The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.

Objective: To determine the association between anthropometric parameters and 20 meter shuttle run test (20 m SRT) score among children and adolescents. Methods: The convenient sampling method was conducted to select 3 192 primary and secondary school students in Baoan District, Shenzhen, based on the street school types school from April to May 2019. Height, weight, 20 m SRT score and general demographic indicators were assessed and collected. Individuals were divided into two groups based on the dose response correlation between different anthropometric parameters (the Z score of height, weight and BMI) and 20 m SRT score analyzed with the restricted cubic spline. The association between the Z score of height and 20 m SRT score was further analyzed using the Spearman correlation analysis. Logistic regression analysis was used to analyze separately the relationship different anthropometric parameters and 20 m SRT score. Results: The Z value of weight and 20 m SRT score showed a non linear dose response association ( P <0.01), the significant but weak linear correlation between the Z value of height and 20 m SRT score ( r=0.06, P <0.05). The prevalence rate on the low level of the Z value of 20 m SRT score in 3 192 children and adolescents was 44.7%, and the gender ( χ 2=14.02, P <0.01) and grade difference ( χ 2=93.28, P <0.01) were both statistically significant. There was no significant relationship between the Z value of height and 20 m SRT score grade among total population, different genders and different grades ( P > 0.05). Compared with the reference group on the Z value of weight ≤-0.23, individuals with the Z value of weight >-0.23 had the low level of 20 m SRT score ( OR =0.61, P <0.05). Compared with the reference group on the Z value of BMI ≤ 0.25, individuals with the Z value of weight >0.25 had the low level of 20 m SRT score ( OR =0.45, P <0.05). Stratified for gender and grade, the above significant relationship on the Z value of weight, Z value of BMI and 20 m SRT score were still observed ( P <0.01). Conclusions The higher height Z value shows on correlations with 20 m SRT score, but the positive association is found between weight and BMI Z value and the 20 m SRT score. The cardiopulmonary fitness improvement may be more effective among children and adolescents when tuking weight and BMI Z scores into consideration.

Objective:To investigate the effects of chest pain center construction in basic-level hospitals on treatment time and short-term prognosis in patients with acute ST-elevation myocardial infarction.Methods:A total of 162 patients with acute ST-elevation myocardial infarction who received percutaneous coronary intervention (PCI) in The First People's Hospital of Jiande between November 2014 and November 2018 were included in this study. Among them, 66 patients who received treatment in The First People's Hospital of Jiande between November 2014 and October 2016 were included in the control group. The remaining 96 patients who received treatment between November 2016 and November 2018 were included in the study group. The underlying diseases, PCI success rate, first medical contact-to-balloon time, door-to-balloon time, in-hospital mortality, incidence of heart failure on the next day of PCI, length of hospital stay, hospital medical cost were retrospectively analyzed.Results:There were no significant differences in underlying disease composition ratio and PCI success rate between the two groups (both P > 0.05). There were significant differences in first medical contact-to-balloon time [(185.2 ± 53.7) minutes vs. (108.6 ± 46.4) minutes, t = 6.128], door-to-balloon time [(121.5 ± 23.2) minutes vs. (68.7 ± 14.3) minutes, t = 7.341], length of hospital stay [(10.3 ± 3.5) days vs. (7.2 ± 2.8) days, t = 5.128], hospital medical cost [(43 582.0 ± 7 186.5) yuan vs. (35 479.0 ± 4 213.1) yuan, t = 8.361], in-hospital mortality [6.1% vs. 3.1%, χ2 = 4.784], the incidence of heart failure on the next day of PCI [13.6% vs. 4.2%, χ2 = 8.253] between the control and study groups (all P < 0.05). Conclusion:Establishment of a standardized chest pain center construction in basic-level hospital can greatly shorten the first medical contact-to-balloon time, door-to-balloon time and length of hospital stay, improve the cardiac function and prognosis of patients with myocardial infarction, and reduce medical cost.

Objective:To examine whether sleep status and social jet lag are related to the mental health behaviors in children and adolescents, providing a reference for preventing and improving children and adolescents' mental health behaviors.Methods:A large cross-section was conducted in Baoan District, Shenzhen, from April to May 2019. A total of 30 188 adolescents and children in grades 1-12 in 14 schools were included. The growth trajectory and health index questionnaire of primary and secondary school students were designed to evaluate the sleep status. Mental health behavior problems among students were accessed using the parents' and students' versions of the Strengths and Difficulties Questionnaire. After controlling for confounding factors of demographic variables, including gender, age, parental education level, academic performance, learning burden, and noise impact, a multivariate logistic regression model was used for statistical analyses.Results:The sleep duration of four grades students were 90.4％,90.1％, 98.2％, and 98.4％, respectively. 19.9％ did not have a post-lunch nap. 19.6％ had a wake-up delay of more than or equal to 2 h weekend morning. 35.1％ had an inconsistent bedtime and 15.5％ had an inconsistent awakening time. The multivariate logistic regression model showed that compared with 8-9 h, the sleep duration of elementary school juniors at night less than or equal to 7 h, 7-8 h increased the risk of psychological behavior problems. The sleep time more than 9 h was negatively correlated with psychological behavior problems. The sleep duration of elementary school seniors less than or equal to 7 h increased the risk of psychological behavior problems. The sleep duration of middle school and high school students less than or equal to 6 h increased psychological behavior problems. The ORs (95％ CI) appeared as 2.53(1.85-3.47), 2.41(1.11-5.25), respectively. The ones with a sleep time more than 9 h also increased the risk, and ORs (95％ CI) appeared as 2.37(1.40-4.01), 5.38 (1.79-16.1), respectively. Both the absence of post-lunch nap and the nap time less than 0.5 h were risk factors for psychological behavior problems in primary and middle school students. The nap time over 1-2 h was also a risk factor for high school students' psychological behavior problems. Waking up at irregular times in the morning, going to bed at varying times in the evening, and delaying getting up for more than or equal to 2 h on weekends were all risk factors for psychological and behavioral problems among primary and middle school students. The ORs (95％ CI) of psychological behavior problems of elementary school juniors and seniors, middle school and high school students were 2.07 (1.45-2.97), 1.57 (1.09-2.26), 2.66 (2.06-3.44), 2.48 (1.96-3.15), respectively. Conclusions:Sleep duration, no post-lunch sleep, and daily intraindividual variability of sleep is positively associated with poor mental health. Additionally, social jet lag is associated with mental health problems in students. It is noted that delaying sleep within half an hour on the weekends of elementary school juniors is significantly associated with an increase in bad mental behavior.

Objective:To analyze the relationship between migration time and the prevalence of myopia of children and adolescents aged between 6 and 18 years old in Shenzhen.Methods:From April to May 2019, 26 618 children and adolescents from 14 schools in six streets of Baoan District, including Fuyong, Shajing, Xin′an, Xixiang, Songgang and Shiyan, were included in the study by using random cluster sampling method. The demographic characteristics, migration status, self-reported myopia, screen time in the last seven days, outdoor activities in the last one month and other information were collected through the questionnaire. The differences of myopia among children and adolescents with different characteristics were compared by χ 2 test, and the relationship between migration time and the prevalence of myopia was analyzed by multivariate unconditional logistic regression model. Results:The age of 26 618 study participants was (12.37±3.49) years old, and the overall prevalence of myopia was 49.4%. Multivariate logistic regression analysis showed that after controlling for relevant confounding factors, compared with migrant children and adolescents of migrant workers who migrated for 1-2 years, those of migrant workers who had migrated for more than 6 years had a higher risk of myopia [ OR (95% CI): 1.48 (1.14-1.92)]. After being grouped by phase of school, in the lower grade group of primary school, the children and adolescents of migrant workers who had migrated for more than 6 years had a higher risk of myopia compared with those of migrant workers who migrated for 1-2 years [ OR (95% CI): 1.96 (1.20-2.74)]. In the high school group, compared with the children and adolescents of migrant workers who migrated for 1-2 years, those of migrant workers who had migrated for 3-5 years and ≥6 years had a higher risk of myopia [ OR (95% CI): 6.03 (1.29-28.15) and 6.52 (1.51-28.11), respectively]. Conclusion:The migration time is related to the prevalence of myopia of the children and adolescents of migrant workers.

Objective:To analyze the relationship between migration time and the prevalence of myopia of children and adolescents aged between 6 and 18 years old in Shenzhen.Methods:From April to May 2019, 26 618 children and adolescents from 14 schools in six streets of Baoan District, including Fuyong, Shajing, Xin′an, Xixiang, Songgang and Shiyan, were included in the study by using random cluster sampling method. The demographic characteristics, migration status, self-reported myopia, screen time in the last seven days, outdoor activities in the last one month and other information were collected through the questionnaire. The differences of myopia among children and adolescents with different characteristics were compared by χ 2 test, and the relationship between migration time and the prevalence of myopia was analyzed by multivariate unconditional logistic regression model. Results:The age of 26 618 study participants was (12.37±3.49) years old, and the overall prevalence of myopia was 49.4%. Multivariate logistic regression analysis showed that after controlling for relevant confounding factors, compared with migrant children and adolescents of migrant workers who migrated for 1-2 years, those of migrant workers who had migrated for more than 6 years had a higher risk of myopia [ OR (95% CI): 1.48 (1.14-1.92)]. After being grouped by phase of school, in the lower grade group of primary school, the children and adolescents of migrant workers who had migrated for more than 6 years had a higher risk of myopia compared with those of migrant workers who migrated for 1-2 years [ OR (95% CI): 1.96 (1.20-2.74)]. In the high school group, compared with the children and adolescents of migrant workers who migrated for 1-2 years, those of migrant workers who had migrated for 3-5 years and ≥6 years had a higher risk of myopia [ OR (95% CI): 6.03 (1.29-28.15) and 6.52 (1.51-28.11), respectively]. Conclusion:The migration time is related to the prevalence of myopia of the children and adolescents of migrant workers.

Objective:To observe the clinical efficacy and safety of decitabine combined with low-dose cytarabine in treatment of high-risk myelodysplastic syndrome.Methods:The data of 47 newly treated MDS patients who had high-risk or above scores according to revised international prognostic scoring system (IPSS-R) in the Affiliated Hospital of Qingdao University from January 2016 to September 2018 were retrospectively analyzed. The patients were divided into decitabine combined with low-dose cytarabine group (15 cases) and decitabine group (32 cases). The clinical efficacy and adverse reactions in two groups were compared.Results:After 4 courses of treatment, the bone marrow remission rate, partial remission rate and hematologic remission rate was 20.0% (3/15), 6.7% (1/15), and 13.3% (2/15), respectively in decitabine combined with low-dose cytarabine group, and was 28.1% (9/32), 3.1% (1/32), and 9.4% (3/32), respectively in decitabine group, and there were no statistically differences of both groups (both P > 0.05). The overall response rate in decitabine combined with low-dose cytarabine group was higher than that in decitabine group [93.3% (14/15) vs. 62.5% (20/32), P = 0.037], and the complete remission rate in decitabine combined with low-dose cytarabine group was higher than that in decitabine group [53.3% (8/15) vs. 21.9% (7/32), P = 0.046]. The 1-year overall survival (OS) rate of decitabine combined with low-dose cytarabine group was 86%; and the median OS time of decitabine combined with low-dose cytarabine group was 24 months (95% CI 15.5-32.5 months), which was higher than that of decitabine group (20 months), but there was no statistically significant difference ( χ2 = 0.058, P = 0.810). The incidence of grade Ⅲ-Ⅳ bone marrow suppression and infection in decitabine combined with low-dose cytarabine group was higher than that in decitabine group, but there were no statistically significant differences of both groups (both P > 0.05). Grade Ⅲ-Ⅳ bone marrow suppression and infection were commonly found within the first 2 courses of treatment in decitabine combined with low-dose cytarabine group, and the adverse reactions gradually decreased in the subsequent treatment. Conclusions:Decitabine combined with low-dose cytarabine can achieve better remission rate and prolong survival time for MDS patients with high-risk and above. There is no significant increase in the incidence of grade Ⅲ-Ⅳ bone marrow suppression and infection. For high-risk MDS patients who are not suitable or unable to receive hematopoietic stem cell transplantation, it can be the preferred option.

Objective To observe the effect of myocardial transcription factor MRTF-A on myocardium inflammation and its mechanism.Methods Totally 30 rats were randomly divided into the sham,ischemia-reperfusion (myocardial ischemia 30 min and reperfusion 2 h),and MRTF-A groups(myocardial ischemia 30 min and reperfusion 2 h & Lentivirus infection MRTF-A) (n=10 each group).Serum myocardial enzyme activity was detected by biochemical analysis,myocardial infarct size detected by TTC,and degree of myocardial injury was measured by HE staining.The TLR4 and TRIF expression was analyzed by immunohistochemistry and qPCR.Results Compared with the sham group,the MRTF-A group significantly increased the activity of serum myocardial enzymes CK-MB and LDH (P＜0.05).The infarct area of myocardial tissue was gray-white,and the infarct area was (54.31±3.07)％ (P ＜ 0.05).Myocardial fibrosis was disorder,myocardial cell was swollen and burst,and inflammatory cell infiltration was obvious.Protein and mRNA expressions of TRL4 and TRIF were significantly up-regulated (P＜0.05).Compared with the ischemia-reperfusion group,the levels of CK-MB and LDH were significantly reduced after myocardial infection with MRTF-A (P＜0.05).The myocardial infarction area was significantly reduced to (16.74±4.26)％ (P＜ 0.05).The myocardial structure was nearly normal with mild edema.Protein and mRNA expression of TRL4 and TRIF decreased significantly (P＜0.05).Conclusions The overexpression of transcription factor MRTF-A in myocardial cells alleviates the myocardial ischemia reperfusion injury by inhibiting the TLR4/TRIF signaling pathway and reducing the serum myocardial enzyme activity and myocardial damage.

Aim Drug repositioning is to find new indications for existing drugs,however,potential drug-disease relationships are often hidden in millions of unknown relationship.With the analyzing of medical big data,we predict the potential drug-dis-ease relationships.Methods Based on the assumption that similar drugs tend to have similar indications,we applied a rec-ommendation-based strategy to drug repositioning.First,we col-lected the information of known drug-disease therapeutic effect, side effect,drug characters and disease characters;second,we calculated the drug-drug similarity measurements and disease-disease similarity measurements;last,we used a collaborative filtering (CF)method to predict unknown drug-disease relation-ships based on the known drug-disease relationships by integra-ting the similarity measurements,and built a ranking list of pre-diction results.Results The experiments demonstrated that a-mong the TOP 500 of the list,1 2.8% were supported by clinical experiments or review,and 20% were supported by model or-ganism or cell experiments.Conclusion Compared to the clas-sification model and random sampling results,the CF model can effectively reduce the false positives.

Objective To observe the impact of mesenchymal stem cells (BMSCs) transplantation on myocardial myocardin-related transcription factor-A (MRTF-A) and bcl-2 expression in rats with experimental myocardial infarction (MI).Methods Thirty rats were randomly divided into sham,MI and MI + BMSCs (1 × 106 injected into 4 infarct points immediately post coronary artery ligation) groups (n =10 each).One week later,TUNEL was used to detect cardiomyocyte apoptosis,the myocardial expression of MRTF-A and bcl-2 was detected by laser scanning confocal microscope and Western blot.In vitro plasmid of MRTF-A and co-transfection with plasmids of MRTF-A and bcl-2 or mutated bcl-2 transfection into cardiomyocyte was applied to evaluate the relationship between MRTF-A and bcl-2.Results The number of apoptotic cardiomyocytes in the sham group,MI group and MI + BMSCs group were (4.05 ± 1.56) ％,(62.38 ± 8.41) ％ and (22.36 ±+ 6.17) ％,respectively (P ＜ 0.05).The protein expression of MRTF-A and bcl-2 in the MI group were significantly lower than those in sham group,while significantly upregulated in MI + BMSCs group (P ＜ 0.05 vs.MI).In cultured neonatal rat cardiomyocyte,the expression of bcl-2 protein was significantly upregulated after transfection with MRTF-A plasmid,and bcl-2-luciferase activity significantly increased after co-transfection with plasmids of MRTF-A and bcl-2-luciferase,however,the positive regulatory effect of MRTF-A was abolished after transfection with mutated bcl-2.Conclusion Mesenchymal stem cells transplantation can effectively reduce cardiomyocyte apoptosis in this rat MI model,and upregulate the expression of MRTF-A.Consequent up-regulated bcl-2 expression might be involved in the beneficial effects of BMSCs transplantation in this model.