnaire to investigate the life quality of breast cancer patients with chemotherapy. The rank sum test was used to evaluate the survival of breast cancer patients with chemotherapy. The grade logistics univariate and multivariate analyses were used to analyze the factors of prognosis and life quality of breast cancer patients. Results The median fun scores of QLQ-BR23 scale in the groups of <35 months,36~59 months and more than 60 months were 0,0,and 66. 67,respectively( P<0. 05). The median scores of annoy caused by alopecia were 33. 33,33. 33, and 10. 33 in three groups mentioned above,respectively(P<0. 05). The median scores of physical function of QLQ-C30 scale for modified radical mastectomy,segment plus sentinel and breast-conserving patients were 66. 67,66. 67,and 73. 33,respectively(P<0. 05). The median scores of nausea and vomiting in the modified radical mastectomy was 16. 67,and others were 0;the median scores of shape physique of QLQ-BR23 in three groups were 91. 67,100 and 100,respectively( P<0. 05);the median scores of sexual function were 0,16. 67 and 50,respectively(P<0. 05),and the median scores of sexual fun were 0,33. 33 and 66. 67,respectively(P<0. 05). To analyze the total symptoms of life quality,causing borrow money and pathological classification were the factors affecting the total life quality of breast cancer patients with chemotherapy(P<0. 05). The total symptoms of life quality were analyzed. Univari-ate analysis showed that borrows money due to illness and ductal carcinoma in pathological classification had significant. Conclusion The life quality of breast cancer patients with chemotherapy is mainly related to the pathological stage of patients and whether they have economic pressure.

Objective The objective of this study was to investigate the relationship between the methylation of phosphodies-terase 4C(PDE4C)gene in peripheral blood leukocytes,and its interaction with environmental factors and the pathogenesis of breast cancer. Methods A case-control study was conducted to select 402 cases of breast cancer and 470 cancer-free controls from Octo-ber 2010 to December 2014. The specific DNA methylation-modified quantitative PCR method was used to detect the methylation of PDE4C gene. The use of crossover analysis and multivariate logistic regression was used to analyze the relationship between the level of gene methylation and its interaction with environmental factors and the pathogenesis of breast cancer. Results PDE4C methylation was not found to be significantly associated with the onset of breast cancer. High-frequency/high-intake of whole grains,vegetables, onion-based plants,poultry,milk,and regular exercise could reduce the risk of breast cancer;high-frequency/high-intake of pork, irregular menstrual cycle,and a high psychological stress index could increase the risk of breast cancer. PDE4C hypermethylation had a significant combining effect with edible onion-producing plants greater than 3 times/week,with an OR of 0. 373(95% CI:0. 208~0. 668,P=0. 001). Conclusion Hypermethylation of PDE4C is not an independent risk factor for breast cancer,and its combination with environmental factors affects the risk of breast cancer.

Objective The aim of this study was to investigate the relationship between STAT1,STAT3 gene promoter CpG island methylation status and prognosis of patients with colorectal cancer(CRC)and the prognostic factors of CRC patients. Methods The cohort study was conducted to biosamples and follow up 239 patients with primary colorectal cancer pathologically diagnosed in Cancer Hospital of Harbin Medical University(Tumor Hospital). The methylation status of STAT1,STAT3 gene promoter CpG island was analyzed by methylation specific high-resolution melting curve(MS-HRM). Results The survival rates of 239 patients with colorectal cancer at 1 year,3 years and 5 years were 94. 90% ,86. 00% and 67. 20% ,respectively. The methylation status of STAT1 and STAT3 genes was not associated with postoperative survival in colorectal cancer patients( STAT1:HR=0. 85,95% CI:0. 55 ~1. 30,P=0. 44;STAT3:HR=0. 75,95% CI:0. 36~1. 58,P=0. 45). Dukes stage(HR=1. 31,95% CI:1. 14~1. 51,P<0. 01)and intraoperative intestinal stapler use(HR=1. 98,95% CI:1. 25 ~3. 14,P<0. 01) were important factors affecting the prognosis of colorectal cancer patients. The risk of death in patients with stage D and Dukes was significantly higher than that in stages A and B (HR=1. 31,95% CI:1. 14~1. 51,P<0. 01). Intestinal anastomosis was used during operation. The patient′s prognosis was better than that of patients without an intestinal stapler. However,gender,age,tumor location,gross tumor type,histological classification and postoperative chemotherapy were not associated with the prognosis of colorectal cancer. Conclusion Dukes stage is an independent factor affecting the prognosis of colorectal cancer. The prognosis of patients with intestinal stapler is better than that of non-users. The methylation status of STAT1 and STAT3 in peripheral blood is not a biomarkers for the prognosis of patients with colorectal cancer.

Objective Comprehensive evaluated the characteristics and differences of prevalence of hypertension in cold and non-cold areas,to provide evidence-based prevention strategies for establishment and perfection hypertension prevention and control suitable for China's national conditions in cold area.Methods Northeast China (Heilongjiang,Jilin,Liaoning),Inner Mongolia,Ningxia,Gansu,Qinghai,Tibet and Xinjiang were classified as cold area,and the rest were non-cold area.Use hypertension as a search term,literatures on the prevalence of hypertension were retrieved in WanFang Data,CqVip,CNKI,SinoMed and Pubmed database from January 1 1995 to May 1 2017,then the relevant data were screened and extracted.Heterogeneity was estimated and corresponding effect model was selected.Publication bias was evaluated by funnel plot,Egger test and Begg test.Comprehensive meta-analysis V2 was used for Meta analysis,stratified analysis of age,gender,province and region was did.Results In China,the pooled prevalence of hypertension was 27.00％.The pooled awareness rate of hypertension was 50.80％,the pooled treatment rate of hypertension was 40.40％,and the pooled control rate was 6.80％.The pooled prevalence in cold area was 29.70％ and 26.30％ in non-cold area,respectively,the difference of prevalence between cold and non-cold areas was significant (P ＜ 0.05).After the stratified analysis of age and gender,the pooled prevalence in men and women in cold area had a increased trend than that in non-cold area;the pooled prevalence in ＜ 30,40-,50-,and 60-＜ 70 years old groups in cold area was higher than that in non-cold area.The pooled prevalence was the highest in Tibet (40.70％) and north and northeast China area (30.40％,29.20％),and the lowest in Hainan (16.70％) and southern China area (20.70％).Conclusions In China,the pooled prevalence of hypertension is 27.00％,which is higher in cold area than non-cold area.The pooled prevalence is the highest in Tibet and north and northeast China,and the lowest in Hainan and Southern China.

Objective To analyze the epidemic characteristics of brucellosis in Nangang District of Harbin City,and to provide a scientific basis for making strategies in prevention and control of the disease.Methods Descriptive epidemiological methods were used,epidemic characteristics (time distribution,regional distribution and population distribution) of the disease in Nangang District of Harbin City in 2006-2015 were studied,and brucellosis cases were reported online through the national epidemic network.Results A total of 105 cases of brucellosis were reported,the average annual incidence rate was 7.84/100 thousand and no death case.The number of cases was the highest in 2014,it was 21 cases,the incidence rate was 1.57/100 thousand;the number of cases was the least in 2010,it was 3 cases,the incidence rate was 0.22/100 thousand;in 2006,the number of cases was 9,the incidence rate was 0.67/100 thousand;in 2015,the number of cases was 17,the incidence rate was 1.27/100 thousand.The incidence of the disease was mainly concentrated in summer and autumn,accounting for 65.71％ (69/105),the number of summer onset was 38,accounting for 36.19％ (38/105);the incidence of the autumn was 31,accounting for 29.52％ (31/105).In 2006-2012,the incidence of the disease was mainly concentrated in Wanggang and Hongqi townships,accounting for 60.00％ (30/50);after 2013,the cases in urban areas were on the rise,Wanggang and Hongqi townships accounted for 34.55％ (19/55).Incidence of male youth was the highest,male and female incidence ratio was 2.18:1.00 (72:33);incidence peak was 30-60 years old,accounting for 60.95％ (64/105);after analyzing the incidence of occupational groups,farmer was the highest,accounting for 43.81％ (46/105).Transmission route was contact with cattle and sheep and lived in the environment cattle and sheep were breed,the number of cases was 34.Conclusions The incidence of brucellosis in Nangang District of Harbin City is rising after 2013.Disease season focus in summer and autumn,occupation focus in farmers,and the scope of the outbreak has been expanded.We should further strengthen publicity and education in disease focus season,improve the awareness of protection,in order to effectively control the epidemic of brucellosis.

Objective To explore the interaction between family history of diabetes and hyperlipidemia on the risk of diabetes in population with normotension.Methods A multistage stratified probability random sampling was conducted to select a representative sample of urban residents aged 20-74 years in Harbin.A total of 376 diabetes patients with normotension and 3 692 residents with normal blood pressure,normal fasting glucose,and normal 2 hours glucose from OGTT were surveyed.The interaction was evaluated by using crossover analysis and additive model.Results Multivariate logistic regression analysis indicated that there was a possible additive interaction between family history of diabetes and hyperlipidemia on the risk of diabetes.The relative excess risk due to the interaction,the attributable proportion due to the interaction,and the synergy index were 1.97 (95％CI:-0.32-4.26),0.30 (95％CI:0.03-0.57),and 1.54 (95％CI:0.96-2.47),respectively.There were significant combination effects between family history of diabetes and high both total cholesterol and triglyceride,isolated high total cholesterol,and isolated high triglyceride levels;the ORs were 10.55 (95％CI:5.62-19.80),7.81 (95％CI:3.65-16.71) and 5.13 (95％CI:3.22-8.16),respectively.Conclusion There might be synergistic effect between family history of diabetes and hyperlipidemia on the risk of diabetes in population with normotension.

Group cooperative learning is a modem education model.In order to prompt the exploration of the education model in the practice lesson of epidemiology,group cooperative learning method was adopted.There are five key steps for the conduction of group cooperative learning,including task assignment(learning points,research topics,and infomation retrieval) 3-5 days before the task is done,reviewing the key theoretical contents,requiring students to refer to inf'ormation; organizing students to review the theoretical knowledge; students' discussion and making PPT in small groups,team report by representatives,and summing up by teachers at last.Teachers should pay attention to the rationality of interior structure and group members' work.Choosing a proper research subject is very important for arousing the students' interest of study.Based on the active classroom atmosphere and students' feedback,group cooperative learning method plays an important role in promoting the teaching efficiency of practice lesson.However,there are still insufficiencies to be improved.