Objective To evaluate the efficacy and safety of TACE combined with Apatinib versus TACE monothcrapy in the treatment of advanced hepatocellular carcinoma (HCC).Methods A total of 44 patients with advanced HCC were enrolled and divided randomly into group A (n=22) and group B (n=22).The patients in group A were treated with TACE monotherapy while group B were treated with TACE combined with Apatinib.The serum alpha fetoprotein (AFP) levels were compared between the two groups three months after treatment.The objective response rate (ORR) after 3,6,9 and 12 months,the progression-free survival (PFS) and incidence of adverse reactions were also compared.Results The serum AFP levels decreased apparently in two groups three months after treatment,and statistic differences were observed in each group (Z=-2.289,-2.953,both P ＜0.05),while no statistic differences was obtained between the two groups after treatment (Z=-0.126,P＞0.05).No statistic differences were found in ORR between the two groups 3 and 6 months after treatment (both P ＞0.05),while statistic differences were manifested after 9 and 12 months (both P ＜0.05).The medium PFS in group A significantly lower than that in group B (x2 =6.576,P=0.01).The apatinib-related adverse reactions including hypertension,hand-foot syndrome and proteinuria in group B were higher than those in group A,and statistically significant difference were obtained (allP＜0.05).The adverse reactions were relieved after symptomatic treatment.Conclusion TACE combined with apatinib may improve the mid-long term efficacy in patients with advanced HCC.And the relatively safety of TACE combined with apatinib is confirmed.

A certain amount of potassium chloride is required to correct the hypokalemia occuring commonly during perioperation,but the overdosage may be harmful. To investigate the proper dose of KCl,40 adult rabbits were randomly and evenly assigned to be intravenously infused with normal saline(group Ⅰ),or saline containing 4,25 or 50 mmol/L KCI (group Ⅱ,Ⅲ,Ⅳ),at rate of 10 ml?kg~(-1)?h~(-1) during operation respectively. As compared with those before operation,the serum level of potassium decreased significantly in group Ⅰ and Ⅱ, changed unsignificantly in group Ⅲ,and increased in group Ⅳ during and after operation;the potassium amounts in liver and skeletal muscles increased markedly after operation. S-T segment was depressed in group Ⅰ and Ⅱ,T wave became peaked in group Ⅳ, and ECG remained normal in group Ⅲ. it is indicated that intravenous KCl infusion at concentration 25 mmol/L and rate of 10ml?kg~(-1)?h~(-1) may properly correct the hypokalemia during perioperation,and the occurance of perioperatine hypokelemia may be related to the uptake of liver and skeletal muscles

Ten mongrel dogs,divided randomly into a control group (A) and a cerebroplegia group (B) ,were supported by closed-chest cardiopulmonary bypass,subjected to 2 hours of hypothermic circulatory arrest at 18 C. In group B, oxygenated asanguineous solution 50ml/kg was infused into the carotid artery at the onset of arrest. and 10 ml/kg was supplemented every 30 minutes during 2hours arrest. Nothing was infused in group A. Then all animals were rewarmed to 37 C and killed 6 hours later At five time points cerebral cortex was collected to study adnosine triphosphate (ATP),malondialde hyde (MDA) and ultrastructure. Electroencephalography (EEG) was recorded continuously. In group A, ATP content decreased gradually from the beginning of arrest to the end of the experiment (P

Objective To investigate the effect of liver phosphatidylinosital 3-kinase/protein kinase B (PI3-K/AKT) pathway on the decrease of insulin sensitivity in fetal growth restriction (FGR) rats.Methods Twenty pregnant female rats were randomly divided into two groups one day after conception:normal-protein group and low protein group (n=10,respectively).Rats in low-protein group was given low protein diet (8.00％ protein) during pregnancy to build FGR model,while normal-protein group was given normal protein diet (20.00％ protein).On day 3,7,14,30,60 and 90 after birth,fasting blood samples of 8 male FGR offsprings from low-protein group and 8 normal offsprings from normal-protein group were collected to measure fasting plasma glucose and insulin level.Then insulin resistance index and insulin sensitivity index were calculated to determine insulin sensitivity.On day 7,14,30,60 and 90 after birth,liver tissue of 8 male FGR and normal offsprings were collected,insulin receptor substrate 1,2 (IRS1/IRS2)and glucose transporter 4 (GLUT4) mRNA expression were measured by real-time fluorescence polymerase chain reaction and the protein expressions of IRS1,PI3-K (subunit p110β),and AKT and phosphorylated AKT (pAKT) were measured by Western blot.The relationships between the expression changes of key molecules of PI3-K/AKT pathway and insulin sensitivity were analyzed by correlation and multiple linear regression method.Results (1) Mean birth weight of baby rats in low-protein group was significantly lower than that of normal-protein group [(4.92±0.36) g vs (6.43±0.59) g,t=14.73,P＜0.05].The incidence of FGR in low-protein group was 88.2％ (97/110); and for male offsprings,it was 94.1 ％ (48/51).(2) Compared to normal offsprings,fasting plasma glucose levels of male FGR offsprings were significantly higher from the age of 60 days to 90 days.Insulin levels and insulin resistance index were significantly higher and insulin sensitivity index was lower from the age of 30 days to 90 days,P＜0.05 respectively.(3) Compared to normal offsprings,IRS1 (0.45 ± 0.02 vs 0.68± 0.03,t=16.633,P＜0.05) and IRS2 mRNA (0.34±0.10 vs 0.70±0.19,t=4.864,P＜0.05) expressions in FGR offsprings were lower from day 7 after birth to day 90 (0.48±0.03 vs 0.59±0.05,t=5.237,P＜0.05; 0.49±0.20 vs 0.70±0.11,t=2.253,P＜0.05).There were no differences in expressions of GIUT4 mRNA and AKT protein between two groups (P＞ 0.05).IRS1,PI3-K and pAKT protein expressions of FGR offsprings decreased significantly from day 14 (0.22±0.05 vs 0.52±0.11,t=7.024,P＜0.05; 0.46±0.03 vs 0.97±0.08,t=17.508,P＜0.05; 0.62±0.10 vs 0.89±0.08,t=6.100,P＜0.05) to day 90 (1.11±0.08 vs 1.32±0.14,t=3.714,P＜0.05; 0.63±0.07 vs 1.00±0.19,t=5.206,P＜0.05;0.28±0.03 vs 0.45±0.10,t=4.880,P＜0.05).(4) The pAKT protein expression level of FGR rats was positively correlated with insulin sensitivity index (r=0.704,P＜0.05) ; while negatively correlated to the level of fasting plasma glucose (r=-0.609,P＜0.05),fasting insulin (r=-0.561,P＜0.05) and insulin resistance index (r =0.577,P＜ 0.05).Conclusions The changes of some key molecules' expressions of PI3-K/AKT pathway in liver might be involved in the insulin resistance in FGR rats.

Objective:To explore the hepatocyte insulin sensitivity of intrauterine growth retardation ( IUGR) rats and establish an insulin resistance cell model in vitro.Methods: An IUGR animal model was established by protein malnutrition during the mother pregnancy .On 60 d and 90 d after birth , the offspring rats were fasted for 12 hours and then their angular vein blood was collected to measure the fasting plasma glucose and fasting serum insulin level , then the insulin resistance index ( HOMA-IR) and insulin sensitivity index ( ISI) were calculated .The insulin sensitivity was evaluated by HOMA-IR and ISI.Primary hepatocytes from each group were respectively isolated by two-step perfusion with collage-nase and were defined as normal hepatocytes group and IUGR hepatocytes group .The normal hepatocyte group was divided into two groups: control group and insulin induction group .Insulin induction group was established by primary cultures of normal hepatocyte incubated with varying dilutions of insulin . CCK-8 was used to detect the viability of the cultured hepatocytes .Glucose oxidase-peroxidase method kit was used to measure glucose consumption of the hepatocytes .Results:HOMA-IR was significantly higher in IUGR rats than in the normal rats at the age of 60 days ( t=-17 .02 , P<0 .05 ) and 90 days ( t=-12.52, P<0.05).ISI was significantly lower than in the normal rats aged 60 days (t=5.61, P<0.05) and 90 days (t=12.42, P<0.05).There were no significant differences in hepatocyte viability among the control group , IUGR group and insulin induction group after incubation of 48 h on day 60 (F=1.34, P=0.29) and day 90 (F=0.22, P=0.81).The glucose consumption of the IUGR group and insulin induction group were significantly decreased compared with the control group on day 60 ( F=9.28, P=0.002) and day 90 (F=56.60, P<0.001), while there was no significant difference be-tween the IUGR group and insulin induction group (P=0.08, P=0.10).Conclusion:The insulin sen-sitivity of hepatocytes of IUGR rats decreased from adolescence to adulthood .High-dilution insulin may induce insulin resistance cell model in vitro.

Objective To investigate the roles of phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway and its regulatory protein peroxisome proliferator-activated receptor γ (PPAR γ) and phosphatase and tension homologue deleted on chromosome 10 (PTEN) in regulating insulin sensitivity in rats with fetal growth restriction (FGR).Methods Sixteen pregnant rats were randomly divided into two groups including FGR and control groups on the 12th day of pregnancy (eight in each group).The FGR group was given low protein diet (8％ of casein) and restriction diet to establish the neonatal rat model of FGR.All maternal rats after delivery and newborn rats after weaning on 21 days after born were fed with normal diet.Each time blood samples were collected from eight newborn rats of each group to measure levels of fasting plasma glucose (FPG) and fasting insulin(FINS) at the time points of 21 days,two and four months after birth.Then insulin resistance index (IRI) and insulin sensitivity index (ISI) were calculated to evaluate insulin sensitivity.Expression of PI3K,AKT,PPAR γγ,PTEN and glucose transporters 4 (GLUT4) in skeletal muscle at mRNA and protein levels were measured at 21 days,two and four months after birth with real time fluorescence polymerase chain reaction and Western blot,respectively.Relationships between the expression of key molecules of PI3K/AKT signaling pathway and insulin sensitivity were analyzed.T-test,and Pearson's correlation analysis were used for statistical analysis.Results (1) The average birth weight of newborn rats in the FGR group was lower than that of the control group [(4.37± 0.69) vs (7.03±0.55) g,t=-20.75,P＜0.05].The incidence of FGR in the FGR group was 93.33％ (70/75).(2) Compared with normal offspring,those in the FGR group showed significantly increased FPG [two months after birth:(5.53± 0.58) vs (7.49 ± 0.38) mmol/L,t=8.08;four months afterbirth:(6.35±0.66) vs (8.94±0.90) mmol/L,t=6.58],FINS [two months afterbirth:(9.18±0.66) vs (14.67± 1.90) mU/L,t=7.71;four months after birth:(33.08±2.76) vs (56.33±2.81) mU/L,t=16.71] and IR1 (two months after birth:2.25±0.31 vs 4.90±0.81,t=8.63;four months after birth:9.30±0.90 vs 22.44±3.10,t=1 1.51),but decreased ISI (two months after birth:0.020 ± 0.002 vs 0.009± 0.001,t=-10.1 4;four months after birth:0.005±0.000 vs 0.002 ±0.000,t=-14.91) at two and four months after birth (all P＜0.05).(3) Compared with normal offspring,those in the FGR group showed decreased expression of PI3K (21 days after birth:0.082±0.028 vs 0.019±0.004,t=-6.29;two months after birth:0.020±0.003 vs 0.010±0.005,t=-4.78;four months after birth:0.014±0.004 vs 0.003±0.001,t=-7.87) and GLUT4 (21 days after birth:0.132±0.057 vs 0.041 ±0.019,t=-4.32;two months after birth:0.183±0.084 vs 0.069±0.017,t=-3.74;four months after birth:0.248±0.069 vs 0.113±0.040,t=-4.74) at mRNA level at 21 days,two and four months after birth (all P＜0.05).Compared with normal offspring,decreased expression of PPAR γ (two months after birth:0.028±0.002 vs 0.012±0.005,t=-3.70;four months after birth:0.030±0.008 vs 0.012±0.005,t=-3.80) and increased expression of PTEN (two months after birth:0.020±0.004 vs 0.045±0.014,t=5.09;four months after birth:0.023±0.007 vs 0.034±0.009,t=2.57) at mRNA level were observed in offspring of the FGR group at two and four months after birth (all P＜0.05).(4) Compared with normal offspring,expression of PI3K protein (21 days after birth:0.22±0.01 vs 0.17±0.02,t=-6.62;two months after birth:0.27±0.03 vs 0.16±0.02,t=-7.25;four months after birth:0.18±0.01 vs 0.09±0.02,t=-9.79) and GLUT4 protein (21 days after birth:0.21 ±0.01 vs 0.03±0.01,t=-27.29;two months after birth:0.10±0.01 vs 0.06t±0.01,t=-3.90;four months after birth:0.13 ±0.01 vs 0.08± 0.02,t=-8.10) decreased in offspring in the FGR group at 21 days,two and four months after birth (all P＜0.05).Compared with normal offspring,those in the FGR group showed decreased expression of PPAR γ protein (two months after birth:0.10 ± 0.01 vs 0.07± 0.01,t =-7.29;four months after birth:0.09±0.01 vs 0.08±0.01,t=-2.83),but increased expression of PTEN at protein level (two months after birth:0.10±0.01 vs 0.15±0.02,t=6.01;four months after birth:0.09±±0.01 vs 0.13±0.02,t=5.51) at two and four months after birth (all P＜0.05).(5) The IRI levels in offsprings in the FGR group were negatively correlated with the expression of PI3K,GLUT4 and PPAR γ at protein level (two months after birth:r=-0.90,-0.92 and-0.79;four months after birth:r=-0.92,-0.75 and-0.73,all P＜0.05),but positively correlated with the expression of PTEN at protein level (r=0.87 and 0.86,both P＜0.05) at two and four months after birth.Conclusions The abnormal expression of the key molecules of PI3K/AKT signaling pathway precedes the decrease of insulin sensitivity in newborn rats with FGR and the expression regulatory protein PPAR γ and PTEN are also changed,suggesting that these molecules may induce the impairment of insulin sensitivity in rats with FGR and be involved in the development of insulin resistance.

Objective To discuss the feasibility of neuroendoscopic third ventriculostomy for chronic posttraumatic hydrocephalus (PTH).Methods Nineteen cases of chronic PTH treated with neuroendoscopic third ventriculostomy between October 2010 and October 2014 were analyzed retrospectively.There were 13 males and 6 females, aged 11-57 years (mean, 36.3 years).Trauma resulted from traffic accidents in 14 cases, falls in 4 cases and blunt object hitting in 1 case.Of the 19 cases analyzed, 5 had Glasgow Coma Scale (GCS) score of 13-15, 5 had score of 9-12 and 9 had score of 5-8 at admission.Results of operation were assessed with the Canada multicenter evaluation criteria.Prognosis was analyzed with the Glasgow Outcome Scale (GOS).Results All cases were followed up for mean 13.6 months (range, 6-26 months).Improvement of symptoms was achieved in 17 cases, but was not seen in 2 cases.Of the 2 cases, one required ventriculoperitoneal shunt two weeks after ineffective ventriculostomy, and one required second ventriculostomy one month after the presence of stoma blockage.No serious complications occurred.At follow-up, 9 cases had GOS score of 5, 8 cases had score of 4 and 2 cases had score of 3.Conclusions Neuroendoscopic third ventriculostomy is in line with the physical characteristics in cerebrospinal fluid circulation, which implies no shunt implantation, less operative trauma and less complications.The procedure is an effective approach for chronic PTH.

Objective To explore the effect of methylation of peroxisome proliferator-activated receptor γ(PPARy) gene promoter in liver and its mRNA expression changes on decreasing of insulin sensitivity in fetal growth restriction (FGR) rats.Methods Twenty pregnant rats were randomly divided into two groups on their first day of pregnancy:normal-protein group (NP) and low-protein group (LP),ten in each.During pregnancy the LP group rats were fed with low-protein diet (8.00％ protein),while the NP group rats were fed with normal-protein diet (20.00％ protein).The offspring rats were fed with standard feed after 21 days of birth.Male offsprings in NP group were as control offsprings,and male FGR offsprings in LP group ware as FGR offsprings.At day 3,7,14,30,60 and 90,fasting blood of offsprings was collected to measure fasting plasma glucose (FPG) and fasting insulin(FINS).Then insulin resistance index of homeostasis model assessment (HOMA-IR) and insulin sensitivity index (ISI) were calculated to evaluate insulin sensitivity.At day 7 and 90,liver tissue of male offsprings was collected to extract DNA and total RNA.The methylation level of PPARγ gene promoter and its mRNA expression were detected by methylation specific-polymerase chain reaction (MS-PCR) and reverse transcription-RCR,respectively.The relationships between methylation of PPARγ gene promoter and mRNA expression and insulin sensitivity were analyzed by Pearson correlation and nonparametric test method.Results (1) The mean offspring birth-weight of LP group was (4.92±0.36) g,which was lower than that [(6.43±0.59) g] of control group (t=14.73,P＜0.05).In LP group,the incidence of FGR offspring was 88.2％ (97/110) and the FGR incidence of male ones was 94.1％ (48/51).(2) At day 90,compared with control offsprings,FPG [(8.95±1.83) mmol/L vs (6.21±1.14) mmol/L,t=-3.291,P＜0.05],FINS [(59.57±9.89) mU/Lvs (36.10±7.32) mU/L,t=-4.916,P＜0.05] and HOMA-IR (0.967±0.297 vs 0.410±0.135,t=-4.472,P＜0.05) of FGR offsprings were significantly higher; while ISI of FGR offspring was lower than that of control offsprings (-3.043±0.294 vs -2.172±0.354,t=4.774,P＜0.05).(3) There was no significant difference in methylation degree of PPARγ gene promoter in liver between FGR and control offsprings at day 7 (0/8 vs 2/8,Fisher exact test,P＞0.05).The methylation degree of PPARγ gene promoter in liver in FGR offsprings was significantly higher than that of control offsprings at day 90 (8/8 vs 2/8,Fisher exact test,P＜0.05).Compared with control offsprings,PPARγ gene mRNA expression level of FGR offsprings decreased significantly at day 90 (4.3.07±7.51 vs 146.72± 40.66,t=7.09,P＜0.05).mRNA expression of PPARγ gene was the lowest in exhaustive methylation offsprings (27.2± 1.6),and then in partial methylation ones (47.3±33.0),the highest in no methylation ones (144.6 ± 21.2) (P＜0.05).(4) The correlation analysis showed that PPARγ mRNA expression level negatively correlated to the level of FPG (r=-0.819),FINS (r=-0.906) and HOMA-IR (r=-0.860),P＜0.05 respectively; but positively correlated to ISI level (r=0.947,P＜0.05).Conclusions Hypermethylation in promoter region of PPARγ gene might inhibit gene transcription,and be involved in the occurrence of insulin resistance in FGR rats.

Objective To explore the effects of folic acid and vitamin B12 supplement in maternal lactation on insulin resistance in fetal growth restriction (FGR) in rat offspring.Methods Eighteen Sprague-Dawley female rats and male rats were used.Pregnant rats were randomly divided into two groups at 12 days:normal-protein group (NP,n=6) and low-protein group (LP,n=12).The were 84 FGR newborn pups in LP group (93.3％,84/90).Forty-eight FGR newborn pups were randomly selected and divided into two groups (24 in each group):intervention group and non-intervention group.The intervention group was fed with high folate and vitamin B12 in the diet;and non-intervention group and NP group were fed normal diet.All of the newborn pups were weaned at 21 days after birth and then fed with normal diet.At days 21,60 and 120 d after birth,eight pups were randomly selected from each group and fasting plasma glucose (FPG),fasting insulin (FINS),blood diglyceride (TG) and cholesterol (TC) were measured.The insulin resistance index (IRI) and insulin sensitivity index (ISI) were calculated to evaluate insulin sensitivity.Variance and Student-Newman-Keuls tests were used for statistical analysis.Results (1) The incidence of FGR:Birth weight of LP offspring [(4.44±0.58) g] was significantly lower than that of NP ones [(7.03±0.56) g] (t=15.75,P ＜ 0.05).(2) FPG and FINS:at day 21 after birth,FPG of the non-intervention group,intervention group and NP group was (4.8±0.3),(4.8±0.4) and (4.6±0.3) mmol/L (F=0.57),respectively;FINS was (4.2± 0.2),(4.5 ±0.4) and (4.3 ±0.1) mU/L (F=0.31),respectively;and there was no significant difference among the three groups (both P ＞ 0.05).At day 60,FPG of the three groups was (7.5±0.4),(6.9± 1.0) and (5.5±0.6) mmol/L (F=17.14);FINS was (14.7± 1.9),(10.7± 1.0) and (9.2± 0.7) mU/L (F=38.34),respectively.At day 120,FPG was (8.9±0.9),(8.0±0.8) and (6.4±0.7) mmol/L (F=21.60);FINS was (56.3±2.8),(38.2±2.5) and (33.1 ±2.8) mU/L (F=164.46).FPG and FINS were highest in the non-intervention group,and lowest in NP group,with significant differences among the three groups of pups (all P ＜ 0.05).(3) IRI and ISI:at day 21,IRI of the non-intervention group,intervention group and the control group was 0.9±0.1,0.9±0.1 and 0.9±0.2 (F=0.49);ISI was-(3.0±0.7),-(3.0±0.1) and-(3.0±0.3) (F=0.69);and there was no significant difference among the three groups (both P ＞ 0.05).At day 60,IRI of the three groups was 4.9±0.8,3.3±0.3 and 2.2±0.3 (F=49.48);ISI was-(4.7±0.2),-(4.3±0.1) and-(3.9±0.1) (F=63.47).At day 120,IRI of the three groups was 22.4±3.1,13.6±2.0 and 9.3±0.9 (F=75.15);ISI was -(6.2 ± 0.1),-(5.7 ± 0.1) and-(5.3 ± 0.1) (F=104.42);and there were significant differences among the three groups (all P ＜ 0.05).(4) TC and TG:at day 21,TC of the non-intervention group,intervention group and the control group was (2.0±0.1),(2.0±0.1) and (2.0±0.1) mmol/L (F=0.10);TG was (0.75±0.1),(0.77±0.1) and (0.74±0.1) mmol/L (F=0.33);and there was no significant difference among the three groups (both P ＞ 0.05).At day 60,TC of the three groups was (2.3 ± 0.1),(2.2 ± 0.1) and (2.0± 0.2) mmol/L (F=8.34);TG was (1.5 ± 0.2),(1.2±0.1) and (1.0±0.2) mmol/L (F=17.93).At day 120,TC was (2.4±0.2),(2.2±0.1) and (2.1 ±0.1) mmol/L (F=6.12);TG was (1.7±0.5),(1.2±0.3) and (l.0±0.1) mmol/L (F=9.80).The TC and TG were highest in the non-intervention group and the lowest in the control group;and there were significant differences among the three groups (all P ＜ 0.05).Conclusion Supplementing folic acid and vitamin B12 in maternal lactation can improve in some extent insulin resistance in FGR rats,but not sufficient enough to completely repair glucose and lipid metabolism.

Objective To evaluate the remission situation of early re-induction with priming low dose regimen containing G-CSF in treating acute myeloid leukemia (AML).Methods Ninety-seven AML patients in our hospital from March 2015 to January 2017 were retrospectively analyzed.All cases adopted the standard DA regimen for conducting the induction chemotherapy,among them,38 cases had significant residual disease on 14 d of induction chemotherapy,21 cases adopted the low dose priming regimen for conducting the early re-induction chemotherapy,17 cases adopted the tandard DA gregimen for conducting the re-induction chemotherapy.The complete remission(CR) rate and and adverse reactions were compared between two groups.Results The total CR rate in all 97 cases was 60.8％;among 38 cases needing re-induction chemotherapy,the CR rate in the priming regimen re-induction group was 76.2 ％,which was significantly higher than 41.2 ％ in the DA regimen re-induction group,the difference was statistically significant (P=0.028);the occurrence rates of side effects such as infection and cytopenia during re-induction chemotherapy process had no difference between two groups(P＞0.05).Conclusion For AML patients with obvious residual disease on 14 d of induction chemotherapy,adopting low dose priming regimen in re-duction chemotherapy has higher CR,which is superior to the standard DA regimen.