Objective To investigate the hemodynamics of increasing portal venous pressure(PVP) in hepatocellular carcinoma patients complicated with hepatic arterioportal vein fistulas (HAPVF)and the diagnosis and therapy of intractable upper gastrointestinal hemorrhage caused by HAPVF.Methods One hundred and fifteen cases of hepatocellular carcinoma with upper gastrointestinal hemorrhage were checked by hepatic arteriography and were treated through orifices embolization in cases with severe HAPCF by coils and/or ethanol. Results Twenty-six out of 31 patients suffering intractable upper gastrointestinal hemorrhage have severe HAPVF(the main stem of portal veins are visible).However,there are only 15 patients with light HAPVF among the 84 patients who have mild upper gastrointestinal hemorrhage (the main stem of portal veins are invisible).After the embolization,all of the 26 patients who have severe HAPVF stopped bleeding.Among them,the main stem of hepatic arteries are occluded in 2 patients. Conclusion The existence of severe HAPVF should be taken into consideration when intractable upper gastrointestinal hemorrhage occurs in hepatocellular carcinoma patients,and it can be diagnosed through hepatic artery DSA.Orifice embolization is the most effective method for such kind of hemorrhage.

Objective To investigate whether recombinant human endostatin can create a time window of vascular normalization prior to vascular pruning to alleviate hypoxia in Lewis lung carcinoma in mice. Methods Kinetic changes in morphology of tumor vasculature in response to recombinant human endostatin were detected under a confocal microscope with immunofluorescent staining in Lewis lung carcinomas in mice. The hypoxic cell fraction of different time was assessed with immunohistochemical staining . Effects on tumor growth were monitored as indicated in the growth curve of tumors . Results Compared with the control group vascularity of the tumors was reduced over time by recombinant human endostatin treatment and significantly regressed for 9 days. During the treatment, pericyte coverage increased at day 3, increased markedly at day 5, and fell again at day 7. The vascular basement membrane was thin and closely associated with endothelial cells after recombinant human endostatin treatment, but appeared thickened, loosely associated with endothelial cells in control tumors. The decrease in hypoxic cell fraction at day 5 after treatment was also found. Tumor growth was not accelerated 5 days after recombinant human endostatin treatment. Conclusions Recombinant human endostatin can normalize tumor vasculature within day 3 to 7, leading to improved tumor oxygenation. The results provide important experimental basis for combining recombinant human endostatin with radiation therapy in human tumors.

AIMTo determine the involvement of extracellular signal-regulated kinase 1/2 (ERK1/2) pathway in the expression of endothelin receptor type B (ETB) during culture.

METHODSSB386023, a specific inhibitor for ERK1/2 pathway, was used to define the intracellular signaling pathway for the upregulation of ETB receptors and sarafotoxin 6c (S6c), a selective agonist for ETB receptors, induced contraction in isolated rat superior mesenteric arteries. The contraction was recorded by a sensitive in vitro myograph and the receptor mRNA was quantified by a real-time PCR. The phosphorylated ERK1/2 proteins were analyzed by phosphoELISA assay.

RESULTSS6c induced strong contractile responses of the artery after culture for 24 h, while there was no response to S6c in fresh vessel segments. The enhanced contractile response to S6c paralleled with an increase of mRNA for ETB receptors. The phosphorylated ERK1/2 proteins significantly increased after culture for 3 h. After co-culture with SB386023 for 24 h, S6c-induced contractions significantly decreased with reduction of Emax from (217 +/- 14) % to (127 +/- 23) % (P <0.01). This response paralleled with a decreased level of ETB receptor mRNA.

CONCLUSIONERK1/2 pathway was involved in the up-regulation of ETB receptors on smooth muscle cells isolated from rat mesenteric arteries during culture.

Animals ; Cells, Cultured ; Male ; Mesenteric Arteries ; cytology ; Mitogen-Activated Protein Kinase 1 ; antagonists & inhibitors ; metabolism ; Mitogen-Activated Protein Kinase 3 ; antagonists & inhibitors ; metabolism ; Muscle Contraction ; drug effects ; Muscle, Smooth, Vascular ; cytology ; metabolism ; Organ Culture Techniques ; Phosphorylation ; RNA, Messenger ; biosynthesis ; genetics ; Rats ; Rats, Sprague-Dawley ; Receptor, Endothelin B ; biosynthesis ; genetics ; Signal Transduction ; Up-Regulation ; Vasoconstrictor Agents ; pharmacology ; Viper Venoms ; pharmacology

Objective To study the effects of erythrecyte on brain edema after traumatic intrace- rebral hemorrhage(TICH)and explore the mechanisms of erythrocyte in brain edema development follow- ing TICH.Methods Firstly,the brain injury model of SD rat was established by applying a free-fall- ing device,then whole blood(WB),lysed RBC(LRBC)or parked RBC(PRBC)were infused with ste- reotactic guidance into injured cortex to produce the model of TICH.All rats were killed at 1,3,and 5 days after injury.The brain water content was measured,immunohistochomistry(SABC)was applied to test HO-1 and TNF-?expressions.Results 1.In WB group,PRBC group and TBI group,the brain water content was the highest on the third day.The brain water content of LRBC group was markedly higher on the first day than on the third and fifth days.Comparison among the four groups showed the wa- ter content was the highest on the 1st day in LRBC group,and on the 3rd day in WB and PRBC groups; there was no significant difference among the four groups on 5th day.2.The positive expression of HO-1 and TNF-?coincided with the change of the water content in groups of WB,PRBC and LRBC.Conclu- sions In rat model of TICH,RBC plays an important role in delayed brain edema formation(3 days after injury),but has no influence at early stage(1 day after injury).The mechanisms of delayed brain edema involves RBC breakdown and inflammation reaction.

Background The proliferation and migration of vascular endothelial cells is a primary link during angiogenesis.Studies showed that heat shock protein B6 (HspB6) promotes the secretion of multiple angiogenesis-related factors and therefore leads to neovascularization.Understanding the effects of neutralizing HspB6 antibody on the biological behavior of human choroidal vascular endothelial cells has an important significance in the target treatment of choroidal neovacularization diseases.Objective This study was to address the role and mechanism of neutralizing HspB6 antibody in tube formation of human choroidal vascular endothelial cells.Methods Human choroidal vascular endothelial cell line was normally cultured and harvested for total RNA extraction.Expressions of HspB6 mRNA and protein in human choroidal vascular endothelial cells were detected by reverse transcription PCR (RT-PCR) and flow cytometry (FCM).The cells were seeded on 96-well plate covered with matrigel at the density of 2×104/hole.Then the neutralizing HspB6 antibody at the concentration of 100 μg/Land 500 μg/L was added into the medium respectively,and the control cells were set without the addition of HspB6 antibody.The number of capillary tubes was calculated 12 hours after culture by three-dimensional matrigel assay.In addition,0,50,100,500 μg/L of neutralizing HspB6 antibody were added into the cell medium separately for 24hours,cell counting kit-8 (CCK-8) method was employed to assay the inhibitory rate(IR) of the cells.Transwell test was used to count the cell number across chamber membrane for the evaluation of migration ability of the cells.The apoptosis of the cells was assayed by FCM.Results Both HspB6 mRNA and protein were expressed on human choroidal vascular endothelial cells.The number of capillary tube formation of human choroidal vascular endothelial cells was (67.25±5.75),(60.39±6.41) and (39.76±10.73) /field in the 0,100 and 500 μg/L neutralizing HspB6 antibody groups,with significant difference among them (F =10.210,P =0.012),and the tube number was significantly less in the 500 μg/L neutralizing HspB6 antibody group compared with 0 μg/L neutralizing HspB6 group (P =0.005).The IR of neutralizing HspB6 antibody to the cellular proliferation and migration was enhanced with the increases of concentration and time lapse(Fconcentration =7.485,P =0.002 ; Ftime =16.684,P =0.001).The number of the cells through Transwell chamber membrane was 14.0 ± 2.5,11.1 ± 0.8,6.6 ± 0.1,6.7 ± 0.2 in the 0,50,100,500 μg/L neutralizing HspB6 antibody group respectively,and that in the 100 μg/L and 500 μg/L neutralizing HspB6 antibody group was lessened in comparison with the 0 μg/L neutralizing HspB6 antibody group(both at P=0.000).The apoptosis rate of the cells was (22.73 ± 2.53)％ in the neutralizing HspB6 antibody group,which was significantly lower than (13.33±2.08) ％ of the control group (t=4.967,P=0.008).Conclusions Neutralizing HspB6 antibody inhibits capillary tube formation of human choroidal endothelial cells in vitro in dose-and timedependent manner,probably through suppressing the proliferation and migration and promoting the apoptosis of choroidal endothelial cells.

OBJECTIVETo investigate the effect of heat exposure during the second week of pregnancy on placental development and intrauterine growth of fetal rats.

METHODS24 pregnant rats were either exposed or not to a temperature of 35∓1 degrees celsius; during the second week of pregnancy. The body weight gain of the pregnant rats was measured regularly, and in late pregnancy, the pregnant rats were dissected and the number, weight, length, tail length, appearance of the offspring rats, number of live and still births, and the placental weight were recorded. The expressions of HSP70, Bax and Bcl-2 in the placenta were determined.

RESULTSCompared with the control group, the pregnant rats in heat exposure group had significantly lower body weight at the end of pregnancy and gestational weight gain, and the body weight, body length and tail length of the offspring rats were also significantly lower or smaller (P<0.05). The placental weight was comparable between the two groups. The placental expressions of HSP70,Bax,and Bcl-2 were significantly higher in the heat exposure group than in the control group (P<0.05).

CONCLUSIONHeat exposure during the second trimester of pregnancy has adverse effects on placental development and intrauterine growth of the fetal rats by inducing heat shock response of placental tissue and apoptosis of the placental cells.

OBJECTIVETo evaluate the effect of post-treatment PSA kinetics on the prognosis of prostate cancer (PCa).

METHODSWe retrospectively reviewed the clinical data of 114 cases of locally advanced PCa treated by maximal androgen blockade (MAB) combined with brachytherapy, and analyzed the association of the changes in PSA kinetics with the prognosis of the patients.

RESULTSThe median survival time of the patients was 81 (15 - 144) months, with 1-, 3- and 5-year survival rates of 91. 23%, 78.07% and 68.42% , respectively. Univariate analysis indicated that the baseline PSA level, PSA nadir, the time of PSA decreasing to nadir, PSA doubling time, and the extent of PSA declining were all predictive factors for the survival time of the PCa patients. Multivariate analysis demonstrated that PSA nadir, the time of PSA decreasing to nadir, and the extent of PSA declining were three independent prognostic factors, which prolonged the long-term survival of the patients by 1.7, 3.2 and 6.8 times, respectively.

CONCLUSIONFor locally advanced PCa treated by MAB combined with brachytherapy, PSA nadir <1 micro g/L, the time to nadir <3 months, and the extent of PSA declining >96% are independent prognostic factors.

Aged ; Aged, 80 and over ; Androgens ; administration & dosage ; therapeutic use ; Brachytherapy ; Humans ; Male ; Middle Aged ; Prognosis ; Prostate-Specific Antigen ; metabolism ; Prostatic Neoplasms ; metabolism ; therapy ; Retrospective Studies

Animals ; Female ; Macrophages ; microbiology ; Mice ; Mice, Inbred BALB C ; Microscopy, Electron ; Mycobacteriophages ; physiology ; Mycobacterium tuberculosis ; virology ; Virus Replication

Objective To evaluate the efficacy and safety of biphasic insulin aspart 30 (BIAsp30)plus metformin in type 2 diabetes subjects switching from basal insulin plus oral antidiabetic drugs (OAD)Methods During 16 weeks, multiple-center, open-label, and single-arm study including 2 weeks of screening period,4 weeks of run-in period,and 16 weeks of treatment period were carried out. Subjects with type 2 diabetes mellitus inadequately controlled on basal insulin therapy with or without oral antidiabetic drugs were switched to twice-daily BIAsp30 plus metformin with dose titration to achieve fasting plasma glucose target. Results Of the 293 Chinese subjects exposed to trial drugs [age: ( 54.0±9.6 ) years, diabetes duration: ( 8.54±5.49 ) years, body mass index: (24.89±3.28)kg/m2, baseline HbA1c: 8.16% ±0.89%], 122 were previously treated with basal insulin analogues and 169 with human basal insulin. At end of the trial ,the mean reduction of HbA1 c was 1.30% ±0.96% (P＜0. 01 ). The proportion of patients achieved HbA1c＜7.0% and HbA1c ≤6.5% was 60.4% and 38.9% respectively. 8-point plasma glucose measurements showed significant improvements at all the time points examined ( all P＜0. 01 ) ,and the average value of all 8 points measured decreased from ( 10.53±2.58 ) mmol/L atbaseline to (7.79± 1.58 ) mmol/L at the end of treatment ( P＜0. 01 ), reduced by 2.76 mmol/L. Postprandial glucose increments were significantly reduced after breakfast ( -1.73 mmol/L,P＜0.01 )and dinner ( -1.28 mmol/L,P＜0.01 ), while no significant reduction was observed after lunch ( -0.09 mmol/L, P = 0. 734 5 ). No severe adverse effect and no major hypoglycemia were reported. The overall hypoglycaemia rate was 2.68 events/subject year. The average weight gain was (0. 76 ±0. 14 )kg (P＜0. 0l ). Conclusion Twice-daily BIAsp30 plus metformin is effective and safe to type 2 diabetic subjects inadequately controlled on basal insulin treatment.BIAsp30 treatment should be considered for type 2 diabetic subjects who have unsatisfactory response to previous basal insulin treatment.

OBJECTIVETo analyze the clinical characteristics and effects of rehabilitation treatment on hemophiliacs with iliopsoas hemorrage.

METHODSThe hemophilia patients with iliopsoas bleeding treated in Peking Union Medical College Hospital between January 2006 to December 2010 were enrolled. The clinical characteristics including symptoms, signs, complications, and rehabilitation treatment were analyzed retrospectively.

RESULTSAll of the forty-one hemophiliacs with iliopsoas bleeding were male, 20 cases wee the left bleeding, 18 the right, and 3 the bilateral. The median median age was 18 (6 - 61) years old(y). The median age of the iliopsoas bleeding for the first time was 17 (6 - 20) y. 34 patients accompanied with femoral nerve injury, 19 of them had secondary knee bleeding on the same side. 20 patents had quadriceps atrophy. Pelvic pseudotumor developed in 2 patients and permanent abnormal posture in 2 patients. The main finding of the ultrasound image was low-echo mass in iliopsoas muscles or inguinal region. 34 patients received rehabilitation therapy for 8 - 12 weeks under the support of factor replacement, complete hematomas absorption in 33 of them, with hip range of motion recovering back to baseline. 27 of 32 (84.4%) cases with femoral nerve injury got quadriceps strength above 4/5 grade, 20 cases of femoral nerve injury (62.5%) still had numbness on front of their thigh after treatment.

CONCLUSIONSIn this cohort of iliopsoas bleeding, most of the patients are adolescent. High prevalence of the femoral nerve injury and the secondary knee bleeding are found. Rehabilitation treatment under the support of factor replacement is safe and effective on hematoma absorption and neurological function recovery.

Adolescent ; Adult ; Child ; Hematoma ; etiology ; rehabilitation ; Hemophilia A ; complications ; rehabilitation ; Hemorrhage ; etiology ; rehabilitation ; Humans ; Male ; Middle Aged ; Muscular Diseases ; diagnosis ; etiology ; rehabilitation ; Psoas Muscles ; physiopathology ; Retrospective Studies ; Young Adult