Gastric cancer is a kind of disease with high incidence and mortality rate,most gastric cancer cases are diagnosed in an advanced,and chemotherapy is the main treatment.Drug resistance is one of the most important causes of therapy failure in gastric cancer patients.It has revealed that the mechanism of tumor resistance mainly involves alterations in cell cycle and proliferation,enhanced DNA repair capacity,defective apoptosis,damaged host immune,altered metabolism of drugs and so on.In recent years,an important molecule-microRNA(miRNA)that regulates the biological behavior of cell has attracted more and more attention.Studies have confirmed that numerous miRNAs can regulate the drug resistance of gastric cancer cells via BCL-2 signaling pathway,PTEN/PI3K/AKT pathway,ABCB1(MDR1/P-gp),autophagy,cell cycle and so on.

Objective To observe the diagnostic value of telomerase,VEGF,CD44_ V6 ,MMP_2,MMP_9and their combined examination in distinguishing malignant pleural effusion from benign one.Methods Sixty patients with pleural effusions were observed,thirty of them sufferring from malignant pleural effusion and thirty of them sufferring from benign one.The expression of telomerase,CD44_ V6 ,VEGF,MMP_2,MMP_9were tested in the pleural effusion by RT-PCR and ELISA technique.The sensitivity and the specificity of each examination method were calculated,in order to find out appropriate combination.Results As single-item detection,the diagnosetic value of VEGF was the best,the cutoff of VEGF was 181.1pg/ml,the sensitivity of VEGF examination was 90.0%,and the specificity was 86.7%.The sensitivity and the specificity of combined examination VEGF+CD44_ V6 and VEGF+MMP_2 were the best,the sensitivity of VEGF+CD44_ V6 was 83.3%,and the specificity was 90.0%.The sensitivity of VEGF+MMP_2 was 80.0% and the specificity was 93.3%.Conclusion The level of telomerase,VEGF,CD44_ V6 ,MMP_2,MMP_9in malignant pleural effusion is clearly higher than that in benign pleural one,the difference having significant statistic meaning.VEGF has higher sensitivity and specificity .Of combined examination,VEGF+CD44_ V6 and VEGF+MMP_2 have higher sensitivity and specificity.

Objective:To explore the changes of neuron-specific enolase (NSE) and S-100β protein (S-100β) during perioperative period in infants undergoing living liver transplantation and examine the effect of brain injury.Methods:From January 2015 to January 2016 in Department of Anesthesiology First Central Clinical College Tianjin Medical University, study group was composed of forty infants of congenital biliary atresia with an age range of (4-12) months, a body weight of (4-10) kg and American Society of Anesthesiologists (ASA) class Ⅲ/Ⅳ. Another 40 infants undergoing general surgery were selected as control group. In study group, blood samples were harvested from central vein pre-operation (T0), before skin incision (T1), 30 min after anhepatic phase (T2), 1 h of neohepatic phase (T3) and 24h after hepato-reperfusion (T4). In control group, blood samples were collected at pre-operation (T0) and 24 h post-operation (T4). Serum levels of S-100β, NSE, heart rate (HR), mean arterial blood pressure (MAP), central venous pressure (CVP) and bispectral index (BIS) were monitored at T1-4 and end of surgery. All children were assessed by Bayley Scale of Infant Development (BSID) at Day 1 pre-operation and 2/4 weeks post-operation for observing mental and motor development status. The results were described with mental development index (MDI) and psychomotor development index (PDI). Pediatric anesthesia emergence delirium (PAED) was employed for evaluating the severity of delirium during the recovery stage at 30 min and 2/4h post-extubation.Results:In study group, serum levels of S-100β and NSE changed significantly during non-hepatic and neohepatic reperfusion phases. After inferior vena cava occlusion, serum concentrations of S-100β and NSE spiked ( P<0.05) and gradually recovered during neohepatic reperfusion period ( P<0.05). No significant inter-group difference existed in serum S-100β or NSE at T4 ( P>0.05). In study group, as compared with Day 1 pre-operation, MDI/PDI decreased at Week 2 post-operation ( P<0.05) and increased from Month 1 post-operation ( P<0.05). Both MDI and PDI were lower than control group before and at Week 2 post-operation ( P<0.05). MDI/PDI of study group basically reached the preoperative level at Month 1 post-operation ( P<0.05). In control group, no significant difference existed in MDI/PDI at Day 1 pre-operation and Week 2/4 post-operation ( P>0.05). In study group, the delirium rate was up to 30% post-extubation and decreased at 2/4h post-extubation. In control group, the incidence of delirium was low at 30 min and 2/4h post-extubation ( P<0.05). Conclusions:Perioperative evaluations of serum levels of NSE and S-100β are significant for predicting the postoperative onsets of delirium and cognitive impairment in children with living donor liver transplantation.

Objective To explore the effects of impaired glucose metabolism and impaired blood lipoprotein metabolism on heart rate variability(HRV) in aged male hypertension patients and to have an insight into the correlation between the years of impaired glucose metabolism and the patients’ HRV. Methods 120 male subjects were divided into three groups: simple hypertension patients (group A, 40 people), hypertension patients with diabetes mellitus (group B, 40 people), and hypertension patients with diabetes mellitus and impaired blood lipoprotein metabolism (group C, 40 people). All subjects had 24h recordings of ECG. The data of HRV time domain were collected and analyzed to gain an insight into the effects of the impaired glucose metabolism and impaired blood lipoprotein metabolism on patients’ HRV. In group C, patients were divided into normal TC subgroup and high TC subgroup according to the index of TC (TC

Objective By detecting the variation of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) DNA methylation in preeclampsia-like mouse models generated by different ways, to explore the roles of multifactor and multiple pathways in preeclampsia pathogenesis on molecular basis. Methods Established preeclampsia-like mouse models in different ways and divided into groups as follows: (1) Nw-nitro-L-arginine-methyl ester (L-NAME) group: wild-type pregnant mouse received subcutaneous injection of L-NAME;(2) lipopolysaccharide (LPS) group:wild-type pregnant mouse received intraperitoneal injection of LPS; (3) apolipoprotein C-Ⅲ (ApoC3) group: ApoC3 transgenic pregnant mouse with dysregulated lipid metabolism received subcutaneous injection of L-NAME;(4)β2 glycoprotein I (β-2GPI) group:wild-type pregnant mouse received subcutaneous injection ofβ-2GPI. According to the first injection time (on day 3, 11, 16 respectively), the L-NAME, LPS and ApoC3 groups were further subdivided into:pre-implantation (PI) experimental stage, early gestation (EG) experimental stage, and late gestation (LG) experimental stage.β-2GPI group was only injected before implantation. LCHAD gene methylation levels in placental were detected in different experimental stage. Normal saline control groups were set within wild-type and ApoC3 transgenic pregnant mice simultaneously. Results (1) CG sites in LCHAD DNA:45 CG sites were detected in the range of 728 bp before LCHAD gene transcription start site, the 5, 12, 13, 14, 15, 16, 19, 24, 25, 27, 28, 29, 30, 31, 32, 34, 35, 43 CG sites were complex sites which contained two or more CG sequences, others were single site which contained one CG sequence. The 3, 5, 6, 11, 13, 14, 18, 28 sites in L-NAME, LPS, ApoC3 and β-2GPI groups showed different high levels of methylation; the 16, 25, 31, 42, 44 sites showed different low levels of methylation; other 32 sites were unmethylated. (2) Comparison of LCHAD gene methylation between different groups:the methylation levels of LCAHD gene at 3, 11, 13, 14, 18 sites in L-NAME, LPS, ApoC3 andβ-2GPI groups were significantly higher than those in the normal saline control group (P<0.05); and the methylation levels of 42, 44 sites in these groups were significantly lower than those in the normal saline control group (P<0.05). (3) Methylation of LCHAD gene at the same site between different experimental stages: ① The 3, 11, 18 sites of EG experimental stage was significantly lower than PI and LG experimental stage in L-NAME group (P<0.05);the 3, 11, 18 sites of PI experimental stage was significantly lower than EG and LG experimental stage in LPS group (P<0.05);these sites of PI experimental stage was significantly higher than EG and LG experimental stages in ApoC3 group (P<0.05).②The methylation of site 5 in L-NAME and LPS groups were significantly higher than that of the normal saline control group (P<0.05), and the LG experimental stages were significantly higher than other stages, but in ApoC3 group , only PI and EG stages were significantly higher than the normal saline control group (P<0.05).③At site 6 in L-NAME group which showed high methylation level was significantly higher than the same site in other groups which showed low methylation level (P<0.05).④At 13, 14 sites, earlier preeclampsia onset caused a lower methylation level in L-NAME group, but PI experimental stage was significantly higher than EG and LG experimental stages in LPS group (P<0.05), EG experimental stage was significantly higher than PI and LG experimental stages in ApoC3 group (P<0.05). ⑤ At site 28, earlier preeclampsia onset caused a higher methylation level in L-NAME group, but PI experimental stage was significantly lower than EG and LG experimental stages in LPS group (P<0.05), EG experimental stage was significantly higher than PI and LG experimental stages in ApoC3 group (P<0.05).⑥The 16, 25, 31 sites in ApoC3 group were significantly higher than other groups (P<0.05). ⑦ At site 42 in β-2GPI group was unmethylated, but it in other groups showed low methylation level, the methylation level of site 42 inβ-2GPI group was significantly lower than that in other groups (P<0.05). Conclusions The methylation of 6 and 42 CG sites may be related to LCHAD gene expression in placenta of L-NAME and β-2GPI induced preeclampsia-like models respectively;LCHAD gene expression and DNA methylation may not have obviouscorrelation in LPS and ApoC3 induced preeclampsia-like models. Differences exist in LCHAD DNA methylation in preeclampsia-like models generated by different ways, revealed a molecular basis to expand our understanding of the multi-factorial pathogenesis of preeclampsia.

Objective To evaluate the relationship between 18F-FDG uptake and P-gp expression in Bcap37 or Bcap37/MDR1 tumor-bearing BALB/c nude mice.Methods Bcap37 or Bcap37/MDR1 cells were injected into BALB/c nude mice (1× 107cells/ml,0.2 ml/mouse) to construct mice models.Bcap37 (n=5) or Bcap37/MDR1 (n=5) tumor-bearing mice fasted for 6 h before imaging.After anesthesia,the mice were injected with 7.4 MBq of 18F-FDG via tail vein.The dynamic microPET scans were carried out for 90 min.On the microPET images,the ROI was drawn and the TAC was obtained.The next day,those 10 mice underwent dynamic microPET scans after injected with elacridar (GF120918) and 18F-FDG.Another 10 mice,5 with Bcap37 tumors and 5 with Bcap37/MDR1 tumors,were used.After 7.4 MBq 18F-FDG with or without 2.0 mg/kg GF120918 was administered via tail vein,microPET images were acquired at 60 min.ROI was drawn over the tumors and SUV was obtained.Two-sample t test was used to analyze the data.Results GF120918 did not significantly alter the 18F-FDG accumulation curve in Bcap37 tumors,but significantly enhanced the 18F-FDG accumulation in Bcap37/MDR1 tumors.GF120918 did not influence 18F-FDG uptake (SUV) in Bcap37 tumors (1.052±0.028,1.028±0.045,t =1.792,P＞0.05),but significantly increased the SUV in Bcap37/MDR1 tumors (1.015±0.043,0.712±0.031,t=3.365,P＜0.05);The SUV of 18 F-FDG in Bcap37 tumors was significantly higher than that in Bcap37/MDR1 tumors without injection of GF120918 (t =3.952,P＜0.05).The SUV was not significantly different when GF120118 was injected (t=1.835,P＞0.05).Conclusions 18F-FDG is a substrate of P-gp.18F-FDG imaging combined with GF120918 injection may be an effective noninvasive method for the detection of tumor's MDR.

Objective To evaluate the effect of P-gp inhibitors of verapamil (VER) and GF120918 on 18F-FDG uptake in Bcap37 and Bcap37/multidrug resistancce (MDR)1 cell lines in vitro,and to explore the relationship between 18F-FDG uptake and P-gp expression at cellular level.Methods Bcap37 and Bcap37/MDR1 cells were seeded into 6-well plates at a density of 1 × 106 per well.Three days later,37 kBq/ml 18F-FDG,or 37 kBq/ml 18F-FDG + 100 μmoL/L VER,or 37 kBq/ml 18F-FDG + 50 μmol/L GF120918 were added into each well.Mter incubated for 10,30,60 and 120 min at 37 ℃ and in 5％ CO2,the medium was removed and the cells were washed three times with 1 ml ice-cold PBS immediately.The radioactivity of 18 F-FDG was measured using a gamma counter.The uptake of 18F-FDG was expressed as the ratio of 18F-FDG radioactivity in Bcap37 or Bcap37/MDR1 cells and the overall radioactivity added to the cells in each well.The t test was used for statistical analysis.Results 18F-FDG uptake was higher in Bcap37/MDR1 cells than that in Bcap37 cells after incubated for 10 min.The uptake rate was (1.88 ±0.19) ％ in Bcap37/MDR1 cells and (1.37 ± 0.18) ％ in Bcap37 cells (t =7.832,P ＜ 0.05).On the contrary,18 F-FDG uptake was significantly higher in Bcap37 cells than that in Bcap37/MDR1 cells after incubated for 60 and 120 min.The uptake rates were (2.29 ±0.23)％ and (2.34 ±0.15)％ in Bcap37 cells,(1.47 ±0.14)％ and (1.53 ±0.22)％ in Bcap37/MDR1 cells (t =8.437,8.283,both P ＜ 0.05).18 F-FDG uptake was significantly higher with VER or GF120918 in Bcap37/MDR1 cells than that without VER or GF120918 after the incubation of 60 and 120 min (t =9.032,9.243 and 8.765,8.803,all P ＜ 0.05).The uptake rates with VER or GF120918 were (2.45 ±0.21)％ and (2.46 ±0.25)％,(2.50 ±0.24)％ and (2.48 ±0.27)％.There was no significant difference of 18F-FDG uptake in Bcap37 cells with or without VER or GF120918.Conclusions 18F-FDG is a substrate of P-gp at cellular level.P-gp may act as an efflux pump to reduce 18F-FDG uptake in Bcap37/MDR1 cells.The uptake of 18F-FDG can be used to evaluate the function of P-gp in tumor cells.

Objective To evaluate the safety and effectiveness of endourological techniques in the treatment of benign prostate hyperplasia (BPH) in elderly high-risk patients.Methods A total of 202 BHP patients over 70 years old were treated with endourological techniques and followed up for 3-24 months.Patients were divided into transurethral resection of the prostate(TURP) group (n=90)and transurethral plasmakinetic resection of the prostate(PKRP) group (n =112).Results Compared with pre-treatment,the scores of IPSS and quality of life (QOL),residual urine volume and Qmax were improved in the TURP group after treatment [(6.3±1.2) vs.(27.8±2.5),(1.0±0.4)vs.(5.5±1.1),(18.0±2.8) ml vs.(95.0±18.0) ml,(17.5±1.4) ml/s vs.(5.4±2.0) ml/s,respectively,all P＜0.05].Compared with before treatment,the scores of IPSS and QOL,residual urine volume and Qmax were also improved in the PKRP group after treatment [(8.4 ± 2.5) vs.(27.9±2.3),(1.0±0.4) vs.(1.5±0.5),(25±4) mlvs.(150±26) ml,(19±2.3) ml/svs.(7.0±2.3) ml/s,respectively,all P＜0.05].There were no significant differences in IPSS,QOL,Qmax and RUV between the two groups after treatment (P＞0.05),but the complication incidence was less in PKRP group than in TURP group (6.25％ vs.22.2％,x2 =10.99,P＜0.05).Conclusions PKRP is a safe and effective therapy for elderly high risk patients with BPH.The individual treatment,intensive monitoring and adjustment before operation,and skilled manipulation are the key points to the successful operation.

The effect of realgar nanoparticles (NPs) on endogenous small molecules in rat kidney was analyzed by mass spectrometry-based metabolomics.The relationship between the changes of metabolites and the nephrotoxicity of realgar NPs was also discussed to provide a basis for the further toxicity study and the clinical application of realgar NPs.SD rats were randomly divided into seven groups,including control group,three doses (40,200,1 000 mg/kg) of relegar and realgar NPs groups,respectly.After 28 days of continuous intragastric administration,all rats were sacrificed and their serum and kidney samples were collected.The toxic effect of realgar NPs on kidney tissues were examined by biochemical analysis and histopathologic examination,which revealed a dosedependent nephrotoxicity induced by realgar NPs.The LC-MS and GC-MS analysis were performed for the subsequent metabolomics study.A series of 32 metabolites were found to be altered significandy in the kindey of realgar NPs treated rats,and might serve as potential nephrotoxicity biomarkers.The results of metabolic pathway analysis indicated that the nephrotoxicity of realgar NPs might be associated with the disorders of the amino acids and phosphatidic acid metabolism.

Objective To evaluate the efficacy of left ventricular ejection time (LVET) in guiding the volume management during liver transplantation.Methods Sixty American Society of Anesthesiologists physical status Ⅱ or Ⅲ patients,aged 32-64 yr,weighing 54-93 kg,of Child-Pugh grade A or B liver function,scheduled for elective the first liver transplantation with general anesthesia,were divided into either control group (group C) or transesophageal echocardiography (TEE) monitoring group (group TEE),with 30 patients in each group.In group C,the fluctuating range of mean arterial pressure,heart rate and central venous pressure was maintained less than 20％ of the baseline value,and the urine volume was maintained ＞1 ml · kg-1 · h-1.LVET was maintained between 0.35-0.40 s in group TEE.The consumption of intraoperative vasoactive agents (dopamine,norepinephrine,epinephrine),volume of fluid infused,volume of blood transfused,blood loss and urine volume were recorded.The occurrence of adverse events was observed during the perioperative period,and postoperative extubation time and intensive care unit residence time were also recorded.Results Compared with group C,the consumption of intraoperative dopamine and norepinephrine was significantly decreased,the urine volume was increased,the incidence of myocardial ischemia,pulmonary edema and renal failure in the perioperative period was decreased,and the postoperative extubation time and intensive care unit residence time were shortened in group TEE (P＜0.05).There was no significant difference between the two groups in the volume of crystalloid,colloid,red blood cells and plasma infused or blood loss (P＞0.05).Conclusion LVET produces good efficacy in guiding the volume management during liver transplantation.