Objective: The bacterial superantigen staphylococcal enterotoxin A (SEA) has the potent ability of inducing T cell activation as well as directing activated T cells to kill tumour cells. However, its application in the tumour treatment is limited due to its systemic immune activation.In order to minimize its side effects SEA liposomes is prepared and their toxcicity in vivo is investigated . Methods: SEA liposomes were prepared by the method of reverse-phase evaporation . SEA liposomes were administered intravenously . In vivo the toxcicity of SEA liposomes was investigated by the measurement of blood pressure, colonic temperature and breath rate of New Zealand rabbits. Mice plasma TNF-? and IFN-? level were determined by ELISA . Results:After iv administration of SEA liposomes, significant reduction of mice plasma TNF-? and IFN-? level was observerd. As compared to free SEA, liposomal SEA had less effect on blood pressure, colonic temperature and breath rate of the rabbits. Conclusion:SEA Liposomes had relatively low toxicity. These advantage was probably due to its lower systemic immune activation effect and inducing consequent lower systemic TNF-? and IFN-? level.

Animals ; Cardiovascular System ; chemistry ; Female ; Group II Phospholipases A2 ; blood ; Group IV Phospholipases A2 ; blood ; Group V Phospholipases A2 ; blood ; Group X Phospholipases A2 ; blood ; Male ; RNA, Messenger ; genetics ; Rats ; Rats, Wistar

Hepatocellular carcinoma (HCC) combined with inferior vena cava (IVC) tumor thrombosis is regarded unresectable.Most of the patients received non-surgical treatment or gave up treatment,and the prognosis of these patients is poor.As the development of surgical treatment,the success rate of surgical treatment for HCC combined with IVC tumor thrombosis is increasing yearly.In May of 2012,one patient with HCC combined with IVC tumor thrombosis received hepatic Ⅴ,Ⅶ and Ⅷ segmentectomy + tumor thrombosis removal from the IVC at the Second Affiliated Hospital of Harbin Medical University.Preoperative computed tomography showed space-occupying lesions in the segments Ⅴ,Ⅶ and Ⅷ,and the IVC was filled with tumor thrombi.The volume of the left liver was 489 cm3,which was under the limit for survival.In order to preserve the remnant liver,right hepatectomy with reservation of hepatic segment Ⅵ,and the tumor thrombi in the IVC were removed with total hepatic vascular exclusion.The patient was recovered with no tumor recurrence or metastasis at postoperative month 18.

BACKGROUND: It is of great importance in improving the clinical effect of human islet allograft to study and design models of such large animals as pigs or primates preclinically.OBJECTIVE: To evaluate the effect of different doses of streptozotocin (STZ) on inducing diabetes type Ⅰ models of nonhuman primates.DESIGN, TIME AND SETTING: A contrast observational animal experiment was performed in the Cell Transplantation and Gene Therapy Center, the Third Xiangya Hospital of Central South University from October 2007 to December 2008. MATERIALS: A total of 21 adult male rhesus monkeys were divided into a 125 mg/kg STZ group (n =5), a 75 mg/kg STZ group (n=5) and a 50 mg/kg STZ group (n=11).METHODS: STZ weighed with regard to body mass of animals was prepared into 25 g/L STZ solution with buffer that was prepared in advance. After being filtered and degermed, the new-prepared STZ of 125 mg/kg, 75 mg/kg and 50 mg/kg were administered by intravenous injection into the experimental monkeys respectively, which took 1-5 minutes.MAIN OUTCOME MEASURES: Liver and renal function, glucose metabolism and histomorphological changes of animals during 1-16 weeks following administration.RESULTS: In 125 mg/kg STZ group, two rhesus monkeys died, in 8 hours following STZ administration, of serious hypoglycemia caused by severely damaged pancreas β cells; All rhesus monkeys in this group had got significantly increased liver transaminase, serum creatinine and urea nitrogen at week 1 following STZ administration, which reached a peak during 2-4 weeks; One rhesus monkey in this group showed severe shortage of endogenous trypsin and hyperglycemia irreversible by exogenous insulin following STZ administration, and finally died at day 13 following STZ administration due to the glucose metabolic disorder, ketoacidosis, liver and renal failure; The other two survivors in this group kept high level of liver transaminase,urea nitrogen and serum creatinine throughout the observation period. In 75 mg/kg STZ group, rhesus monkeys presented significantly increased liver transaminase, serum creatinine and urea nitrogen at week 1-2 following STZ administration; After 4 weeks following administration, their liver and renal function presented with abnormality of different degrees; One rhesus monkey in this group had got injured renal function, decreased power of resistance, eyelid edema, general dropsy and irreversible infected rump after injection of STZ, and finally died at the end of week 5 following administration; Another rhesus in this group presented with irreversible continuous hyperglycemia, inappetence and significantly decreased weight, and finally died ofsystemic failure at week 9 following administration. In the 50 mg/kg STZ group, renal function of monkeys were slightly affected, with a transient mild rise which return to the normal level by the end of week 4 following administration; Only 3 animals in this group appeared eyelid edema during 1-4 weeks following administration which disappeared afterwards.CONCLUSION: STZ of 50 mg/kg is possibly the optimal dose for inducing diabetes models in most rhesus monkeys.

Objective To detect anti-M3 receptor antibodies in primary Sj(o)gren's syndrome(pSS)patients and to explore its association with clinical manifestations.Methods Anti-M3 antibodies were tested in 70 patients with pSS,50 patients with systemic lupus erythematosus(SLE)and 76 normal controls with ELISA and Western blot.The correlation between anti-M3 antibodies and other clinical manifestations was analyzed.Results (1)The positive rate of anti-M3 antibodies in pSS Was 47.14% using ELISA and 60.00% using Western blot in SLE 4.00% using ELISA and 12.00% using Western blot and in normal controls 14.47% using ELISA and 15.79% using Western blot.(2)The incidence of sehirmer test,tear break-up time(BUT),whole saliva flow rate,punctate epithelial erosions(PEE)on the corneas and external eye examination were not significantly different between the anti-M3 positive and negative groups.(3)The incidences of IgG,rheumatoid factor,SSB and fluorescence index(FI)＞3 were higher in the positive group than in the negative group using EUSA.Conclusion The positive rate of anti-M3 antibodies is higher in pSS than in SLE and normal controls and in some degree it has correlation with the lesion in salivary gland.

OBJECTlVE To expIore the intervention effect of Iosartan on the Iung oxidative injury in-duced by paraquat(PQ). METHODS AduIt maIe SD rats were randomIy divided into 4 groups:normaI controI group,PQ intoxication group(rats were treated with singIe ig PQ 40 mg·kg-1 ),Iosartan inter-vention for 7 and 14 d groups(rats were ig given Iosartan 10 mg·kg-1 daiIy for 7 and 14 consecutive days after PQ was given). AII rats were sacrificed on the 16th day to obtain Iung tissues. HE staining was used to observe the Iung pathoIogicaI changes. The activities of superoxide dismutase(SOD),cataIase (CAT)and totaI antioxidant capacity(T-AOC)and content of Iipid peroxide(LPO)were detected by spectrophotometry. ReaI-time quantitative PCR was used to investigate the NF-κB mRNA expression in Iung tissue. RESULTS PathoIogicaI examination showed that acute Iung injury and significant Iung fibro-sis appeared in PQ intoxication group but were reversed by Iosartan. The IeveIs of SOD,CAT and T-AOC decreased whiIe the content of LPO in PQ intoxication group increased significantIy compared with controI group(P﹤0.05). Compared with PQ intoxication group,the IeveIs of SOD,CAT and T-AOC in-creased and the content of LPO decreased in Iosartan intervention for 7 and 14 d groups(P﹤0.05),and the IeveIs of T-AOC and LPO in Iosartan intervention for 7 and 14 d groups and the activities of SOD and CAT in Iosartan intervention for 14 d group nearIy returned to normaI. The mRNA expression of NF-κB was upreguIated after rats were exposed to PQ,downreguIated in Iosartan intervention for 7 and 14 d groups in rat Iung tissues( P﹤0.05),but nearIy returned to normaI. CONCLUSlON Oxidative stress may be invoIved in the acute PQ poisoning process and Iosartan might have intervention effect on acute PQ Iung damage by improving the antioxidant capacity and downreguIating the mRNA expression of NF-κB.

Objective To investigate the expression of activated ERK (p-ERK) and activated p38 (p-p38) in the keratinocytes of condyloma acuminata (CA) lesions. Methods Fifty cases of HPV 6/11 CA were diagnosed by in situ hybridization. The expression and distribution of p-ERK and p-p38 in CA lesions and 25 normal human skins (foreskins) were detected by immunohistochemistry technique (En Vision). Results ①The results showed that the expression of p-ERK and p-p38 in keratinocytes of CA lesions were significantly higher than those in normal epidermis (P

Objective: To analyze the CYP2C19 gene polymorphism in patients with upper digestive system diseases in Anhui Province, so as to provide evidence for individual treatment. Methods: The 307 patients with upper digestive system diseases in the Department of Gastroenterology, The 901st Hospital of Combined Service Force of People＇s Liberation Army were selected. The CYP2C19 genotypes were detected by DNA microarray microarray. The CYP2C19 genotypes and metabolic types in different genders, ages and diseases were analyzed. Results: There were 197 males ( 64.17% ) and 110 females ( 35.83% ) , with the age of ( 58.00±16.13 ) years old. The gene frequency of CYP2C19*1, CYP2C19*2 and CYP2C19*3 was 62.70%, 32.25% and 5.05%, respectively. There were 119 cases (38.76%) of *1/*1 ( 636GG, 681GG ), 129 cases ( 42.02% ) of *1/*2 ( 636GG, 681GA ) , 18 cases (5.86%) of *1/*3 ( 636GA, 681GG ) , 29 cases ( 9.45% ) of *2/*2 ( 636GG, 681AA ) , 11 cases ( 3.58% ) of *2/*3 ( 636GA, 681GA ) , and 1 cases ( 0.33% ) of *3/*3 ( 636AA, 681GG ). In terms of metabolisms, there were 119 cases ( 38.76% ) of fast metabolism type, 147 cases (47.88%) of intermediate metabolism type and 41 cases (13.35%) of slow metabolism type. There were no significant differences in CYP2C19 genotypes and metabolic types among the patients with different gender, age and digestive system diseases ( P＞0.05 ). Conclusion The CYP2C19 genotypes of patients with upper digestive system diseases were polymorphic, mainly the fast metabolism type and the intermediate metabolism type, which could provide reference for the clinical medication of individualized treatment of proton pump inhibitors.

In the present study, a new compound named 17-(6-cinnamamido-hexylamino-)-17-demethoxygeldanamycin (CDG) was obtained by introducing the cinnamic acid (CA) group into the 17-site of geldanamycin (GDM). The anti-cancer effects of CDG in vitro and in vivo were evaluated. MTT assay was used to examine the inhibitory effect of CDG on the proliferation of MCF-7, HepG2, H460 and SW1990 cells. Immunofluorescent staining flow cytometry combined with Annexin V-FITC/PI staining were used to detect apoptotic cells. Transwell assay was used to analyze the effect of CDG on cell invasion and migration ability. Western blotting was used to detect the expression levels of RAF-1, EGFR, AKT, CDK4 and HER-2 of MCF-7, HepG2 and H460 cells. The toxicities of CDG and GDM were evaluated in mice. Using the subcutaneously transplanted MCF-7 xenograft in nude mice, inhibitory effect was evaluated in vivo. The results showed that CDG inhibited the proliferation of cancer cells (IC50: 13.6-67.4 microg.mL-1). After exposure to CDG for 48 h, most cells presented typical morphologic changes of apoptosis such as chromatin condensation or shrunken nucleus. The rates of apoptosis of MCF-7, HepG2, H460 and SW1990 cells incubated with 10 microg.mL-1 CDG were 23.16%, 27.55%, 22.21%, 20.47%, respectively. A dose-dependent reduction of migration of four cell lines was found after exposure to CDG. The decreased levels of RAF-1, EGFR, AKT, CDK4 and HER-2 showed that CDG possessed HSP90 inhibitory effect. The result of animal toxicity test on the mice suggested that CDG had lower toxicity than GDM. Meanwhile, CDG inhibited the growth of MCF-7 xenografts of athymic mice.
Animals ; Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Apoptosis ; drug effects ; Benzoquinones ; chemical synthesis ; chemistry ; pharmacology ; Cell Line, Tumor ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Cyclin-Dependent Kinase 4 ; metabolism ; Female ; HSP90 Heat-Shock Proteins ; antagonists & inhibitors ; Humans ; Lactams, Macrocyclic ; chemical synthesis ; chemistry ; pharmacology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Invasiveness ; Neoplasm Transplantation ; Proto-Oncogene Proteins A-raf ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Random Allocation ; Receptor, Epidermal Growth Factor ; metabolism ; Receptor, ErbB-2 ; metabolism ; Tumor Burden ; drug effects ; Xenograft Model Antitumor Assays

For patients with malignant pancreatic cancer combined with vascular invasion,radical pancreaticoduodenectomy with vascular resection and anastomosis is the treatment of choice.Because this procedure is difficult to manage and with high risks,it is a great challenge to surgeons.A 50-year old patient with pancreatic head cancer whose portal vein and superior mesenteric vein were involved received radical pancreaticoduodenectomy in the Second Affiliated Hospital of Harbin Medical University.In the surgery,the tumor and its surrounding tissues were dissected,and then the portal vein and splenic vein were reconstructed.The patient was discharged at the 10th day after the surgery with favorable prognosis.