ObjectiveTo unearth novel circRNA-miRNA-mRNA network and potential drugs in ischemic stroke. MethodsData from the GEO database were utilized， focusing on three datasets （GSE115697， GSE51586， and GSE137482） that examine RNA expression levels in middle cerebral artery occlusion （MCAO） mouse models. Differentially expressed mRNA （DEmRNA）， DEcircRNA， and DEmiRNA were identified using the Limma package in R. A comprehensive strategy combining bioinformatics tools such as MiRWalk and StarBase was employed to identify circRNA-miRNA-mRNA networks associated with ischemic stroke. Hub sub-networks were screened and visualized using Cytoscape software. Functional analyses of the ceRNA networks were performed using Gene Ontology （GO） enrichment and Kyoto Encyclopedia of Genes and Genomics （KEGG） pathway analysis， with pathways containing more than 10 enriched genes and an false discovery rate （FDR） ＜ 0.05 considered statistically significant. Lastly， the Connectivity Map （CMap） was applied to identify potential therapeutic drugs for ischemic stroke and the MCAO model was established in wild-type mice to verify the therapeutic effect. ResultsTotally， 1，249 DEmRNA， 294 DEmiRNA and 70 DEcircRNA were identified and it was found that 3 circRNA-miRNA-mRNA networks might be closely related to ischemic stroke. Based on these findings， Austricine， Metyrapone and Desoxypeganine were the most likely drugs that able to reverse the changes caused by stroke-related ceRNA networks. Metyrapone， taken as an example， was validated to improve neurological function damage on the first （P=0.001 4） and second （P=0.016 1） days post-surgery and reduce infarct volume （P=0.004 9）， thereby exerting a neuroprotective effect in ischemic stroke. ConclusionsOur study provides a novel insight into the pathogenesis and therapy of ischemic stroke from the perspective of circRNA-miRNA-mRNA regulatory network. The three drugs predicted in our research provide new clues for the treatment of ischemic stroke.

Objective:To analyze the association of sedentary time and physical activity with the risk of developing chronic obstructive pulmonary disease (COPD) in non-smoking women aged 40 years and above in Songjiang District, Shanghai.Methods:Based on a natural population-based cohort in Songjiang, a total of 18 707 non-smoking women who were aged 40 years and above and without COPD at baseline survey were enrolled in the study. Cox proportional risk regression model was used to analyze the associations of the duration of sedentary behavior, physical activity with the risk for COPD at baseline survey, and the hazard ratio ( HR) of risk for COPD and its 95% CI were calculated. Stratified analyses were performed based on age, BMI, history of respiratory diseases and so on. Sensitivity analyses were conducted by excluding the cases diagnosed with COPD within one year after the baseline survey. Results:As of March 31, 2024, a total of 691 new COPD cases had been recorded after a median follow-up time of 6.96 years with an incidence density of 53.22 per 10 000 person-years. After adjusting for relevant confounders, in the tertile subgroups of sedentary time, the risk for COPD reduced by 17% in the short sedentary time group compared with the long sedentary time group ( HR=0.83,95% CI:0.70-0.99). Compared with the low physical activity level and long sedentary time group, the risk for COPD reduced by 24% in the high physical activity level and short sedentary time group ( HR=0.76, 95% CI: 0.61-0.95) and by 23% in the low physical activity level and short sedentary time group ( HR=0.77, 95% CI: 0.60-0.97). Compared with the non-physical exercise and long sedentary time group, the risk for COPD reduced by 28% in the non-physical exercise and short sedentary time group ( HR=0.72, 95% CI: 0.60-0.87). These associations remained when the cases diagnosed with COPD within one year of the baseline survey were excluded. Conclusions:Increasing physical activity and reducing sedentary time have beneficial effects to prevent COPD in non-smoking women, and reducing sedentary time alone may also reduce the risk for COPD if increasing physical exercise or other physical activity is not possible.

Objective:To compare the infection status of severe fever with thrombocytopenia syndrome (SFTS) between the non-endemic area (Yixian county, Huangshan city) and the endemic area (Qianshan city, Anqing city) in Anhui province, and to explore the possibility of Yixian county being a natural focus of SFTS, thereby providing a scientific basis for the formulation of prevention and control strategies.Methods:In Xidi town, Yixian county, and Shuihou town, Qianshan city, one administrative village with the highest number of reported cases in the past three years was selected as the study village in each area, along with one control village with no reported cases. The study investigated the total antibody positivity rates of SFTS virus (SFTSV) in natural populations and host animals, as well as the density and virus-carrying rate of the vector ticks. Differences in total antibody positivity rates between the two regions were compared.Results:The total SFTSV antibody positivity rates in the natural population and host animals in the surveyed villages (control villages) of Qianshan city and Yi county were 8.7% and 8.0% (3.3%, 4.1%) and 0.0%, 9.1% (50.0%, 66.7%), respectively. There was no statistically significant difference in the infection rates of the natural population and host animals between the surveyed villages (control villages) in different endemic regions (all P>0.05). In the surveyed villages of Qianshan city and Yi county, the free-living tick densities were 1.4 ticks/hour per flag and 1.7 ticks/hour per flag, respectively; the parasitic tick densities were 0.4 ticks/host and 2.5 ticks/host, respectively; the tick infestation rates were 33.3% and 35.3%, respectively; and the tick density indices were 1.3 ticks/host and 7.2 ticks/host, respectively. Conclusions:The natural populations and host animals in some areas of Yixian county exhibit high SFTSV infection rates, and the tick density is also high, suggesting that the region may have become a natural focus of SFTS. Therefore, it is necessary to further strengthen capabilities in surveillance, diagnosis, and clinical treatment to address the potential risk of SFTS outbreaks.

Objective:To analyze the association of sedentary time and physical activity with the risk of developing chronic obstructive pulmonary disease (COPD) in non-smoking women aged 40 years and above in Songjiang District, Shanghai.Methods:Based on a natural population-based cohort in Songjiang, a total of 18 707 non-smoking women who were aged 40 years and above and without COPD at baseline survey were enrolled in the study. Cox proportional risk regression model was used to analyze the associations of the duration of sedentary behavior, physical activity with the risk for COPD at baseline survey, and the hazard ratio ( HR) of risk for COPD and its 95% CI were calculated. Stratified analyses were performed based on age, BMI, history of respiratory diseases and so on. Sensitivity analyses were conducted by excluding the cases diagnosed with COPD within one year after the baseline survey. Results:As of March 31, 2024, a total of 691 new COPD cases had been recorded after a median follow-up time of 6.96 years with an incidence density of 53.22 per 10 000 person-years. After adjusting for relevant confounders, in the tertile subgroups of sedentary time, the risk for COPD reduced by 17% in the short sedentary time group compared with the long sedentary time group ( HR=0.83,95% CI:0.70-0.99). Compared with the low physical activity level and long sedentary time group, the risk for COPD reduced by 24% in the high physical activity level and short sedentary time group ( HR=0.76, 95% CI: 0.61-0.95) and by 23% in the low physical activity level and short sedentary time group ( HR=0.77, 95% CI: 0.60-0.97). Compared with the non-physical exercise and long sedentary time group, the risk for COPD reduced by 28% in the non-physical exercise and short sedentary time group ( HR=0.72, 95% CI: 0.60-0.87). These associations remained when the cases diagnosed with COPD within one year of the baseline survey were excluded. Conclusions:Increasing physical activity and reducing sedentary time have beneficial effects to prevent COPD in non-smoking women, and reducing sedentary time alone may also reduce the risk for COPD if increasing physical exercise or other physical activity is not possible.

Objective:To compare the infection status of severe fever with thrombocytopenia syndrome (SFTS) between the non-endemic area (Yixian county, Huangshan city) and the endemic area (Qianshan city, Anqing city) in Anhui province, and to explore the possibility of Yixian county being a natural focus of SFTS, thereby providing a scientific basis for the formulation of prevention and control strategies.Methods:In Xidi town, Yixian county, and Shuihou town, Qianshan city, one administrative village with the highest number of reported cases in the past three years was selected as the study village in each area, along with one control village with no reported cases. The study investigated the total antibody positivity rates of SFTS virus (SFTSV) in natural populations and host animals, as well as the density and virus-carrying rate of the vector ticks. Differences in total antibody positivity rates between the two regions were compared.Results:The total SFTSV antibody positivity rates in the natural population and host animals in the surveyed villages (control villages) of Qianshan city and Yi county were 8.7% and 8.0% (3.3%, 4.1%) and 0.0%, 9.1% (50.0%, 66.7%), respectively. There was no statistically significant difference in the infection rates of the natural population and host animals between the surveyed villages (control villages) in different endemic regions (all P>0.05). In the surveyed villages of Qianshan city and Yi county, the free-living tick densities were 1.4 ticks/hour per flag and 1.7 ticks/hour per flag, respectively; the parasitic tick densities were 0.4 ticks/host and 2.5 ticks/host, respectively; the tick infestation rates were 33.3% and 35.3%, respectively; and the tick density indices were 1.3 ticks/host and 7.2 ticks/host, respectively. Conclusions:The natural populations and host animals in some areas of Yixian county exhibit high SFTSV infection rates, and the tick density is also high, suggesting that the region may have become a natural focus of SFTS. Therefore, it is necessary to further strengthen capabilities in surveillance, diagnosis, and clinical treatment to address the potential risk of SFTS outbreaks.

Objective:To explore the incidence of chronic obstructive pulmonary disease (COPD) in a cohort aged 40 years and above in Songjiang District, Shanghai, and to analyze the association of Mediterranean diet pattern and dietary approaches in stopping hypertension pattern (DASH) with the risk of developing COPD.Methods:Based on a natural population cohort in Songjiang District, Shanghai, 27 474 adults aged 40 years and above who did not have COPD at baseline were enrolled in the study. The Cox proportional risk regression model was used to analyze the association of baseline Mediterranean diet pattern score and DASH score with the risk of COPD, and the hazard ratio ( HR) of the risk and its 95% CI were calculated. Restricted cubic spline was used to analyze the nonlinear association between the two diet scores and the risk of COPD. Stratified analyses were performed according to gender, age, smoking status, etcetera. Sensitivity analyses were conducted by censoring cases diagnosed within one year after the baseline survey or people with a history of malignant tumor disease. Results:As of June 30, 2023, after a median follow-up time of 6.21 years, there were 1 089 (4.0%) new COPD cases with an incidence density of 64.00 per 10 000 person-years. After adjusting for relevant confounders, in the Mediterranean tertile subgroups under diet pattern score, the risk of developing COPD could be reduced by approximately 14% in the intermediate scoring group ( HR=0.86, 95% CI: 0.75-0.99) and 15% in the highest scoring group ( HR=0.85, 95% CI: 0.72-0.99) compared to the lowest scoring group. The association remained after censoring cases diagnosed within one year of the baseline survey ( HR=0.82, 95% CI: 0.70-0.95; HR=0.82, 95% CI: 0.68-0.97) or censoring people with a history of malignant tumor disease ( HR=0.84, 95% CI: 0.73-0.97; HR=0.84, 95% CI: 0.71-0.99). No statistical association was found between the DASH score and the risk of COPD. Conclusions:The Mediterranean diet pattern was associated with a lower risk of COPD. Increasing the intake of vegetables, fruits, legumes, and whole grains and decreasing the intake of red meat and others can reduce the risk of COPD. No association was found between the DASH dietary pattern and the risk of COPD in this community population.

Objective:To investigate the characteristics of enterovirus (EV) VP1 gene from cases with hand, foot and mouth disease (HFMD) in Songjiang district of Shanghai in 2019.Methods:Samples from suspected HFMD cases were detected using real-time fluorescence reverse transcription polymerase chain reaction (RT-PCR). Human rhabdomyosarcoma (RD) cells were used for EV culture. VP1 genes of the isolated EV A species were sequenced. The sequences of nucleotide and amino acid of EV A species were used in phylogenetic and homology analysis by MEGA X software.Results:Totally 207 HFMD specimens were detected in 2019, of which 188 specimens were screened positive for EV. The positive rates of Coxsackievirus (CV)-A6, CV-A16, CV-A10 and CV-A4 were 47.34% (89/188), 41.49% (78/188), 3.72% (7/188) and 2.66% (5/188), respectively. Other EV species were 4.79% (9/188) positive and EV-A71 was not detected. During the summer epidemic peak of HFMD (May to July), B1 gene subtype of CV-A16 was detected more frequently, of which B1a and B1b evolutionary branches were prevalent together. The CV-A6 virus of D3a branch dominated in secondary peak of autumn and winter (September to December). CV-A10 and CV-A4 were sporadic and both respective strains belonged to subtypes of C2 gene. Compared with the prototype strains, the nucleotide (amino acid) sequence homologies of CV-A6, CV-A16, CV-A10 and CV-A4 VP1 genes were 79.22%-81.78% (95.97%~-97.19%), 62.70%-65.54% (90.10%-91.30%), 81.76%-82.65% (91.63% -92.03%) and 81.09%-81.79% (97.27%-97.67%), respectively.Conclusions:The diversity and complexity of HFMD pathogen epidemic increase the difficulty of HFMD prevention and control. The expansion of EV surveillance programs and the studies on the molecular epidemiology of EV are helpful for the prevention and control of HFMD.

Objective:To investigate the prognostic significance of different IDH mutations and accompanying gene mutations in patients with non-M 3 acute myeloid leukemia (AML) . Methods:Second-generation sequencing was performed to detect the mutations of 22 genes in 389 patients with AML in the First Affiliated Hospital of Zhengzhou University from June 2016 to December 2018, and Kaplan-Meier and Cox regression models were used to analyze the prognostic factors.Results:The mutation frequency of IDH1 and IDH2 was 6.2% and 8.7% , respectively, in all patients without co-mutation. The IDH2 mutant group had an older age, higher proportion of bone marrow primitive cells, more common normal karyotype, and more common RUNX1 and SRSF2 mutations compared with IDH2 wild-type group. Univariate analysis of variance showed that the median OS and PFS of IDH1 mutation group were significantly shorter than those of the wild-type group ( P<0.05) . IDH2 mutation as a single variable and IDH2R140 mutation had no significant effect on the prognosis, while different mutation sites had different effects. Compared with the IDH2 wild-type group, the IDH2R172 mutation group had lower complete remission (CR) rate and shorter median OS and PFS ( P<0.05) . In patients with normal karyotypes or aged ≥50 years, IDH2 mutation as a single variable had no significant effect on the prognosis, IDH1 mutation and IDH2R172 mutation were associated with poor OS and PFS ( P<0.05) , and IDH2R140 mutation had no significant effect on OS and PFS. Approximately 74.1% (43/58) of patients with IDH mutation simultaneously carried other gene mutations; however, the number of accompanying gene mutations had no significant effect on the prognosis. Among 58 patients with IDH mutation, the CR rate of patients with NPM1 mutation was significantly higher than that of patients in the NPM1 wild-type group (81.8% vs 36.4% , P=0.014) , the median OS in patients with DNMT3A mutation was lower than that of patients with DNMT3A wild type [4.0 months (95% CI 3.8-4.2) vs 6.3 months (95% CI 2.4-10.2) , P=0.041) ]. Multivariate analysis showed that age ≥60 years and white blood cell count ≥100×10 9/L were independent risk factors for OS and PFS, while CR after two courses of treatment and hematopoietic stem cell transplantation were independent prognostic favorable factors for OS and PFS. Conclusion:In patients with AML (non-M 3) , IDH gene mutations often coexisted with other gene mutations, and different subtypes and accompanying gene mutations of IDH have different prognostic significance.

COVID-19 is a public health emergency currently. In this study, a scale-free network model is established based on the Spring Migration data in 2020.The cities is clustered into three different modules. The epidemic of the cities in the black module was the most serious, followed by the red and the cyan. The black module contains 9 cities in Zhejiang province and 8 cities in Guangdong province, most of them located in the southeast coastal economic belt. These cities should be the key cities for epidemic prevention and control.

Objective:To investigate the characteristics of pulmonary function changes and its possible influencing factors in patients with pneumoconiosis.Methods:In December 2019, pneumoconiosis patients hospitalized in four departments of occupational diseases in Hunan Occupational Disease Prevention and Control Hospital from December 2015 to December 2016 were selected as subjects. Lung function including forced vital capacity (FVC) , FVC%, forced expiratory volume in one second (FEV1) , FEV1%, forced expiratory volume in one second / forced vital capacity (FEV1/FVC) , diffusion capacity of the lung foe carbon monoxide% (DLCO%) 、maximal expiratory rlow 75% (MEF75%) , maximal expiratory rlow 50% (MEF50%) and maximal expiratory rlow 25% (MEF25%) were tested, and collect their age, occupation history, smoking history and Chronic Obstructive Pulmonary Disease Self Rating Questionnaire (CAT) score. They were followed up after 3 years to analyze the 3-year decline rates of lung function indicators and their relationship with stage of pneumoconiosis, age, smoking index, baseline values of lung function and CAT score.Results:265 cases were studied effectively. After 3 years, the values of 9 lung function indicators of pneumoconiosis patients were significantly lower than those of 3 years ago ( P<0.05) . The decline rates of FEV1%, FEV1/FVC, MEF75%, MEF50% and MEF25% were positively correlated with the stage of pneumoconiosis ( r=0.250, 0.290, 0.219, 0.280, 0.141, P<0.05) . The decline rates of FEV1% and MEF75% were positively correlated with smoking index ( r=0.148, 0.152, P<0.05) . The decline rates of DLCO% and MEF25% were positively correlated with the baseline value of initial pulmonary function ( r=0.276, 0.153, P<0.05) , while the decline rates of FEV1%, FEV1/FVC and MEF50% were negatively correlated with the baseline values of initial pulmonary function ( r=-0.215, -0.146, -0.214, P<0.05) . The decline rates of FVC%, FEV1%, MEF75% and MEF50% were positively correlated with the changes of CAT scores ( r=0.147, 0.208, 0.210, 0.196, P<0.05) . Logistic regression analysis showed that old age and high initial value of DLCO% were the risk factor for the decline of DLCO% ( OR=1.105、1.078, P<0.05) .High smoking index was the risk factors for the decline of MEF75% ( OR=1.016, P<0.05) . High stage and the increase of CAT score were the risk factors for the decline of MEF50% ( OR=1.548, 1.162, P<0.05) . High initial value of MEF25% was the risk factor for the decline of MEF25% ( OR=1.010, P<0.05) . Conclusion:The pulmonary function index of pneumoconiosis patients declined significantly in 3 years. The stage of pneumoconiosis, age, smoking index and degree of pulmonary function damage were related to the decline rate of pulmonary function.