Due to substantial morbidity and high complications, diabetes mellitus is considered as the third "killer" in the world. Medicinal fungal polysaccharides, as water-soluble macromolecular substances with low toxicity, exhibit diversified pharmacological actions such as immune regulation, anti-tumor, antivirus, antioxidant, anti-aging, hypoglycemic effect and improving liver and kidney function. In recent year, a number of investigators reported medicinal fungal polysaccharides showed good anti-diabetes and hypoglycemic activity, and their acting mechanisms involved in glycometabolism and β cell function, e. g. promoting glycogen synthesis, promoting glycolysis, inhibiting the activity of α-glucosidase, promoting insulin secretion, increasing insulin sensitivity, enhancing antioxidation. Therefore, the hypoglycemic activity and its mechanisms of action of medicinal fungal polysaccharides showed characteristics of multiple effects, multi-target, and multi-pathway regulation. These finding suggest that medicinal fungal polysaccharides are a promising source for the development of discovery of anti-diabetic agent.
Animals ; Carbohydrate Metabolism ; drug effects ; Fungal Polysaccharides ; pharmacology ; Humans ; Hypoglycemic Agents ; pharmacology ; Insulin Resistance ; Insulin-Secreting Cells ; drug effects ; Oxidative Stress ; drug effects

AIM:To observe the expression of hypoxia-inducible factor 1 (HIF-1) and neuroglobin (NGB) in piglet cortex during deep hypothermic circulatory arrest.METHODS:Wuzhishan piglets were randomly assigned to car-diopulmonary bypass group ( CPB group) , 40 min of circulatory arrest ( CA) at 18 ℃ without cerebral perfusion ( DHCA group) or with selective antegrade cerebral perfusion ( SACP group) .After 180 min of reperfusion, cortical tissue was har-vested for determining HIF-1αand NGB expression by HE staining, Western blot and real-time PCR.RESULTS:Severer cerebral injury was observed in DHCA group than that in SACP group.After 180 min of reperfusion, HIF-1αprotein and mRNA levels were significantly higher in DHCA group than those in CPB group (P<0.05).Accordingly, SACP animal had higher levels of HIF-1αprotein and mRNA than those in DHCA group (P<0.05).Simultaneously, higher NGB pro-tein and mRNA levels were found in DHCA group than those in CPB group after 180 min of reperfusion ( P<0.05) .The SACP animal had higher levels of NGB protein and mRNA than those in DHCA group (P<0.05).CONCLUSION:Up-regulation of HIF-1 and NGB are involved in the mechanism against cerebral injury resulting from DHCA in the cortex and possibly a part of cerebral protective effect of SACP.

Currently available monotherapies of oral nucleoside/nucleotide analogs or interferon are unable to achieve a sustained and effective response in most of patients with chronic hepatitis B (CHB). The objective of the present study was to compare the efficacy and safety of pegylated interferon (Peg-IFN) alpha-2b plus adefovir dipivoxil combination therapy versus Peg-IFN alpha-2b alone. Sixty-one HBeAg-positive chronic hepatitis B patients were randomized to receive Peg-IFN alpha-2b alone (1.5 μg/kg once weekly) or Peg-IFN alpha-2b plus adefovir (10 mg daily) for up to 52 weeks. Efficacy and safety analyses were performed on all participants who received at least one dose of study medication. The rate of HBeAg seroconversion and undetectable HBV-DNA were evaluated after 52 weeks of therapy. At the end of treatment, 11 of 30 (36.7%) patients receiving combination therapy achieved HBeAg seroconversion versus 8 of 31 (25.8%) in the monotherapy group (P=0.36). In contrast, the percentage of patients with undetectable serum HBV DNA was significantly higher in the combination group than in the monotherapy group (76.7% vs. 29.0%, P<0.001). Thyroid dysfunction was more frequent in the combination group than in the monotherapy group (P<0.05). In HBeAg-positive CHB, combination of Peg-IFN alpha-2b and adefovir for 52 weeks resulted, at the end of treatment, in a higher virological response but without significant impact on the rate of HBeAg seroconversion and possibly an adverse effect on thyroid function.

Objective To separate and amplify Hantaan virus(HV)in serum of hemorrhagic fever patients with renal syndrome(HFRS)in Heilongjiang,and look for its difference from intemational standard type strain(76-118strains).Methods HVs of different phase in the 8erum of 50 HFRS patients were separated and amplified by RTnested-PCR,its products were analyzed the amplified by sequencing.Results Detectable rate of HV in the patients serum was 36.36%(8/22)in 7 days after onset,it Was 13.04%(3/23)in patients having an onset 8 days to 14 days earlier,5 cases were not detectable 15 days after onset.Comparing the sequence of HV S gene fragment,sample 1,9,18,31,37,38,44 strain had a homology of 90.24%,86.72%,89.97%,89.16%,86.45%,87.26%and 89.43%to 76-118 strains,respectively.Conclusions The positive rate is the highset in 7 days after onset.Nucleotide sequence difference exists between pathogenic strain of Heilongjiang's HV and international standard strain,indicating that not only hosts but also locations can affect HV.

OBJECTIVETo investigate the role of connective tissue growth factor (CTGF) induced TGF-beta 1 in the transdifferentiation of human hypertrophic scar fibroblast (HSFb).

METHODSHuman hypertrophic scar fibroblasts were cultured in vitro, 5 cell samples were stimulated with TGF-beta 1 (0, 2.5, 5.0, 7.5, 10.0 ng/mL, respectively) for 48 hours; other cell samples were divided into: normal control (NC) group, CTGF group (with addition of 10 ng/mL rhCTGF into culture medium), TGF-beta 1 group (with addition of 10 ng/mL TGF-beta 1 into culture medium), CTGF ASODN group (with addition of 10% FBS-DMEM after transfection of CTGF ASODN), CTGF ASODN + TGF-beta 1group (with addition of 10 ng/mL TGF-beta 1 after transfection of CTGF ASODN). Expression of CTGF was determined by Western blotting with stimulation of different concentration of TGF-beta 1. Expression of alpha-smooth muscle actin (alpha-SMA) was measured by Western blotting. Positive cell rate of alpha-SMA was examined by flow cytometry.

RESULTSWith stimulation of 10.0 ng/mL TGF-beta 1, the expression of CTGF was obviously higher than that of non-stimulation (P < 0.05). Expression of alpha-SMA in the CTGF group and the TGF-beta 1 group was obviously higher than that in NC group (P < 0.01), while there was no obvious difference among NC, CTGF ASODN, CTGF ASODN + TGF-beta 1 groups (P > 0.05). The positive cell rate of alpha-SMA in NC, CTGF, TGF-beta 1, CTGF ASODN, CTGF ASODN + TGF-beta 1 groups was (10.8 +/- 2.8)%, (29.1 +/- 4.0)%, (28.7 +/- 4.8)%, (10.7 +/- 2.3)%, (14.3 +/- 2.9)%, respectively, which was similar to expression of alpha-SMA on statistic analysis.

CONCLUSIONSCTGF is one of the most important downstream efforts for TGF-beta 1 in inducing the transdifferentiation of HSFb.

Cell Differentiation ; drug effects ; Cells, Cultured ; Cicatrix, Hypertrophic ; metabolism ; Connective Tissue Growth Factor ; pharmacology ; Fibroblasts ; cytology ; drug effects ; metabolism ; Humans ; Transforming Growth Factor beta1 ; pharmacology

OBJECTIVETo implement simultaneous integrated boost intensity-modulated radiotherapy(SIB-IMRT) plans for upper esophageal carcinoma and investigate the dose profiles of tumor and electively treated region and the dose to organs at risk (OARs).

METHODSSIB-IMRT plans were designed for two patients with upper esophageal carcinoma. Two target volumes were predefined: PTV1, the target volume of the primary lesion, which was given to 67.2 Gy, and PTV2, the target volume of electively treated region, which was given to 50.4 Gy. With the same dose-volume constraints, but different beams arrangements (3, 5, 7, or 9 equispaced coplanar beams), four plans were generated. Indices, including dose distribution, dose volume histogram (DVH) and conformity index, were used for comparison of these plans.

RESULTSThe plan with three intensity-modulated beams could produce good dose distribution for the two target volumes. The dose conformity to targets and the dose to OARs were improved as the beam number increased. The dose distributions in targets changed little when the beam number increased from 7 to 9.

CONCLUSIONSFive to seven intensity-modulated beams can produce desirable dose distributions for simultaneous integrated boost (SIB) treatment for upper esophageal carcinoma. The primary tumor can get higher equivalent dose by SIB treatments. It is easier and more efficient to design plans with equispaced coplanar beams. The efficacy of SIB-IMRT remains to be determined by the clinical outcome.

Aged ; Dose-Response Relationship, Radiation ; Esophageal Neoplasms ; radiotherapy ; Female ; Humans ; Male ; Radiation Dosage ; Radiotherapy Planning, Computer-Assisted ; methods

A simple, sensitive, selective, and reproducible liquid chromatography-tandem mass spectrometric method was developed for the simultaneous determination of repaglinide and metformin in human plasma using d5-repaglinide and d6-metformin as internal standards (ISs). After a simple protein precipitation using acetonitrile as the precipitation solvent, both analytes and ISs were separated on a Venusil ASB C 18 (150 mm x 4.6 mm, 5 microm) via gradient elution using acetonitrile--10 mmol x L(-1) ammonium acetate as the mobile phase. A chromatographic total run time of 7.5 min was achieved. Mass spectrometric detection was conducted with atmospheric pressure chemical ionization under positive-ion and multiple-reaction monitoring modes. The method was linear over the 0.2 to 60.0 ng x mL(-1) concentration range for repaglinide and over the 4 to 1 000 ng x mL(-1) range for metformin. For both analytes, the intra- and inter-accuracies and precisions were within the +/- 15% acceptable limit across all concentrations. The validated method was successfully applied to a clinical bioequivalence study.
Administration, Oral ; Adolescent ; Adult ; Area Under Curve ; Carbamates ; administration & dosage ; blood ; pharmacokinetics ; Chromatography, Liquid ; Drug Stability ; Female ; Humans ; Hypoglycemic Agents ; administration & dosage ; blood ; pharmacokinetics ; Male ; Metformin ; administration & dosage ; blood ; pharmacokinetics ; Middle Aged ; Piperidines ; administration & dosage ; blood ; pharmacokinetics ; Tandem Mass Spectrometry ; Therapeutic Equivalency ; Young Adult

OBJECTIVETo investigate the clinicopathological features of nonalcoholic steatohepatitis (NASH) and elucidate its diagnosis and differential diagnosis.

METHODSLiver biopsy tissues and clinical data of 32 patients with NASH were collected and the clinicopathological findings by HE and Masson staining were evaluated for NASH grading.

RESULTSBallooning degeneration of the liver cells and fibrosis around hepatic sinusoid was scarce in mild NASH cases and increased in moderate to severe cases. Steatotic and inflammatory cells in the liver lobes decrease in liver cirrhosis related to seatohepatitis.

CONCLUSIONBallooning degeneration of the liver cells and fibrosis around the hepatic sinusoid have important value in differential diagnosis of mild from moderate to severe NASH, and correct histological grading benefits clinical intervention and prognostic evaluation of NASH.

Adult ; Biopsy, Needle ; Diagnosis, Differential ; Fatty Liver ; diagnosis ; pathology ; Female ; Humans ; Image Interpretation, Computer-Assisted ; Liver ; pathology ; Male ; Middle Aged ; Prognosis

To study the effects of Qingdai compound on proliferation and apoptosis of K562 cells, as well as the expression of bcr/abl and JWA mRNA, K562 cells were treated in culture with different concentrations of Qingdai compound (2.5, 5, 7.5, 10 and 20 mg/ml) and harvested at 24 hours. Then morphological changes were observed by light microscopy (LM); expressions of bcr/abl and JWA were detected with semi-quantitative RT-PCR. The results showed that morphological changes were observed as the increment of the Qingdai compound concentration. Inhibition effects on proliferation and apoptosis in K562 cells were seen. A concentration-dependent decreases were found in bcr-abl and JWA mRNA expression of K562 cells. Qingdai compound partially inhibited proliferation and induced apoptosis of K562 cells. Expressions of both bcr/abl and JWA, which took part in cell proliferation and apoptosis, were down-regulated in a dose dependent manner. In conclusion, Qingdai compound can partially inhibit the expressions of bcr/abl and JWA genes in K562 cells, and the clinical effect of Qingdai compound on CML may be associated with apoptosis of leukemic cells.
Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; pharmacology ; Fusion Proteins, bcr-abl ; genetics ; Gene Expression Regulation, Neoplastic ; drug effects ; Heat-Shock Proteins ; genetics ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; K562 Cells ; RNA, Messenger ; biosynthesis ; genetics ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo investigate the effect of early escharectomy on resting energy expenditure (REE) in severely burned patients dynamically with the metabolic monitoring and diagnostic system.

METHODSFifty-six adult male patients with severe burns were divided into early escharectomy (group A, n = 39, escharectomy within 5 PBDs) and non-early escharectomy (group B, n = 17, escharectomy after 5 PBDs) groups. The wounds of full thickness and deep partial thickness burn in the two groups were all excised and covered with allogeneic skin and autologous micro-skin in the first operation. The changes in REE were observed dynamically at the bedside of the patients with the metabolic monitoring and diagnostic system. The plasma contents of IL-6, IL-8, TNF-alpha and LPS from 9 patients in group A and 7 in group B were also determined dynamically.

RESULTSAll patients survived. The REE in both groups was elevated markedly, but REE in group A was lower compared with group B before and after escharectomy within 14 days. (P < 0.05). The plasma level of IL-6, IL-8, TNF-alpha and LPS in group A were obviously lower than those in group B (P < 0.05).

CONCLUSIONThe hypermetabolic response of burn patients with severe burns could be lowered by early escharectomy, and it seemed to be related to the decrease of the release of proinflammatory mediators.

Adult ; Basal Metabolism ; Burns ; metabolism ; physiopathology ; surgery ; Humans ; Interleukin-6 ; blood ; Interleukin-8 ; blood ; Lipopolysaccharides ; blood ; Male ; Postoperative Care ; Time Factors ; Treatment Outcome ; Tumor Necrosis Factor-alpha ; metabolism