Objective: To investigate the effect of oligosaccharide grape seed proanthocyanins (GSPE) on dextran sulphate sodium salt (DSS)-induced ulcerative colitis (UC) in mice and its mechanisms. Methods: SPF-class C57 mice were randomly divided into normal group, model group, positive group (sulfasalazine group), and GSPE groups (125, 250, 500 mg/kg). The normal group was given pure water, and the other groups were free to drink 3% DSS aqueous solution for 7 d to induce the model of UC in mice. The changes of body weight, hematochezia and stool type were recorded every day. After seven days of treatment, blood, colons and spleens were collected, and the length of the colon and the weight of the spleen were recorded. HE staining was used to evaluate the pathological changes of colonic mucosa in mice. The expression of interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor TNF-α in serum and colon tissues and the levels of NO, MDA, and SOD were detected by ELISA. The changes of HO-1, NF-κB, and Nrf2 in colonic epithelial cells were analyzed by immunohistochemistry. Results: Compared with the model group, the body weight of mice in GSPE groups (250, 500 mg/kg) decreased relatively slowly, and the symptoms of diarrhea and hematochezia were improved significantly. The content of IL-1β, IL-6, TNF-α, NO, and MDA in serum and colon tissues was much lower in the administration groups than those in the model group, while the content of SOD was significantly higher (P < 0.01). The pathological tissue analysis showed that the pathological damage of colonic mucosa in the high dose group of GSPE was obviously decreased. Immunohistochemical analysis showed that GSPE groups significantly decreased the expression of NF-κB and increased the expression of Nrf2 and HO-1 (P < 0.01). Conclusion: GSPE could effectively improve the symptoms of UC induced by DSS, and regulate the expression of oxidative stress-related proteins Nrf2, HO-1 and inflammatory pathway protein NF-κB, and then affect the changes of oxidative stress indicators SOD, MDA and inflammatory factors. Therefore, GSPE plays an important role in the treatment and prevention of UC.

Objective To study the clinical features of gallbladder small cell carcinoma (GSCC),to improve the diagnosis and treatment of GSCC.Methods We retrospectively analyzed the clinical data of GSCC patients at our hospital from January 2000 to January 2012,and made a collective review of the literature.Results In this series,there were four female cases,one male case,the age at the first diagnosis was between 42-67,with the median age of 57.The main complain was pain and dis-comfort on the up and right abdomen.Tumor located in the bottom of gallbladder in 3 cases,and in the body in 2.Cholelithiasis was complicated in 4 cases.2 patients received radical resection of GSCC,followed by adjuvant chemotherapy of VP-16 and cisplatin,radioactive therapy in one.Postoperatively,these two were followed up for 45 and 32 mons with tumor free survival.3 cases received palliative resection,followed by adjuvant chemoradioactive therapy or intervention treatment,these three were followed up to 8,11,30 months respectively to their death for tumor recurrence.Conclusions GSCC is a rare disease,the initial symptoms are not often specific and easily misdiagnosed.The prognosis of GSCC is poor.

Objective To summarize and analyze the clinical feature,therapeutic mnethods and prognosis of colorectal small cell carcinoma.Methods From January 2000 to January 2012,15 patients of colorectal small cell carcinoma were analyzed retrospectively.Results There were 12 male cases,3 females.The age at diagnosis was between 39-71 years,with median age of 60.SCC located in the rectum in 12 cases,in the colon in 3 cases.The time from the onset of symptoms to final diagnosis was from 1 to 12 months.The diameter of tumors varied from 2.5 to 8.0 cm.13 cases received up-front surgery,including radical tumor resection in 6 cases,palliative resection in 7 cases,and neoadjuvant-chemotherapy followed by palliative resection in one case.The initial Ⅰ,Ⅲ B,Ⅳ B stage were 1 case,6 cases and 8 cases,respectively.The overall median survival time is 11 months,1,2 year's survival rate is 40.0％ and 20.0％,respectively.Conclusions Colorectal SCC is less common and the prognosis is poor.Multimodality management,with radical surgical resection of the primary lesion followed by standard adjuvantchemotherapy,affords good local disease control and a fair survival.

OBJECTIVETo study the effect of Mudan Granule (MD) on the glucose metabolism and beta cell function in monosodium glutamate (MSG) induced obese mice with insulin resistance (IR).

METHODSMSG obese mice were induced by subcutaneous injecting MSG (4 g/kg for 7 successive days in neonatal ICR mice). Forty MSG mice with IR features were recruited and divided into four groups according to body weight, fasting blood glucose, triglyceride (TG), total cholesterol (TC), and the percentage of blood glucose decreased within 40 min in the IR test, i.e., the model group (Con), the low dose MD group, the high dose MD group, and the Metformin group (Met). Besides, another 10 ICR mice were recruited as the normal control group (Nor). The water solvent of 2.5 g/kg MD or 5 g/kg MD was respectively administered to mice in the low dose MD group and the high dose MD group. Metformin hydrochloride was given to mice in the Met group at 0.2 g/kg body weight. Equal dose solvent distilled water was administered to mice in the Nor group and the Con group by gastrogavage, once per day. All medication was lasted for 15 weeks. Insulin tolerance test (ITT) and oral glucose tolerance test (OGTT) were performed after 6 weeks of treatment. Beta cell function was assessed by hyperglycemic clamp technique. The morphological changes in the pancreas were evaluated by hematoxylin-eosin (HE) staining. Changes of iNOS, NF-kappaB p65, and p-NF-kappaB p65 in the pancreas were tested.

RESULTSCompared with the Nor group, the blood glucose level, AUC, and fasting blood insulin, ONOO-contents, iNOS activities, and the expression of iNOS, NF-kappaB p65 subunit, pNF-kappaB p65 subunit obviously increased; decreased percentage of blood glucose within 40 min in ITT, glucose infusion rate (GIR), Clamp 1 min insulin, and Max-Insulin obviously decreased in the Con group (P < 0.05, P < 0.01). Compared with the Con group, the aforesaid indices could be improved in the Met group (P < 0.05, P < 0.01). In the low dose MD group, AUC, iNOS activities, and the expression of iNOS and p-NF-kappaB p65 subunit obviously decreased; percentage of blood glucose within 40 min in ITT and GIR obviously increased (P < 0.05, P < 0.01). In the high dose MD group, AUC, ONOO-contents, iNOS activities, and the expression of iNOS, NF-kappaB p65 subunit, and p-NF-KB p65 subunit obviously decreased; percentage of blood glucose within 40 min in ITT, Max-Insulin, and GIR obviously increased (P < 0.05, P < 0.01).

CONCLUSIONMD could significantly improve IR and functional disorder of 3 cells in MSG obese mice, which might be associated with lowering inflammatory reaction in the pancreas.

Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Female ; Insulin Resistance ; Insulin-Secreting Cells ; drug effects ; metabolism ; Male ; Metformin ; pharmacology ; Mice ; Mice, Inbred ICR ; Mice, Obese ; Obesity ; chemically induced ; metabolism ; Pancreas ; cytology ; drug effects ; Sodium Glutamate

This study is to evaluate the effects of the metformin (Met) on β cell function of diabetic KKAy mice. Female diabetic KKAy mice selected by insulin tolerance test (ITT) were divided randomly into two groups. Con group was orally administered by gavage with water, Met group with metformin hydrochloride at a dose of 0.2 g x kg(-1) for about 12 weeks. ITT and glucose tolerance tests (OGTT) were determined. Beta cell function was assessed by hyperglycemic clamp. Pancreatic biochemical indicators were tested. The changes of gene and protein expression in the pancreas and islets were also analyzed by Real-Time-PCR and immunostaining. Met significantly improved glucose intolerance and insulin resistance in KKAy mice. Fasting plasma glucose and insulin levels were also decreased. In addition, Met markedly increased glucose infusion rate (GIR) and elevated the Ist phase and maximum insulin secretion during clamp. It showed that Met decreased TG content and iNOS activities and increased Ca(2+) -Mg(2+)-ATPase activity in pancreas. Islets periphery was improved, and down-regulation of glucagon and up-regulated insulin protein expressions were found after Met treatment. Pancreatic mRNA expressions of inflammation factors including TLR4, NF-κB, JNK, IL-6 and TNF-α were down-regulated, p-NF-κB p65 protein levels also down-regulated by Met. And mRNA expressions of ion homeostasis involved in insulin secretion including SERCA2 and Kir6.2 were up-regulated by Met. Met increased SIRT5 expression level in pancreas of KKAy mice under the hyperglycemic clamp. These results indicated that chronic administration of Met regulated pancreatic inflammation generation, ion and hormone homeostasis and improved β cell function of diabetic KKAy mice.
Animals ; Blood Glucose ; Diabetes Mellitus, Experimental ; drug therapy ; Down-Regulation ; Female ; Glucose Tolerance Test ; Homeostasis ; Inflammation ; drug therapy ; Insulin ; secretion ; Insulin Resistance ; Insulin-Secreting Cells ; drug effects ; Interleukin-6 ; metabolism ; Metformin ; pharmacology ; Mice ; NF-kappa B ; metabolism ; Pancreas ; drug effects ; Tumor Necrosis Factor-alpha ; metabolism

AlM:To explore the primary culture conditions for four kinds of lens epithelial cells ( LECs) of rat, rabbit, dog, and human, and measure their growth characteristics.METHODS:The lens capsule or anterior capsular tissue of rat, rabbit, dog and patient were removed by different methods, and they were cut into tiny pieces for primary culture by modified tissue adherent method. The morphological features of four kinds of LECs were observed under an inverted microscope.RESULTS: Four kinds of LECs of rat, rabbit, dog and human could be cultured primarily by tissue adherent method. With the evolution of tissue source, the adherent capacity of LECs gradually strengthened, cells form were changed from irregular polygon to oval, nucleus rounded and cytoplasm enriched gradually. Four kinds of LECs had fibrotic changes after several passages.CONCLUSlON: LECs of rat, rabbit, dog and human can be primarily cultured. This method lays the foundation for the mechanism research of caratact and related fields on the cellular and molecular levels.

Locoweeds are presently defined as those species of the genera Oxytropis and Astragalus (family Leguminosae) that specifically contain the key toxic constituent,swainsonine.After ingesting locoweeds,livestock can develop poisoning disease characterized by chronic dysfunction of the nervous system,which causes severe economic losses to the pastoral areas.In addition,swainsonine has attracted a great attention from toxicology and medicine fields,due to its dual role of toxicity and pharmacological activity.This review not only summarizes the latest research progress of toxicity and its poisoning mechanism,pharmacological activity,source,and biosynthesis pathway of swainsonine,but also speculates the possible regulatory enzymes involved in the synthesis pathway.Moreover,the future research on swainsonine is also looked ahead,which provide references for the prevention and treatment of locoism.

OBJECTIVE To investigate the effects and mechanisms by which JQ-R regulated the glucose metabolism and improves insulin sensitivity in diabetic KKAy mice and insulin-resistant L6 myotubes. JQ-R is a mixture of refined extracts from Coptis chinensis, Astragalus membranaceus and Lonicera japonica, three major herbs of JinQi-JiangTang tablet. METHODS Diabetic KKAy mice were adminis-tered JQ-R (100 mg·kg-1or 200 mg·kg-1BW) for 10 weeks. Levels of fasting plasma glucose, lipids, insulin and hemoglobin A1c were monitored.Systemic insulin sensitivity was quantified using the eugly-cemic clamp.The effect of JQ-R on the expressions of the enzymes involved in insulin signaling,oxidative stress and inflammation(Akt,NFκB,IΚBα, JNK, Erk, p38 MAPK) were measured in L6 insulin-resis-tant myotubes. RESULTS JQ-R showed beneficial effects on glucose homeostasis and insulin sensi-tivity in diabetic KKAy mice after 10 weeks treatment. JQ-R also ameliorated the plasma lipid profiles. Moreover,JQ-R can directly reverse the decreased activity of SOD and increased MDA levels as well as activity of iNOS in insulin resistant L6 cell induced with palmitic acid(PA).The expressions of phos-phorylation of NF-κB p65,IκBα,JNK1/2 and Erk1/2 were also decreased after JQ-R treatment.It was also shown that the insulin-stimulated glucose uptake increased significantly after JQ-R treatment,with upregulated expression of phosphorylation of Akt. CONCLUSION JQ-R ameliorated the glucose and lipid metabolism and insulin sensitivity in diabetic KKAy mice. In vitro treatment with JQ-R directly enhanced insulin stimulated glucose uptake in insulin resistant myotubes with improved insulin signal-ling and inflammatory response and oxidative stress state.

Objective To investigate bladder anatomical changes and dose variation in patients with cervical cancer.Methods We analyzed 20 patients,undergoing external beam radiotherapy scanning cone beam CT(CBCT)before each fraction.Bladder was contoured on each CBCT,was projected onto the planning CT and assesses anatomical changes and dose variation.Results A total 451 CBCT images,for 20 patients were collected for analysis,show more change in bladder volume and position.In 15 cases bladder volume and V45 had no significant correlation(r=0.225 -0.473,all P>0.05),4 cases shows negative correlation(r=-0.564,P<0.05;r=-0.597,P<0.01;r=-0.942,P<0.01;r=-0.816,P<0.01),1 case shows positive correlation(r=0.662,P<0.01).Have more than the criteria(V45≤50%)number is 64/451(14.2%)in whole treatment.Conclusions For most patients by filling adequacy bladder,bladder dose variation is acceptable:CTV lager for individual patients should be closely observed its regression,implementation of the offline or online calibration.

Objective:To purify HLA-DR molecules. Methods: Anti-HLA-DR antibody L243 was purified and coupled with CNBr activated Sepharose 4B gel. Immunoaffinity column was used to purify HLA-DR molecules. Results:Twenty micrograms of HLA-DR molecules were isolated from about 5 g Epstein-Barr virus-transformed human B lymphoblastoid cell line RAJI lysates by affinity chromatography. The purified HLA-DR molecules existed in α/β heterodimers form and could bind to conformation-dependent antibody L243. These HLA-DR molecules were separated into two strands,α and β,by boiling denaturation. These results are the basis for studying MHC Ⅱ binding peptide motif and CD4＋ T cell epitopes of antigens in future.