1.Role of the iNOS/IRS1/AKT/GSK-3β signaling pathway in chronic intermittent hypoxia-induced insulin resistance
Meina Jin ; Xueli Zhou ; Haibo Li ; Wei Bai ; Chuxuan Jia ; Li Gao ; Lijue Ren ; Qingyu Chen ; Rui Wang ; Hua Li ; Cuiying Wei
Acta Universitatis Medicinalis Anhui 2025;60(2):210-217
Objective :
To pathological changes and inducible nitric oxide synthase(iNOS), phosphorylated insulin receptor substrate 1 serine 307(p-IRS1ser 307), phosphorylated protein kinase B serine 473(p-AKTser 473), glycogen synthase kinase-3β(GSK-3β), and gluconeogenic synthase(GS) proteins were observed in the liver of rats under the condition of chronic intermittent hypoxia-replicated oxygen in control. And to explore the role of iNOS/IRS1/AKT/GSK-3β signaling pathway in chronic intermittent hypoxia-induced insulin resistance.
Methods :
Forty SD rats were randomly divided into a control group(NC group) and an experimental group(CIH group), with 20 rats in each group. The NC group was placed in a normoxic environment for 12 weeks, while the CIH group was first subjected to intermittent hypoxia for 8 weeks, and then resumed normoxic rearing until the 12th week. Fasting blood glucose(FBG) and fasting insulin(FINS) were measured at baseline, week 8 and week 12, and liver tissues were taken for pathology and measurement of iNOS, p-IRS1ser 307, p-AKTser 473, GSK3β and GS levels, to compare the differences between groups.
Results:
t baseline, there was no significant difference in liver pathology between the two groups, and the observed indexes were not statistically significant(P>0.05); at 8 weeks, compared with the NC group, liver pathology in the CIH group showed significant disorganization of hepatic blood sinusoids and hepatocyte cords, obvious hepatocyte edema, smaller nuclei, increased lymphocyte infiltration, and a small number of fat vacuoles, significantly higher levels of FBG, FINS, insulin resistance index(HOMA-IR), iNOS mRNA, p-IRS1ser 307 protein, GSK-3β protein levels, and decreased p-AKTser 473 protein and GS protein levels, all of which were statistically significant(allP<0.05). IRS1ser 307 protein, GSK-3β protein levels were increased, p-AKTser 473 protein and GS protein levels were decreased, and the differences were statistically significant(allP<0.05); at 12 weeks, no lymphocyte infiltration was seen in the CIH group compared with that of the NC group and fat vacuoles significantly increased, and there was no improvement in the other pathological damage that had already occurred, and the levels of p-AKTser 473 protein significantly increased. AKTser 473 protein level significantly increased, p-IRS1ser 307 protein and GS protein levels were significantly reduced, all of which were statistically significant(allP<0.05), and the rest of the observational indexes were not statistically significant. Pearson′s correlation analysis showed that HOMA-IR of CIH group was significantly positively correlated with the levels of iNOS mRNA, p-IRS1ser 307 protein, and GSK-3β protein at 8 weeks(r=0.874, 0.817,0.872;allP<0.05), and significantly negatively correlated with the levels of p-AKTser 473 protein and GS protein(r=-0.886,-0.879;allP<0.05).
Conclusion
Chronic intermittent hypoxia can lead to hepatic pathological damage that cannot be reversed even by reoxygenation interventions and may mediate the development of insulin resistance by upregulating the IRS1/AKT/GSK-3β signaling pathway through the upregulation of iNOS mRNA expression.
2.Thymol improves the core symptoms of autism through regulating scinderin expression
Chuxuan WANG ; Lijuan YU ; Mingqi LÜ ; Yingbo LI
Journal of Chongqing Medical University 2025;50(7):957-962
Objective:To explore the effect of thymol on improving the core symptoms of autism through regulating scinderin expres-sion in autism spectrum disorder(ASD)rats by constructing valproic acid-induced ASD rat model and intervening with thymol.Methods:The ASD-like behaviors of rats were observed using three box social experiment,open field experiment,and youth social ex-periment.RNA-seq was used to detect the expression of RNA in the prefrontal cortex of rats.The protein level of scinderin in the pre-frontal cortex of rats was measured by Western blot.Results:Compared with the rats in the control group,the rats in the model group showed ASD-like behaviors,including decreased social ability,impaired social preference,decreased exploration ability,and repeated stereotyped behavior.Compared with the control group,the model group showed reduced standing times(P<0.001)and increased self combing time(P=0.003).Moreover,the expression level of scinderin in the prefrontal cortex increased in model rats.After thymol treat-ment,the ASD-like behaviors in the model group were significantly improved.Compared with the model group,the number of standing times in the intervention group increased(P<0.001)and the self grooming time decreased(P=0.004).The expression of scinderin basi-cally returned to the normal level.Conclusion:The abnormal expression of scinderin in the prefrontal cortex of ASD model rats can lead to ASD-like behaviors.Thymol intervention can reduce the expression of scinderin and improve the core symptoms of ASD.
3.Effect of occupational factors on pre-diabetes mellitus among iron and steel workers
Yajing LIAO ; Chuxuan XU ; Chongqi MA ; Zhenwei QIN ; Yajiao SU ; Hongru ZHU ; Xiaotong ZHANG ; Chan LI ; Xiaoming LI ; Zhaoyang WANG ; Juxiang YUAN ; Hongmin FAN
Chinese Journal of Epidemiology 2020;41(6):929-933
Objective:To investigate the prevalence of pre-diabetes mellitus (PDM) and the impact of occupation-related factors on PDM, among workers from a steel company in Tangshan city, Hebei province.Methods:Clustering sampling method was used to select a steel company and to carry out occupational health-related physical checkup programs for eligible workers who had working in this company for longer than one year. The study began in February and ended up in June, 2017. Workers who were with FPG level as ≤6.9 mmol/L, and free from diabetes, were selected as the subjects for this study. Questionnaires were used and physical examinations and FPG testing conducted.Results:The total number of subjects in this study was 4 173, of which 2 648 appeared as pre-diabetic, with the prevalence rate as 63.4 %. Increase of the PDM prevalence was in parallel with the length of service, among the workers. The risk for the pre-diabetes in those who worked more than 8 hours per day was 1.696 times higher than those who worked less than or equal to 8 h/d (95 %CI:1.517-1.937). Compared with those workers without exposures to heat, noise or carbon monoxides, the proportion of pre-diabetes appeared higher in workers exposed to heat, noise or CO with OR=1.782 (95 %CI: 1.205-2.636), 1.815 (95 %CI: 1.209-2.794) and 1.653 (95 %CI: 1.158-2.361), respectively. Risks for those who were exposed to heat or noise were higher than those who were free from exposure to any occupational hazards ( OR=2.098, 95 %CI: 1.296-3.397). Prevalence rates of pre-diabetes in those who were exposed to heat, noise or CO, were higher than that those who were not. Conclusion:Working hours and exposures to heat, noise or CO appeared as influential factors on PDM.
4.Comparison of efficacy and safety between thulium laser and high frequency electric knife on peroral endoscopic myotomy
Chuxuan BIN ; Haiyun SHI ; Peng LI ; Yongjun WANG ; Shutian ZHANG
Chinese Journal of Digestive Endoscopy 2018;35(6):391-395
Objective To evaluate the efficacy and safety of 1 940 nm thulium laser on peroral endoscopic myotomy (POEM) for treatment of patients with achalasia of cardia. Methods Fifteen patients undergoing POEM in Beijing Friendship Hospital from February 2016 to November 2016 were enrolled and divided into 1 940 nm thulium laser group ( n=7) and high frequency electric knife group ( n=8) using zelen′s design, with followed-up for three months. The operation time, success rate, efficacy, and complications were compared between the two groups. Results All the procedures were successfully completed. There was no significant difference on baseline between the two groups ( P>0. 05). The time of total operation, creating submucosal tunnel, myotomy, and closing incision were not significantly different between the two groups (all P>0. 05). The bleeding amount, creating tunnel bleeding amount, and myotomy bleeding amount were not significantly different between the two groups (all P>0. 05). The complication rate during operation and one week after operation was not significantly different between the two groups ( P=0. 76).The time of creating mucosal incision for the 1 940 nm thulium laser group was longer than that of the high frequency electric knife group ( 3. 7 ± 3. 0 min VS 2. 3 ± 1. 3 min, P= 0. 02). After one month of follow-up, the efficiency of the 1 940 nm thulium laser group and the high frequency electric knife group was 100. 0%(7/7) and 87. 5%(7/8), respectively (P=0. 33), and the complication rate was 14. 3%(1/7) and 12. 5%(1/8), respectively (P=0. 92). After three months of follow-up, the efficiency of the two groups was 100. 0%(7/7) and 75. 0%( 6/8), respectively ( P=0. 16), and the complication rate was 28. 6%(2/7) and 12. 5%(1/8), respectively (P=0. 60). Conclusion 1 940 nm thulium laser and high frequency electric knife both have good utility on POEM.1 940 nm thulium laser decreases the operating time and bleeding compared with high frequency electric knife.
5.Effects of time targeted management on the control of thrombolysis time window in acute ischemic stroke
Danhui? LI ; Xiaohua XIE ; Hui CHEN ; Xiaoqun LI ; Wei TAN ; Jiwen ZHANG ; Chuxuan GU ; Fenhong WANG
Chinese Journal of Modern Nursing 2015;(23):2760-2763
Objective To explore targeted time management to shorten the time from arriving hospital to thrombolysis ( DNT ) . Methods A total of 42 suspected acute ischemic stroke ( AIS ) patients were underwent the targeted time management from pre-hospital until emergency thrombolysis while other 24 cases from 120 to hospital started from the time arriving Emergency Department. The complete rate of targeted time management and DNT compared with before management. Results In the control group, the hospital received 42 pre-hospital patients suspected with AIS in 3 hrs, and completed all targets 31 cases with pass rate of 73. 8%; the experimental group acquired 38 cases and achieved targets 35 cases with pass rate of 92. 1% (χ2 =4. 625,P<0. 05). In the experimental group, the pass rate of pre-hospital Emergency Department, CT detection, thrombolysis preparation were 100% (38/38), 94. 7% (18/19), 94. 7%(18/19) higher than 61. 9% (26/42), 55. 6% (10/18), 58. 8% (10/17) (χ2 =18. 095,5. 727,4. 779;P <0. 05). A total of 17 cases underwent thrombolysis with DNT of ( 68. 65 ± 23. 75 ) min while 19 cases in the experimental group with DNT of (35.50±2.98)min(Z=5.106,P<0.01),and4casescomingfrom120withDNTof(46.40±5.68) min (Z= -4. 092,P <0. 05). Conclusions To utilize pre-hospital time reasonable, we make the thrombolysis process early, regulate the process, manage each segment time targeted, find out and improve the reasons for overdue segment, make clear individual responsibility, which can shorten the DNT and be benefit patients.


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