Aneurysm, Dissecting ; complications ; Coronary Aneurysm ; complications ; Coronary Artery Disease ; complications ; Female ; Humans ; Middle Aged

OBJECTIVETo explore the impact of 5-fluorouracil (5-FU) on glucose metabolism and pancreatic pathology.

METHODSTwenty Wistar rats were divided into 5-FU group(n=10, chemotherapy was administered intraperitoneally to animals at a dose of 20 mg/kg daily for continuous 5 days) and control group (n=10, sodium chloride was administered intraperitoneally to animals with the same dose at the same time ). Glucose tolerance was evaluated 2 and 7 days following 5-FU treatment by serial measurement of blood glucose before and after an oral glucose load. Plasma insulin concentration was determined by radioimmunoassay. Pancreatic pathology was examined with morphological method and the ultrastructural changes of β cells were observed by transmission electron microscope.

RESULTSFasting blood glucose level was significantly higher in the 5-FU group than that in the control group [(7.6±0.9) mmol/L vs. (4.6±0.6) mmol/L at day 2; (8.9±1.0) mmol/L vs. (4.7±0.6) mmol/L at day 7, P<0.01]. Insulin releasing test indicated that the early phase insulin response to glucose load was significantly diminished in animals treated with 5-FU at day 2. Insulin level was significantly lower in the 5-FU group than that in the control group at 30 min (P<0.01). The peak secretion time of plasma insulin in 5-FU group was at 60 min, similar to the control group; and plasma insulin level decreased more slowly. Plasma insulin level was higher in 5-FU groups than in control groups on 120 min and 180 min. At day 7, Insulin level was lower in the 5-FU group than that in the control group on 60 min, and the peak secretion time of plasma insulin was delayed to 120 min. Plasma insulin level was significantly increased in 5-FU group than that in control group on 180 min(P<0.01). No gross histopathological damage to the pancreas was observed at day 2 and 7 following administration of 5-FU. The structural changes of mitochondria were mainly the quantities of secretory granule diminished at day 7 under transmission electron microscope. Dilated rough endoplasmic reticula, swollen mitochondria, and the presence of adipose drops in lysosomes were found in few cells.

CONCLUSIONS5-FU-induced hyperglycemia appears to be mediated in part by a relatively deficient insulin secretion to glucose stimulation. A relative deficiency in insulin secretion following 5-FU treatment appears to be related to β cells function impairs with islet cell ultrastructural changes induced by 5-FU.

Animals ; Blood Glucose ; drug effects ; metabolism ; Female ; Fluorouracil ; pharmacology ; Insulin ; blood ; Male ; Pancreas ; drug effects ; pathology ; Rats ; Rats, Wistar

OBJECTIVETo study the possible etiological role of MLH1 gene 415G/C polymorphism in sporadic Chinese colorectal cancer (CRC) patients.

METHODSNinety-seven sporadic CRC patients and 138 normal controls were collected from Hubei Provincial Cancer Hospital and the People's Hospital of Wuhan University. In addition, five CRC families including 6 patients and their 19 first-degree relatives were also recruited. Genomic DNA was extracted from peripheral blood samples. Gene mutation was analyzed by PCR-RFLP. MLH1 mRNA expression in colorectal mucosa was analyzed by RT-PCR.

RESULTSThe frequency of MLH1 gene CC genotype was significantly higher in sporadic CRC patients than that in controls (P=0.035, OR=5.29, 95% CI: 1.07-26.04). In the CRC families, the C allele frequency of CRC patients and their relatives was increased, compared with sporadic CRC patients and normal controls, respectively (P=0.003 and P=0.006). MLH1 mRNA expression of colorectal mucosa was similar in different genotypes.

CONCLUSIONMLH1 gene 415G/C polymorphism might be a risk factor to sporadic CRC in Chinese. The mutation does not affect the MLH1 mRNA expression. For first-degree relatives from CRC families, carriers of MLH1 415C allele have a high risk to CRC.

Adaptor Proteins, Signal Transducing ; genetics ; Adult ; Aged ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Colorectal Neoplasms ; genetics ; DNA Mutational Analysis ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Middle Aged ; MutL Protein Homolog 1 ; Nuclear Proteins ; genetics ; Polymorphism, Single Nucleotide ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo assess the indication, surgical and post-operative complications of the multivisceral transplantation.

METHODSThe post-transplant complications of 8 patients who underwent multivisceral transplantation between May 2004 and May 2010 were analyzed. There were 7 male and 1 female, aged from 28 to 65 years. Five patients who suffered from non-resectable advanced upper abdominal malignancy experienced the liver, stomach, spleen, pancreas, duodenum, omentum and variable amounts of the colon resection, and then underwent standard multivisceral transplantation (included liver, stomach, pancreaticoduodenal and small bowel). After underwent hepatectomy while retaining the native pancreas and entire gastrointestinal, three recipients with end-stage liver cirrhosis and type 2 insulin-dependent diabetes mellitus (IDDM) was performed combined en bloc liver/pancreaticoduodenal transplantation.

RESULTSSince the third day post-operation, all recipients no longer needed exogenous insulin and had normal blood glucose concentrations. Two weeks after transplantation, their liver function almost became normal. For the 5 recipients who suffered abdominal malignancy, the longest survival period was 326 days. Cause of death are recurrent tumor (n = 2), multiple organ failure (n = 3). All the 5 patients experienced infection. For 3 patients suffered cirrhosis and IDDM, the longest survival was over 18 month. Excepting the case 8 died of graft versus host disease, all were still living without apparently post-transplant complication.

CONCLUSIONSMultivisceral transplantation is an alternative in the treatment of the patients with benign massive abdominal pathologies. Careful patient selection and technical modification are crucial to improve the outcome of these patients.

Abdomen ; surgery ; Adult ; Aged ; Duodenum ; transplantation ; Female ; Follow-Up Studies ; Humans ; Liver Transplantation ; Male ; Middle Aged ; Organ Transplantation ; Pancreas Transplantation ; Retrospective Studies

OBJECTIVETo summarize the treatment outcomes after combined en bloc liver and pancreas transplantation.

METHODSFive patients with end-stage liver disease and type 2 diabetes mellitus received combined en bloc liver and pancreas transplantation after hepatectomy.

RESULTSFive operations were performed successfully. The operative time ranged from 9 to 16 hours and blood loss from 1600 to 3000 ml. Postoperatively, one patients developed pulmonary infection, one died of graft-versus-host disease(GVHD), and one experienced acute renal failure. No intestinal fistula, anastomotic leakage, biliary complications, chronic and acute rejection and pancreatitis were seen. Liver function index including alanine aminotransferase, aspartate aminotransferase and total bilirubin returned to normal levels a week after surgery, while levels of C peptide and blood glucose resumed within 1 to 2 weeks. Apart from 1 case died of GVHD, the other 4 maintained normal liver function during the follow up ranging from 2 to 23 months and no insulin was required for the diabetes.

CONCLUSIONCombined en bloc liver and pancreas transplantation is technically feasible and an effective treatment for multi-organ diseases.

Adult ; Diabetes Mellitus, Type 2 ; complications ; surgery ; Female ; Humans ; Liver Failure ; complications ; surgery ; Liver Transplantation ; Male ; Middle Aged ; Pancreas Transplantation ; Retrospective Studies

Acquired Immunodeficiency Syndrome ; drug therapy ; metabolism ; virology ; Adult ; Anti-HIV Agents ; pharmacology ; therapeutic use ; Drug Resistance, Viral ; Female ; HIV-1 ; drug effects ; physiology ; Humans ; Male

OBJECTIVETo investigate the drag-reducing effect of polyethylene oxide (PEO) on the velocity of red blood cells in rat cremaster microcirculation.

METHODSBlood samples were collected from 6 Wistar male rats (100-110 g) via the post-orbital venous plexus. The red blood cells were separated by centrifugation and labeled by fluorescinisothiocyate (FITC). After successful establishment of cremaster model, the labeled red blood cells were injected into the jugular vein, and the microcirculation was observed and recorded under fluorescence microscope. The hemodynamic parameters and microcirculation video was recorded every 4 min since 4 min before PEO or normal saline injection. Both PEO (10 ppm) and normal saline was injected into the same rat in random sequence at a constant rate of 3.5 ml/h for 20 min followed by observation for another 20 min. The velocity of the labeled-red blood cells was determined by IPP 6.0 software.

RESULTSCompared with normal saline, PEO significantly increased the velocity of the red blood cells in the rat cremaster microcirculation (498.7-/+182.89 microm/s vs 773.54-/+308.27 microm/s, P=0.012). No significant changes in the heart rate and arterial blood pressure were observed during the experiment (P=0.836, P=0.420).

CONCLUSIONPEO at an extremely low concentration can significantly increase the velocity of the red blood cells in rat cremaster microcirculation and produces no significant impact on heart rate and arterial blood pressure.

Animals ; Blood Flow Velocity ; drug effects ; Male ; Microcirculation ; drug effects ; physiology ; Muscle, Smooth ; blood supply ; Polyethylene Glycols ; pharmacology ; Rats ; Rats, Wistar ; Testis

OBJECTIVETo assess the spectrum of causes, clinical features, differences between disease phases, and prognosis of extrinsic allergic alveolitis (EAA).

METHODSPatients with EAA diagnosed at Peking Union Medical College Hospital from August 1983 to May 2007 were analyzed retrospectively. Their medical records were examined to gather clinical, laboratorial, radiological, and histopathological data. Patients were divided to three phases (acute, subacute, and chronic) according to clinical presentations. Follow-up data regarding treatment response, subsequent radiological and pulmonary function studies, and clinical outcomes were collected.

RESULTSA total of 21 cases were enrolled. Among them, 11 were subacute, 10 were chronic. The most common exposure was pet birds (6 cases, 28.6%). The primary abnormality of pulmonary function was restriction and/or reduction in diffusing capacity (12 cases, 63.2%). The most common findings on high-resolution computed tomography (HRCT) were ground-glass opacities (13 cases, 68.4%) and centrilobular nodules (8 cases, 42.1%). Airway obstruction in pulmonary function test, emphysema, lung cysts, and fibrosis on HRCT were more frequently seen in chronic than in subacute patients, though the differences were not statistically significant. Bronchoalveolar lavage fluid (BALF) showed lymphocytosis. The total cell count and the percentage of neutrophils were significantly higher in subacute than in chronic patients (P<0.05). Nonnecrotizing granulomas were seen in 8 (47.1%) cases. Improvement or normalization in symptoms, radiography, and pulmonary function test after treatment were seen in all 18 patients with available follow-up data. Five patients recurred.

CONCLUSIONSThe characteristic abnormalities of pulmonary function, findings on HRCT, and pathology are essential for all phases of EAA, and the atypical manifestations such as obstruction and fibrosis can also be present frequently, particularly in chronic cases. Differential cell counts of BALF are related to the phase of the disease. The treatment response and prognosis of EAA are good.

Adolescent ; Adult ; Aged ; Alveolitis, Extrinsic Allergic ; diagnosis ; diagnostic imaging ; etiology ; pathology ; Bronchoalveolar Lavage Fluid ; immunology ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Prognosis ; Radiography

Background: Metastatic colorectal cancer (mCRC) patients with progressive disease after all available standard therapies need new medication for further treatment. Famitinib is a small-molecule multikinase inhibitor, with promis-ing anticancer activities. This multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial was designed to evaluate the safety and efficacy of famitinib in mCRC. Methods: Famitinib or placebo was administered orally once daily. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), quality-of-life (QoL), and safety. Results: Between July 18, 2012 and Jan 22, 2014, a total of 167 patients were screened, and 154 patients were rand-omized in a 2:1 ratio to receive either famitinib (n = 99) or placebo (n = 55). The median PFS was 2.8 and 1.5 months in the famitinib and placebo groups (hazard ratio = 0.60, 95% confidence interval = 0.41–0.86, P = 0.004). The DCR was 59.8% and 31.4% (P = 0.002) and the ORR was 2.2% and 0.0% (P = 0.540) in the famitinib and placebo groups, respectively. The most frequent grade 3–4 adverse events were hypertension (11.1%), hand-foot syndrome (10.1%), thrombocytopenia (10.1%), and neutropenia (9.1%). Serious adverse events occurred in 11 (11.1%) patients in the famitinib group and 5 (9.1%) in the placebo group (P = 0.788). The median OS of the famitinib and placebo groups was 7.4 and 7.2 months (P = 0.657). Conclusion: Famitinib prolonged PFS in refractory mCRC patients with acceptable tolerability. Trial registration This study was registered on ClinicalTrials.gov (NCT01762293) and was orally presented in the 2015 ASCO-Gastrointestinal Symposium

BACKGROUNDThis study was aim to explore the characteristics of phenotypic resistance of resistant strains of HIV type-1 (HIV-1) subtype B and to compare the concordance between the phenotypic resistance and genotypic resistance.

METHODSThe genotypic resistance assay for the HIV-1 clinical isolates was performed. One isolate without resistance mutation was chosen as a drug-sensitive reference strain and seven subtype B isolates with resistance mutations were phenotypically tested. Fifty percent inhibitory concentrations (IC50) between resistant and sensitive viruses were compared. The resistance extent was determined by the folds of the increased IC50. The concordance between the phenotypic resistance and genotypic resistance was also analyzed.

RESULTSIC50 of resistant isolates were 0.0006 - 0.1300 micromol/L for zidovudine (AZT), 0.0016 - 0.0390 micromol/L for lamivudine (3TC), 0.0104 - 0.4234 micromol/L for nevirapine (NVP), and 0.0163 - 0.1142 micromol/L for indinavir (IDV), respectively. Genotypic and phenotypic resistance assays indicated that the resistant strains were intermediately and highly resistant to nucleotide analog reverse transcriptase inhibitors and non-nucleotide analog reverse transcriptase inhibitors. The phenotypic assay was consistent with the genotypic assay. For measuring the potential resistance, the genotypic assay was more sensitive than the phenotypic. In evaluating the resistance to protease inhibitors, these two assays were discrepant.

CONCLUSIONSBoth the phenotypic and genotypic assays indicate that the resistant viruses exist in HIV-infected patients in China who have received treatment. Phenotypic and genotypic assays have high concordance, and the genotypic assay could replace the phenotypic assay to predict the HIV-1 resistance.

Anti-Retroviral Agents ; pharmacology ; China ; Drug Resistance, Viral ; genetics ; HIV-1 ; drug effects ; genetics ; Humans ; Mutation ; Phenotype