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 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.

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.

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.

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 efficacy and safety of domestic bortezomibˉbased chemotherapy for patients with multiple myeloma (MM). Methods The clinical data of 60 MM patients treated with domestic bortezomibˉbased chemotherapy regimen (the observation group) in the First Affiliated Hospital of Zhengzhou University from April 2018 to October 2018 were retrospectively analyzed, which were compared with 112 MM patients treated with original treatment regimen (the control group) at the same hospital from November 2010 to November 2014. According to the disease stage, the patients were divided into newly diagnosed MM (NDMM) group and relapsed refractory MM (RRMM) group, and efficacy and adverse reactions of domestic bortezomib were evaluated. Results The total response rate (ORR) of the observation group was 71.7% (43/60), severe complete response (sCR) + complete response (CR) rate was 16.7% (10/60), very good partial response (VGPR) rate was 18.3% (11/60), and partial response (PR) rate was 36.7% (22/60). The ORR of NDMM group (45 cases) and RRMM group (15 cases) was 82.2% (37/45) and 40.0% (6/15), respectively, and the difference was statistically significant (χ2＝ 9.877, P < 0.05). There was no significant difference between ISS stage Ⅰ+Ⅱ and stage Ⅲ [ORR: 75.7% (28/37) vs. 65.2% (15/23), respectively; χ2＝0.764, P >0.05]. ORR and CR rates in the NDMM group and RRMM group of the observation group and the control group were not statistically different (all P>0.05). In the treatment of bortezomibˉbased chemotherapy, the common adverse reaction was peripheral neuropathy, mostly belonging to grade 1-2. Other side effects included hematocytopenia, gastrointestinal events and herpes zoster, which could be alleviated or restored to normality after supportive treatments. One patient died of pulmonary infection, respiratory failure and septic shock during the intermittent period of chemotherapy. Conclusion ORR of domestic bortezomibˉbased chemotherapy in treatment of the patients with MM is high, and the incidence of adverse reactions shows no significant increase compared with original drugs.

Objective To explore the efficacy and prognosis of haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HSCT) for severe aplastic anemia (SAA).Methods The clinical data were retrospectively analyzed for 40 SAA cases undergoing haplo-HSCT from September 2013 to February 2018.The conditioning regimen contained cyclophosphamide,fludarabine and antithymocyte globulin with or without busulfan or low-dose total body irradiation.Cyclosporin A,short-term methotrexate and mycophenolate mofetil were dosed for preventing graft versus host disease (GVHD).The median counts of mononuclear cell and CD34+ stem cell were 5.3(2.0～13.5) × 108/kg and 5.6 (1.6 ～ 15.9) × 106/kg respectively.Results Among them,hematopoietic reconstitution was achieved (n =36,90.0 ％).The median times for myeloid engraftment and platelet engraftment were 15(10-25) and 17(10～58) days respectively.The incidence of acute graft-versushost disease(aGVHD)was (35.0± 6.8) ％.The incidence of chronic GVHD (cGVHD) was (23.0 ±7.4) ％.And 28 SAA cases (70.0 ％) survived during a median follow-up period of 353(30～1226)days,The cumulative overall survival (OS) was (67.8 ± 7.8) ％,the average survival time (883 ± 82)days and transplantation-related death (TRM) within 100 days (10.0 ± 3.1) ％.Conclusions Haplo-HSCT is an effective treatment for SAA patients.And a larger number of cases are required for enhancing OS.