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Objective To study the effect of hyperbaric oxygen in the treatment of severe traumatic brain injury.Methods One hundred and ninety-four patients with severe traumatic brain injury were selected.The patients were divided into control group and observation group according to admission date (even number or odd number) with 97 cases each.The control group received only neurosurgical treatment, and the observation group received hyperbaric oxygen combined with neurosurgical treatment.The therapeutic effects of the 2 groups were compared.Results The waking time in observation group was significantly shorter than that in control group: (50.19 ± 5.23) h vs.(191.52 ± 9.67)h,the Glasgow coma scale(GCS)score and functional independence measure(FIM)score after treatment were significantly higher than those in control group:(12.21 ± 1.41)scores vs.(8.54 ± 1.38) scores and (85.91 ± 10.24) scores vs.(67.63 ± 9.76) scores, and there were statistical differences (P<0.05).The good recovery rate in observation group was significantly higher than that in control group:43.30%(42/97)vs.17.53%(17/97),the rate of plant survival and death was significantly lower than that in control group:10.31%(10/97)vs.31.96%(31/97),and there was statistical difference(P<0.05).The observation group did not appear hyperbaric oxygen treatment related adverse reactions.The incidences of lung infection,upper gastrointestinal bleeding and renal function impairment in the observation group were significantly lower than those in control group:15.46%(15/97)vs.38.14%(37/97),5.15%(5/97)vs.16.49% (16/97) and 6.19% (6/97) vs.16.49% (16/97), and there were statistical differences (P<0.05).Conclusions Compared with only neurosurgical treatment in patients with severe traumatic brain injury,hyperbaric oxygen combined with neurosurgical treatment has more advantages in shortening the waking time,improving self-care ability and prognosis,and reducing complications.
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Objective To develop the finite element model of six-year-old child occupant lower extremity with higher biofidelity and validate the model of knee joints,as well as analyze the biomechanical responses of growth plate under frontal impact load and injury mechanisms of the knee joint by using this model.Methods The sixyear-old child occupant lower extremity with growth plate was modeled based on children's anatomy and CT images,and corresponding material properties of the lower extremity model were assigned.The model was validated according to biomechanical experiments by Kerrigan et aL and Haut et aL and then was used to analyze the injury results of growth plate with different material properties.Results The model validation was qualified by comparing the curves from the experimental and simulation results.The growth plates at knee regions could change injury patterns of the child occupant lower extremity fracture.The material properties of growth plate could affect threshold of axial damage of the femur as well as relative position of the fracture.Conclusions The validated model can be used for related study and application on biomechanical responses and injury mechanisms of sixyear-old child occupant lower extremities.
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Objective To study the effect of mitogen-activated protein kinas/extracellular signalregulated kinase (MAPK/ERK) signaling pathway on cell proliferation modulated by Sonic Hedgehog (Shh) signaling in fibroblast-like synoviocytes (FLS) isolated from patients with active rheumatoid arthritis (RA).Methods The synovial tissue were collected by the synovial arthroscopic debridement or arthroscopic synovectomy of RA patients with active disease activity [disease activity score(DAS)28 ≥3.2].The RA-FLS were primarily cultured by the explanted culture,and then were treated with Shh agonist purmorphamine,inhibitor cyclopamine or MAPK/ERK signaling pathway inhibitor U0126,respectively.Western blotting was used to examine the phosphorylation level of ERK 1/2 (p-ERK1/2),which was the critical protein of MAPK/ERK signaling.The cell proliferation activity was detected using cell proliferation and cytotoxicity kit-8 (CCK8),and the cell proliferation rate was detected using a flow cytometry.Analysis of variance and Kruskal-Wallis H(K) test were used for statistical analysis.Results Compared with the control group,purmorphamine transiently increased p-ERK1/2 protein at the concentration of 1 μmol/L,and the peak activations of p-ERK1/2 took place at 15 min (P＜0.01).Cyclopamine and U0126 decreased the expression ofp-ERK1/2 protein (P＜0.01).After the RA-FLS treated with purmorphmine(1 μmol/L)for 48 hours,the cell proliferation activity was (114±4)％ and the percentage of S phase cells was (8.39±0.60)％,which was significantly higher than those of the control group (100±0)％ (P＜0.01) and (3.29±0.69)％ (P＜0.01).After treated with cyclopamine (10 μmol/L) for 48 hours,the cell proliferation activity of RA-FLS was (89±1)％ (P＜0.05) and the percentage of S phase cells was (1.53±0.22)％ (P＜0.05).When co-treated with purmorphamine (1 μmol/L) and U0126 (10 μmol/L),the cell proliferative activity was (89±2)％ (P＜0.05) and the percentage of S phase cells was(1.07±0.25)％(P＜ 0.05).Conclusion Shh may promote proliferation of RA-FLS via modulating MAPK/ERK signaling,which in turn contributes to hyperplasia of synovium and ultimately leading to RA.
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AIM:To determine the effects and mechanisms of interleukin-22 (IL-22) on the fibroblast-like sy-noviocytes ( FLSs) from rheumatoid arthritis ( RA) patients.METHODS:RA-FLSs were cultured by tissue culture meth-od.RA-FLSs were incubated with different concentrations of IL-22 (0,1,10,100μg/L) for 24 h, 48 h and 72 h.The cell viability was examined by CCK-8 assay.IL-22 at concentration of 10 μg/L was used to stimulate RA-FLSs for 24 h, and the change of cell cycle distribution was identified by flow cytometry.The effects of IL-22 at concentrations of 0, 1, 10, 100μg/L and/or STA-21 (a STAT3 inhibitor at concentrations of 0, 25, 50μmol/L) on the protein levels of Bcl-2 and p-STAT3 in the RA-FLSs were determined by Western blot.RESULTS:Compared with control group, stimulation of rhIL-22 at different concentrations for 24 h, 48 h and 72 h, the cells viabilityof RA-FLSs were obviously increased ( P<0.05 ) . After co-cultured with 10 μg/L rhIL-22 for 24 h, the percentages of RA-FLSs were obviously increased in the G2/M+S phase and decreased in the G0/G1 phase.At the same time, rhIL-22 increased, but STA-21 decreased the protein levels of Bcl-2 but p-STAT3 in the RA-FLSs obviously (P<0.05).Treatment with STAT3 inhibitor STA-21 reversed the effect of IL-22-induced Bcl-2 upregulation in the RA-FLSs ( P<0.01 ) .CONCLUSION: STAT3 is critical in the process of IL-22-induced Bcl-2 upregulation in RA-FLSs, indicating that IL-22 may play a role in the apoptosis of RA-FLSs.
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Objective To evaluate the efficacy and safty of antiviral treatment for chronic hepatitis B ( CHB ) patients in second trimester of pregnancy.Methods Seventy-nine CHB patients in second trimester of pregnancy were collected from Hangzhou First People’ s Hospital and Xixi Hospital of Hangzhou during January 2010 to December 2013.Patients were divided into antiviral treatment group ( n=47) and the control group (n=32) according to their own wishes.Patients in antiviral treatment group were given lamivudine or telbivudine treatment plus hepatoprotective medication, while those in control group were only given hepatoprotective medication.All pregnant women were observed for 12 weeks after childbirth and the neonates were followed-up for 6 months after birth.The liver function, HBV DNA loads, HBV serological markers were measured;adverse effects during pregnancy, blocking rates of mother-to-child transmission and the growth of neonates were documented.t test or Chi-square test was used for statistical analysis.Results Alanine aminotransferase ( ALT) normalization rate and HBV DNA negative rate in antiviral treatment group before childbirth were 88.6%(39/44) and 84.1%(37/44) , while those in the control group were 60.0%(18/30) and 0 (χ2 =8.27 and 50.46, P0.05).No patient in antiviral treatment group terminated pregnancy due to abnormal liver function or adverse effect of drugs, while 2 out of 30 patients (6.7%) in the control group terminated the pregnancy, but the difference between two groups was not of statistical significance (χ2 =1.01, P >0.05).Mother-to-child transmission of HBV was successfully blocked in antiviral treatment group, while 3 cases (11.5%) in control group were failed (χ2 =5.19, P0.05).Conclusion Antiviral treatment can improve liver function, inhibit HBV replication and reduce the risk of mother-to-child transmission, and is safe for CHB patients in second trimester of pregnancy.
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Objective To study the role of RICTOR on rheumatoid arthritis-fibrobast-like synoviocytes (RA-FLS) activation.Methods FLS were isolated from the primary synovial tissues,which were obtained during joint replacement surgery or arthroscopy from three patients with RA.RA-FLS were stimulated with TNF-α at the dose of 10 ng/ml and 20 ng/ml for 48 h.The expression of RICTOR was detected by western blotting.Chemically synthesized RICTOR gene targeted for double-stranded siRNAs were transfected into RA-FLS by cationic liposome.After being transfected with RICTOR siRNA for 48 h,RA-FLS was treated with or without TNF-α for 48 h.The expression of RICTOR was evaluated by western blotting,and the cell viability was analyzed by methylthiazoltetrazolium (MTT) assay.The data were analyzed using analysis of variance (ANOVA) and LDL-t test.Results The expression of RICTOR protein was significantly higher in the TNF-α stimulated group (at the dose of 10 ng/ml and 20 ng/ml for 48 h) than that in the control group (bothP＜0.05),while the mean change of RICTOR/GAPDH ratios of band optical density x+s was 0.35±0.06 for the control group,0.60±0.09 for the TNF 10 ng/ml group and 1.10±0.12 for the TNF 20 ng/ml group.Moreover,the expression of RICTOR protein was obviously decreased in RICTOR siRNA transfection groupthan that in control after being trans-fected for 96 h (both P＜0.05),and ratios of control group,RICTOR (-)/TNF-α(-) group and RICTOR(-)/TNF-α(+) group was 0.498 4±0.140 1,0.012 8±0.002 0,0.042 5±0.027 3respectively.After the silence of RICTOR,the cell viability decreased in RA-FLS,no matter with or without TNF-α for 48 h later (both P＜0.05).Conclusion These results indicat that RICTOR might play an important role in the TNF-α associated activation of RA-FLS.
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Objective To compare the efficacy and safety ofetanercept injection 50 mg once weeklycombined with methotrexate (MTX) therapy for patients withactive rheumatoid arthritis.Methods This studyconsists of 2 parts：a 12-week double-blind treatmentperiod (part A) followed by a 12-week open-labelsafety study period (part B).The randomization oftreatments in double-blind treatment period was completedthrough the clinical operations randomization environment(CORE) system.During part A,the subjects wererandomly assigned to the etanercept 50 mg or placebo group. The dosage regimen for etanercept was 50 mgadministered subcutaneously once weekly while MTX wasadministered orally.All subjects who completed partA received 50 mg etanercept once weekly and MTX1 during theopen-label treatment.The primary endpointwas ACR 20 response at week 12.Secondary endpoint variablesincluded physician／patient global assessmentsof disease activities,duration of morning stiffness,painvisual analog scale (VAS),health assessment questi onnaire (HAQ),CRP level and tender and swollen joint counts .The results of safety between the two groupswere compared.The primary endpoint and other secondarybinary endpoints were analyzed using the Fisher’sexact test.For continuous endpoints.the change frombaseline was analyzed with analysis of covariance.Results One hundred and fifty six subjects satisfiedmodified intent-to-treat (mITT) population were enrolled during part A,of which 77 subjects were in theetanercept+MTX group,and 79 subjects were in theplacebo+MTX group respectively.A total of 149 subjectscompleted part A.As early as week 4.the ACR 20response achieved 39％ (30,77) in the etanerceptgroup,which was significantly higher than that of theplacebogroup [16％(13／79),P<0.001].At week 12,the ACR 20respouse achieved 62％(48,77)in the etanercept group and 23％(18／79) in the placebo group (P<0.01).Fromweek 4,other study endpoints including physician global assessment,patient globalassessment,duration of morning stiffness,painVAS,HAQ,CRPlevel,tender joint counts,swollen joint counts were alsocompared.The results showed that all above efficacyendpoints in the etanercept+MTX group were better than thoseof the placebo+MTX group(P<0.01).Butthere Was no significant difference in the total adverseeriects between the two groups.ConclusionEtanercept 50 mg once weekly + MTX treatment for 24 weeks iswell tolerated.During the first 12-weektreatment period,the etanercept group has shown a rapidefficacy onset and a significantly better therapeuticeffect compared to that of the placebo group.
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Objective To evaluate the short-term efficacy and safety of etanercept treatment in Chinese patients with active ankylosing spondylitis ( AS ). Methods This was a 12-week multicenter,double-blind, placebo-controlled, randomized phase Ⅲ clinical study. The first part was a 6-week placebocontrolled period followed by a 6-week open-label period. The primary efficacy endpoint was the percentage of subjects achieving a 20% improvement in assessment in ankylosing spondylitis (ASAS) ( ASAS 20). The secondary efficacy endpoints were the percentage of patients achieving a 40% improvement in ASAS (ASAS 40), achieving a 50% improvement in ASAS( ASAS 50), achieving a 70% improvement in ASAS (ASAS 70), and ASAS 5/6 responses at all visits, and the improvement in subject global assessment,physician global assessment, nocturnal and total back pain, bath AS functional index ( BASFI ), bath AS disease activity index (BASDAI), spinal mobility, joint assessment and quality of life assessment. All subjects in the study were evaluated for safety. Results The primary endpoint, ASAS 20 at week 6, was achieved by 86. 5% (64/74) patients in the etanercept group compared to 29. 5% (23/78) patients in the placebo group(P ＜0. 001 ). As early as week 2, the percentages of patients achieving the ASAS 20 between the two groups were significantly different. Furthermore, the majority of secondary efficacy end points were also significantly improved. Most of adverse events (AE) were mild in nature, the commonest adverse events were elevated liver function levels, injection site reactions and nasopharyngitis. No death or serious AE were observed. Conclusion Etanercept can improve symptoms fastly,significantly and safely in Chinese patients with active AS.
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Objective To investigate the autophagy and the expression of its related genes in the peripheral blood mononuclear cells (PBMCs) of active systemic lupus erythematosus (SLE) patients.Methods Patients with newly onset or recently-diagnosed SLE (n=20) were enrolled.RA patients (n=10) and healthy blood donors (n=10) were used as controls.PBMCs from all subjects were immediately isolated by Ficoll-Hypaque density gradient centrifugation.And then monocytes were removed by wall sticking method.The morphology was observed using transmission electron microscopy (TEM).Messenger RNA (mRNA) expression of Beclin 1 and microtubule-associated protein 1-light chain 3 (MAPLC3) were determined by reverse transcription polymerase chain reaction (RT-PCR) and real-time quantitative RT-PCR respectively.Results TEM showed autophagic phenomenon in PBMCs from active SLE.On the mRNA level,expression of Beclin 1 and LC3 was significantly increased in fresh isolated SLE cells as compared with RA or healthy donor's PBMCs.Conclusion Based on these results,we can conclude that autophagy occurs in active SLE and the expression of its related genes is significantly higher in active SLE than in RA or normal controls.The enhanced autophagy may indicate its role in the pathogenesis of SLE.
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BACKGROUND: Rheumatoid factor (RF) is a kind of autoantibody which is routinely used as a factor in patients with rheumatoid arthritis (RA) to evaluate disease activity and severity.But in clinical practice, it occurs frequently that RF values do not decrease according to clinical improvement in RA patients. OBJECTIVE: To investigate the association between rheumatoid factor (RF) and activity or disease severity of RA.DESIGN, TIME AND SETTING: A randomized cross-sectional study was performed in the Department of Rheumatology and Immunology, the Third Affiliated Hospital of Sun Yat-sen University during September 2006 and September 2007.PARTICIPANTS: Seventy-six patients,65 females and 11 males,mean age of (44±13) years,with RA diagnosed according to the American College of Rheumatology (ACR) criteria for RA were included in this study. METHODS: Seventy-six patients with active RA were randomly recruited and assessed for functional status,radiographic change,joint pain,morning stiffness, tender joint count (TJC), tender joint score (TJS), swollen joint count (SJC), swollen joint score (SJS), Health Assessment Questionnaire (HAQ), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP),RF,and hemoglobin. The method of Pearson correlation or Spearman rank correlation was performed for assessing the association between RF and these indices separately, normally distributed data for Pearson correlation, nonnormally distributed data for Spearman rank correlation. MAIN OUTCOME MEASURES: Correlation of RF with above mentioned factors. RESULTS: None of the correlation coefficients between RF and indices including age,disease duration, functional status,radiographic change,joint pain, morning stiffness, TJC,TJS,SJC,SJS,HAQ,ESR,CRP,hemoglobin were significant (P＞0.05). CONCLUSION: No associations between RF and activity or severity of RA are studied.
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AIM: To determine the influence of interleukin-1?(IL-1?) and ?(IL-1?) gene polymorphisms on rheumatoid arthritis(RA) disease severity and secretion of IL-1?. METHODS: The study included 136 RA patients and 102 healthy controls. PCR-RFLP was used to detect site mutation at IL-1 gene. Meanwhile the IL-1? was also measured in the supernatant of the cultured and stimulated peripheral blood mononuclear cells(PBMC). RESULTS: No difference in the allele frequencies or genotypes of the IL-1? gene polymorphisms was found between the controls and RA patients.IL-1? allele 2 was overrepresented in patients with erosive RA but not in nonerosive patients. The patients with IL-1? allele 2 had a higher swollen joint index, higher tender joint index and erythrocyte sedimentation rate than those without IL-1? allele 2.The IL-1? in supernatant of stimulated PBMC from patients with IL-1? allele 2 had a higher level than that from those without allele 2. CONCLUSION: IL-1 gene polymorphisms may influence the occurrence of RA. Detection of IL-1? allele 2 have a potential prognostic value in RA.
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AIM: To investigate the effect of IL-1 gene polymorphism on the expression of IL-1? mRNA in patients with rheumatoid arthritis. METHODS: The method of FQ-RT-PCR was used to detect the expression of IL-1? mRNA in peripheral blood mononuclear cells separated from rheumatoid arthritis patients with different IL-1? genotype. RESULTS: The expression levels of IL-1? mRNA in 20 patients who carried IL-1? 2*2 genotype were higher than patients who carried no 2*2 genotype and normal subjects. Significant difference existed among three groups. CONCLUSION: IL-1? gene polymorphism influences the transcription of IL-1?. [