1.Role of mito-KATP channels in sevoflurane postconditioning-induced inhibition of oxygen-glucose deprivation and restoration-induced pyroptosis in primary rat cardiomyocytes
Limin ZHANG ; Dongxue ZHANG ; Wenbo SUN ; Rui LI ; Xingliao LUO
Chinese Journal of Anesthesiology 2017;37(7):883-887
Objective To evaluate the role of mitochondrial ATP-seusitive potassium (mito-KATP) channels in sevoflurane postconditioning-induced inhibition of oxygen-glucose dcprivation and restoration (OGD/R)-induced pyroptosis in primary rat cardiomyocytes.Methods Cardiomyocytes of newborn Sprague-Dawley rats (<48 h after birth) were cultured in vitro and seeded in 6-well dishes (2 cm in diameter)or in 96-well plates.The cells were divided into 6 groups (n =15 each) using a random number table:control group (group C),OGD/R group (group O),sevoflurane postconditioning group (group Sev),sevoflurane postconditioning plus 5-hydroxydecanoate (5-HD) group (group SH),5-HD group (group H) and OGD/R plus 5-HD group (group HO).The cardiomyocytes were subjected to oxygen-glucose deprivation for 4 h followed by restoration of oxygen-glucose supply for 24 h.After oxygen-glucose restoration,the cardiomyocytes in the culture media were exposed to 2% sevoflurane for 1 h to perform sevoflurane postconditioning.At 1 h before oxygen-glucose deprivation,a specific mito-KATP channel blocker 5-HD 100 μmol/L was added to the culture media.Cardiomyocytes were cultured in normal culture atmosphere in group C.Cardiomyocytes were collected at 24 h of oxygen-glucose restoration.Cell pyroptosis was detected by double flow cytometry AlexaFour488 (caspase-1 FLICA staining) and TMR red (DNA staining) staining.The pyroptosis rate was calculated.The cell survival rate was measured by methyl thiazolyl tetrazolium assay.The content of reactive oxygen species (ROS) in mitochondria was determined by 2',7'-dichlorofluorescin diacetate assay.The mitochondrial membrane potential (MMP) was measured by using JC-I fluorescent probe.The expression of interleukin-1beta (IL-1β) was determined by Western blot.Results Compared with group C,the pyroptosis rate and ROS content were significantly increased,the cell survival rate and MMP were decreased,and the expression of IL-1β was up-regulated in group O (P<0.05).Compared with group O,the pyroptosis rate and ROS content were significantly decreased,the cell survival rate and MMP were increased,and the expression of IL-1β was down-regulated in group Sev (P<0.05).Compared with group Sev,the pyroptosis rate and ROS content were significantly increased,the cell survival rate and M MP were decreased,and the expression of IL-1β was up-regulated in group SH (P<0.05).Compared with group SH,the pyroptosis rate and ROS content were significantly increased,the cell survival rate and MMP were decreased,and the expression of IL-1β was up-regulated in group H O (P<0.05).Conclusion The mechanism by which sevoflurane postconditioning inhibits OGD/R-induced pyroptosis in primary rat cardiomyocytes is probably associated with increasing mito-KATP channel opening.
2.Association between hypersensitive C reactive protein and the incidence of acute kidney injury insubarachnoid hemorrhagic patients-a research on the clinical perspective
Dongxue WANG ; Yidan GUO ; Yin ZHANG ; Chaoxia LI ; Yang LUO
Chinese Journal of Laboratory Medicine 2017;40(8):573-577
Objective To evaluate the association between hypersensitive C reactive protein (hs-CRP) and the incidence of acute kidney injury in subarachnoid hemorrhage(SAH) patients.Methods It retrospectively recruited 213 cases of computerized tomography validated SAH patients from the neurology ICU from Beijing Tiantan Hospital between January 2012 and January 2015.The average age was (56.29±11.95) years old,and the patients were divided into AKI and non-AKI groups according to Kidney Disease: Improving Global Outcomes (KDIGO) diagnosis standards, Clinical features of AKI and Non-AKI patients including serum levels of hs-CRP were compared and multi-logistic regression was applied to find the risk factors concerning with the incidence of AKI.Receiver operating characteristics (ROC) curve was also plotted to evaluate the diagnostic value of hs-CRP towards the incidence of AKI.Results A total of 25 (11.74%) patients developed AKI.Average age of the SAH patients in both AKI and non-AKI groups were (63.60±12.21) years old vs.(55.31±11.60) years old(t=-3.33, P<0.05).The ratios of diabetics were were 28.00% vs.11.17% (χ2=5.47,P<0.05) and the ratio of proteinuria were 80.00% vs.34.57%, respectively (χ2=3.83, P<0.05).The median of serum creatinie were 63.72(51.45, 79.72)μmol/L vs.53.21(45.27, 65.62)μmol/L (P<0.05), and serum hs-CRP were (14.12±5.03)mg/L vs.(10.23±6.76)mg/L (P<0.05), and the ratios of antibiotics application were 84.00% vs.43.08% (P<0.05 for all).Multi-logistic regression analysis showed that serum hs-CRP was an independent risk factors for AKI after age, serum creatinine at admission were adjusted.[OR (95% CI) was 3.33(1.13, 9.85),P<0.05 for all].The area under curve of ROC was 0.69 (P<0.05), and the cut-off point of serum hs-CRP under the maximum Youden index was 13.85 mg/L.Conclusion Serum hs-CRP is an independent risk factor of theincidence of AKI in SAH patients, the significantly increase of serum hs-CRP might be an important predictor of the incidence of AKI in SAH patients.
3.Lateral and posterior single cage combined with unilateral pedicle screw fixation for lumbar degenerative disease
Dongxue YAN ; Yongji HUANG ; Guangbin MA ; Jun LUO ; Junzu HU ; Rongchi XIAO
Chinese Journal of Tissue Engineering Research 2014;(4):541-546
BACKGROUND:Most of lumbar degenerative diseases, such as lumbar instability, lumbar disc herniation and discogenic lumbago, need lumbar spinal fusion for the spine stability, but the choice of internal fixation approaches is controversial.
OBJECTIVE:To compare the effectiveness between lateral lumbar interbody fusion with single cage and single cage combined with unilateral pedicle screw fixation for the 4th and 5th single-level lumbar degenerative disease.
METHODS:The clinical data of patients with single-level lumbar degenerative diseases (L4 and L5) undergoing lateral lumbar interbody fusion with single cage in 30 cases (experimental group) and single cage combined with unilateral pedicle screw fixation in 45 cases (control group) were analyzed retrospectively, and the curative effects were compared between the two groups.
RESULTS AND CONCLUSION:Al patients in the two groups were fol owed up for 13 months on average (ranged from 10 to 37 months). The incisions in the two groups were stage I healing. One case in the experimental group occurred cage displacement, but no obvious syndromes were detected. No significant difference in the effective rate after operation, hospital stay, and volume of drainage was detected (P>0.05). The operative time and bleeding volume in experimental group were better than those in the control group (P<0.05). ODI and JOA scores were significantly improved after treatment when compared with preoperative ones in the two groups (P<0.05), but no significant difference was visible between the two groups (P>0.05). The effectiveness of lateral lumbar interbody fusion with single cage and single cage combined with unilateral pedicle screw fixation for single-level degenerative lumbar diseases was similar. However, the former has the advantages of less invasion and quick recovery.
4.Role of ERK signaling pathway in inhibition of OGD/R-induced apoptosis in rat cortical neurons by sevoflurane: the relationship with mPTP
Chunling WU ; Limin ZHANG ; Dongxue ZHANG ; Wenbo SUN ; Rui LI ; Xingliao LUO
Chinese Journal of Anesthesiology 2016;36(4):452-455
Objective To evaluate the role of extracellular signal-regulated kinase (ERK) signaling pathway in inhibition of oxygen-glucose deprivation and restoration (OGD/R)-induced apoptosis in rat cortical neurons by sevoflurane and the relationship with mitochondrial permeability transition pore (mPTP).Methods The rat cortical neurons were cultured in vitro and seeded in 6-well or 12-well culture plates.The neurons were randomly divided into 4 groups (n =18 each) using a random number table:control group (group C);OGD/R group (group O);sevoflurane group (group OS);sevoflurane + ERK1/2 inhibitor PD98059 group (group OSP).The neurons were subjected to O2-glucose deprivation for 90 min followed by restoration of O2-glucose supply for 24 h in group O.The neurons were incubated with 2% sevoflurane for 2 h after OGD/R in group OS.OGD/R was performed at 1 h after ERK1/2 inhibitor PD98059 30 μmol/L was added,and the neurons were incubated with 2% sevoflurane for 2 h after OGD/R in group OSP.At 24 h of restoration of O2-glucose supply,the expression of phosphorylated ERK1/2 (p-ERK1/2) in neurons was measured by Western blot,the neuronal apoptosis was detected using Annexin V-FITC/PI double staining combined with flow cytometry,and the opening of mPTP was determined through measuring the optical density at 540 nm.The apoptosis rate was calculated.Results Compared with group C,the expression of p-ERK1/2 in neurons was significantly up-regulated,and the apoptosis rate and mPTP opening were significantly increased in group O (P<0.05).Compared with group O,the expression of p-ERK1/2 in neurons was significantly up-regulated,and the apoptosis rate and mPTP opening were significantly decreased in group OS (P<0.05).Compared with group OS,the expression of p-ERK1/2 in neurons was significantly down-regulated,and the apoptosis rate and mPTP opening were significantly increased in group OSP (P<0.05).Conclusion The mechanism by which sevoflurane inhibits OGD/R-induced apoptosis in rat cortical neurons is related to inhibition of mPTP opening after activation of ERK signaling pathway.
5.Risk factors and clinical outcomes of acute kidney injury among subarachnoid hemorrhagic patients
The Journal of Practical Medicine 2017;33(21):3514-3517
Objective To explore the risk factors and clinical outcomes of acute kidney injury(AKI) among subarachnoid hemorrhagic(SAH)patients. Methods We retrospectively reviewed and analyzed the clini-cal data of 269 SAH patients from the neurology ICU between Jan. 2012 and Oct. 2013. Clinical features of AKI and non-AKI patients were compared.Multi-logistic regression was done to find the risk factors concerning with the incidence of AKI. Results A total of 39(14.5%)patients developed AKI.The patients with AKI appeared to be older at age,higher at NIHSS score,lower at GCS score than the non-AKI patients(P<0.05 for all).Moreover, the percentage of proteinuria,infectious complications and diuretics administration were significantly higher in the AKI patients(P<0.05 for all).Multi-logistic regression analysis showed that independent risk factors of AKI were age,GCS score and infectious complication[OR(95% CI)were 1.037(1.006,1.068),0.873(0.802,0.951), 3.624(1.543,8.514),respectively;P < 0.05 for all]. The AKI patients also had a higher hospital mortality rate (28.2%)vs.that in non-AKI(0.8%,P<0.01). Conclusions AKI has a higher incidence among SAH patients and AKI patients tend to have higher hospital mortality rate. Prevention of AKI seems to be very important among these patients.
6.Development and evaluation of a high-fat/high-fructose diet-induced nonalcoholic steatohepatitis mouse model.
Jing LIU ; Yinlan LIU ; Wenjun WANG ; Yan LUO ; Zhenjie ZHUANG ; Qibin JIAO ; Jianyu CHEN ; Dongxue BIAN ; Xiaojie MA ; Yunhao XUN ; Mingli ZHU ; Junping SHI
Chinese Journal of Hepatology 2014;22(6):445-450
OBJECTIVETo develop and evaluate a mouse model of nonalcoholic steatohepatitis (NASH) induced by a high-fat and high-fructose (HFHFr) diet.
METHODSSix-week-old C3H mice were randomly divided into groups for HFHFr diet experimental modeling, high fat-only (HF) diet controls, high fructose-only (HFr) diet controls, and standard chow (SC) diet controls. The standard HFHFr diet was modified so that it consisted of 76.5% standard chow, 12% lard, 1% cholesterol, 5% egg yolk powder, 5% whole milk powder, and 0.5% sodium cholate, along with 20% fructose drinking water. At the end of experimental weeks 4, 8, and 16, measurements were taken for the NASH-related parameters of body mass, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), lipid profile, and wet liver weight (upon sacrifice). In addition, histological changes in the liver were evaluated by hematoxylin-eosin (HE) and oil red O staining. The significance of differences between groups was assessed by statistical analysis, using the
METHODSof t-test, Wilcoxon rank sum test, x2 test, F test or Fisher's test as appropriate.
RESULTSAs compared to the mice in the SC group at the corresponding time points, the mice in the HFHFr and HF groups showed significantly higher body mass and wet liver weight, as well as more extensive and robust lipid disposition in hepatic tissues as evidenced by oil red O staining. However, HE staining indicated that the HFHFr and HF groups had different degrees of macrosteatosis accompanied with intralobular inflammatory foci, with the former showing more remarkable NASH-related histological changes. Analysis at the end of week 16 showed that about 80% of the mice in the HFHFr group had developed NASH [nonalcoholic fatty liver disease (NAFLD) activity score (NAS): less than 5]. The levels of low-and high-density lipoprotein (LDL and HDL) cholesterol, as well as the levels of ALT and AST, were increased from the end of week 4 to the end of week 8 for the HFHFr and HF groups. At the end of week 16, the two groups differed in the extent of increase in total cholesterol and LDL and HDL cholesterol, with only the HFHFr group showing statistically significant changes. Specifically, at the end of week 16, the HFHFr group showed ALT levels of 108.5 +/- 93.34 U/L (F=5.099, P =0.005 vs. HF group: 44.30 +/- 35.71 U/L, HFr group: 46.70 +/- 17.95 U/L, SC group: 24.70 +/- 6.57 U/L), AST levels of 316.30 +/- 208.98 U/L (F=6.654, P=0.001 vs. HF: 132.12 +/- 75.43 U/L, HFr: 143.30 +/- 38.53 U/L, SC: 122.60 +/- 12.76 U/L), total cholesterol levels of 5.18 +/- 0.58 mmol/L (F=72: 470, P =0.000 vs. HF: 3.94 +/- 0.75 mmol/L, HFr: 2.30 +/- 0.50 mmol/L, SC: 2.02 +/- 0.24 mmol/L), HDL cholesterol levels of 3.05 +/- 0.49 mmol/L (F=25.413, P =0.000 vs. HF: 2.65 +/- 0.54 mmol/L HFr: 1.77 +/- 0.47 mmol/L, SC: 1.58 +/- 0.16 mmol/L), LDL cholesterol levels of 1.11 +/- 0.23 mmol/L (F =83.297, P =0.000 vs. HF: 0.72 +/- 0.17 mmol/L, HFr: 0.27 +/- 0.04 mmol/L, SC: 0.20 +/- 0.05 mmol/ L).
CONCLUSIONThe present study suggests that a mouse model of NASH can be successfully induced by a 16-week modified HFHFr diet.
Animals ; Diet, High-Fat ; Disease Models, Animal ; Fructose ; administration & dosage ; Male ; Mice ; Mice, Inbred C3H ; Non-alcoholic Fatty Liver Disease
7.The association between blood glucose levels of children with type 1 diabetes mellitus and parental educational levels based on mobile health APP
Dongxue ZHENG ; Wenhao ZHANG ; Xueying ZHENG ; Sihui LUO ; Jianping WENG ; Chaofan WANG
Journal of Chinese Physician 2023;25(3):330-334,341
Objective:To explore the correlation between blood glucose level and parental education level in children with type 1 diabetes mellitus (T1DM) based on mobile health APP.Methods:The data of T1DM children enrolled in China′s T1DM registration management program and registered to use TangTangquan ? were collected, as well as the blood glucose monitoring information uploaded quarterly after registration. Children were divided into low education group (middle school or below) and high education group (junior college or above) according to their parents′ education level. Blood glucose levels were compared between the two groups at different time points. Spearman correlation analysis and multivariate logistic regression analysis were used to evaluate the correlation between blood glucose level and parents′ education level in children with T1DM. Results:A total of 2 263 eligible children with T1DM were included and 1 246 were female (55.1%). The median age was 7.9(4.4, 11.4)years and T1DM duration was 0.07(0.02, 0.46)years. Among them, 1 513 cases were in the low-education group while 750 cases were in the high-education group. Within three years after registration, the glucose levels of each interval in the low-education group were increasing gradually (all P<0.05 except post-breakfast glucose). The glucose levels of each interval in the high-education group in the third year were lower than those in the low-education group (all P<0.05 except nocturnal glucose). The result of multivariate logistic regression analysis showed that after the adjustment of factors including T1DM duration and treatment, parental educational levels were still the separate related factors of premeal glucose, bedtime glucose and nocturnal glucose (premeal glucose: OR=0.385, 95% CI: 0.164-0.874, P=0.025; bedtime glucose: OR=0.444, 95% CI: 0.204-0.949, P=0.038; nocturnal glucose: OR=0.226, 95% CI: 0.582-0.747, P=0.020). Conclusions:The blood glucose levels of children with T1DM were negatively associated with parental educational levels. It is suggested that parental educational levels should be taken into consideration in the management of T1DM for children.