Metformin has been applied for 50 year.In recent years,new studies found that metformin could reduce glucose through activating inhibition of dipeptidyl peptidase Ⅳ(DPP Ⅳ) and enhancing the biological effect of glucagon-like peptide-1(GLP-1).In addition,metformin can reduce vascular disease risk of patients with type 2 diabetes by improving insulin resistance and the effect of reducing total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),blood coagulation factor Ⅶ,plasminogen activator inhibitor-1(PAI-1) and proteinuria.Merformin can't change blood pressure of patients with type 2 diabetes,however,it can significantly reduce the salt-sensitive blood pressure of patients with obesity.Metformin has also been applied to patients with polycystic ovary syndrome(PCOS).It can induce ovulation,decrease the rate of abortion and have effect on hypertrichosis and hyperandrogenism.Besides,metformin has been the focus of the treatment of non-alcoholic fatty liver disease.

Objective To investigate the value of end-tidal carbon dioxide partial pressure (PET CO2 )in fluid resuscitation in severe acute pancreatitis(SAP)patients.Methods SAP patients under mechanical ventilation with the need of a fluid challenge test were included.Hemodynamic parameter cardiac index(CI)and PET CO2 were conducted before and after the fluid challenge test.The value of ΔPET CO2 was used to predict fluid responsiveness. Results Totally 43 patients with SAP were prospectively recruited.31 patients had volume responsiveness, 12 patients had no volume responsiveness.Compared with no volume responsiveness group,volume responsiveness group led to a greater increase in ΔCI[(0.9 ±0.3)vs.(0.2 ±0.3),t =3.24,P <0.05]and ΔPET CO2 [(4.1 ± 1.9)vs.(0.7 ±1.2),t =4.01,P <0.05].ΔPET CO2 and ΔCI were correlated(r =0.74,P <0.05).The area under ROC curve of ΔPET CO2 was 0.872(95% CI 0.754 ~0.923,P <0.05).An increase of 5% in ΔPET CO2 predicted fluid responsiveness with a sensitivity of 86.7%,and specificity of 89.5%.Conclusion The change of ΔPET CO2 induced by fluid challenge test is an effective way to predict fluid responsiveness in SAP patients.

OBJECTIVE:To establish the method for the simultaneous determination of 4 flavonoids in rat plasma sample, such as quercetin-3-O-sophoroside,isoquercitrin,hyperin,rutin. METHODS:8 SD rats were selected and given Poacynum hender-sonii leaf extract suspension intragastrically 0.1 g/kg(calculated by extract). The blood sample 1 mL was collected from orbit 1 h after medication. The contents of 4 flavonoids were determined by microemulsion liquid chromatography(MELC)after centrifuga-tion. The separation was performed on Zorbax SB-C18 column with mobile phase consisted of microemulsion [polyoxyethylene lau-ryl ether-n-butanol-ethyl acetate-triethylamine-water (volume ratio was 2.5:3.0:1.7:0.3:92.5,pH=5.0)] at the flow rate of 0.8 mL/min. The column temperature was set at 30 ℃,and detection wavelength was 360 nm. Sample size was 10 μL,and internal standard was bergenin. It was compared with HPLC method using organic solvent as mobile phase(mobile phase consisted of 0.2%phosphoric acid solution-acetonitrile,gradient elution,other condition same as MELC method). RESULTS:In rats plasma,the lin-ear range of quercetin-3-O-sophoroside,isoquercitrin,hyperin,rutin were 10-1000 ng/mL(r≥0.9980). The limits of quantitation was 10 ng/mL(S/N=10). RSDs of precision,stability and reproducibility tests were all below 7.5%(n=5). Average sample recov-eries were between 97.4%-98.5% and RSDs were less than 5.3%(n=5). Extraction recoveries were between 88.7%-100.3%(RSD≤6.14%,n=5). The methodological evaluation results of MELC and HPLC method were all in line with the regulations of pharmacopeia,and the results of blood concentration betweenthem were similar. Compared with HPLC method, MELCmethod could shorten detection time(10 min vs. 40 min)andreduce the amount of organic solvent (0.38 mL vs. 28 mL).CONCLUSIONS:Established MELC method is rapid,simpleand green,and can be used for 4 flavonoids from P. henderso-nii leaf in rat plasma sample.

Objective To evaluate the effects of repeated sevoflurane anesthesia on long-term cognitive function in lactating rats.Methods Twenty-four healthy Spragne-Dawley rats,aged 7 days,weighing 14-17 g,were randomly divided into 3 groups (n =8 each):control group (group C),2.6 ％ sevoflurane group (group S1),and 1.5％ sevoflurane group (group S2).At 7,14 and 21 days after birth,2.6％ and 1.5％ sevoflurane and carrier gas were inhaled for 1 h in groups S1,S2 and C,respectively.Visible plafform trial was carried out on 28 and 29 days after birth,and the swimming speed of the rats was recorded.Place navigation test was performed on 32-36 days after birth,and the escape latency was recorded.Spatial probe test was carried out on 36 days after birth,and the time spent in the platform quadrant,swimming distance and the number of times crossing the platform quadrant was recorded.Results Compared with group C,the escape latency was significantly prolonged in groups S1 and S2 (P ＜ 0.05).The escape latency was significantly longer in group S1 than in group S2 (P ＜0.05).There were no significant differences between the three groups in the swimming speed,time spent in the platform zone,swimming distance and the number of times crossing the platform quadrant (P ＞ 0.05).Conclusion Repeated inhalation of sevoflurane during lactation can impair the long-term declarative memory,which is concentration-related,while it has no effects on the associative learning in rats.

Objective: To evaluate the applications and problems of statistical methods for articles published in《Chinese Circulation Journal》. Methods: We reviewed the statistical methods for original articles published in《Chinese Circulation Journal》in 2010, 2011 and 2015; general status with problems was analyzed and the situations were compared among different years. Results: A total of 404 articles were enrolled, statistical hypothesis testing was performed in 366 of them, 32 had descriptive statistics only and 6 articles were meta-analysis. The most frequently used statistical methods were student'st-test (57.4%), followed by chi-squared analysis (56.7%), analysis of variance (35.2%) and regression analysis (23.0%). The main statistical problems in Methods included in described method un-matched to really used method and insufifcient or wrong description. The proportion of insufifcient or wrong description in 2010 and 2011 was 36.6% (71/194), while in 2015 was 26.2% (55/210),P=0.02. The major wrong application of statistical approach was ignoring design with improper method and using unsatisifed precondition for speciifc analysis. The proportion of improper statistical method application in 2010 and 2011 was 19.1% (33/173), in 2015 was 19.7% (38/193),P=0.88. Conclusion: The quality of statistics was improved in 2015 than 2010 and 2011 for articles published in《Chinese Circulation Journal》; while there were still problems at certain degree, enhanced statistical review should be conducted in medical journals.

The brain-gut axis is an important pathway for the interaction between the central nervous system and the gastrointestinal tract. Ischemic stroke can promote the imbalance and displacement of intestinal flora, and the intestinal flora and its metabolites in turn can affect the occurrence, development and outcome of ischemic stroke. This article reviews the related literature on ischemic stroke and intestinal flora, in order to review the relationship between the two and related mechanisms, and to prospect the stroke treatment of targeting intestinal flora.

Objective:To investigate the clinical characteristics of idiopathic hypereosinophilic syndrome (IHES) with gastrointestinal manifestations,and to improve the level of diagnosis and treatment of IHES. Methods:The clinical materials, process of diagnosis and treatment and prognosis of 9 patients diagnosed as IHES with gastrointestinal manifestations were retrospectively analyzed. Results:The average age of 9 patients was (22.66± 12.86)years old,and the ratio of male and female was about 1.25∶ 1. The main clinical manifestations included abdominal pain,diarrhea and abdominal distension.The eosinophil percentages in peripheral blood and bone marrow of the patients were (42.66 ± 19.88 )% and (39.33 + 15.99 )%, respectively.The ascites exudate cytology examination showed eosinophil infiltrated.The results of gastroscope or colonoscope showed mucosal hyperemia and edema,scattered bleeding spots, and dark red granular hyperplasia; the colon was affected frecuently.The histological biopsy confirmed that the mucosal was infiltrated by eosinophils.The abdominal CT of 6 patients showed that the walls of stomach or bowel were thickened.The abdominal symptoms disappeared,and the ascites was absorpted in 9 patients after the treatment of glucocorticoid.After 2 years of follow up,2 patients had relapse, others had no recurrence.Conclusion:Performing the routine diagnosis and treatment of gastrointestinal diseases, the clinicians should consider the possibility of IHES in order to avoid the misdiagnosis and delayed treatment. When IHES is diagnosed,steroid treatment should be performed in preference.

Objective To assess the histological characteristics of cervical cancer using intravoxel incoherent motion magnetic resonance imaging ( IVIMMRI) and to investigate the performance of IVIMMRI in evaluation of the efficacy of concurrent chemoradiotherapy in the treatment of intermediate/advanced cervical cancer. Methods Pelvic MRI scans, containing T2WI, IVIM (14 b values, b=0?1 000 s/mm2), and contrast?enhanced T1 scans were performed in 23 patients pathologically diagnosed with intermediate/advanced cervical cancer ( stage ≥Ⅱb ) before chemoradiotherapy, after two and four weeks of treatment, and at the end of treatment. The IVIMMRI data were processed with the bi?exponential model to generate three parameters, containing pure diffusion coefficient ( D ) , pseudodiffusion coefficient ( D?) , and perfusion fraction ( f ) . Apparent diffusion coefficient ( ADC ) was obtained using the mono?exponential model. The IVIMMRI parameters were measured at each time point and their dynamics and correlation were analyzed. Results The ADC, D, and f values were significantly higher after complete treatment ( 0?96 × 10-3 vs. 1?77 × 10-3 mm2/s, P=0?000;0?76 × 10-3 vs. 1.34± 0?12 × 10-3 mm2/s, P=0?000;0?14% vs. 0?24%, P=0?012). The above three values significantly increased after two weeks of treatment (all P=0?000) and kept increasing until the end of the treatment. In contrast, the D? value was reduced from the second week to the end of the treatment. Conclusions IVIMMRI can monitor the dynamic functional changes and early tumor responses during chemoradiotherapy for cervical cancer, which holds promise for clinical application.

OBJECTIVE:To provide reference for vancomycin-induced neutropenia adverse reactions/adverse events in clinical diagnosis. METHODS:With a case of children with neutropenia treated by long-course and large-dose vancomycin,PubMed and CNKI were retrieved to collect related literature and the literature was analyzed. RESULTS:Neutropenia may be associated with vancomycin,based on causality criterion of adverse reaction in China. CONCLUSIONS:Vancomycin-induced neutropenia in chil-dren is most likely associated with prolonged exposure induced by infusion,vancomycin dosage should be reduced or stopped,and routine blood and plasma concentration should be closely monitored.

Objective To investigate the effects of 17-methoxyl-7-hydroxy-benzene-furabcgakcone( MHBFC ) on isoproterenol-induced ventricular remodeling in mice. Methods Isoproterenol(ISO)was given subcutaneously(1 mg·kg-1, twice per day for 7 d)to induce ventricular remodeling in mice. Mice were divided into normal control group,model group, captopril group,MHBFC low and high-dose groups. 65 mg·kg-1 captopril was given by intragastric administration in captopril group,2. 5,5. 0 mg·kg-1 MHBFC were given by intravenous injection in MHBFC low and high-dose groups. At the end of the 7th day,the hearts of the mice were weighted,and myocardial hypertrophy index was expressed as heart weight/body weight, double kidneys weight/body weight and lung weight/body weight( HW/BW,KW/BW and LW/BW). Colorimetric method was used to determine the content of hydroxyproline( Hyp)in heart,the activity of superoxide dismutase( SOD)and the content of malondialdehyde( MDA)in serum. The histological changes were observed by HE and Masson’s staining,the changes of cross section area( CSA),collagen volume fraction,( CVF)and perivascular circumferential collagen area( PVCA)were determined. Results Compared with the model group,MHBFC potently inhibited cardiomyocyte hypertrophy,decreased the HW/BW, KW/BW and LW/BW,improved cardiac pathology changed,increased the of activity SOD,decreased the content of MDA in serum and the content of Hyp in heart tissue(P﹤0. 01 or P﹤0. 05),decreased the CVF and PVCA(P﹤0. 01). Conclusion MHBFC possesses protective effects against ISO-induced ventricular remodeling in mice,which may be related to its actions in reducing the oxidative stress and improving the antioxidant activity of the body.