1.Diabetes-associated sleep fragmentation impairs liver and heart function via SIRT1-dependent epigenetic modulation of NADPH oxidase 4.
Yuanfang GUO ; Jie WANG ; Dongmei ZHANG ; Yufeng TANG ; Quanli CHENG ; Jiahao LI ; Ting GAO ; Xiaohui ZHANG ; Guangping LU ; Mingrui LIU ; Xun GUAN ; Xinyu TANG ; Junlian GU
Acta Pharmaceutica Sinica B 2025;15(3):1480-1496
Although clinical evidence suggests that nonalcoholic fatty liver disease is an established major risk factor for heart failure, it remains unexplored whether sleep disorder-caused hepatic damage contributes to the development of cardiovascular disease (CVD). Here, our findings revealed that sleep fragmentation (SF) displayed notable hepatic detrimental phenotypes, including steatosis and oxidative damage, along with significant abnormalities in cardiac structure and function. All these pathological changes persisted even after sleep recovery for 2 consecutive weeks or more, displaying memory properties. Mechanistically, persistent higher expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) in the liver was the key initiator of SF-accelerated damage phenotypes. SF epigenetically controlled the acetylation of histone H3 lysine 27 (H3K27ac) enrichment at the Nox4 promoter and markedly increased Nox4 expression in liver even after sleep recovery. Moreover, fine coordination of the circadian clock and hepatic damage was strictly controlled by BMAL1-dependent Sirtuin 1 (Sirt1) transcription after circadian misalignment. Accordingly, genetic manipulation of liver-specific Nox4 or Sirt1, along with pharmacological intervention targeting NOX4 (GLX351322) or SIRT1 (Resveratrol), could effectively erase the epigenetic modification of Nox4 by reducing the H3K27ac level and ameliorate the progression of liver pathology, thereby counteracting SF-evoked sustained CVD. Collectively, our findings may pave the way for strategies to mitigate myocardial injury from persistent hepatic detrimental memory in diabetic patients.
2.Melatonin receptor 1a alleviates sleep fragmentation-aggravated testicular injury in T2DM by suppression of TAB1/TAK1 complex through FGFR1.
Xiaohui ZHANG ; Xinyu TANG ; Ting GAO ; Yuanfang GUO ; Guangping LU ; Qingbo LIU ; Jiahao LI ; Jie WANG ; Mingrui LIU ; Dongmei ZHANG ; Yufeng TANG ; Junlian GU
Acta Pharmaceutica Sinica B 2025;15(7):3591-3610
A major obstacle in type 2 diabetes mellitus (T2DM) is sleep fragmentation (SF), which negatively affects testicular function. However, the underlying mechanisms remain to be elucidated. In this study, we demonstrate that SF induces testicular damage through a mechanism involving lipid metabolism, specifically mediated by melatonin (MEL) receptor 1a (MT1). T2DM mice with SF intervention displayed several deleterious phenotypes such as apoptosis, deregulated lipid metabolism, and impaired testicular function. Unexpectedly, sleep recovery (SR) for 2 consecutive weeks could not completely abrogate SF's detrimental effects on lipid deposition and testicular function. Interestingly, MEL and MT1 agonist 2-iodomelatonin (2IM) effectively improved lipid homeostasis, highlighting MEL/2IM as a promising therapeutic drug for SF-trigged testicular damage. Mechanistically, MEL and 2IM activated FGFR1 and sequentially restrained the crosstalk and physical interaction between TAB1 and TAK1, which ultimately suppressed the phosphorylation of TAK1 to block lipid deposition and cell apoptosis caused by SF. The ameliorating effect of MEL/2IM was overtly nullified in Fgfr1 knockout (Fgfr1-KO +/- ) diabetic mice. Meanwhile, testicular-specific overexpression of Tak1 abolished the protective effect of FGF1mut on diabetic mouse testis. Our findings offer valuable insights into the molecular mechanisms underlying the testicular pathogenesis associated with SF and propose a novel therapeutic approach for addressing male infertility in T2DM.
3.Occurrence of hyperactivity behavior and its relationship with neuropsychological development in children aged 3-6 in Yunnan Province
Chinese Journal of School Health 2024;45(8):1106-1110
Objective:
To investigate the prevalence of hyperactivity behavior in children aged 3-6 in Yunnan Province, to explore its relationship with neuropsychological development, so as to provide clues for early prevention and intervention of attention deficit hyperactivity disorder (ADHD) in children.
Methods:
A total of 1 321 children aged 3 to 6 from 10 kindergartens in 5 prefectures (cities) of Yunnan Province were selected by stratified random sampling method from October 2022 to May 2023. Teacher Rating Scale (TRS) was used to investigate childrens hyperactive behavior and coexistent behavior. A qualified evaluator applied the Developmental Scale for Children Aged 0-6 Years to assess the development of 5 ability areas of gross motor movement,fine movement,adaptive ability,language and social behavior. Statistical analysis was performed using Wilcoxon rank sum test and χ2 test. Binary Logistic regression was applied to analyze the score of their hyperactivity behavior and its relationship with other behavior problems and neuropsychological development.
Results:
The detection rate of hyperactivity behavior was 8.6% in children aged 3 to 6 years, 12.8% in boys and 4.1% in girls (χ2=31.53, P<0.01). The detection rate of hyperactivity in 3yearold children was 13.9%, which was higher than that in 4yearold (9.2%) and 5yearold children (7.0%) (χ2=8.73, P<0.05). The detection rate of inattentionpassivity of rural children (14.6%) was higher than that of urban children (5.9%) (χ2=22.23, P<0.01). Binary Logistic regression analysis showed that the higher the level of adaptive development, the lower the risk of hyperactivity (OR=0.58, 95%CI=0.39-0.86), the higher the risk of hyperactivity (OR=0.57, 95%CI=0.35-0.91), the higher the risk of conduct problems (OR=0.57, 95%CI=0.37-0.87), inattentionpassivity (OR=0.49, 95%CI=0.33-0.74) were also at lower risk (P<0.05). Children with higher levels of fine motor development had a lower risk of inattentionpassivity (OR=0.59, 95%CI=0.37-0.93, P<0.05).
Conclusions
Hyperactivity in boys and inattentionpassivity in rural children requires more attention. It is necessary to strengthen childrens early adaptive ability and fine motor training to prevent hyperactive behavior and inattention.
4.Construction and Experimental Validation of Chemically-induced Cough Model Based on Cough Waveforms
Yunhang GAO ; Ling JIA ; Han LI ; Ling SONG ; Cong GUO ; Tengfei CHEN ; Hongping HOU ; Weiya CHEN ; Guangping ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):230-236
ObjectiveTo construct a cough model induced by chemical stimuli by whole-body plethysmography (WBP) for counting coughs based on cough waveforms, and use this model to explore the antitussive effect of GK-A. MethodDifferent chemical stimuli were used to induce coughs in mice or guinea pigs. Respiratory waveforms were monitored by WBP, and the recognizable and typical cough waveforms were selected for cough counting. Guinea pigs were induced to cough with different concentrations of citric acid or capsaicin, and cough waveforms were used to optimize the stimulation conditions. The optimized guinea pig model of cough was validated with dextromethorphan, and the optimized guinea pig model of capsaicin-induced cough was used to evaluate the antitussive effect of GK-A. ResultWBP could count the coughs induced by capsaicin and citric acid in guinea pigs by recognizable and typical respiratory waveforms. The optimized stimulation conditions were capsaicin concentration of 100 µmol·L-1 and nebulization for 2 min. The validation results showed that compared with the model group, the dextromethorphan group of guinea pigs had reduced coughs (P<0.05) and prolonged cough latency (P<0.01). GK-A prolonged the cough latency (P<0.05) and reduced coughs (P<0.05) in the mouse model of ammonia-induced cough. In the guinea pig model of capsaicin-induced cough, GK-A prolonged cough latency (P<0.05), reduced coughs (P<0.05), and decreased substance P (SP) content in the guinea pig serum (P<0.05, P<0.01). ConclusionA guinea pig model of capsaicin-induced cough was successfully established based on cough waveform counting, which provided an objective and accurate cough counting method. GK-A has antitussive effects, possibly by inhibiting the neuropeptide SP.
5.The effect of Xinmailong injection on microcirculation in patients with septic shock
Guangping WU ; Xin YIN ; Jianzhuo HE ; Liheng GUO
The Journal of Practical Medicine 2024;40(5):627-631
Objective To observe the effect of Xinmailong injection on microcirculation in patients with septic shock,so as to understand the application effect and value of Xinmailong injection in patients with septic shock.Methods A total of 82 patients with septic shock treated in the intensive care unit of our hospital were selected as the research objects and randomly divided into two groups.41 patients in the control group were treated with conventional septic shock cluster therapy,and 41 patients in the treatment group were treated with Xinmailong injection on the basis of cluster therapy in the control group.Then hemodynamic parameters(HR,CVP,CO,MAP,SVR),hemorheology(whole blood reducing viscosity,hematocrit,fibrinogen,platelet aggregation rate),microcirculation perfusion indexes(oxygenation index,blood lactate level,SCVO2,Pcv-aCO2)and 28-day survival rate were detected and compared between the two groups before and after treatment.Results Before treatment,there were no significant differences in hemodynamic parameters,blood rheology and microcirculation perfusion indexes between the two groups(P>0.05).After treatment,the above test results of the two groups were signifi-cantly improved,and the test results of the treatment group were significantly better than those of the control group,and the 28-day survival rate was also better than that of the control group.The differences were statistically significant(P<0.05).Conclusion Xinmailong injection can significantly improve the hemodynamic parameters,blood rheology and microcirculation perfusion indexes,and improve the 28-day survival rate of patients with sepsis.It has a positive clinical effect in the treatment of septic shock patients.
6.Evaluation of the relationship between HtrA and streptococcus mutans isolated from the children with different caries experience *
Jianghua YANG ; Xiyuan GUO ; Guangping WANG ; Mingxia LI ; Xingrong LIU
Chongqing Medicine 2013;(24):2834-2836
Objective To evaluate the relationship between mRNA and protein expression of HtrA and Streptococcus mutans i-solated from the children with different caries experience and to provide the theoretical and experimental basis on prediction of dent-al caries in deciduous teeth .Methods The strains of Streptococcus mutans isolated from children with different carious experiences in the preliminary experiments were divided into three groups :high caries-susceptible group ,middle caries-susceptible group ,caries-free group .All strains were reanimated on the agar plate of MS ,and after smear pure culture examination ,typical bacteria were in-cubated in BHI ,then purified nucleic acid and extracted all the RNA of streptococcus mutans by reverse transcription PCR and de-tected it by agarose gel electrophoresis integrality .Synthetic cDNA and take further PCR amplification with cDNA products .Ob-serve records results by Gel imaging system .HtrA of target gene and electrophoresis image were gray scan by Gel quantitative soft-ware Gel-Pro analyzer 4 .0 was used to analyze relative expression value of gene .After purifying protein ,collected total protein of Streptococcus mutans strains by Western Blot method ,then tested the concentration of total protein sample .The results of Chemilu-minescence imaging were scanned into computer by Bio-Rad analyzing system ,calculated the gray value by software Quantity One 4 .4 .0 which showed the relative expression level of protein .Results There were significant differences in HtrA mRNA and protein expression of different Streptococcus mutans isolated from the children with different caries susceptibility .high caries-susceptible group> middle caries-susceptible group> caries-free group (P< 0 .05) .Conclusion There were significant differences in HtrA mRNA and protein expression of different Streptococcus mutans isolated from the children with different caries susceptibility .The higher caries susceptibility the group was ,the more HtrA mRNA and protein the strain express .
7.Histological and morphological changes of Oncomelania hupensis snails by calcium cyanamide
Meng XIA ; Liang DING ; Wangyuan WEI ; Guangping LI ; Fengying GUO ; Xianglin CHEN ; Jiagang GUO
Chinese Journal of Schistosomiasis Control 2010;22(2):174-175,Ⅳ
Objective To observe the effects of calcium cyanamide (Rongbao) on the histological and morphological changes of Oncomelania hupensis snails in order to explore its molluscicidal mechanisms.Methods The serial snails' slides were fixed after soaking in a concentration of Rongbao leached liquor at different time.The histological and morphological changes of the snails were compared among these slides.Results After soaking in the Rongbao leached liquor for 48 h,the mantle epithelia,respiratory epithelia of the gill,liver cells,and muscle cells of gastropods were injured seriously,which resulted in the death of the snails directly.The death rates of the snails were 96.70% and 100% after soaking in the Rongbao leached liquor for 48 h and 72 h,respectively.Conclusion Rongbao is an effective molluscicide by damaging the several snail tissues.
8.Left atrial function and structure changes after catheter ablation in patients with atrial fibrillation
Xiaohuan WANG ; Guangping LI ; Fangming GUO ; Gang XU ; Yunshan CAO
Clinical Medicine of China 2009;25(5):485-487
Objective To investigate the left atrium (LA) function and structure changes in the paroxysmal atrial fibrillation (AF) patients after catheter ablation using tissue Doppler imaging. Methods After complete pul-monary vein, radiofrequency ablation guided by Ensite NavX System, LA systolic function and LA diameter, volume, mean mitral gradient and mitral annulus early and advanced diastolic peak velocity were assessed in 32 cases of par-oxysmal AF patients,which were compared with age-matched controls before and after 24 hours, 1 week, 1 month) AF ablation. Results AF did not occur again in 32 AF paroxysmal patients after isolation. LA diameter and volume in AF groups before ablation were larger than controls(P<0.01), which were also larger 24 hours after ablation than before (P>0.05 ), but LA volume was larger than before (P<0.05), and decreased in I week after ablation (P< 0.05), but had no significant difference compared with controls in 1 month(P>0.05 ) ;mitral annulus advanced di-astolic peak velocity decreased in AF groups before ablation (P<0.01 )and was lower than that 24 hours after cathe-ter ablation (P<0.05 ), but increased after 1 week (P<0.05 or P <0.01 ), and had no significance after 1 month. Conclusion Catheter ablation is the effective way to manage AF because LA is distended and atrial systolic func-tion is reduced within 24 hours after procedure, then gradually increased in a week and will nearly recover to that be-fore procedure in a month, which may be correlated with LA repair, implicating that postprocedural thromboembollc risk and procedure injury should be taken into consideration.
9.Risk factors of acute myocardial infarction following primary percutaneous coronary intervention among elderly patients
Fangming GUO ; Xiaohuan WANG ; Guangping LI ; Xin CHEN ; Yuguang JIN
Journal of Geriatric Cardiology 2009;6(2):67-70
Background and Objective Large randomized controlled trials have demonstrated that percutaneous coronary intervention (PCI) with the routine use ofdrug-eluting stents is safe and effective, however, the patients older than 75 years undergoing PCI are at increased risk for major adverse cardiac events, so that the patients are usually excluded from this trial. The aim of the present study was to assess the early clinical outcome and risk factors in old patients with acute ST elevation myocardial infarction (STEMI) following primary PCI. Methods We analyzed the outcome after stenting in 136 patients older than 60 years in our coronary care unit with acute STEMI, and the patients were further classified in 2 age groups: patients≥75 years and <75 years. Results Though the older group had a higher prevalence of adverse baseline characteristics and lower final TIMI flow than those of the younger, the procedural success had no difference between two groups. The main adverse clinical events (MACE) for the old group was a little higher comparing with the younger in 12-month following up. Conclusions Our study suggest that drug-eluting stent implantation in elderly patients with acute ST elevation myocardial infarction has high initial procedural success rates despite having more severe baseline risk characteristics, and to shorten the time form symptom onset to PC1 and improve final TIMI flow strategy may decrease MACE among old patients following PCI.
10.Clinical study on right ventricular function of pulmonary thromboembolism
Fangming GUO ; Guangping LI ; Yan TANG ; Xiuqin SONG ; Jun YANG
Clinical Medicine of China 2008;24(9):869-871
Objective To study the right ventricular function of patients with pulmonary thromboembolism by using color Doppler ultrasound.Methods 31 patients with acute pulmonary thromboembolism,compared with 31 vohnteers,were enrolled in this study.The right ventricular anterior wall movement,right ventricular end diastolic volume,right ventricular ejection fraction,and myocardial performance index were observed by echocardiography.Resuits The right atrium diameter,right ventricles diameter,right ventrieular end diastolic volume and pulmonary artery inner diameter in study group were much larger than that in control group (P<0.01),and the right ventricular anterior wall movement and right ventrieular ejection fraction decreased in study group (P<0.01).Tricuspidal annular E peak velocity tended to be decreased,isovolumie relaxation time and isovolumic contraction time were prolonged and myocardial performance index was increased (P<0.01).Right ventricular myocardial performance index showed significant correlation with right ventrieular ejection fraction (r=0.78,P<0.01),isovolumic relaxation time and isovolumic contraction time(rl=0.88,r2=0.57,P<0.01).Conclusion The right ventricular function in patients with pulmonary thromboembelism is decreased and myocardial performance index is a sensitive index which can be used to reflect right ventricular function in pulmonary thromboembolism.


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