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Objective:To explore the role and mechanism of tubastatin A (TubA) in alleviating brain injury after cardiac arrest and cardiopulmonary resuscitation (CA-CPR) by inhibiting endoplasmic reticulum stress-mediated cell apoptosis in swine.Methods:Twenty-three conventional male white swine, weighing 33-40 kg, aged 4 to 6 months, were divided into 3 groups by random number table method: sham group ( n=6), CA-CPR group ( n=9), and TubA group ( n=8). The CA-CPR swine model was established by 9 min of electrically induced CA through pacing catheter in the right ventricle and then 6 min of CPR in the CA-CPR group. The CA-CPR swine model was established by the same method, and then a dose of 4.5 mg/kg of TubA at 5 min after resuscitation was intravenously infused in the TubA group. The serum concentrations of neuron specific enolase (NSE) and S100β protein (S100β) were measured using ELISA before modeling and at 1, 2, 4 and 24 h after resuscitation. Neurological deficit score (NDS) was evaluated at 24 h after resuscitation. Thereafter, the animals were euthanized, and brain cortex tissues were harvested, and the expression levels of caspase-12 and caspase-3 were measured using immunohistochemistry. Cell apoptosis index was detected by TUNEL assay. The variables among the three groups were compared with one-way analysis of variance and the Bonferroni hoc test using SPSS software. Results:Twenty-four h after resuscitation, the serum concentrations of NSE and S100β were significantly increased, and NDS was markedly elevated in the CA-CPR and TubA groups compared with the sham group (all P<0.05). Compared with the CA-CPR group, serum concentration of NSE starting 2 h after resuscitation and serum concentration of S100β starting 1 h after resuscitation were significantly decreased in the TubA group [NSE (ng/mL): (23.1±2.0) vs. (20.2±2.0) at 2 h, (28.4±2.3) vs. (23.7±1.9) at 4 h, (32.1±2.7) vs. (26.6±2.0) at 24 h; S100β (pg/mL): (2239±193) vs. (1923±101) at 1 h, (2817±157) vs. (2360±141) at 2 h, (3384±250) vs. (2691±210) at 4 h, (3965±303) vs. (3119±260) at 24 h, all P<0.05], and NDS was markedly reduced (240±30 vs. 63±44, P<0.05). At 24 h after resuscitation, brain cortex tissue detection showed that the expression levels of caspase-12 and caspase-3 were significantly increased, and cell apoptosis index was markedly elevated in the CA-CPR and TubA groups compared with the sham group (all P<0.05). However, the expression levels of caspase-12 and caspase-3 were significantly decreased [caspase-12:(7.1±0.7) vs. (4.2±0.4); caspase-3: (13.3±1.6) vs. (7.7±0.8), all P<0.05], and cell apoptosis index was markedly reduced in the TubA group compared to the CA-CPR group [(31.1±8.6) vs. (17.3±2.2), P<0.05]. Conclusions:TubA alleviates brain injury and neurological dysfunction after CA-CPR in swine, which may be related to the inhibition of cell apoptosis mediated by endoplasmic reticulum stress.
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OBJECTIVE@#To investigate whether the acetaldehyde dehydrogenase 2 specific activator, Alda-1, can alleviate brain injury after cardiopulmonary resuscitation (CPR) by inhibiting cell ferroptosis mediated by acyl-CoA synthetase long-chain family member 4/glutathione peroxidase 4 (ACSL4/GPx4) pathway in swine.@*METHODS@#Twenty-two conventional healthy male white swine were divided into Sham group (n = 6), CPR model group (n = 8), and Alda-1 intervention group (CPR+Alda-1 group, n = 8) using a random number table. The swine model of CPR was reproduced by 8 minutes of cardiac arrest induced by ventricular fibrillation through electrical stimulation in the right ventricle followed by 8 minutes of CPR. The Sham group only experienced general preparation. A dose of 0.88 mg/kg of Alda-1 was intravenously injected at 5 minutes after resuscitation in the CPR+Alda-1 group. The same volume of saline was infused in the Sham and CPR model groups. Blood samples were collected from the femoral vein before modeling and 1, 2, 4, 24 hours after resuscitation, and the serum levels of neuron specific enolase (NSE) and S100 β protein were determined by enzyme-linked immunosorbent assay (ELISA). At 24 hours after resuscitation, the status of neurologic function was evaluated by neurological deficit score (NDS). Thereafter, the animals were sacrificed, and brain cortex was harvested to measure iron deposition by Prussian blue staining, malondialdehyde (MDA) and glutathione (GSH) contents by colorimetry, and ACSL4 and GPx4 protein expressions by Western blotting.@*RESULTS@#Compared with the Sham group, the serum levels of NSE and S100β after resuscitation were gradually increased over time, and the NDS score was significantly increased, brain cortical iron deposition and MDA content were significantly increased, GSH content and GPx4 protein expression in brain cortical were significantly decreased, and ACSL4 protein expression was significantly increased at 24 hours after resuscitation in the CPR model and CPR+Alda-1 groups, which indicated that cell ferroptosis occurred in the brain cortex, and the ACSL4/GPx4 pathway participated in this process of cell ferroptosis. Compared with the CPR model group, the serum levels of NSE and S100 β starting 2 hours after resuscitation were significantly decreased in the CPR+Alda-1 group [NSE (μg/L): 24.1±2.4 vs. 28.2±2.1, S100 β (ng/L): 2 279±169 vs. 2 620±241, both P < 0.05]; at 24 hours after resuscitation, the NDS score and brain cortical iron deposition and MDA content were significantly decreased [NDS score: 120±44 vs. 207±68, iron deposition: (2.61±0.36)% vs. (6.31±1.66)%, MDA (μmol/g): 2.93±0.30 vs. 3.68±0.29, all P < 0.05], brain cortical GSH content and GPx4 expression in brain cortical was significantly increased [GSH (mg/g): 4.59±0.63 vs. 3.51±0.56, GPx4 protein (GPx4/GAPDH): 0.54±0.14 vs. 0.21±0.08, both P < 0.05], and ACSL4 protein expression was significantly decreased (ACSL4/GAPDH: 0.46±0.08 vs. 0.85±0.13, P < 0.05), which indicated that Alda-1 might alleviate brain cortical cell ferroptosis through regulating ACSL4/GPx4 pathway.@*CONCLUSIONS@#Alda-1 can reduce brain injury after CPR in swine, which may be related to the inhibition of ACSL4/GPx4 pathway mediated ferroptosis.
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Male , Animals , Swine , Phospholipid Hydroperoxide Glutathione Peroxidase , Ferroptosis , Brain Injuries , Glutathione , Cardiopulmonary Resuscitation , Ligases , IronABSTRACT
Objective:To evaluate the effect of Alda-1 on ferroptosis in cardiomyocytes after cardiac arrest and cardiopulmonary resuscitation in swine.Methods:Twenty-two healthy male white swine, weighing 35-43 kg, were divided into 3 groups using a random number table method: sham operation group (group S, n=6), cardiac arrest-cardiopulmonary resuscitation group (group CA-CPR, n=8) and Alda-1 group ( n=8). The animals only underwent the general preparation in group S, and the swine model of cardiac arrest and cardiopulmonary resuscitation was developed by 8 min of electrically induced cardiac arrest through the pacing catheter in the right ventricle followed by 8 min of cardiopulmonary resuscitation in CA-CPR and Alda-1 groups.Alda-1 0.88 mg/kg was intravenously injected at 5 min after resuscitation in group Alda-1, and the equal volume of vehicle was administered instead in the other two groups.Stroke volume (SV) and global ejection fraction (GEF) were measured using PiCCO before developing the model and at 1, 2 and 4 h after resuscitation (T 0-3). Venous blood samples were collected from the femoral vein to measure the concentrations of serum cardiac troponin (cTnI) by enzyme-linked immunosorbent assay at T 0-3, and at 24 h after resuscitation (T 4). The animals were then sacrificed, and myocardial tissues in the left ventricle were harvested to measure the expression of acyl-CoA synthetase long-chain family member 4 (ACSL4) and glutathione peroxidase 4 (GPX4) (by Western blot), iron deposition (by Prussian blue staining), 4-hydroxy-2-nonenal (4-HNE) content (by enzyme-linked immunosorbent assay), and malondialdehyde (MDA) and glutathione (GSH) contents (by colorimetry). Results:Compared with group S, SV and GEF were significantly decreased at T 1-3, the serum concentrations of cTnI were increased at T 1-4, myocardial ACSL4 expression was up-regulated, GPX4 expression was down-regulated, iron deposition and contents of 4-HNE and MDA were increased, and the content of GSH was decreased in CA-CPR and Alda-1 groups ( P<0.05). Compared with group CA-CPR, SV and GEF were significantly increased at T 2-3, the serum concentrations of cTnI were decreased at T 3-4, myocardial ACSL4 expression was down-regulated, GPX4 expression was up-regulated, iron deposition and contents of 4-HNE and MDA were decreased, and the content of GSH was increased in group Alda-1 ( P<0.05). Conclusions:Alda-1 can alleviate myocardial injury after cardiac arrest and cardiopulmonary resuscitation in swine and further improve cardiac dysfunction, and the mechanism may be related to inhibition of cell ferroptosis.
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Objective@#To explore the correlation of health literacy and mobile phone use dependence with psychopathological symptoms in middle school students.@*Methods@#22 628 middle school students in Shenyang, Bengbu, Xinxiang, Ulanqab, Chongqing and Yangjiang were enrolled by multistage cluster sampling method from November 2015 to January 2016. Chinese Adolescent Interactive Health Literacy Questionnaire (CAIHLQ), Self-rating Questionnaire for Adolescent Problematic Mobile Phone Use (SQAPMPU) and Multidimensional Sub-health Questionnaire of Adolescents (MSQA) were applied to acquire basic characteristics, health literacy, mobile phone use dependence and psychopathological symptoms of subjects. Subjects were classified into three groups, low level (<P25), medium level (P25-P75) and high level (>P75), according to the percentile of the questionnaire score. Multivariate logistic regression model was used to analyze the correlation of health literacy, mobile phone with psychopathological symptoms.@*Results@#The students were (15.4±1.8) years old with 10 990 boys (48.6%). The score of health literacy of students were (104.1±18.7) points. The rate of mobile phone use dependence was 25.4% (5 752/22 628) and the rate of psychopathological symptoms was 29.1% (6 581/22 628). Compared with high health literacy level, medium and low health literacy levels were related to psychopathological symptoms, with OR (95%CI) about 2.30 (2.10-2.52) and 5.40 (4.89-5.97), respectively. Compared with mobile phone use independence, mobile phone use dependence was related to psychopathological symptoms, with OR (95%CI) about 3.60(3.37-3.85). The highest rate of psychopathological symptoms occurred in students with mobile phone use dependence and low health literacy level [68.0% (1 345/1 977)], with OR (95%CI) about 19.59 (17.07-22.48).@*Conclusion@#Health literacy and mobile phone use dependence are related factors of psychopathological symptoms in middle school students.
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Objective@#The purpose of this study was to examine the association between health literacy (HL) and the incidence of injuries in middle school students in China.@*Methods@#From November 2013 to February 2014, middle school students in Liaoning, Henan, and Guangdong provinces, Chongqing municipality, Xinjiang Uygur Autonomous Region were selected by using cluster sampling method. A total of 27 044 questionnaires were issued and 25 378 questionnaires were valid. According to the Chinese Adolescent Interactive Health Literacy Questionnaire (CAIHLQ), scores were conducted a tripartite group. Multiple logistic regression analyses were conducted to examine the association between HL and injuries.@*Results@#The scores of CAIHLQ were 103.55±23.91 among 25 378 students. The detection rate of self-injuries and unintentional injuries was 27.5% (n=6 971) and 47.8% (n=12 119). Compared with the students with high HL, the OR (95%CI) values of self-injuries among students with low and middle HL were 2.56 (2.35-2.79) and 1.96 (1.81-2.12). Compared with the students with high HL, the OR (95%CI) values of unintentional injuries among students with low and middle HL were 1.63 (1.53-1.73) and 1.47 (1.37-1.58).@*Conclusion@#The risk of self-injuries and unintentional injuries of middle school students is related to HL.
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Objective To investigate the interaction between health literacy,mobile phone dependence and unintentional injuries in middle school students,and to provide guidance for prevention on unintentional injuries in adolescents.Methods From November 2015 to January 2016,a questionnaire survey was conducted among 22 628 middle school students in Shenyang of Liaoning province,Bengbu of Anhui province,Xinxiang of Henan province,Ulanqab of Inner Mongolia Autonomous Region,Chongqing and Yangjiang of Guangdong province.Chinese Adolescent Interactive Health Literacy Questionnaire (CAIHLQ),Self-rating Questionnaire for Adolescent Problematic Mobile Phone Use (SQAPMPU),and Unintentional Injuries Assessment Scale and demographic variables were used to measure the health literacy,mobile phone dependence and unintentional injuries among the Chinese middle school students.Results The detection rates of mobile phone dependence and unintentional injuries were 25.4％ and 46.7％,respectively.The rates of unintentional injuries of middle school students with mobile phone dependence and with low,medium and high health literacy were 53.6％,44.4％ and 48.8％,48.1％,41.7％.Factors as mobile phone dependence,low and middle health literacy were positively related to unintentional injuries (OR=1.452,1.196,1.364).However,the multiplicative interaction between mobile phone dependence and health literacy on unintentional injuries was noticed significant (OR=1.217,95％CI:1.041-1.422).Conclusions Our results showed that the prevalence of unintentional injuries was relatively high in middle school students.Health literacy and mobile phone dependence seemed related to unintentional injuries.Interaction between health literacy and mobile phone dependence on unintentional injuries appeared significant.
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Objective To investigate the interaction between health literacy,mobile phone dependence and unintentional injuries in middle school students,and to provide guidance for prevention on unintentional injuries in adolescents.Methods From November 2015 to January 2016,a questionnaire survey was conducted among 22 628 middle school students in Shenyang of Liaoning province,Bengbu of Anhui province,Xinxiang of Henan province,Ulanqab of Inner Mongolia Autonomous Region,Chongqing and Yangjiang of Guangdong province.Chinese Adolescent Interactive Health Literacy Questionnaire (CAIHLQ),Self-rating Questionnaire for Adolescent Problematic Mobile Phone Use (SQAPMPU),and Unintentional Injuries Assessment Scale and demographic variables were used to measure the health literacy,mobile phone dependence and unintentional injuries among the Chinese middle school students.Results The detection rates of mobile phone dependence and unintentional injuries were 25.4％ and 46.7％,respectively.The rates of unintentional injuries of middle school students with mobile phone dependence and with low,medium and high health literacy were 53.6％,44.4％ and 48.8％,48.1％,41.7％.Factors as mobile phone dependence,low and middle health literacy were positively related to unintentional injuries (OR=1.452,1.196,1.364).However,the multiplicative interaction between mobile phone dependence and health literacy on unintentional injuries was noticed significant (OR=1.217,95％CI:1.041-1.422).Conclusions Our results showed that the prevalence of unintentional injuries was relatively high in middle school students.Health literacy and mobile phone dependence seemed related to unintentional injuries.Interaction between health literacy and mobile phone dependence on unintentional injuries appeared significant.
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Objective@#To examine the relationship between the prevalence of self-reported myopia and outdoor activities among middle school students and to explore the influence factors of the self-reported myopia.@*Methods@#A total of 12 979 participants were recruited from junior and senior middle school students in in Shenzhen, Nanchang, Zhengzhou and Shenyang by random cluster sampling method between December 2015 and March 2016. All participants completed an anonymous questionnaire to collect the information of demographic characteristics, self-reported myopia, outdoor activities, etc. 12 603 out of 12 979 copies of questionnaire were valid. The prevalence of self-reported myopia was compared among middle school students with different characteristics. Logistic regression models were used to analyze the relationship between myopia and outdoor activities.@*Results@#The prevalence of self-reported myopia among middle school students was 69.6% (8 766/12 603); which was separately 52.1% (1 216/2 335) in seventh grader, 61.6% (1 459/2 369) in eighth grader, 69.0%(1 470/2 129) in ninth grader, 80.0% (1 812/2 265) in freshmen, 79.4% (1 622/2 042) in sophomore, and 81.1%(1 187/1 463) in junior. The prevalence of self-reported myopia showed an increasing trend with the increase of grade (χ2=639.67, P<0.001). The prevalence of self-reported myopia was separately 63.5%(4 927/7 756) in non-myopic parents group, 78.0%(2 664/3 415)in either myopic parent group, and 82.1%(1 175/1 432) in both myopic parents group(χ2=328.28, P<0.001). Outdoor activities were associated with self-reported myopia. Binary logistic regression analysis showed that the risk of self-reported myopia was significantly increased by always staying at home in extracurricular time among the middle school students (OR=1.58, 95%CI: 1.36-1.82). The risk of self-reported myopia were significantly decreased by always physical exercise and recreational activities after school among middle school students: the ORs were separately 0.67 (95%CI: 0.57-0.78) for physical exercise and 0.77 (95%CI: 0.64-0.92) for recreational activities. After stratified analysis by the parents' myopia status, in non-myopic parents group, exercise and recreational activities after school among middle school students decreased the risk of myopia: the ORs were separately 0.68 (95%CI: 0.55-0.82) for physical exercise and 0.76 (95%CI: 0.61-0.95) for recreational activities; in either myopic parent group, OR(95%CI) were separately 0.65 (0.47-0.90) and 0.68 (0.47-0.98).@*Conclusion@#Outdoor activities was negatively associated with self-reported myopia among middle school students. However, the parents' myopia status may affect the protective effect.
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Objective@#To explore the relationship between adverse experience in childhood, social support, and physical and psychological sub-health status among middle school students in 3 cities in China.@*Methods@#15 278 adolescents were selected as subjects from 20 junior and senior middle schools located in 3 cities of China by stratified cluster sampling method. The survey collected the demographic information, ACEs, social support and physical-psychological status. A total of 14 820 valid questionnaires were retained for analysis. We assessed ACE score (count of six categories of childhood adversity), social support (adolescent social support questionnaire), and the prevalence of two outcomes: physiological and psychological sub-health status. Logistic regression was used to analyze the relationship between adverse childhood experiences, social support, and physiological and psychological sub-health status.@*Results@#The prevalence of physiological and psychological sub-health status were 26.4% (3 917/14 820) and 24.1%(3 572/14 820), respectively. A total of 89.4% (13 247/14 820) reported at least 1 adverse childhood experiences. The rates of physiological and psychological sub-health status were higher among girls (28.1%(2 092/7 443), 26.0%(1 932/7 443)) than boys (24.7%(1 825/7 377), 22.2%(1 640/7 377)). Among adolescents without ACEs, the rate of physiological and psychological sub-health status were 15.4%(243/1 573) and 10.4%(163/1 573), for those with 5-6 ACEs, the rate were 40.9%(636/1 556) and 43.6%(678/1 556). Among adolescents with higher social support, the rate of physiological and psychological sub-health status were 19.9%(724/3 635) and 13.0%(474/3 635) for those with lower social support, the rate of physiological and psychological sub-health status were 35.9%(1 403/3 913) and 39.0%(1 528/3 913). The rates of physiological and psychological sub-health status were higher with more ACE exposure or less social support. At each level of ACE exposure, physiological and psychological sub-health status were less in those with greater social support. For example, among adolescents reporting 5-6 ACEs, those in the lowest tertile of social support increased the risk of physiological sub-health status than those in the highest tertile (adjusted prevalence ratio (95%CI)=1.79 (1.23-2.56)); for those reporting no ACEs, the ratio was 3.04 (1.91-4.83). Among adolescents reporting 5-6 ACEs, those in the lowest tertile of social support increased the risk of psychological sub-health status than those in the highest tertile (adjusted prevalence ratio (95%CI)=3.77 (2.57-5.52)); for those reporting no ACEs, the ratio was 3.97(2.33-6.76).@*Conclusion@#The findings suggest that ACEs should be considered as risk factors for physiological and psychological sub-health status among middle school students. Across a range of exposures to ACEs, less social support was associated with more physiological and psychological sub-health status. Identifying those with ACE exposure who also have lower social support could be used to improve the health of adolescents.
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Objective@#The aim of this study was to describe the distribution of neck-shoulder symptoms among middle school students, and to explore its influence factors.@*Methods@#A cross-sectional survey was conducted on 24 middle schools in Shenyang, Zhengzhou and Shenzhen by purposive sampling method. In each middle school, 3 to 4 classes were selected from each grade all the students in the selected class would be recruited to the survey to investigate the demographic characteristics, neck-shoulder symptoms, physical exercise time, academic stress, screen behavior, sedentary behavior and other information by questionnaire. A total of 10 566 questionnaires were issued and 10 270 valid questionnaires were withdrawn. The prevalence of neck-shoulder symptoms among students were compared by different characteristics. Logistic regression models were applied to examine influencing factors associated with neck-shoulder symptoms.@*Results@#The prevalence of neck-shoulder symptoms among middle school students was 19.2% (1 968/10 270), while it was 22.6% (1 137/5 039) among girls and 15.9% (831/5 231) among boys; the difference showed statistical significance (P<0.001). The prevalence of neck-shoulder symptoms was separately 13.3% (253/1 901) in seventh grade, 16.8% (326/1 942) in eighth grade, 18.5% (299/1 617) in ninth grade, 21.8% (417/1 915) in sophomore, 21.4% (345/1 611) in junior, 25.5% (328/1 284) in senior; the difference showed statistical significance (P<0.001). The multivariate logistic regression analysis showed that in the last 3 months, students who always playing mobile phone ≥40 min continuously (OR=4.66, 95%CI: 3.95-5.49), watching TV ≥40 min continuously (OR=4.01, 95%CI: 3.39-4.73), using computer ≥40 min continuously (OR=3.61, 95%CI: 3.09-4.23), doing homework ≥60 min continuously (OR=3.25, 95%CI: 2.79-3.79), the average daily sitting time ≥10 h (OR=4.95, 95%CI: 4.25-5.77), and always sitting ≥90 min continuously (OR=5.18, 95%CI: 4.42-6.06) were risk factors of neck-shoulder symptoms.@*Conclusion@#The prevalence of neck-shoulder symptoms was high among middle school students in China, especially girls in senior grades. Long time, high frequency video behaviors and sedentary behaviors were related to the occurrence of neck-shoulder symptoms among middle school students.