ObjectiveTo investigate the effects and mechanisms of Fangji Fulingtang （FFD） on mitochondrial function in the mouse model of myocardial fibrosis （MF）. MethodsSixty SPF-grade male C57BL/6J mice were randomly allocated into six groups （n=10 per group）： control， model， low-dose， medium-dose， and high-dose （3.315， 6.63， and 13.26 g·kg^-1， respectively） FFD， and captopril （20 mg·kg^-1）. MF was induced by subcutaneous injection of isoproterenol （10 mg·kg^-1·d^-1） in other groups except the control group for 14 consecutive days， with simultaneous gavage of corresponding drugs. Left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） were measured by echocardiography. Serum levels of creatine kinase-MB （CK-MB）， cardiac troponin I （cTnI）， N-terminal pro-brain natriuretic peptide （NT-pro BNP）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） were determined by enzyme-linked immunosorbent assay （ELISA）. Malondialdehyde （MDA）， superoxide dismutase （SOD）， and glutathione （GSH） levels were measured by biochemical assays. Reactive oxygen species （ROS） were detected by dihydroethidium （DHE） fluorescence staining. Hematoxylin-eosin （HE）， Masson's trichrome， and wheat germ agglutinin （WGA） staining were performed to evaluate myocardial structure and fibrosis. Mitochondrial ultrastructure and function were assessed by transmission electron microscopy， adenosine triphosphate （ATP） colorimetric assay， and JC-1 fluorescence staining. The protein levels of phosphorylated adenosine monophosphate-activated protein kinase α subunit （p-AMPKα）， AMPKα， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， mitofusin 2 （MFN2）， pyruvate kinase M2 isoform （PKM2）， lactate dehydrogenase A （LDHA）， and hypoxia-inducible factor 1 alpha （HIF-1α） were analyzed by Western blot. ResultsCompared with the control group， the model group exhibited decreased LVEF and LVFS， increased heart weight index and heart weight-to-tibia length ratio （P<0.01）， elevated levels of myocardial injury markers （CK-MB， cTnI， and NT-pro BNP）， inflammatory cytokines （TNF-α， IL-1β， and IL-6）， and MDA， along with reduced SOD and GSH levels （P<0.01）. Enhanced interstitial collagen deposition and cardiomyocyte hypertrophy were observed in the model group （P<0.01）. Transmission electron microscopy and JC-1 staining revealed mitochondrial swelling， crista disruption， decreased ATP content， and reduced red/green fluorescence ratio in the model group （P<0.01）. Western blot analysis demonstrated downregulation of p-AMPKα， PGC-1α， and MFN2 and upregulation of PKM2， LDHA， and HIF-1α in the model group （P<0.01）. Compared with the model group， treatment with FFD or captopril improved LVEF and LVFS， reduced heart weight index and heart weight-to-tibia length ratio （P<0.05， P<0.01）， lowered the serum levels of CK-MB， cTnI， NT-pro BNP， TNF-α， IL-1β， IL-6， and MDA， increased the SOD and GSH levels （P<0.05， P<0.01）， attenuated the myocardial fibrosis and cardiomyocyte hypertrophy （P<0.01）， and restored the mitochondrial ultrastructure. The medium and high-dose FFD groups as well as the captopril group showed increased ATP production and red/green fluorescence ratio （P<0.05， P<0.01）. Furthermore， FFD upregulated the expression of p-AMPKα and PGC-1α while downregulating the expression of LDHA and HIF-1α （P<0.05， P<0.01）. ConclusionFFD activates the AMPK/PGC-1α/MFN2 signaling pathway and inhibits the PKM2/LDHA/HIF-1α axis to restore mitochondrial function and energy metabolic homeostasis， thereby attenuating isoproterenol-induced myocardial fibrosis.

ObjectiveTo investigate the effects and mechanisms of Fangji Fulingtang （FFD） on mitochondrial function in the mouse model of myocardial fibrosis （MF）. MethodsSixty SPF-grade male C57BL/6J mice were randomly allocated into six groups （n=10 per group）： control， model， low-dose， medium-dose， and high-dose （3.315， 6.63， and 13.26 g·kg^-1， respectively） FFD， and captopril （20 mg·kg^-1）. MF was induced by subcutaneous injection of isoproterenol （10 mg·kg^-1·d^-1） in other groups except the control group for 14 consecutive days， with simultaneous gavage of corresponding drugs. Left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） were measured by echocardiography. Serum levels of creatine kinase-MB （CK-MB）， cardiac troponin I （cTnI）， N-terminal pro-brain natriuretic peptide （NT-pro BNP）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） were determined by enzyme-linked immunosorbent assay （ELISA）. Malondialdehyde （MDA）， superoxide dismutase （SOD）， and glutathione （GSH） levels were measured by biochemical assays. Reactive oxygen species （ROS） were detected by dihydroethidium （DHE） fluorescence staining. Hematoxylin-eosin （HE）， Masson's trichrome， and wheat germ agglutinin （WGA） staining were performed to evaluate myocardial structure and fibrosis. Mitochondrial ultrastructure and function were assessed by transmission electron microscopy， adenosine triphosphate （ATP） colorimetric assay， and JC-1 fluorescence staining. The protein levels of phosphorylated adenosine monophosphate-activated protein kinase α subunit （p-AMPKα）， AMPKα， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， mitofusin 2 （MFN2）， pyruvate kinase M2 isoform （PKM2）， lactate dehydrogenase A （LDHA）， and hypoxia-inducible factor 1 alpha （HIF-1α） were analyzed by Western blot. ResultsCompared with the control group， the model group exhibited decreased LVEF and LVFS， increased heart weight index and heart weight-to-tibia length ratio （P<0.01）， elevated levels of myocardial injury markers （CK-MB， cTnI， and NT-pro BNP）， inflammatory cytokines （TNF-α， IL-1β， and IL-6）， and MDA， along with reduced SOD and GSH levels （P<0.01）. Enhanced interstitial collagen deposition and cardiomyocyte hypertrophy were observed in the model group （P<0.01）. Transmission electron microscopy and JC-1 staining revealed mitochondrial swelling， crista disruption， decreased ATP content， and reduced red/green fluorescence ratio in the model group （P<0.01）. Western blot analysis demonstrated downregulation of p-AMPKα， PGC-1α， and MFN2 and upregulation of PKM2， LDHA， and HIF-1α in the model group （P<0.01）. Compared with the model group， treatment with FFD or captopril improved LVEF and LVFS， reduced heart weight index and heart weight-to-tibia length ratio （P<0.05， P<0.01）， lowered the serum levels of CK-MB， cTnI， NT-pro BNP， TNF-α， IL-1β， IL-6， and MDA， increased the SOD and GSH levels （P<0.05， P<0.01）， attenuated the myocardial fibrosis and cardiomyocyte hypertrophy （P<0.01）， and restored the mitochondrial ultrastructure. The medium and high-dose FFD groups as well as the captopril group showed increased ATP production and red/green fluorescence ratio （P<0.05， P<0.01）. Furthermore， FFD upregulated the expression of p-AMPKα and PGC-1α while downregulating the expression of LDHA and HIF-1α （P<0.05， P<0.01）. ConclusionFFD activates the AMPK/PGC-1α/MFN2 signaling pathway and inhibits the PKM2/LDHA/HIF-1α axis to restore mitochondrial function and energy metabolic homeostasis， thereby attenuating isoproterenol-induced myocardial fibrosis.

Objective To investigate the clinical efficacy of enhanced recovery after surgery (ERAS) in the radical gastrectomy for gastric cancer.Methods The clinical data of 140 patients undergoing radical gastrectomy for gastric cancer at the Affiliated Hospital of Qingdao University from April 2011 to June 2013 were prospectively analyzed.A double-blind,randomized,controlled study was performed in the 140 patients,and all of them were divided into the ERAS group (patients undergoing perioperative management according to enhanced recovery rehabilitation program) and the control group (patients undergoing perioperative management) based on a random numble table.The inflammatory markers,nutritional index and postoperative recovery of patients were observed.Patients of the ERAS group were followed up by telephone interview within the first 24 hours after discharge,and by outpatient examination since the second week after discharge.The follow-up was ended at postoperative day 30.Patients of the control group were reexamined at the third week after discharge.The measurement data with normal distribution was presented as x ± s.The comparison between groups was evaluated with an independent sample t test.The trend analyses for variables were done using repeated measures ANOVA.The count data were analyzed using the chi-square test or Fisher exact probability.Results Eighty patients were screened for eligibility,and were allocated into the ERAS group (40 patients) and the control group (40 patients).The total protein in serum (TP),albumin (Alb),prealbumin,TNF-α,IL-6,c-reactive protein,resting energy expenditure (REE),glycemic index,insulin index and Insulin resistance index in the 2 groups showed a range of variations at postoperative day 1,3,and 5,and these were (61 ±5)g/L,(34 ±3)g/L,(160 ± 18)g/L,(12.3 ±2.3)mmol/L,(101 ±34)ng/L,(43 ± 11)g/L,(1 336 ± 105)kal/d,(7.6 ±0.8)mmol/L,(16.8 ±3.5)mU/L and 5.7 ±1.3 in the ERAS group at postoperative day 1,and (58 ± 4) g/L,(31 ± 4) g/L,(147 ± 18) g/L,(15.3 ± 2.2) mmol/L,(122 ±37)ng/L,(56 ±27) g/L,(1 450 ± 164)kal/d,(9.3 ± 1.4) mmol/L,(30.5 ±6.8) mU/L and 12.5 ±3.2 in the control group,respectively,showing a significant difference between the 2 groups (F =31.63,8.03,67.36,147.04,9.63,6.84,16.10,54.85,104.51,139.47,P ＜0.05).The duration of fever,time to flatus,duration of hospital stay,hospital expenses,numeric rating scale and quality of life (QOL) were (2.9 ±0.9) days,(2.9 ± 0.6) days,(7.6 ± 2.1) days,(28 495 ± 4 722) yuan,1.4 ± 1.0 and 15.4 ± 0.9 in the ERAS group after operation,and (3.8 ±0.6)days,(3.5 ±0.7)days,(8.9 ±2.6)days,(35 318 ±7 610)yuan,2.4 ± 1.1 and 14.4 ± 1.2 in the control group,respectively,with a significant difference between the 2 groups (t =-0.91,-3.66,-2.85,-4.82,-4.20,3.92,P ＜0.05).Two patients were complicated with respiratory diseases,1 patient received reoperation and 1 was readmitted to the hospital at postoperative day 30 in the ERAS group.Three patients had respiratory diseases,1 received reoperation and 2 were readmitted to the hospital at postoperative day 30 in the control group,with no significant difference between the 2 groups (P ＞ 0.05).Conclusions ERAS is safe and feasible for the perioperative treatment of patients with gastric cancer,meanwhile it could reduce the surgical stress,shorten the duration of hospital stay and improve QOL and postoperative complications,ERAS might take effects by reducing insulin resistance and decreasing REE.Registry This study was registered with the Chinese Clinical Trial Registry with the registry number of ChiCTR-TRC-10001611.

Objective To investigate the relationship between gene polymorphism of transcripion factor 7-like 2 (TCF7L2) at positions rs290487, rs11196205, rs11196218 and gestational diabetes mellitus (GDM) in Chinese women.Methods In 1140 unrelated pregnant Northern Chinese women (335 women with GDM, 158 gestational cases with impaired glucose tolerance and 647 pregnant non-diabetic controls) ,three single nucleotide polymorphisms (rs290487, rs11196205, and rs11196218) in the TCF7L2 gene were genotyped using ligase detection reaction (LDR).In the present study, cases with GDM and impaired glucose tolerance (IGT) were indistinguishable clinically and biochemically, and were combined into case group.Results The frequency of C allele of rs290487 was 41.6% in case group, being significantly higher than that in control group (36.3%, P=0.012).There was significant difference in the frequency of CC genotype between case group and control group (18.7% vs 14.0%, P=0.033).Compared with T allele carriers, CC genotype carriers had a 1.418-fold increased risk of GDM (95% CI 1.028-1.955).After adjusting for age, body mass index, family history of diabetes,systolic blood pressure,and diastolic blood pressure, pregnant women with CC genotype carriers of rs290487 were more prone to hyperglycemia compared with the T allele carriers (OR 1.518, 95% CI 1.064-2.166).Conclusions The TCF7L2 rs290487 variant may contribute to the genetic predisposition to GDM.CC genotype is likely to be associated with an increased risk of GDM in the pregnant Chinese women.

Objective To study the plasma and intratumoral levels of ghrelin, leptin and their relationship and clinical significance in patients with pancreatic endocrine tumor.Methods Preoperative plasma levels of ghrelin and leptin were detected by ELISA in 11 patients with pancreatic endocrine tumors and 28 normal controls.Expressions of ghrelin and its receptor GHS-R 1A were tested in 11 tumors and 27 paired control tissues by immunohistochemistry staining, and they were correlated with the clinicopathological characteristics.Results The plasma levels of ghrelin was ( 16.0 ± 5.0) pg/ml, which was significantly lower than that in normal controls [ (21.0 ± 2.0) pg/ml, P = 0.047 ].The plasma levels of leptin was (0.34 ±0.03 ) ng/ml, which was not significantly different with that in normal controls [ 0.38 ± 0.04) ng/ml ].There was positive association between plasma levels of leptin and ghrelin (P =0.015 ), but was not associated with clinicopathological parameters.The plasma levels of leptin in control group was positively associated with BMI (P = 0.002), but they were not associated in patients with tumor.The expression rate of ghrelin in tumor tissue was significantly lower than that in control group (64% vs 100%, P = 0.004 ).But the expression rate of GHS-R I A was not significantly different between the two groups.The expression of ghrelin and GHS-R1A in tumor was not significantly associated with clinicopathological parameters.Conclusions The ghrelin and its receptor GHS-R 1A were extensively expressed in pancreatic endocrine tumors, and the serum levels of ghrelin and leptin was changed.

Objective To evaluate the values of continuous subcutaneous insulin/rapid insulin analoguc infusion in desensitization for allergy to recombinant human insulin. Methods Two patients allergic to recombinant human insulin received desensitization therapy by continuous subcutaneous insulin lispro infusion. The diluted insulin lispro solution was pumped with initial basal rate of O. O1 U/h, and the basal rate and insulin lispro concentration increased gradually until the insulin dosage for clinical treatment was reached. After that, continuous subcutaneous insulin lispro infusion was replaced by regimen of insulin lispro subcutaneous injection plus oral hypoglycemic agents. Results Local wheals were not observed in both two patients during continuous subcutaneous insulin lispro infusion or during bolus subcutaneous injection of insulin lispro after desensitization. Conclusion The desensitization therapy by continuous subcutaneous insulin/rapid insulin analogue infusion can be applied for allergy to recombinant human insulin.

OBJECTIVEDiscussion on utility and purposed value of obesity and abdomen obesity when body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR) used as indexes predicting hypertension, hyper-blood glucose, and both clusters, to provide scientific basis for the decision on the indexes and their cut-off points of obesity and abdomen obesity in Chinese people.

METHODSUsing the data of diabetes mellitus (DM) from epidemiological studies carried out in 11 provinces/autonomous regions/municipalities of China from July 1995 to June 1997. Partial relative analysis, logistic multi-factors regression analysis, interaction analysis were used. Relative risk (RR), attributable risk proportion (ARP) and population attributable risk proportion (PARP) of hypertension, hyper-blood glucose, and the both cluster as BMI, WC, WHR with the different cut off points were analysed.

RESULTS1) The correlations between BMI, WC and blood pressure, blood glucose were better than the WHR. 2) After adjusted by age, sex, occupation leisure physical activity, education degree and the family history of DM, the results suggested that BMI, WC, WHR were important predictive factors, with relative importance as BMI > WC > WHR. 3) There were augment interactions on BMI, WC and WHR with hypertension, hyper-blood glucose, with the interaction of BMI and WC in particular. Their pure attributable interaction proportion were from 5.95% to 29.34%. 4) The values of RR were about 2.5 when BMI >/= 23, >/= 24 and >/= 25, suggesting the relationship with exposure factors and diseases were with medium and high maleficent extent. Their ARP were from 0.580 to 0.623 with PARP from 0.259 to 0.425. The values of RR were from 2.06 to 3.08 as WC >/= 85 cm in males, WC >/= 80 cm in females while WC >/= 90 cm in males, WC >/= 80 cm in females, which suggested that the relationship with exposure factors and diseases were in medium and high maleficent extent. Their ARP were from 0.515 to 0.676 while PARP from 0.241 to 0.431.

CONCLUSIONSSince the maleficent extent of exposure factors to diseases, the acceptability for overweight and obesity in population, and the prevention and care for overweight and obesity were just in the introduction stage in China. The utility value of predicted hypertension, hyper-blood glucose in BMI and WC seemed to be better then in WHR. We suggested that BMI used as the obesity index, with the diagnostic cut-off point BMI >/= 24. WC as the abdomen obesity index. The diagnostic cut-off points are suggested to be WC >/= 85 cm in males, and WC >/= 80 cm in females.

Adult ; Aged ; Blood Glucose ; metabolism ; Blood Pressure ; physiology ; Body Constitution ; Body Mass Index ; Diastole ; Female ; Humans ; Hyperglycemia ; diagnosis ; physiopathology ; Hypertension ; diagnosis ; physiopathology ; Logistic Models ; Male ; Middle Aged ; Obesity ; physiopathology ; Predictive Value of Tests ; Systole

435 patients with type 2 diabetes were divided into 2 groups according to their fatty liver,then the relations between fatty liver and various parameters in two groups were observed and analyzed by statistical methods.Body mass index,HbA_1c and triglyceride were the risk factors for fatty liver.The prevalences of metabolic syndrome,hypertension and coronary heart disease in fatty liver group were significantly higher than those in the control group.