Background Stromal-derived factor 1α /chemokine receptor 4(SDF-1α/CXCR4) axis is one of the important signals which mediates several different activities such as chemotaxis,adhesion,proliferation and survival resulting in recruitment to sites of immune and inflammatory reactions.Considerable evidence suggests that CXCR4/SDF-1α axis is involved in tumor angiogenesis and plays a key role in the development of ocular neovascularization.Objective The purpose of this study was to explore the effect of CXCR4 antagonist on the development of cxperimental corneal neovascularization(CNV).Methods CNV model was established in the left eye of 8-weekold clean BALB/c mouse by putting the filter with 1 mol/L NaOH at the central cornea for 40 seconds.The animals were randomizcd into hyaluronate group and CXCR4 antagonist group,and the edydrops was topically administered respectively on the day of modeling 4 times per day for 14 days.CNV was examined under the slit lamp at the fourteenth day,and then the corneal suspension and section were made.Expressions of CXCR4 mRNA and protein in corneas were detected using RT-PCR and Western blot.The CD31 level in cornea was assayed by flowcytometry and immunochemistry.The expression of VEGF in burned corneas and suspension from mouse peritoneal macrophages stimulated with CXCR4 antagonist in vitro was detected by ELISA.The use of the animal followed Ragulations for the Administration of Affairs Concerning Experimental Animals by State Science and Technology Commission.Results Two weeks after corneal alkali burn,the growth of CNV peaked under the slit lamp.Compared with hyaluronate group,CNV was obviously decreased in the CXCR4 antagonist group.Immunochemistry showed that intensity of positive staining for CD31 in cornea in the CXCR4 antagonist group was weaker than the hyaluronate group.Flowcytometry clarified that CD31 positive cells rate was 9.50％ ±2.34％ in the CXCR4 antagonist group and 17.50％ ±3.16％ in the hyaluronate group,showing a significant difference between them (t=-7.312,P＜0.05).In 2,4,7 days after cornea alkali burn,the expressions of CXCR4 mRNA and protein were significantly enhanced in burn corneas compared with normal corneas(P＜0.01 ;P＜0.05).ELISA showed that the VEGF expression level in corneal tissue and supernatant of mouse peritoneal macrophages in vitro were significantly lower in the CXCR4 antagonist group than that of hyaluronate group(t =10.927,5.151,P＜0.05).The expression level of VEGF in corneal suspension was lower in the GM-CSH+CXCR4 antogonist group than that in the GM-CSH group (P＜0.05).Conclusions CXCR4 antagonist can reduce experimental CNV by down-regulating VEGF expression in cornea.

Objective:To investigate the possibility of using radioiodine labeled framework region(FR)antisense oligonucleotides(ASONs)as an imaging agent or antisense therapeutic radiopharmaceu-tical in lymphoma.Methods:A 18-mer partial phosphorothioate oligonucleotide sequence was synthe-sized and grafted in 5'with a tyramine group which was further radioiodinated.Radioiodination of the tyra-mine derivatized oligonucleotides was performed using the chloramine T method.(1)Normal CD-1 micewere injected via a tail vein with 148 kBq (125)~I-FR-ASON(2-3?g).Animals were sacrificed at the endof 1,2,4 and 24h,and tissue samples were studied.(2)Liposome-mediated 3.33 MBq (131)I-FR-ASON(7-9?g)were injected intralumorally into tumor-bearing BALB/c mice(6 weeks after innculation of10~7 Namalwa cells)meanwhile liposome-mediated (131)~I labeled sense oligonucleotides served as controls.Biodistribution was monitored by sequential scintigraphy and organ radioactivity measurement 24h afterinjection.Percentage of the injected dose per gram of tumor and tumor/non-tumor tissue ratios(T/NT)were calculated tot each group of mice and the difference between two groups was assessed.Results:The5′tyramine group allowed specific and stable radinlabeling of the ASON with radioiodine.The radioactivi-ty reached its peak 1h after injection,and then decreased rapidly in normal mice after intravenous ad-ministration of (125)~I-FR-ASON.The liver,stomach and intestine played an important role in biodistributionand radioactivity counts were low in bone,brain and blood.When (131)I-FR-ASON was injected intratumor-ally into mice grafted with Namalwa cell line,images showed the tracer accumulated in the tumor,Imme-diately after intratumoral administration,only the tumor was visible.Scintiscans performed at the end of 1and 2h showed elimination of the tracer from the tumor to the abdomen and at the end of 24h the tumorwas clearly seen.Percentage of the injected dose per gram of tumor and T/NT ratios for the sense group(control)were significantly lower than those of the antisense group.Conclusion:Radiolabeled Ig FRASON showed high specificity in V1 family B-cell lymphoma,which should be further investigated for nu-clear medicine imaging application and radionuclide antisense therapy.

OBJECTIVETo study the protective effect of hyperoxia solution on acute lung injury caused by phosgene poisoning by observing the changes of PaO2 and malondialdehyde (MDA) contents, superoxide dismutase (SOD) activity in serum and Glutathione (GSH/GSSG) contents in lung tissues.

METHODSThe rabbits were divided into normal control group, hyperoxia solution (H0) and balance salt (BS) groups. Group HO and Group BS inhaled phosgene and the former was given intravenously hyperoxia solution (which was replaced by balance salt solution in Group BS). The content of MDA and the activity of SOD in serum were observed at different time points, the amount of GSH and GSSG in lung tissue were also measured.

RESULTS(1) The serum MDA contents increased and PaO2, SOD activity decreased significantly in Group HO and Group BS along with time increasing as compared with control group. The contents of GSH in lung tissue decreased in two groups compared with that in control group, however the contents of GSSG ascended instead. (2) At 3 and 8 h of the experiment, PaO2 of Group HO [(9.91 +/- 0.49), (9.15 +/- 0.46) mm Hg respectively] were significantly higher than those of Group BS [(9.03 +/- 0.76), (8.11 +/- 0.57) mm Hg respectively] (P < 0.01). The contents of MDA of Group HO (3.66 +/- 0.35), (5.31 +/- 0.15) micromol/L respectively] were lower than those of Group BS [(4.32 +/- 0.26), (7.4 +/- 0.33) micromol/L respectively] (P < 0.01). SOD activity in Group HO [(237.37 +/- 29.96), (208.10 +/- 18.80) NU/ml respectively] were higher than those of Group BS [(195.02 +/- 21.44), (144.87 +/- 21.26) NU/ml respectively] (P < 0.05 or P < 0.01). The content of GSSG lung tissue in Group HO (423.67 +/- 38.21) micromol/L were lower than those of Group BS (523.85 +/- 43.14) mol/L (P < 0.01). There were no significant differences in the content of GSH in lung tissues between Group HO and group BS.

CONCLUSIONHyperoxia solution can reduce acute lung injury of rabbits following phosgene poisoning.

Acute Lung Injury ; etiology ; metabolism ; pathology ; Animals ; Glutathione Peroxidase ; metabolism ; Hyperoxia ; Lung ; drug effects ; metabolism ; pathology ; Malondialdehyde ; analysis ; Oxygen ; administration & dosage ; pharmacology ; Phosgene ; poisoning ; Rabbits ; Superoxide Dismutase ; metabolism

OBJECTIVETo study the biological behavior of cardial cancer and its influence on surgical management.

METHODSComplete clinicopathologic data of 46 cases with cardial cancer undergoing radical gastrectomy was investigated retrospectively. The relationships between tumor Borrmann type, depth of invasion, growth pattern, lymph node metastasis and 5-year survival rate postoperative were analyzed.

RESULTSOf 46 cases, Borrmann type III, Type IV and Type II was 76% (35/46), 18% (8/46) and 6% (3/46) respectively; 5-year survival rate was 40% (14/35), 0 (0/8) and 100% (3/3) respectively. In respect of the depth of invasion, pT(2) was 31% (14/46) cases with 71% (10/14) lymph node metastasis; and 5-year survival rate was 64% (9/14). pT(3) was 15% (7/46) cases with 86% (6/7) lymph node metastasis; and 5-year survival rate was 57% (4/7). And pT(4) was 54% (25/46) cases with 92% (23/25) lymph node metastasis; and 5-year survival rate was 12% (3/25). The growth pattern in 87% (40/46) cases was infiltrative; and 5-year survival rate was 28% (11/40); the growth pattern in 13% (6/46) cases was expansive; and 5-year survival rate was 100% (6/6).

CONCLUSIOND(2)(+) radical total gastrectomy should be performed on the developed cardial cancer, and if necessary, resection of body and tail of pancreas should be chosen.

Aged ; Aged, 80 and over ; Cardia ; Female ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; Stomach Neoplasms ; pathology ; surgery

OBJECTIVETo investigate clinical effects and mechanism of Tangweikang (TWK) in treating diabetic gastroparesis.

METHODSNinety diabetic gastroparesis patients were randomly assigned to 3 groups. Besides conventional hypoglycemic treatment, the 30 patients in the treated group were given TWK and the 30 in the control group were given Domperidone additionally, while to the 30 in the blank group, no additional drug was given. The clinical efficacy and the changes in level of motilin and gastric emptying rate were observed.

RESULTSTWK showed significant effects in improving clinical symptoms of patients, increasing gastric emptying rate, promoting gastrointestinal kinetics, shortening gastric emptying time and was beneficial to the control of blood sugar, including the 2 h post-prandial blood sugar and fructosamine. The curative rate and total effective rate in the treated group were 63.33% (19/30) and 93.33% (29/30) respectively, significantly different to those in the control group 26.67% (8/30) and 63.33%, also different to those in the blank group 23.33% (3/ 30) and 10.00%, respectively (P < 0.01). The clinical efficacy in the treated group was superior to that in the other two groups.

CONCLUSIONTWK has favorable therapeutic efficacy in treating DGP.

Aged ; Antiemetics ; therapeutic use ; Diabetes Complications ; drug therapy ; Domperidone ; therapeutic use ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Gastroparesis ; drug therapy ; etiology ; Humans ; Male ; Middle Aged ; Phytotherapy ; Treatment Outcome

OBJECTIVETo observe the dynamic immunity of the porcine cancellous bone scaffold(PCBS) after transplantation and provide experimental evidences for amending and clinical use.

METHODSThe PCBS was gained through physical and chemical disposals to porcine cancellous bone and was implanted subcutaneously in rabbit. The histological investigation and the expression of Th1 (such as IL-2, IFN-gamma) and Th2 (such as IL-4, IL-10) mRNA were measured by HE, RT-PCR respectively in 1,2,4,8,12 week postoperation.

RESULTSHE revealed: Inflammation cells (lymphocytes and monocytes) were shown abundantly in the surrounding tissue in 1 week and were decreased gradually since 2 week. At 12 week, there were few inflammation cells in the surrounding tissue. RT-PCR revealed: The mRNA expression level of Th1 cytokines such as IL-2, IFN-gamma was high in 1 week and began to fall since 2 week. At 12 week, the mRNA expression level of Th1 cytokines was low; The mRNA expression level of Th2 cytokines such as IL-4, IL-10 was low in 1 week, rose gradually since 2 week and reached tiptop in 8 week. At 12 week, the mRNA of Th2 cytokines maintained high level expression.

CONCLUSIONSThe porcine cancellous bone scaffold excitate immunoreaction was transitory inflammation after implantation.

Animals ; Bone Transplantation ; immunology ; Cytokines ; metabolism ; RNA, Messenger ; genetics ; Rabbits ; Swine ; Th1 Cells ; metabolism ; Th2 Cells ; metabolism ; Tissue Scaffolds ; Transplantation, Heterologous

OBJECTIVETo summarize the clinical features of idiopathic premature ovarian failure (POF) and explore the early diagnosis and intervention.

METHODSA retrospective study was conducted in 39 women with idiopathic POF treated between February, 2009 and January, 2010. The clinical data of the patients including the menstrual feature, POF incidence, vaginal ultrasound and pregnancy outcomes were investigated.

RESULTSOne patient had primary amenorrhea and 38 had secondary amenorrhea with an average duration of amenorrhea of 5.82 years. Abrupt cessation occurred after 1-2 menstruations following the menarche in 2 cases (5.1%) and without identifiable preceding signs in 9 cases (23%). The mean uterine and ovarian volume was significantly smaller in POF group than in the control group. Antral follicle count (AFC) was also significantly lower in POF group. Vaginal ultrasound detected at least one ovary in 89.7% and follicular activity in 79.5% of the POF patients. Evidence of ovulation was found in 12 patients, and spontaneous pregnancy occurred in 2 patients with a pregnancy rate of 5.1%.

CONCLUSIONPatients with menstrual disturbance, polymenorrhea and oligomenorrhea are at risk of developing POF, in which case regular detection of the mean uterine volume, ovarian volume and AFC by vaginal ultrasound may help in early POF detection. Close monitoring can be necessary in the course of hormone replacement therapy, and timely intervention with assisted reproductive techniques may increase the chance of pregnancy.

Adult ; Female ; Humans ; Pregnancy ; Primary Ovarian Insufficiency ; diagnosis ; Retrospective Studies ; Risk Factors ; Young Adult

Objective A resistin binding peptide (RBP) was selected by phage display in our previous work. Studies had shown that RBP could antagonize the role of resistin on the lipid metabolism and endocrine function of adipose tissue, but whether RBP affects the insulin secretion of pancreatic cells is still unknown. The aim of this study is to assess the effect of RBP on basal insulin secretion in RINm5F insulinoma cells. Methods The cell viability was measured by 3-[4,5-dimethyhhiazol-2-yl]-2,5-diphenyltetra-zolium bromide (MTT) cytotoxicity assay. The supernatants were assayed for insulin content by enzyme linked immunosorbent assay (ELISA). Reverse transcriptase-PCR assay and Western blotting were used to determine the expression of glucose transporter 2 (GLUT2) involved in insulin secretion. Cytosolic Ca2+, the trigger of insulin exocytosis, was analyzed with the fluorescent probe FURA-3/AM. Results RBP did no effect on the cell viability with a concentration of 10-8-10-12mol/L of 2 hours intervention. But it stimulated basal insulin secretion of RINm5F cells, accompanied by up-regulated increased expression of GLUT2 and elevated concentration of cytosolic Ca2+. Conclusion RBP could stimulate basal insulin secretion without affecting the cell viability.

This study was purposed to explore the mechanisms of drug resistance of HL-60/ADR cells and to compare the reversal drug-resistance effects of antisense oligonucleotides (AS ODN) of XIAP (X-linked inhibitor of apoptosis protein) and AS ODNs of MRP (multidrug resistance-associated protein) by use alone or in combination. Reverse transcription-PCR and Western blot were applied to detect the expression of XIAP, BCL-2, MRP and MDR1 in mRNA and protein levels of HL-60 cells and HL-60/ADR cells, respectively. Fully phosphorothioated AS ODN of XIAP and MRP was delivered into HL-60/ADR cells with Lipofectamine 2000 in the form of liposome-ODN complexes alone or in combination. CCK-8 cell viability assay was used to determine the effect of AS ODN of XIAP and MRP used alone or in combination on the chemotherapy sensitivity of HL-60/ADR cells to daunorubicin (DNR). Reverse transcription-PCR and Western blot were applied to examine the changes of XIAP, MRP in mRNA and protein levels respectively. The results showed that MRP and XIAP were both significantly higher in HL-60/ADR cells than those in HL-60 cells. AS ODN of XIAP and MRP down-regulated the expression of XIAP and MRP in HL-60/ADR cells and increased the sensitivity of HL-60/ADR cells to DNR, respectively. AS ODN of XIAP + MRP did not enhance the inhibition expression of XIAP in HL-60/ADR cells but increased the sensitivity of HL-60/ADR cells to DNR significantly as compared with AS ODN of XIAP (P < 0.05). AS ODN of XIAP + MRP did not increase the concentration of DNR nor enhanced the inhibition expression of MRP in HL-60/ADR cells but increased the sensitivity of HL-60/ADR cells to DNR significantly (P < 0.05), as compared with AS ODN of MRP. It is concluded that both XIAP and MRP may be involved in the drug resistance mechanisms of HL-60/ADR cells. Drug-resistance of HL-60/ADR cells can be reversed significantly when antisense oligonucleotides of XIAP and MRP were used in combination.
Doxorubicin ; pharmacology ; Drug Resistance, Multiple ; genetics ; Drug Resistance, Neoplasm ; genetics ; HL-60 Cells ; Humans ; Multidrug Resistance-Associated Proteins ; biosynthesis ; genetics ; Oligonucleotides, Antisense ; pharmacology ; RNA, Messenger ; biosynthesis ; genetics ; X-Linked Inhibitor of Apoptosis Protein ; biosynthesis ; genetics

OBJECTIVETo observe the effect of rosuvastatin on left ventricular cardiac function, arteriosclerotic plaque and high sensitive C-reactive protein (hs-CRP) in hypertensive patients with mild elevation of LDL-C.

METHODSSeventy-nine patients with a SBP of 140-179 mmHg and/or a DBP of 90-109 mmHg and mild elevated LDL-C were treated with rosuvastatin for 12 months (n=40) or not (n=39). The changes of hs-CRP, arteriosclerosis plaque and cardiac function at the end of the 12-months treatment relative to the baseline levels were analyzed.

RESULTSAfter 12 months of treatment, LDL-C was decreased by 33.2% in rosuvastatin group but remained unchanged in patients without rosuvastatin treatment. The left ventricular peak filling rate (LVPFR) increased significantly from 1.85 to 2.59 (P<0.05) and the serum levels of hs-CRP reduced significantly (P<0.05) after rosuvastatin treatment. The size of the plaques reduced significantly after a 12-month rosuvastatin therapy.

CONCLUSIONRosuvastatin therapy on the basis of conventional anti-hypertensive drugs can obviously improve the left ventricular diastolic function and produce favorable effects on arteriosclerotic plaques.

Aged ; Arteriosclerosis ; complications ; pathology ; C-Reactive Protein ; metabolism ; Cholesterol, LDL ; blood ; Female ; Fluorobenzenes ; therapeutic use ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; therapeutic use ; Hyperlipidemias ; drug therapy ; pathology ; physiopathology ; Hypertension ; drug therapy ; pathology ; physiopathology ; Male ; Middle Aged ; Pyrimidines ; therapeutic use ; Rosuvastatin Calcium ; Sulfonamides ; therapeutic use ; Ventricular Function, Left ; drug effects