Animals ; Arthritis, Rheumatoid ; Disease Models, Animal

Tetrahydrobiopterin (BH4) is an essential cofactor for all three nitric oxide synthase (NOS isoforms), which plays an important role in vascular diseases. GTP cyclohydrolase 1 (GCH 1) is the first-step and rate-limiting enzyme for BH4 biosynthesis in its de novo pathway. Common GCH1 gene variant C+243T in the 3'-untranslated region predicts NO excretion. The present study examined the predictive role of GCH 1 gene 3'-UTR C+243T variant in the long-term outcome of ischemic stroke. A total of 142 patients with first-onset ischemic stroke were recruited and detected for genotype of GCH1 3'-UTR C+243T by a TaqMan SNP Genotyping assay. Subsequent vascular events and death were determined over a 5-year follow-up period. The frequency of GCH1 3'-UTR +243 C/T or T/T genotype was significantly increased in patients with endpoint events as compared with those without events (74% vs 57.8%, P=0.06). Cox regression survival analysis indicated that an increased probability of death or new vascular events was found in patients with GCH1 3'-UTR +243 C/T or T/T genotype compared with those with GCH1 3'-UTR C/C genotype (40.6% vs 25.5%), GCH1 3'-UTR +243 C/T or T/T genotype relative to GCH1 3'-UTR C/C genotype was associated with the increased risk of death or vascular events even after adjustment for other risk factors (OR=2.171, 95% CI: 1.066-4.424, P=0.033). It was concluded that GCH1 3'-UTR C+243T variant was an independent predictor of worsening long-term outcomes in patients with first-onset ischemic stroke.

Objective To assess the impact of HLA-A,HLA-B,HLA-DRB1 matching on the prognosis of hematopoietic stem cell transplantation from unrelated donors.Methods A total of 81 patients with hematological malignancies including leukemia,myelodysplastic syndrome(MDS)and lymphoma who underwent hematopoietic stem cell transplantation from unrelated donors from 2007 to 2012 in our department were included in this retrospective analysis.Patients were classified into HLA match group(n=53)and HLA mismatch group(n=28)according to the HLA high-resolution matching.The overall survival (OS),treatmentrelated mortality(TRM),relapse rate(RR),graft-versus-host disease(GVHD)incidence were analyzed.Results The 81 patients were analyzed with a median follow-up of 11.9 months(0.3 to 57.4 months).The OS (66.0％vs 46.4％,P=0.031)and TRM(17.0％vs 42.9％,P=0.017)were significantly different between the HLA match group and HLA mismatch group,while the RR had no significant difference(14.3％vs 32.1％,P=0.111).Multivariate analysis showed HLA matching was an independent prognostic factor of TRM,but not OS.There's no significant difference of aGVHD(22.9％vs 40.9％,P=0.122)and cGVHD (40.0％vs 46.7％,P=0.655)incidence between the two groups,but the incidence of severe aGVHD in HLA match group were much lower(4.2％vs 25.0％,P=0.005)than HLA mismatch group.Conclusion the high-resolution matching of HLA-A,-B,DRB1 affect OS,TRM and the incidence of severe aGVHD in unrelated hematopoietic stem cell transplantation,but not affect RR,the incidence of aGVHD and cGVHD.

Objective A retrospective analysis of patients with T-cell lymphoma (TCL) received autologous peripheral blood stem cell transplantation (APBSCT) was performed to evaluate the outcome of APBSCT.Methods A total of 22 patients who underwent APBSCT from September 2006 to December 2011 in Ruijin hospital were enrolled in the study,including 6 cases of lymphoblastic lymphoma and 16 of peripheral T-cell lymphoma (8 anaplastic large cell lymphoma, 4 PTCL-u, 1 subcutaneous panniculitis-like T-cell lymphoma, 2 nasal type extranodal NK/T and 1 primary cutaneous T-cell lymphoma). All patients were diagnosed based on the WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues. Conditioning regimens were high-dose chemotherapies alone which include 13 cases with BEAM, 4 with ICE and 5 with CBV. The outcomes of the treatment were evaluated according to the revised International Working Group criteria.Results With a median follow-up of 13.1(1-60) months,the predicted 2-year overall survival (OS) and progression-free survival (PFS) after transplantation were (67.6±11.0) ％ and (71.1±11.1) ％,respectively.A total of 6 patients experienced disease progression and 5 patients eventually died of disease. When all these patients based on the remission status before APBSCT (CR1 vs non-CR1) and chemosensitivity (sensitive vs refractory) were further classified, the PFS rates and OS rates were 100 ％ and 91.7 ％ respectively in CR1 or chemosensitive patients which were significantly higher than patients not in CR1 (42.6 ％ ) or with chemoresistant disease (19.0 ％ ). Conclusion Remission status and chemosensitivity at the time of transplantation significantly affect the outcome of APBSCT for TCL patients, thus it can be recommend to perform APBSCT for patients either in CR1 or early stage when the disease remain sensitive to chemotherapy.

Objective To assess the impact of antithymocyte globulin (ATG) on the incidence of graft-vs-host disease (GVHD) in hematopoietic stem cell transplantation from unrelated donors.Methods A total of 92 patients with hematological malignancies including leukemia,myelodysplastic syndrome (MDS) and lymphoma who underwent hematopoietic stem cell transplantation from unrelated donors from January 1999 to December 2011 were included in this retrospective analysis.Patients were classified into ATG group (n =66)and non-ATG group (n =26) according to the GVHD prophylaxis regimen.The incidence of acute GVHD (aGVHD) and chronic GVHD (cGVHD),risk factors of aGVHD and cGVHD and impact of ATG on the overall survival (OS),treatment related mortality (TRM) and relapse rate were analyzed.Results Grade Ⅱ-Ⅳ aGVHD (26.7 ％ vs 44.0 ％,P=0.12) or grade Ⅲ-Ⅳ aGVHD (13.3 ％ vs 8.0 ％,P =0.74) were not significantly different between ATG and non-ATG group.However,the incidence of cGVHD in the ATG group was significantly lower (34.0 ％ vs 72.2 ％,P =0.005) than non-ATG group.The incidence of extensive cGVHD was also significantly reduced (10.0 ％ vs 44.4 ％,P =0.005) compared to non-ATG group.In multivariate analysis,the use of ATG prophylaxis significantly decreased the cGVHD (RR =0.22,95 ％CI 0.081-0.599,P =0.003) while one allele mismatch of human leukocyte antigen (HLA) was associated with increased risk of cGVHD (RR =3.25,95 ％ CI 1.39-7.61,P =0.007).As to the extensive cGVHD,the use of ATG was the only independent factor (RR =0.05,95 ％ CI 0.009-0.240,P ＜ 0.001).With a median follow-up of 12 months (1-84 months),ATG prophylaxis had no impact on OS rate (60.4 ％ vs 43.1％,P =0.41),TRM rate (19.8 ％ vs 34.3 ％,P =0.43) and relapse rate (40.6 ％ vs 33.6 ％,P=0.54).Conclusion In hematopoietic stem cell transplantation from unrelated donors,ATG prophylaxis total dose of 6 mg/kg may significantly decrease the incidence of cGVHD and extensive cGVHD without increase of TRMand relapse rate and impairment of OS.

Background and purpose: High-dose chemotherapy followed by autologous stem cell transplantation (auto-HSCT) is considered as the ifrst line treatment for patients with relapse/refractory lymphoma after conventional chemotherapy. However, most of these patients still relapse the second time. The purpose of this study was to analyze the efifcacy of the consolidation chemotherapy after autologous stem cell transplantation (HSCT) refractory/relapse lymphoma in high risk. Methods:A total of 38 patients with relapsed/refractory lymphoma including Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) were included, who were underwent auto-HSCT in our transplan-tation department from Jan. 2010 to Dec. 2013. In treatment group, 19 patients received 2 courses of consolidation che-motherapy after auto-HSCT every 2 to 3 months, with the regimen of mini-BEAM or modiifed mini-CBV. Another 19 patients had no chemotherapy after auto-HSCT as control group. Results:The median follow-up duration was 17.2 and 7.5 months in the treatment and control group respectively. The follow-up data demonstrated prolonged progression-free survival (PFS) in the treatment group than the control group [24.7 months vs 7.8 months, P=0.029 under intend-to-treat analysis ITT;24.7 months vs 5.2 months, P=0.01 under per protocol analysis(pp)]. There is also a trend of improved overall survival (OS) in the treatment group (P=0.055, ITT). Conclusion:Consolidation chemotherapy after auto-HSCT for refractory/relapsed lymphoma patients delay the relapse and tend to improve the overall relapse rate.

[Objective] To study the relationship between syndrome patterns of traditional Chinese medicine and bcl- 2 oncogene, p53 suppression gene mRNA expressions in precancerous lesions of gastric cancer (PIGC). [Methods] Forty PLGC cases were endoscopically and pathologically confinned, including 24 cases of moderate dysplasia of gastric mucosa, 9 cases of severe dysplasia, 7 cases of incomplete colonic intestinal metaplasia. Of the 40 cases, 10 were complicated with Qi stagnation, 12 with stomach-heat, and 18 with blood stasis, mRNA expression of bcl- 2 oncogene and p53 suppression gene were detected in situ by molecular hybridization method. [Results] The mRNA overexpression of bcl- 2 oncogene and p53 suppression gene were found in PLGC, and the expression was gradually increased with the progress of lesions. In the complicated cases, the mRNA expression of bcl- 2 oncogene and p53 suppression gene were the least in the cases with Qi stagnation and less in the cases with stomach- heat than in the cases with blood stasis. [Conclusion] Abnormal mRNA expression of bcl- 2 oncogene and p53 suppression gene were found in PLGC cases and related with different complicated cases, indicating the specificity of different syndrome patterns.

Objective To investigate the effects of transient plateau factor on acute lung injury induced by phosgene poisoning in rabbits.Methods Forty New Zealand white rabbits of both sexes,aged 2.0-2.5 kg,were randomly divided into 4 groups (n =10 each) using a random number table:control group (group C),plateau factor group (group H),phosgene poisoning group (group P),and phosgene poisoning and plateau factor group (group HP).In group H,the rabbits were exposed to a simulated altitude of 33000 m for 2 h.In group P,the rabbits were exposed to phosgene for 3 min only.In group HP,the rabbits were exposed to phosgene for 33 min and then to a simulated altitude of 3000 m for 2 h.Respiratory rate (RR) was recorded and blood samples were taken before exposure to phosgene (T1),after exposure to phosgene (T2),and at 0,1 and 6 h after onset of exposure to a simulated altitude of 33000 m (T3-5) for determination of PaO2 and oxygenation index (OI) was calculated.The chests were opened at T5 and lungs removed for determination of lung water content (LC) and for microscopic examination.Lung coefficient (LC) was calculated.Results Compared with C group,RR was significantly increased at T3 in group H (P ＜ 0.05),and RR was increased and OI was decreased at T2-5 in P and HP groups (P ＜ 0.05 or 0.01).Compared with P group,RR was increased and OI was decreased at T3-5 in HP group (P ＜ 0.05 or 0.01).LW and LC were significantly higher in P and HP groups than in group C,and in HP group than in group P (P ＜ 0.05 or 0.01).The microscopic examination showed that pathological changes were observed in P and HP groups,however,the changes were severer in HP group.Conclusion Transient plateau factor can obviously aggravate the degree of acute lung injury induced by phosgene poisoning in rabbits.

Objective To explore the effect of Qingkailing on the distribution and contents of neuropeptid Y(NPY)in hippocampus of epileptic rats.Methods Adopt abdominal cavity injection pentetrazole was used to establish the model of epileptic rats.Then content of NPY was assayed by radio-immunity and the distribution was observed by immunohistochemistry.Results The content of NPY in kindling group was significantly higher than that in control group(P

Objective To investigate the relationship between chronic atrophic antral gastritis and the decrease of somatostatin levels in blood and pyloric glands and adaptable protection ability of gastric mucosa.Methods Gastric mucosa biopsy specimen and blood samples were collected to determine the levels of somatostatin(SST)using radioimmunoassay.Histological changes between pre-and post-treatment were observed under light microscope as well as the changes of uhramicrostrucuture under transmission electron microscope.Distribution of SST in gastric mucosa was studied by immunohistochemical staining and then quantified.Results The quantities of gastric antral D cells of chronic atrophic antral gastritis decrease obviously.SST was mainly distributed in D cells of mucosa pyloric gland crypt.The nucleus of mucus epithelial cells in atrophic gastric antral crypt had SST negative staining.Mitochodria swellen,crista broken,rough endoplasmic reticulum distension,mucus secretory granules decreasing,the nuclear membranes disappearing as well as ehromatin integrating could have been seen in the intracytoplasm of mucus epitheliun cells of chronic atrophic gastric antral gastritis.The average level of SST in blood,epithelium and crypt were obviously reduced comparing to that of in the control group.By immunochemistry staining,the SST level in crypt of atrophic gastric antral gastritis Was significantly reduced comparing to that of in control group.With the level of SST in blood＜10 pg/100μl,the probability ratio of emerging atrophy Was 67.7%.Conclusions In case of no systemic inflammatory reaction state,the decreased ability of human pyloric gland D cell in producing SST not only rehtes obviously with human chronic atrophic antral gastritis but also with the weakened adaptable protection ability of gastric mucosa.