2.Heme oxygenase-2 gene deletion protects basal ganglia cells from oxidative injury induced by free Fe2+
Yan QU ; Xiang ZHANG ; Jian-Ning ZHANG ; Hai-Ning ZHEN ; Da-Kuan GAO
Academic Journal of Second Military Medical University 2005;26(4):390-395
Objective:To determine whether heme oxygenase-2(HO-2) gene deletion can attenuate oxidative injury induced by free Fe2+. Methods:Stereotactic injection of 10 μl sterile FeCl2 (10 mmol/L) was made into the right striata of HO-2 knockout mice and wild-type mice. Brain edema severity was measured at 24 h. Cell viability, protein oxidation, and lipid oxidation of the basal ganglia were determined at 72 h. Western blot analysis was applied for heme oxygenase-1 (HO-1) measurement.Results: Brain water content significantly decreased in HO-2 knockout mice at 24 h compared with wild-type mice. Protein oxidation and lipid oxidation significantly decreased in HO-2 knockout mice at 72 h compared with wild-type mice, while the striatal cell viability increased significantly. HO-1 expression at baseline and 72 h was also similar to that in wild-type mice. Conclusion:These results show that HO-2 gene deletion can protect basal ganalia cells from free Fe2+ -mediated oxidative stress injury,suggesting that selective inhibition of HO-2 may have a protective effect on brain oxidative injury.
3.Combining of TNP-470 and 5-Fu in inhibition of adenoid cystic carcinoma in nude mice model.
Xiao-lin NONG ; Da-zhang WANG ; Min MENG ; Nuo ZHOU ; Ning MENG ; Jia-quan LI ; Hong ZHANG
West China Journal of Stomatology 2004;22(4):267-270
OBJECTIVETo study the effect of angiogenesis inhibitor and its combine with chemical drug in suppressing the growth of adenoid cystic carcinoma (ACC).
METHODSAcc-M cells were inoculated subcutaneous into BABL/C nu/nu mice. The mice were divided into control, different dose of TNP-470 treatment groups, 5-Fu treatment group and TNP-470 plus 5-Fu treatment group. Treatments were given 48 hours after inoculation. The mice were sacrificed on the 22nd day and excised tumors were weighted. Tumors were also investigated by immunohistochemistry and ultrastructural observations.
RESULTSTNP-470 100 mg/kg/qod efficiently inhibited the growth of Acc-M tumors. TNP-470 30 mg/kg/qod combined with 50 mg/kg/week 5-Fu also resulted in significant growth inhibit of the tumors. TNP-470 suppressed tumor growth by inhibiting neovascularization, therefore inducing apoptosis of Acc-M cells. All experimental groups had different degrees of VEGF and bFGF express.
CONCLUSIONSince ACC is a slow developing tumor, blood supply is not so sufficient as sarcomas. Angiogensis inhibitor may inhibit its growth in high dosage. Combining medium dosage of angiogensis inhibitor with chemical drug may have synergistic result in inhibiting ACC growth.
Angiogenesis Inhibitors ; pharmacology ; Animals ; Apoptosis ; Carcinoma, Adenoid Cystic ; drug therapy ; Cell Line, Tumor ; Cyclohexanes ; pharmacology ; Fluorouracil ; pharmacology ; Humans ; Mice, Inbred BALB C ; Mice, Nude ; Sesquiterpenes ; pharmacology
4.Management of intractable epistaxis and bleeding points localization.
Da-Zhang YANG ; Jing-Ning CHENG ; Jun HAN ; Ping SHU ; Hua ZHANG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2005;40(5):360-362
OBJECTIVETo investigate the common nasal bleeding points and the management of intractable epistaxis.
METHODSThe bleeding points and its correlation with age distribution, surgical techniques as well as its effects were studied retrospectively in 92 patients, in whom the bleeding points were not found by routine nasal endoscopy and the hemorrhage was not controlled with standard nasal packing.
RESULTSThe bleeding points were found in the following different sites: superior wall of inferior nasal meatus (56.5%, 52/92), olfactory cleft of nasal septum (27.2%, 25/92), posterosuperior wall of middle nasal meatus (8.7%, 8/92) and uncertain (7.6%, 7/92). The results showed that the bleeding points had correlation with age. Epistaxis was well controlled by electrocoagulation in 83 cases, gelfoam packing in 8 cases, and transcatheter maxillary artery embolization in 1 case. There were no complications during a followed-up for 1 - 3 months after management. Among the 92 cases, the numbers of treatment needed to stop bleeding were 82 cases (89.1%) after 1 time of treatment, 9 cases (9.8%) after 2 times and in one case (1.1%) after 4 times.
CONCLUSIONSEndoscopy combined with displacement of the middle and inferior turbinate gives good visualization and direct management of the deeply-sited bleeding points, which were difficult in localization. The combined method provides an effective and safe way to control intractable epistaxis.
Adolescent ; Adult ; Aged ; Electrocoagulation ; Endoscopy ; Epistaxis ; diagnosis ; pathology ; therapy ; Female ; Humans ; Male ; Middle Aged ; Treatment Outcome ; Young Adult
5.Expressions of nucleostemin and Ki-67 in pituitary adenomas and their clinical significance
Lin MA ; Jian-Ning ZHANG ; Xin-Jun WANG ; Ji-Xin SHOU ; Da-Jian ZHANG ; Shu-Yuan YANG
Chinese Journal of Neuromedicine 2008;7(4):343-346
Objective To study the expressions of nucleostemin gene mRNA and Ki-67antigen in pituitary adenomas and investigate the role of nucleostemin gene in the tumorigenesis and development of pituitary adenomas. Methods Seventy-one samples of pituitary adenomas were collected. Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect the expression of nucleostemin gene mRNA in samples. Immunohistochemistry technique was applied to examine Ki-67 antigen expression in the paraffin sections of samples. At the same time,coherent clinical data were collected. Results Nucleostemin gene mRNA was detectable in all samples of pituitary adenomas. Between invasive and noninvasive pituitary adenomas, the difference of nucleostemin expression was extremely significant (P<0.01), and Ki-67 labeling index (LI) was also significantly different (P<0.05). The difference of Ki-67LI between recurrent and non-recurrent groups was significant (P<0.05). There was a positive correlation between nucleostemin gene and Ki-67LIlevels (r=0.237, P<0.05). Conclusions Nucleostemin gene plays an important roles in the invasion of human pituitary adenoma. Expression of nucleostemin gene is positively related to Ki-67 antigen expression, and both may be the valid clinical detection markers for assessing proliferation, invasion and recurrence of pituitary adenomas.
6.An experimental study of polypropylerie combined with flap for trachea reconstruction
Xue-Ning ZHAO ; Bo CONG ; Da-Yu LIU ; Da-Peng LEI ; Ping YE ; Kun LIANG ; Lei YAO ; Zhong-Hua ZHANG ; Xin-Liang PAN
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2008;43(7):533-536
Objective Canine model established for tracheal defect reconstruction,to investigate the outcome of tracheal reconstruction with combination of polypropynene and flap.Methods About 3.5 to 4 centimeter cervical trachea was resected and replaced with artificial trachea made from monofilament knitted polypropylene and surgical flap.Covered stent Was implanted postoperatively.Survival period and quality of life were recorded,brunchofibroscopy,X-ray films and HE sections were perfomed.Results Six dogs survived well and another two died.The causes of death were respiratory failure in 1 and infection in another.Stenosis of anastomosis in 1 Was recorded during survival period.The dogs started drinking and eating on the second postoperative day,no dyspnea Was found.The animals were sacrificed at 2,4,8 weeks and 6 months after surgery.Soft tissue growth Was found in polypropynene net 2 weeks after surgery and more at 4 weeks.The polypropynene net was covered completely with soft tissue at 8 weeks and 6 months postoperatively.the hardness and sustentation degree were enhanced following the growth and fibrosis of soft tissue.The squamous epithelium and columnar epithelium were ohserved healing well by HE staining method.Conclusions One-stage operative artificial trachea made from monofilament knitted polypropylene which has good histocompatibility and surgical flap is the closer artificial trachea to native trachea.It has a promising prospect in clinical use.
7.Expression of recombinant human cytomegalovirus fusion proteins pp150/MDBP fragments and its application.
Da-Dong GUO ; Xue-Qin GAO ; Jin-Xiang HAN ; Yi LIU ; Hua-Ning ZHANG
Chinese Journal of Biotechnology 2006;22(6):956-961
Human cytomegalovirus (HCMV) infection is an ubiquitous herpesvirus disease in human populations. It is rarely pathogenic to healthy adults, yet it may cause severe outcome to organ transplant recipients, the immunocompromised individuals and pregnant women. Using DNA from HCMV AD169 strain as template, the UL32 gene encoding pp150 protein fragment and the UL57 gene encoding MDBP protein fragment were amplified by PCR technique. After the construction of cloning vector pMD18-T-UL32, pMD18-T-UL57, pMD18-T-UL32/UL57 and expression vector pET-11a-UL32/UL57, the recombinant fusion proteins pp150/MDBP were induced with IPTG in BL21 host strain. The results showed that the relative molecular weight of recombinant fusion proteins pp150/MDBP is about 27 kD, the product of fusion proteins takes 17.45% in the total proteins in host bacteria, the analytical result was positive to the fusion proteins pp150/MDBP via Western blot technique, while the purified recombinant fusion proteins have strong antigenicity detected by ELISA and protein chip compared with whole virus antigens from HCMV. It was demonstrated that when used for the detection of serum from the clinical patients it has the same detection rate compared with the whole virus antigen. It needs further research for application.
Cytomegalovirus
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DNA-Binding Proteins
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chemistry
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Electrophoresis, Polyacrylamide Gel
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Enzyme-Linked Immunosorbent Assay
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Gene Expression
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Genetic Vectors
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genetics
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Humans
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Peptide Fragments
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blood
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genetics
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immunology
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isolation & purification
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Phosphoproteins
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chemistry
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Plasmids
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genetics
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Polymerase Chain Reaction
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Recombinant Fusion Proteins
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blood
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genetics
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immunology
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isolation & purification
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Transcription Factors
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chemistry
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Viral Matrix Proteins
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chemistry
8.Experimental therapy of penehyclidine hydrochloride on paraquat-induced acute lung injury.
Qiong NING ; Xiang-dong JIAN ; Jun LIU ; Da-wei LIN ; Feng LIU ; Zhong-chen ZHANG ; Bo ZHAO
Chinese Journal of Industrial Hygiene and Occupational Diseases 2010;28(9):667-670
OBJECTIVETo observe the therapeutic effect and mechanism of penehyclidine hydrochloride on paraquat-induced acute lung injury.
METHODS80 healthy adult male Wistar rats were randomly assigned into control groups (10 rats), 100 mg/kg PQ group (10 rats), 100 mg/kg PQ plus 33 µg/kg penehyclidine hydrochloride treatment group (30 rats), 100 mg/kg PQ plus 66 µg/kg penehyclidine hydrochloride treatment group (30 rats). The two treatment groups were executed respectively at 36 h, 72 h and 7 d. Lung tissues were used to assess histopathological change by HE staining. The level of MMP-2, caveolin-1 and HYP were detected in the lung homogenate. The serum and BALF contents of ET were measured.
RESULTSPathology inspection confirmed that the model of acute rat pulmonary injury were duplicated successfully. The level of MMP-2, HYP in lung tissues and the serum and BALF ET contents in PQ group were (1.77 ± 0.40) µg/g, (2.91 ± 0.79) µg/g, (505.23 ± 124.69) µg/ml, (640.38 ± 136.60) µg/ml. The level of those was higher than that in control group [(0.95 ± 0.66) µg/g, (1.48 ± 0.69) µg/g, (95.48 ± 46.01) µg/ml, (200.40 ± 88.39) µg/ml, P < 0.05]; The above-mentioned index in two treatment groups was lower than that in PQ group (P < 0.05). The caveolin-1 content [(1.77 ± 0.82) µg/g] in PQ group was lower than that in control group [(5.39 ± 1.68) µg/g, P < 0.05]. The level of caveolin-1 in two treatment groups was higher than that in PQ group (P < 0.05).
CONCLUSIONPenehyclidine hydrochloride can decrease the level of MMP-2, HYP in lung tissues and the ET in serum and BALF, increase that of caveolin-1 and lessen the damage induced by paraquat.
Acute Lung Injury ; chemically induced ; drug therapy ; Animals ; Caveolin 1 ; metabolism ; Endothelins ; metabolism ; Hydroxyproline ; metabolism ; Male ; Matrix Metalloproteinase 2 ; metabolism ; Paraquat ; toxicity ; Quinuclidines ; therapeutic use ; Rats ; Rats, Wistar
9.Three year adefovir dipivoxil treatment for hepatitis B e antigen-positive chronic hepatitis B patients.
Ning LING ; Zhi ZHOU ; Da-zhi ZHANG ; Hong REN
Chinese Journal of Hepatology 2007;15(5):346-349
OBJECTIVESTo evaluate the efficacy and safety of adefovir dipivoxil (ADV) treatment in patients with hepatitis B e antigen (HBeAg) positive chronic hepatitis B (CHB).
METHODSThis was a multicenter, randomized, double-blind, placebo-controlled study. It was performed in four steps. First step: subjects were randomly assigned to receive either ADV 10 mg once daily (QD) or matching placebo tablets in a 3:1 ratio for 12 weeks. Second step: at week 12, all subjects started to have open-label ADV 10 mg QD for 28 weeks. Third step: subjects who received ADV in the first 12 weeks were rerandomized to receive either ADV or a placebo in a 2:1 ratio for 12 weeks and subjects who initially received a placebo continued to receive open-label ADV, but they were further assigned into 3 groups: A, B and C. In group A (12 patients), they received a placebo for the first 12 weeks and then ADV for the following 40 weeks. In group B (24 patients), they received ADV for the entire 52 weeks. In group C (12 patients), they received ADV in the first 40 weeks and a placebo in the last 12 weeks. Fourth step: all subjects restarted open-label ADV 10 mg QD for 208 weeks.
RESULTS(1) At week 12, the median decrease in serum HBV DNA levels was 3.7 log10 copies/ml in the ADV group and 0.2 log10 copies/ml in the placebo group (P < 0.01). (2) At week 12, serum ALT normalization was observed in 10 of the 36 subjects (27.8%) in the ADV group and 0 of the 11 subjects (0%) in the placebo group (P < 0.05). (3) In group B the proportion of subjects with serum ALT normalization increased to 66.7% at week 52. As for virological parameters in those subjects rerandomized to a placebo for weeks 40-52 (group C), biochemical benefit was rapidly lost (ALT normalization dropped from 50.0% to 25.0%). (4) At week 40, the median reduction in serum HBV DNA was similar across all treatment groups. In subjects rerandomized to ADV (group A and B), there were further reductions in serum HBV DNA from -3.2 to -3.6 and from -4.4 to -4.6 log10 copies/ml, respectively at week 52. In contrast in subjects rerandomized to a placebo during weeks 40-52 (group C), the median reduction in serum HBV DNA decreased from -3.7 to -0.7 log10 copies/ml at week 52. (5) In week 40, the proportion with undetectable HBV DNA (< 300 copies/ml) was similar in these three groups, while at week 52, the proportion with undetectable HBV DNA (< 300 copies/ml) in group C was 0%. (6) At week 52, the proportion with HBeAg loss in group B was 12.5% (3/24). The ratios of HBeAg seroconversion and HBeAg seroconversion with HBV DNA < or = 10(5) copies/ml were both 8.3%. (7) At week 104, the median reduction in serum HBV DNA was -4.2 log10 copies/ml, which was -4.3 log10 copies/ml at week 156. The proportion with undetectable HBV DNA (< 300 copies/ml) was both 31.0% at week 104 and week 156. The proportion of subjects with serum ALT normalization was 46.3% at week 104, which was 86.4% at week 156. The proportion with HBeAg loss was 23.8% at week 104, which was 31.0% at week 156. The proportion with HBeAg seroconversion was 23.8%. (8) No renal toxic effects were observed.
CONCLUSIONThe treatment with 10 mg ADV QD over 156 weeks was safe and effective in patients with HBeAg-positive CHB.
Adenine ; analogs & derivatives ; therapeutic use ; Adolescent ; Adult ; Aged ; Antiviral Agents ; therapeutic use ; DNA, Viral ; blood ; Double-Blind Method ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; genetics ; immunology ; Hepatitis B, Chronic ; drug therapy ; virology ; Humans ; Male ; Middle Aged ; Organophosphonates ; therapeutic use ; Young Adult
10.Repair full-thickness meniscal defects with injectable tissue engineering technique.
Hai-ning ZHANG ; Ping LENG ; Ying-zhen WANG ; Cheng-yu LÜ ; Xiang-da WANG ; Chang-yao WANG
Chinese Journal of Surgery 2010;48(17):1309-1312
OBJECTIVETo investigate the effectiveness of injectable tissue engineering to repair full-thickness meniscal defects.
METHODSFrom June 2008 to February 2009 full-thickness of meniscal defects were created in the anterior corner of goats, which with no blood supply, in a diameter of 2 mm. Then bone marrow stem cells (BMSCs) was mixed with injectable calcium alginate gel to fill the defects. Other groups include the calcium alginate gel and empty group were served as control groups. At different time points, the animals were sacrificed and macroscopy, microscopy determination, electroscopy and MRI detection were performed to assess the outcomes of repairing.
RESULTSThe meniscal defects had been filled thoroughly in 16 weeks after operation with white, tough and elastic repair tissue similar to normal meniscal fibrocartilage in the tissue engineering groups. The repair tissue was mainly fibrochondrocytes in line with the calcium alginate fiber. Thick matrix secreted by the cells crammed the space between fibers. The view under electroscopy demonstrated that the microstructure of the repair tissue was normal and cells were in a fibrocartilage phenotype.
CONCLUSIONThe full-thickness meniscal defects in regions without blood supply can be reconstructed effectively with injectable tissue engineering.
Alginates ; Animals ; Bone Marrow Cells ; Cells, Cultured ; Disease Models, Animal ; Gels ; Glucuronic Acid ; Goats ; Hexuronic Acids ; Injections ; Male ; Stem Cells ; Tibial Meniscus Injuries ; Tissue Engineering ; methods ; Tissue Scaffolds