AIM:To investigate the role and mechanisms of p21 activated kinase 1(Pak1)in myocardial met-abolic reprogramming(MR)in diabetes mellitus(DM)mice and its protective effects on cardiomyocytes.METHODS:Pak1flox/flox(Pak1f/f)mice and cardiomyocyte-specific Pak1 knockout(Pak1CKO)mice were randomly divided into 4 groups(n=6 per group):Pak1f/f group,Pak1f/f+DM group,Pak1CKO group,and Pak1CKO+DM group.Diabetes was induced by in-traperitoneal injection of streptozotocin.Cardiac function was evaluated by echocardiography 6 weeks after successful mod-eling.Ventricular myocardium was harvested after euthanasia.Myocardial pathological changes and lipid accumulation were assessed by HE staining and oil red O staining.Protein expression levels of Pak1,p-Pak1,peroxisome proliferator-activated receptor α(PPARα),PPARγ,lipoprotein lipase(LPL),carnitine palmitoyltransferase 1(CPT1),scavenger receptor B2(SCARB2/CD36),fatty acid binding protein 3(FABP3),pyruvate dehydrogenase kinase 4(PDK4)and the ratio of phosphorylated pyruvate dehydrogenase E1α subunit(p-PDHA1)to PDHA1 were determined by Western blot.The mRNA expression levels of diacylglycerol acyltransferase 1/2(DGAT1/2)were detected by RT-qPCR.RESULTS:Compared with Pak1f/f group,both Pak1f/f+DM and Pak1CKO groups showed significantly decreased left ventricular ejection fraction(EF)and fractional shortening(FS),as well as increased left ventricular end-diastolic volume(LV Vold)and end-systolic volume(LV Vols)(P<0.01).Significant myocardial pathological damage with excessive lipid accumulation was observed.Myocardial p-Pak1 and Pak1 protein expression decreased(P<0.01),while PPARα,PPARγ,CPT1,LPL,CD36,FABP3,and PDK4 protein expression significantly increased(P<0.01),along with elevated p-PDHA1/PDHA1 ratio(P<0.01).mRNA expression levels of DGAT1 and DGAT2 were significantly reduced(P<0.01).The Pak1CKO+DM group showed the same trend as the Pak1f/f+DM group but with greater severity;compared with the Pak1f/f+DM group,the Pak1CKO+DM group still showed significant differences in all indicators except EF,FS,and LVVold(P<0.05 or P<0.01).CONCLUSION:Myocardial Pak1 protein expression is suppressed in diabetic mice,which mediates MR through activation of the PPARα/γ signaling pathway,resulting in increased myocardial fatty acid uptake and utiliza-tion while reducing glucose oxidation capacity.This leads to lipid accumulation in cardiomyocytes,myocardial damage,and cardiac systolic and diastolic dysfunction.

AIM:To investigate the role and mechanisms of p21 activated kinase 1(Pak1)in myocardial met-abolic reprogramming(MR)in diabetes mellitus(DM)mice and its protective effects on cardiomyocytes.METHODS:Pak1flox/flox(Pak1f/f)mice and cardiomyocyte-specific Pak1 knockout(Pak1CKO)mice were randomly divided into 4 groups(n=6 per group):Pak1f/f group,Pak1f/f+DM group,Pak1CKO group,and Pak1CKO+DM group.Diabetes was induced by in-traperitoneal injection of streptozotocin.Cardiac function was evaluated by echocardiography 6 weeks after successful mod-eling.Ventricular myocardium was harvested after euthanasia.Myocardial pathological changes and lipid accumulation were assessed by HE staining and oil red O staining.Protein expression levels of Pak1,p-Pak1,peroxisome proliferator-activated receptor α(PPARα),PPARγ,lipoprotein lipase(LPL),carnitine palmitoyltransferase 1(CPT1),scavenger receptor B2(SCARB2/CD36),fatty acid binding protein 3(FABP3),pyruvate dehydrogenase kinase 4(PDK4)and the ratio of phosphorylated pyruvate dehydrogenase E1α subunit(p-PDHA1)to PDHA1 were determined by Western blot.The mRNA expression levels of diacylglycerol acyltransferase 1/2(DGAT1/2)were detected by RT-qPCR.RESULTS:Compared with Pak1f/f group,both Pak1f/f+DM and Pak1CKO groups showed significantly decreased left ventricular ejection fraction(EF)and fractional shortening(FS),as well as increased left ventricular end-diastolic volume(LV Vold)and end-systolic volume(LV Vols)(P<0.01).Significant myocardial pathological damage with excessive lipid accumulation was observed.Myocardial p-Pak1 and Pak1 protein expression decreased(P<0.01),while PPARα,PPARγ,CPT1,LPL,CD36,FABP3,and PDK4 protein expression significantly increased(P<0.01),along with elevated p-PDHA1/PDHA1 ratio(P<0.01).mRNA expression levels of DGAT1 and DGAT2 were significantly reduced(P<0.01).The Pak1CKO+DM group showed the same trend as the Pak1f/f+DM group but with greater severity;compared with the Pak1f/f+DM group,the Pak1CKO+DM group still showed significant differences in all indicators except EF,FS,and LVVold(P<0.05 or P<0.01).CONCLUSION:Myocardial Pak1 protein expression is suppressed in diabetic mice,which mediates MR through activation of the PPARα/γ signaling pathway,resulting in increased myocardial fatty acid uptake and utiliza-tion while reducing glucose oxidation capacity.This leads to lipid accumulation in cardiomyocytes,myocardial damage,and cardiac systolic and diastolic dysfunction.

BACKGROUND:Studies have shown that atorvastatin can up-regulate the expression of heme oxygenase-1 and enhance the anti-inflammation and anti-oxidative damage ability of cells.However,whether atorvastatin can regulate macrophage polarization,inhibit inflammation and reduce cholesterol accumulation by inducing heme oxygenase-1 expression remains unclear. OBJECTIVE:To investigate the effect of atorvastatin on polarization,inflammation and cholesterol content of oxidized low-density lipoprotein stimulated RAW264.7 macrophages by inducing heme oxygenase-1 expression and its related mechanism. METHODS:Firstly,RAW264.7 cells were randomly divided into six groups and incubated with different concentrations of atorvastatin for 24 hours.The expression of heme oxygenase-1 protein and cell activity were detected to explore the optimal dose of atorvastatin for subsequent studies.RAW264.7 cells were randomly divided into control group,atorvastatin group and heme oxygenase-1 inhibition group.Cells were preincubated with pure medium,atorvastatin 20 μmol/L and atorvastatin 20 μmol/L + zinc protoporphyrin IX 10 μmol/L for 24 hours,and then oxidized low-density lipoprotein 50 mg/L was added for 48 hours.The polarization of macrophages was detected by flow cytometry.The secretion of inflammatory factors such as transforming growth factor β,interleukin 10,interleukin 1β,and tumor necrosis factor α was detected by ELISA.The expression levels of heme oxygenase-1,LC3II,LC3I,P62,PPARγ and ABCA1 were detected by western blot assay.The intracellular cholesterol content was measured with the oxidose method and the accumulation degree of intracellular lipid droplets was evaluated by oil red O staining. RESULTS AND CONCLUSION:(1)Atorvastatin could induce the expression of heme oxygenase-1 protein in macrophages in a dose-dependent manner.(2)Oxidized low-density lipoprotein could induce macrophages to polarize towards M1,secrete proinflammatory factors,and increase the accumulation of intracellular cholesterol.(3)Compared with the control group,the heme oxygenase-1 protein expression of macrophages was increased after atorvastatin intervention,and the cells turned to M2-type polarization and mainly secreted anti-inflammatory factors such as transforming growth factor-β and interleukin-10.PPARγ,ABCA1,LC3II/I and other signal molecules reflecting cholesterol efflux and autophagy increased,and the contents of intracellular cholesterol and lipid droplets decreased significantly(P<0.05).(4)The heme oxygenase-1 inhibition group treated with zinc protoporphyrin IX significantly reversed the above changes in the atorvastatin group.(5)The results have shown that atorvastatin may promote the polarization of macrophages stimulated by oxidized low-density lipoprotein to M2 type and inhibit inflammation by up-regulating the expression of heme oxygenase-1 and by up-regulating PPARγ/ABCA1 signaling pathway and enhancing autophagy.Atorvastatin can increase the outflow of intracellular cholesterol and reduce the accumulation of intracellular lipids.

Objective:To summarize the repair experience and clinical characteristics of cleft lip and palate in Tibet.Methods:From August 2020 to August 2021, patients with cleft lip and palate treated during the period of corresponding author aid to Tibet were included. The American Association of Anesthesiologists (ASA) was used to assess the anesthesia risk before operation. For the cleft lip repair, Millard rotation advancement technique and reconstruction of nasal-labial muscle tension lines group were used. Modified Von Langenbeck technique was adopted for cleft palate repair. The amount of blood loss and short-term postoperative complications such as hematoma, infection, wound dehiscence, flap circulation disorder and palatal fistula were counted. The Likert five-point scale was used to evaluate the surgical satisfaction of patients with cleft lip and the audiometric evaluation method was used to assess the improvement of cleft palate speech. The data were statistically analyzed by SPSS 20.0 software. The measurement data were expressed by Mean±SD. P<0.05 was considered statistically significant. Results:A total of 46 patients were included, including 26 males and 20 females, aged from 2 to 57 years, with a median of 32 years. There were 36 patients with cleft lip or secondary deformities after cleft lip surgery and 10 patients with cleft palate. Among the 46 cases, ASA Ⅰ was 39, and ASA Ⅱ, ASA Ⅲ were 5 and 2, respectively. There were 5 patients with congenital heart disease, including 2 cases of patent ductus arteriosus and 3 cases of patent foramen ovale. Pulmonary hypertension was found in 8 cases. The average blood loss during the repair of cleft lip and cleft palate was 30 ml and 50 ml, respectively. No postoperative complications such as hematoma, infection, wound dehiscence and palatal fistula occurred. The patients were followed up for 6 to 24 weeks, with an average of 8 weeks. The crista philtra point on the affected side of the patients with cleft lip was fully lowered and was basically symmetrical with the healthy side. The bilateral nostril symmetry was significantly improved compared with that before surgery, and the nasal columella was in the middle. The cleft palate was all closed and the mobility of soft palate was improved. All patients were satisfied with the surgical results, with an average satisfaction score of 4.5. The mean preoperative speech score of patients undergoing cleft palate repair was 1.4 ± 0.5 and the postoperative was 4.3 ± 0.5 ( t=16.16, P<0.001). Conclusion:Compared with the plain area, patients with cleft lip and palate in Tibet have the characteristics such as delayed treatment, the complex of deformity and often combined with other congenital organ malformation. In order to get good result and higher satisfaction rate, it is recommended to use classical surgical technique for the above deformity repair. It is also important to carefully evaluate the risk of general anesthesia.

Objective:To summarize the repair experience and clinical characteristics of cleft lip and palate in Tibet.Methods:From August 2020 to August 2021, patients with cleft lip and palate treated during the period of corresponding author aid to Tibet were included. The American Association of Anesthesiologists (ASA) was used to assess the anesthesia risk before operation. For the cleft lip repair, Millard rotation advancement technique and reconstruction of nasal-labial muscle tension lines group were used. Modified Von Langenbeck technique was adopted for cleft palate repair. The amount of blood loss and short-term postoperative complications such as hematoma, infection, wound dehiscence, flap circulation disorder and palatal fistula were counted. The Likert five-point scale was used to evaluate the surgical satisfaction of patients with cleft lip and the audiometric evaluation method was used to assess the improvement of cleft palate speech. The data were statistically analyzed by SPSS 20.0 software. The measurement data were expressed by Mean±SD. P<0.05 was considered statistically significant. Results:A total of 46 patients were included, including 26 males and 20 females, aged from 2 to 57 years, with a median of 32 years. There were 36 patients with cleft lip or secondary deformities after cleft lip surgery and 10 patients with cleft palate. Among the 46 cases, ASA Ⅰ was 39, and ASA Ⅱ, ASA Ⅲ were 5 and 2, respectively. There were 5 patients with congenital heart disease, including 2 cases of patent ductus arteriosus and 3 cases of patent foramen ovale. Pulmonary hypertension was found in 8 cases. The average blood loss during the repair of cleft lip and cleft palate was 30 ml and 50 ml, respectively. No postoperative complications such as hematoma, infection, wound dehiscence and palatal fistula occurred. The patients were followed up for 6 to 24 weeks, with an average of 8 weeks. The crista philtra point on the affected side of the patients with cleft lip was fully lowered and was basically symmetrical with the healthy side. The bilateral nostril symmetry was significantly improved compared with that before surgery, and the nasal columella was in the middle. The cleft palate was all closed and the mobility of soft palate was improved. All patients were satisfied with the surgical results, with an average satisfaction score of 4.5. The mean preoperative speech score of patients undergoing cleft palate repair was 1.4 ± 0.5 and the postoperative was 4.3 ± 0.5 ( t=16.16, P<0.001). Conclusion:Compared with the plain area, patients with cleft lip and palate in Tibet have the characteristics such as delayed treatment, the complex of deformity and often combined with other congenital organ malformation. In order to get good result and higher satisfaction rate, it is recommended to use classical surgical technique for the above deformity repair. It is also important to carefully evaluate the risk of general anesthesia.

Objective: To assess the quality of data of intervention in population at high risk for HIV/AIDS, especially in female sex workers (FSWs) and men who have sex with men (MSM), in China during 2014-2018, for the purpose of improving intervention data quality. Methods: Data accuracy was evaluated by sampling monthly reported intervention data and comparing the consistency of the information recorded in national HIV/AIDS prevention and treatment information system to original paper records. Data authenticity was assessed by visiting intervention sites and interviewing owners, manager and/or target groups at sites. The assessment results of both national level and provincial level were summarized by year and analyzed with descriptive statistical method. The data quality problems recognized by assessments were summed up. Results: The annual concordance rate of the data recorded in information system to paper records was 94.6%(17 671/18 673) in provincial level assessment and 79.4%(558/703) in national level assessment. Up to 81.6%(8 617/10 559) and 84.4% (249/295) of all sampled intervention sites were annually evaluated as "good" in provincial and state level assessments respectively. The assessment found that the intervention data in original paper records were not completely consistent to that recorded in the information system, the deficiency of ability on intervention data management, and the insufficient coverage and effect of intervention service influenced the intervention data quality. Conclusions In general, the accuracy and authenticity of intervention data were fine in China during 2014-2018. Intervention data quality can be improved through measures of enhancing data quality management, strengthening training for the prevention and intervention in FSWs and MSM, and providing high- quality intervention service.

Objective: To explore the methods of establishing and maintaining community injecting drug user (IDU) cohort. Methods: From June 2014 to June 2017, a community survey was conducted on basis of local needle and syringe exchange site to recruit 200 HIV sero-negative IDU for a prospective cohort study in Longyang district of Baoshan city, Yunan province. Follow-up was carried out every six month to investigate high risk drug use behavior and sexual behavior, and blood samples were collected from them for the tests of HIV and HCV serum antibodies. The cohort would be opened every 12 months to replenish the cohort to 200 subjects. Results: The follow up was conducted for 3 years in 229 IDUs. Cohort follow-up rate was 93.0% (213/229) for 6 months, 92.1% (211/229) for 12 months, 91.7% (200/218) for 18 months, 87.2% (190/218) for 24 months, 86.0% (172/200) for 30 months and 86.0% (172/200) for 36 months. Conclusion The community IDU cohort has a high follow-up rate.

Objective: To assess risk of HIV infection and its risk factors among men who have sex with men (MSM) in Beijing, China. Methods: We conducted a cross-sectional online survey in October, 2017. Inclusion criteria of participants were: aged 18 year or more; resided in Beijing; conducted homosexual activities in past six months; self-reported HIV status as negative or unclear. Demographic information, HIV test history, social media use, and high-risk sexual behaviors were collected by a self-reporting questionnaire, and a HIV risk assessment tool was used to assess HIV risk of MSM, 5 388 particpants were finally enrolled in the study. Logistic regression model was used to analyze factors associated with risk of HIV infection. Results: Of the total 5 388 participants, most were 18-29 years old (64.35%), and the proportion of medium and high HIV risk score was 40.36%. The odds of medium and high HIV risk score among MSM who logged onto the app 1-20 times per week and>20 times per week were higher comparing with those who logged onto the app<1 time per week (OR=1.22, 95%CI: 1.02-1.46; OR=1.69, 95%CI: 1.38-2.06, respectively); MSM who completed college or higher education had lower probability of medium and high HIV infection risk, comparing with those who only had high school education level (OR=1.25, 95%CI:1.09-1.43) or junior or below education level (OR: 1.27, 95%CI: 1.05-1.53); MSM who did not conduct HIV test in past year had lower risk of medium and high HIV infection risk comparing with MSM who conducted HIV test in past year (OR=0.87, 95%CI: 0.77-0.99), and those who reported their HIV infection status unclear had higher probability of medium and high HIV infection risk than MSM who reported their HIV infection status negative (OR: 1.63, 95%CI: 1.44-1.86). Conclusion The proportion of MSM who were in medium and high HIV infection risk score was high in Beijing. Lower level of education, high frequency of social media use, conducted HIV test in past year, and unclear of their own HIV infection status were associated with medium and high level of HIV infection risk.

Objective To analyze the problems in the network direct reporting of information about intervention service conducted in population at high risk for HIV infection in China during 2013-2014,and provide evidence for the improvement of the network direct reporting of the intervention information.Methods The wrong records of the intervention service in population at high-risk were collected from national AIDS prevention and treatment information system.The wrong records,including those found at county (district) level and those found at state level,were analyzed with descriptive statistical method.Results A total of 1 066 wrong records were found during 2013-2014,and average annual wrong record rate was ＜0.1％.Up to 71.3％ (760/1 066) of wrong records occurred in the first half year.The wrong records in eastern,central and western areas accounted for 14.9％ (159/1 066),22.6％ (241/1 066) and 62.5％ (666/1 066) of the total respectively.More wrong records were found in the intervention information for men who have sex with men and injecting drug users than in those for female sex workers.Among the total wrong records,86.4％ (921/ 1 066) were found at county level and 13.6％ (145/1 066) were found at state level.The wrong records were mainly "annual number of persons receiving the first HIV test" and "annual number of persons covered by intervention".Common causes of wrong records were underreporting and delay,staff fault,miscalculation and misunderstanding.Conclusion In general,the wrong record rate in intervention information for population at high risk for HIV infection reported directly through network was low in China.It is necessary to strengthen the recording of the intervention service,the quality control of statistics and network direct reporting and staff training to improve the quality of reported data of intervention service.

OBJECTIVEBenign epilepsy with centro-temporal spikes (BECTs) is a common idiopathic partial epileptic syndrome in childhood, which often affect the pre-school and school-age children and a considerable proportion have comorbidity including lower academic achievement and cognitive impairment. Few studies involved the psychocognitive assessment in such a drug-treatable epileptic syndrome especially in the newly diagnosed and medications-naive group. This study aimed to investigate the cognitive characteristics of children with newly onset BECTs before treatment.

METHODForty-one outpatients with newly diagnosed BECTs who visited the Clinic during the periods from October 2012 to May 2014 before the medications against epilepsy and 41 healthy controls recruited from regular school in Beijing during the period from July 2013 to March 2014, who matched in age and gender underwent battery testing by computerized cognitive testing in epilepsy (CCTE). The BECTs group included 41 children, 20 boys and 21 girls, mean age (8.2 ± 1.7) years, the age of onset of epilepsy 4.5-11.5 years (the age of onset <8 years in 25 cases, ≥ 8 years in 16 cases). The cognitive characteristics and associated factors were analyzed. The primary data including correct answer numbers and reaction times were analyzed by independent sample t-test between the two groups of children with BECTs and healthy controls based on SPSS 18.0 statistical software.

RESULTRaw data of 9 tasks' scores collected from BECTs and healthy control children were continuous variables in accordance with normal distribution. BECTs children performed significantly worse than controls in choice reaction time ((618+158) vs. (524+254) ms), three-dimensional mental rotation (11 ± 10 vs. 18 ± 12) and visual tracing (10 ± 6 vs.15 ± 6), t=2.01, 3.03 and 3.47, P<0.05, <0.01 and <0.001, respectively.While other 6 tasks showed no significant difference between the two groups (P>0.05 for all comparisons). BECTs boys performed significantly worse than girls on simple substraction tasks compared with standard nine score ((4.7 ± 1.5) vs. (5.6 ± 1.2), t=-2.24, P<0.05). Other 8 tasks showed no significant difference between boys and girls (P>0.05 for all comparisons). Other 9 tasks showed no significant differences between the two groups of BECTs children whose age of onset was before 8 years and those who started seizure ≥ 8 years (P all >0.05). The standard nine scores of simple substraction from the three BECTs groups of dominance sides of spikes and waves during NREM showed significant difference (P<0.05). BECTs children with bilateral discharges performed significantly worse than the other two groups dominantly right or left discharges (4.7 ± 1.2 vs. 6.0 ± 1.2 vs. 4.9 ± 1.4, P all <0.05). There was no significant difference between the two groups with right and left side dominance discharges (P>0.05). Other 8 tasks showed no significant differences among the three groups (P>0.05 for all comparisons).

CONCLUSIONAlthough EEG discharges index below 50% during NREM period, while newly diagnosed BECTs children before treatment with medications against epilepsy performed poorer on tasks of choice reaction time, three-dimensional mental rotation, and visual tracing. The two factors of male and bilateral discharges during NREM period correlate with dysfunction of simple subtraction, the mechanism needs further study and the cognitive function of epilepsy children should be evaluated and followed up, in order to provide psychologic baseline data for persistent cognitive disturbance.

Beijing ; Case-Control Studies ; Child ; Child, Preschool ; Cognition ; Cognition Disorders ; diagnosis ; Comorbidity ; Epilepsy, Rolandic ; physiopathology ; Female ; Humans ; Male ; Reaction Time ; Seizures ; physiopathology