AIM:To evaluate effects of different chemotherapeutic agents on reversing the acquired resistance to TRAIL gene and clarify the involved mechanisms in DLD1-TRAIL/R colon cancer cells.METHODS: Human colon cancer cell line DLD1-TRAIL/R cells that were resistant to TRAIL-expressing adenovector(Ad/gTRAIL) were treated with Ad/gTRAIL combined with different chemotherapeutic agents.Then,the cell viability was measured by MTT method,and apoptotic signaling conditions,including activation of caspase-3 and caspase-8,expression of Bax and Bcl-XL,were measured by Western blotting analysis.RESULTS: In vitro data showed that several chemotherapeutic agents,including 5-fluorouracil(5-FU) and mitomycin c(MMC),overcome the acquired resistance to TRAIL gene in DLD1-TRAIL/R colon cancer cells.The combination of Ad/gTRAIL and 5-FU effectively suppressed tumor growth in vivo in subcutaneous tumors established from DLD1-TRAIL/R cells.Further data showed that treatment with the combination of Ad/gTRAIL and 5-FU or MMC led to enhance the activation of caspase-3.Moreover,MMC but not 5-FU induced overexpression of Bax gene that was sufficient to overcome the resistance to TRAIL gene in DLD1-TRAIL/R cells.CONCLUSION: Chemotherapeutic agents,such as 5-FU and MMC,overcome the acquired resistance to TRAIL gene in DLD1-TRAIL/R cells.The candidate mechanisms for MMC but not 5-FU to overcome this resistance might involve the induction of over-expressed Bax protein in DLD1-TRAIL/R cells.

Obejective To explore mechanism and inhibition of thalido-mide ( Tha ) combined with epirubicine ( Epi ) on the growth of trans-planted H22 hepatocellular carcinoma in mice.Methods Forty male Kunming mice were transplanted by right armpit injection of 200 μL (2.0 ×106 cells) H22 tumor cells.Then these mice were randomly di-vided into four groups, ten mice in each group.Saline group, Tha group ( oral 200 mg · kg -1 · d-1 for 10 consecutive days ); Epi group ( intra-peritoneall injection, 50 mg · m-2 , once ) , Tha combined with Epi group ( oral Tha 200 mg · kg -1 · d-1 , for 10 consecutive days; Epi intraperitoneall injection, 50 mg· m-2 , once).The tumor diameter and short diameter was measured every 7 d, and twenty -eighth days were sacrificed by dislocation , tumor tissue was obtained.The expression of B-cell lymphoma-2 ( Bcl -2 ) , Bcl -2 associated X protein ( Bax ) , and vascular endothelial growth factor ( VEGF ) mRNA was measured by RT -PCR.The expression of Bax , Bcl -2 protein was measured by Western blot.The expression of VEGF protein was measured by immunohistochemical.Results After 21 days, compared with saline group (0.90 ±0.01), Epi group (0.67 ±0.01), Tha group (0.62 ±0.02) and combined group (0.43 ±0.01) transplanted tumor volume was decreased (P<0.05).Compared with Epi group and Tha group, combined group transplanted tumor volume was decreased (P<0.05).Compared with saline group, the expression of Bcl-2 and VEGF mRNA and protein was down -regulated ( P<0.05 ) , the expression of Bax mRNA and protein was up-regulated in Epi group, Tha group and combined group (all P<0.05).The expression of Bax, Bcl -2 and VEGF mRNA and protein had significant difference in combined group compared with Tha and Epi group (P<0.05). Conclusion Tha and Epi could inhibit the growth of transplanted H22 hepatocellular carcinoma, related to lower VEGF and Bcl-2 expression as well as higher Bax expression , and Tha combined with Epi might have synergistic effect.

OBJECTIVETo evaluate the efficacy and safety of long-term on-demand use of vardenafil in the treatment of erectile dysfunction (ED).

METHODSWe conducted a questionnaire investigation among 891 ED patients treated by on-demand use of oral vardenafil at 20 mg every 3 days from March 2007 to January 2010, covering the general information of the patients, their need for and attitudes towards the treatment, clinical efficacy and adverse events of the drug, and satisfaction of the patients and their partners after 12 weeks of treatment.

RESULTSTreatment and follow-up were completed in 700 patients, of whom 504 (72%) achieved sufficient hardness and duration of penile erection and overall sexual satisfaction, 84 (12%) admitted to improvement of erectile hardness and duration but not adequate satisfaction, and the other 112 (16%) experienced no significant changes. Significant differences were found in IIEF-5 scores, Rigiscan test results and partners TSS scores before and after the treatment (P < 0.05). Most frequent adverse events included flushing (15%), dizziness and headache (10%), dyspepsia (3%), and nasal congestion (1%).

CONCLUSIONLong-term on-demand use of oral vardenafil, in addition to its safety and good tolerance, can effectively improve the erectile function of ED patients, their success rate of sexual intercourse, and overall quality of sexual life.

Adult ; Erectile Dysfunction ; drug therapy ; Follow-Up Studies ; Humans ; Imidazoles ; adverse effects ; therapeutic use ; Male ; Piperazines ; adverse effects ; therapeutic use ; Sulfones ; adverse effects ; therapeutic use ; Treatment Outcome ; Triazines ; adverse effects ; therapeutic use ; Vardenafil Dihydrochloride ; Vasodilator Agents ; adverse effects ; therapeutic use ; Young Adult

This study was aimed to compare the expression level of eIF4E in patients with leukemia and normal controls, and to explore its role in leukemogenesis. White blood cells were collected in 76 leukemia patients and 10 healthy volunteers. The mRNA and protein expressions of eIF4E were detected by QT-PCR and Western blot in 39 cases of acute myeloid leukemia (AML), 15 cases of chronic myeloid leukemia (CML), 22 cases of acute lymphocytic leukemia (ALL) and 10 healthy volunteers as normal controls. The results demonstrated that compared with normal controls, the absolute expression levels of eIF4E mRNA increased in patients with AML, ALL and CML in blastic phase (P < 0.05), but had no significant change between groups of CML in chronic and accelerated phase although some increasing in group of CML in accelerated phase. The relative expression level of eIF4E mRNA had no significant change in AML, ALL, CML groups except the two subtypes of leukemia M4 and M5. Furthermore, the protein expression level in group of CML in accelerated phase and blastic phase and all acute leukemia patients including AML and ALL were higher than that in normal controls (P < 0.05). It is concluded that although its mRNA relative expressions had no significant change in most leukemia patients, the absolute expression level of eIF4E mRNA and its protein expression is up-regulated in most leukemia patients, which may play an important role in leukemogenesis, so the eIF4E may be a promising target for leukemia therapy and eIF4E-targeted therapy may be an option especially for the relapse and refractory leukemia.
Adolescent ; Adult ; Aged ; Case-Control Studies ; Eukaryotic Initiation Factor-4E ; genetics ; metabolism ; Female ; Humans ; Leukemia ; genetics ; metabolism ; pathology ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Leukemia, Myeloid, Acute ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; RNA, Messenger ; genetics ; Young Adult

Objective To explore the relationship between alcohol drinking and fatty liver disease and its influencing factors.Methods From October to December,2013,a total of 394 people who underwent a physical examination in the medical examination center of Wenzhou central hospital were selected for this study.Anthroposomatology measurement and biochemical tests were conducted.Results There were significantly statistical differences of triglyceride,uric acid and cholesterol in different drinking groups (P <0.05).The prevalence of high triglyceride and uric acid were increased with alcohol consumption (P <0.05).There was no significant difference of alcohol consumption between fatty liver and non -fatty liver group (P =0.42).Logistic regression showed that waist -hip ratio,hypertension,overweight,obesity and hypertriglyceridemia were risk factors of fatty liver,while daily alcohol consumption cannot be thought as risk factor yet. Conclusion Waist -hip ratio,hypertension,overweight -obesity and hypertriglyceridemia were the risk factors of fatty liver.Alcohol consumption could contribute to the prevalence of triglyceride and uric acid.

OBJECTIVETo study the expression of Smo protein and the downstream transcription factor Gli1 protein in Sonic hedgehog signal transduction pathway in gastric carcinoma.

METHODSA tissue microarray was constructed using 85 gastric carcinoma and 25 normal gastric mucosa specimens. The expression of Smo and Gli1 proteins were detected immunohistochemically and the correlation between their expression in gastric carcinoma was analyzed.

RESULTSOnly weak expression, if any, of Smo and Gli1 proteins was detected in normal gastric mucosa, but in papillary adenocarcinoma, tubular adenocarcinoma and poorly differentiated adenocarcinoma, their expressions were significant increased as the differentiation degree was lowered. Smo protein expression in gastric carcinoma was significantly correlated with that of Gli1 protein with correlation coefficient of 0.989 (P<0.001).

CONCLUSIONThe abnormal activity of Sonic hedgehog signal transduction pathway may play an important role in the occurrence of papillary adenocarcinoma, tubular adenocarcinoma and poorly differentiated adenocarcinoma, and this abnormality is associated with Smo protein overexpression, which upregulates the expression of the downstream transcription factor Gli1 protein.

Adenocarcinoma ; metabolism ; pathology ; physiopathology ; Adult ; Aged ; Female ; Hedgehog Proteins ; physiology ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Receptors, G-Protein-Coupled ; biosynthesis ; Signal Transduction ; Smoothened Receptor ; Stomach Neoplasms ; metabolism ; pathology ; physiopathology ; Transcription Factors ; biosynthesis ; Zinc Finger Protein GLI1

OBJECTIVETo explore the possibility of repairing chemically induced acute hepatic injuries with allogeneic bone marrow stem cell (BMSC) transplantation.

METHODSA SD rat model of CCl(4)-induced acute hepatic injury was established, which received transplantation of BMSCs (2.0 ml, 1x10(6)/ml) or normal saline injection into the local liver parenchyma, respectively. The rats were sacrificed at 6 h before and 6 h, 1, and 5 weeks after transplantation, and the livers were prepared for microscopic examination.

RESULTSCellular necrosis, bridging necrosis, congestion in the hepatic sinusoid, and inflammatory cell infiltration were seen in the chemically injured livers 6 h after model establishment, and these changes were ameliorated in rats receiving BMSC transplantation.

CONCLUSIONSAllogeneic BMSC transplantation can repair chemically induced acute liver injuries.

Animals ; Bone Marrow Cells ; cytology ; Carbon Tetrachloride ; toxicity ; Chemical and Drug Induced Liver Injury ; etiology ; pathology ; surgery ; Hematopoietic Stem Cell Transplantation ; methods ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Treatment Outcome

OBJECTIVETo establish a RP-HPLC method for simultaneous determination of total quercetin, kaempferol and isorhamnetin in rat plasma after oral administration of Folium Mori extract (FME).

METHODSAfter a single dose of FME (110 mg/kg) was taken, rat plasma samples were collected. The samples were hydrolyzed with hydrochloric acid (c=3.0 mol/L), the mixed solution was extracted with ether acetone mixture. The total quercetin, kaempferol and isorhamnetin in plasma samples were determined by HPLC, pharmacokinetic parameters were calculated by DAS 3.0 software.

RESULTSThe method was linear over the concentration ranges of 0.0545-8.70, 0.0954-14.7 and 0.0545-8.55 μg/ml for quercetin, kaempferol and isorhamnetin, respectively (r=0.9979, 0.9993, 0.9981). The absolute recoveries were 85.3%-86.1%, 79.4%-86.7% and 62.8%-89.7%, respectively and the assay recoveries were all from 94.7% to 107%. The relative standard deviation (RSD) of intra-and inter-day were less than 9.5% and 9.8%, respectively. The main pharmacokinetic parameters were as follows: T(1/2z) was 92.7, 67.9 and 54.2 h; Tmax was 0.400, 0.400 and 3.87 h; AUC(0-∞) was 68.0, 67.5 and 32.8 mg/h/L; MRT(0-∞) was 128, 85.2 and 72.0 h for quercetin, kaempferol and isorhamnetin, respectively.

CONCLUSIONThe method established in this study is accurate, reliable and reproducible, and can be applied for determination of total quercetin, kaempferol and isorhamnetin in rat plasma after oral administration of FME; the pharmacokinetic studies showed that the distribution of drugs is rapid and elimination is very slow.

Administration, Oral ; Animals ; Chromatography, High Pressure Liquid ; methods ; Flavonols ; blood ; pharmacokinetics ; Kaempferols ; blood ; pharmacokinetics ; Male ; Plant Extracts ; pharmacokinetics ; Quercetin ; blood ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley

BACKGROUNDSustained hypotension during hemodialysis (HD) is an important clinical issue. Plasma adrenomedullin (AM) is increased in HD patients with sustained hypotension, but little is known about whether removing AM can improve hypotension. The objective of this study was to investigate the beneficial effects of hemodialysis using a high-flux dialyzer on removal of increased plasma AM levels and improving low blood pressure in elderly HD patients with sustained hypotension.

METHODSForty-eight elderly patients (age 65 or older) who had undergone maintenance HD for more than one year were recruited and studied. We evaluated plasma levels of AM in sustained hypotension (SH; n = 28) and normotensive (NT; n = 20) patients. The patients with hypotension were further divided into two subgroups and treated with either high-flux dialyzer or low-flux dialyzer for 3 months. Plasma adrenomedullin levels and blood pressure were analyzed at days 0 and 181.

RESULTSPlasma levels of AM were significantly higher in SH than in NT patients ((24.92 ± 3.7) ng/L vs. (15.52 ± 6.01) ng/L, P < 0.05), and were inversely correlated with mean arterial blood pressure (MAP) at pre-HD. After 3 months, the level of plasma AM in high-flux group was decreased ((24.58 ± 4.36) ng/L vs. (16.18 ± 5.08) ng/L, P < 0.05), but MAP was increased ((67.37 ± 4.31) mmHg vs. (74.79 ± 3.59) mmHg, P < 0.05). There was no obvious change in low-flux group.

CONCLUSIONSPlasma AM levels were significantly elevated in elderly HD patients with SH. High-flux dialyzer therapy can decrease plasma AM level and improve hypotension.

Adrenomedullin ; blood ; Aged ; Female ; Humans ; Hypotension ; blood ; Male ; Renal Dialysis

OBJECTIVETo study the feasibility and influence of vagus nerve preservation in radical operation for proximal gastric cancer.

METHODSThirty-two patients with early or T2 cardia cancer from May 2007 to May 2009 were enrolled and randomized into two groups, i.e. vagus nerve preservation group(n=16) and control group(n=16). Two groups were compared with regard to operative time, anastomotic fistula, digestive discomforts, body weight, survival rate, findings on gastroscope and abdominal ultrasonography.

RESULTSThere were no statistically significant differences between the two groups in operative time (2.8 vs. 2.5 h), postoperative complications rate (25.0% vs. 31.3%). No recurrence or mortality was observed after one-year follow-up. However, patients who underwent vagus nerve preservation had less postprandial discomforts(3 vs. 12 cases), bile reflux(3 vs. 10 cases), atrophic gastritis(1 vs. 9 cases), gallstones(1 vs. 8 cases), body mass index, and diarrhea(P<0.05).

CONCLUSIONFor patients with early gastric cancer, preservation of the vagus nerve during radical gastrectomy results in less complications and does not compromise patient survival.

Adult ; Aged ; Cardia ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Prospective Studies ; Stomach Neoplasms ; surgery ; Vagus Nerve ; surgery