Anti-tumour necrosis factor α(anti-TNFα) therapy is an established treatment in inflammatory bowel disease.However, this treatment is associated with high costs and the possibility of severe adverse events represent...Anti-tumour necrosis factor α(anti-TNFα) therapy is an established treatment in inflammatory bowel disease.However, this treatment is associated with high costs and the possibility of severe adverse events representing a true challenge for patients, clinicians and health care systems.Consequently, a crucial question is raised namely if therapy can be stopped once remission is achieved and if so, how and in whom.Additionally, in a real-life clinical setting, discontinuation may also be considered for other reasons such as the patient's preference, pregnancy, social reasons as moving to countries or continents with less access, or different local policy or reimbursement.In contrast to initiation of anti-TNFα therapy guidelines regarding stopping of this treatment are missing.As a result, the decision of discontinuation is still a challenging aspect in the use of anti-TNFα therapy.Currently this is typically based on an estimated, case-by-case, benefit-risk ratio.This editorial is intended to provide an overview of recent data on this topic and shed light on the proposed drug withdrawal strategies.展开更多
To explore a new method for the therapy of the avascular necrosis of the femoral head, the recombinant plasmid pCD-hVEGF 165 was mixed with collagen and was implanted in the necrotic femoral head The expression...To explore a new method for the therapy of the avascular necrosis of the femoral head, the recombinant plasmid pCD-hVEGF 165 was mixed with collagen and was implanted in the necrotic femoral head The expression of vascular endothelial growth factor (VEGF) was detected by RNA dot hybridization and immunohistochemical method The repair of the femoral head was observed by histological method The results showed that the expression of VEGF was detectable in the femoral head treated with VEGF gene Angiogenesis in these femoral heads was more abundant than the control Bone repairing was augmented in the femoral head treated with VEGF gene The results suggest that angiogenesis in bone tissue could be augmented by gene transfection of VEGF and bone repairing would be accelerated accordingly展开更多
AIM To study the innate immune function in ulcerative colitis(UC) patients who fail to respond to anti-tumor necrosis factor(TNF) therapy.METHODS Effects of anti-TNF therapy, inflammation and medications on innate imm...AIM To study the innate immune function in ulcerative colitis(UC) patients who fail to respond to anti-tumor necrosis factor(TNF) therapy.METHODS Effects of anti-TNF therapy, inflammation and medications on innate immune function were assessed by measuring peripheral blood mononuclear cell(PBMC) cytokine expression from 18 inflammatory bowel disease patients pre- and 3 mo post-anti-TNF therapy. Toll-like receptor(TLR) expression and cytokine production post TLR stimulation was assessed in UC "responders"(n = 12) and "non-responders"(n = 12) and compared to healthy controls(n = 12). Erythrocyte sedimentation rate(ESR) and C-reactive protein(CRP) levels were measured in blood to assess disease severity/activity and inflammation. Pro-inflammatory(TNF, IL-1β, IL-6), immuno-regulatory(IL-10), Th1(IL-12, IFNγ) and Th2(IL-9, IL-13, IL-17A) cytokine expression was measured with enzyme-linked immunosorbent assay while TLR cellular composition and intracellular signalling was assessed with FACS.RESULTS Prior to anti-TNF therapy, responders and nonresponders had similar level of disease severity and activity. PBMC's ability to respond to TLR stimulation was not affected by TNF therapy, patient's severity of the disease and inflammation or their medication use. At baseline, non-responders had elevated innate but not adaptive immune responses compared to responders(P < 0.05). Following TLR stimulation, nonresponders had consistently reduced innate cytokine responses to all TLRs compared to healthy controls(P < 0.01) and diminished TNF(P < 0.001) and IL-1β(P < 0.01) production compared to responders. This innate immune dysfunction was associated with reduced number of circulating plasmacytoid dendritic cells(p DCs)(P < 0.01) but increased number of CD4+ regulatory T cells(Tregs)(P = 0.03) as well as intracellular accumulation of IRAK4 in non-responders following TLR-2,-4 and-7 activation(P < 0.001). CONCLUSION Reduced innate immunity in non-responders may explain reduced efficacy to anti-TNF therapy. These serological markers may prove useful in predicting the outcome of costly anti-TNF therapy.展开更多
Objective: The aim of the study is to assess the risk of post-operative outcome in rheumatoid arthritis (RA) patients continuing versus stopping combination therapy of methotrexate (MTX) and hydroxychloroquine (HCQ) o...Objective: The aim of the study is to assess the risk of post-operative outcome in rheumatoid arthritis (RA) patients continuing versus stopping combination therapy of methotrexate (MTX) and hydroxychloroquine (HCQ) or tumor necrosis factor α inhibitors (TNF) prior to surgery. Methods: Using the United States Veterans Affairs (VA) databases, we identified surgical procedures in a 17-year cohort of RA patients. Among those patients, those on MTX + HCQ or MTX + TNF were identified. Post-operative outcome variables include infection, length of post-operative hospital stay and death. Results: We identified a total of 29,708 surgeries in RA patients. Among them, we identified the most recent elective surgeries without pre-operative infection in 16,174 patients. There were 783 and 550 patients on MTX + HCQ and MTX + TNF, respectively. The rates of post-op infection were 5% and 4% for the MTX + HCQ and MTX + TNF continuing medication groups, respectively, similar to the general RA population (5%). Sensitivity analyses at various time points of discontinuation combination therapies prior to surgery did not show significant change in terms of infection. Conclusions: The prevalence of adverse outcome is low. The proportion of post-operative infection in continuing and discontinuing medicine groups is similar for both MTX + HCQ and MTX + TNF. While we were unable to formally compare proportions of post-operative infection among the two groups, these preliminary findings do not support the hypothesis that continuing either MTX + TNF or MTX + HCQ combination during perioperative period increases post-operative infection compared with discontinuation prior to therapy.展开更多
Objective: To explore the clinical efficacy of neurogrowth factor in the treatment of gingival pain and swelling in patients with dental pulp necrosis after root canal therapy and the effect on the serum inflammatory ...Objective: To explore the clinical efficacy of neurogrowth factor in the treatment of gingival pain and swelling in patients with dental pulp necrosis after root canal therapy and the effect on the serum inflammatory cytokines. Methods: A total of 156 patients with gingival pain and swelling after root canal therapy due to dental pulp necrosis were included in the study and randomized into the control group (n=78) and teh treatment group (n=78). The patients in the control group were given metronidazole tablets. On the above basis, the patients in the treatment group were given local injection of neurogrowth factors. 10-day treatment was regarded as one course, and the patients were continuously treated for 2 courses. The improvement of clinical symptoms before and after treatment in the two groups was evaluated. Gingival sulcus index and serum inflammatory cytokines before and after treatment in the two groups were detected and compared. Results: When compared with before treatment, the periodontal soft tissue swelling, tooth mobility, and periapical pain scores after treatment in the two groups were significantly reduced, and those in the treatment group were significantly lower than those in the control group. When compared with before treatment, the gingival sulcus bleeding index 1 and 2 courses after treatment in the two groups was significantly reduced, and that 2 courses after treatment was significantly lower than that after 1 course treatment. The gingival sulcus bleeding index 1 and 2 courses after treatment in the treatment group was significantly lower than that in the control group. When compared with before treatment, the serum IL-8 and IL-6 levels after treatment in the two groups, and TNF-α level after treatment in the treatment group were significantly reduced, and the above indicators in the treatment group were significantly lower than those in the control group. Conclusions: The neurogrowth factors in the treatment of gingival pain and swelling in patients with dental pulp necrosis after root canal therapy can effectively improve the clinical symptoms, and inhibit the inflammatory reaction, with a significant efficacy.展开更多
Ulcerative jejunoileitis is an uncommon clinical syndrome consisting of abdominal pain,weight loss associated with diarrhea,and multiple inflammatory ulcerations and strictures of the small bowel.Ulcerative jejunoilei...Ulcerative jejunoileitis is an uncommon clinical syndrome consisting of abdominal pain,weight loss associated with diarrhea,and multiple inflammatory ulcerations and strictures of the small bowel.Ulcerative jejunoileitis can complicate established celiac disease or develop in patients de novo.Increased levels of tumor necrosis factor-alpha(TNF-α) in the small intestine of patients with untreated celiac disease are associated with a role in the immune pathogenesis of this disorder.No specific therapy has been shown to change the course of ulcerative jejunoileitis.We report a case of severe ulcerative jejunoileitis previously unresponsive to traditional therapies,including high dose corticosteroids and cyclosporine.The patient had a dramatic resolution of symptoms and a complete normalization of endoscopic findings after anti-TNF-α monoclonal antibody,infliximab(Remicade).展开更多
AIM:To investigate the correlation between the appearance of skin lesions and concentration of interleukin(IL)-17A,IL-23 and interferon-γ(IFN-γ)in Crohn’s disease(CD)patients during anti-tumor necrosis factor-α(T...AIM:To investigate the correlation between the appearance of skin lesions and concentration of interleukin(IL)-17A,IL-23 and interferon-γ(IFN-γ)in Crohn’s disease(CD)patients during anti-tumor necrosis factor-α(TNF-α)therapy METHODS:A prospective study included 30 adult patients with CD of Caucasian origin(19 men and 11women;mean age±SD 32.0±8.6 years)during biological therapy with anti-TNF-αantibodies from January2012 to March 2013.Eighteen patients were treated with infliximab,seven with adalimumab and five withcertolizumab.Inclusion criteria were exacerbation of the underlying disease,Crohn’s Disease Activity Index over 300 and the ineffectiveness of previously used non-biological therapies.Patients with a history of psoriasis,atopic dermatitis and other autoimmune skin lesions were excluded from the study.The control group consisted of 12 healthy subjects.A diagnostic survey was carried out,blood tests and careful skin examination were performed,and the serum levels of IL-17,IL-23 and IFN-γwere measured using an enzyme-linked immunosorbent assays technique.Dermatoses that have developed in the course of biological therapy in patients who had no pre-existing skin lesions of similar character were qualified as skin lesions induced by antiTNF-αtherapy.RESULTS:Skin manifestations occurred in 18 of CD patients during the anti-TNF-αtherapy(60%),in the average time of 10.16±3.42 mo following the beginning of the 52-wk treatment cycle.Skin lesions observed in CD patients during biological therapy included psoriasiform lesions(44.4%),and eczema forms lesions(22.2%).In CD patients with drug induced skin lesions significantly higher levels of hemoglobin(13.3±1.5 g/dL vs 10.8±1.9 g/dL,P=0.018)and hematocrit(39.9%±4.5%vs 34.3%±5.4%,P=0.01),as well as a significantly lower level of platelets(268±62×103/μL vs 408±239×103/μL,P=0.046)was observed compared with CD patients without skin manifestations.The concentrations of IL-17A and IL-23in CD patients with skin lesions developed under antiTNF-αtherapy were significantly higher compared to those in patients without lesions(IL-17A:39.01±7.03pg/mL vs 25.71±4.90 pg/mL,P=0.00004;IL-23:408.78±94.13 pg/mL vs 312.15±76.24 pg/mL,P=0.00556).CONCLUSION:Skin lesions in CD patients during bio-logical therapy may result from significantly increased concentrations of IL-17A and IL-23,which are strongly associated with TNF-α/Th1 immune pathways.展开更多
INTRODUCTIONAs stated in the author’s previous articles,severe acute pancreatitis is a multifacetted diseasewith rapid and sometimes fulminating onset and mayresult in many serious complications or even death iftreat...INTRODUCTIONAs stated in the author’s previous articles,severe acute pancreatitis is a multifacetted diseasewith rapid and sometimes fulminating onset and mayresult in many serious complications or even death iftreatment is improper or delayed.Therapeuticmeasures must be directed against these展开更多
INTRODUCTIONThe strongest evidence that H.pylori infection isthe cause of peptic ulcer is that treatment withantibiotics as the only regimen,is not only effectivefor the clearance and eradication of the infection,but ...INTRODUCTIONThe strongest evidence that H.pylori infection isthe cause of peptic ulcer is that treatment withantibiotics as the only regimen,is not only effectivefor the clearance and eradication of the infection,but more importantly for the healing of the ulcer orthe remission of gastric lymphoma.However,it isstill a matter of controversy and research as to展开更多
Objective:To investigate the interference and expression of human glial cell line-derived neurotrophic factor(hCDNF) and soluble TNF alpha(sTMFRⅠ) receptor genes in neural stem cells and to evaluate the roles of thes...Objective:To investigate the interference and expression of human glial cell line-derived neurotrophic factor(hCDNF) and soluble TNF alpha(sTMFRⅠ) receptor genes in neural stem cells and to evaluate the roles of these proteins in the genetic treatment of spinal cord injury.Methods:Full-length of GDNF cDNA(538 bp) and sTMFRⅠcDNA(504 bp) were inserted into the early 1 region of adenovirus genomic DNA respectively and were immediated by the human cytomegalovirus(gene promoter/enhancer). These adenoviruses were propagated in HEK293 cells via homologous recombination for 7-10 days in vivo,then they were used to infect human neural stem ceils.The infection and expression of gene were tested under immunofluorescence.ELISA and Westem-blot after 48 hours.Results:Almost all the cultured cells showed the nestin immunofluorescence positive staining,which was the characteristics of neural stem cell.A great quantity of EGFP and KFP were observed in neural stem cells,which indicated the expression of GDNF and sTMFRⅠ.After transfection of GDNF and sTMFRⅠgenes,many neural stem cells show GFAP and tubulin immunofluorescence positive staining,which meant that most neural stem cells differentiated into neuron at that condition.Conclusions:The infective efficiency of adenovirus is greatly acceptable to neural stem cell,thus adenovirus provide a useful vector for exogenous GDNF and sTMFRⅠgenes expressing in neural stem cells,which is useful for differentiation of neural stem cell.展开更多
Gastroduodenal Crohn’s disease (CD) is rare and the response to standard medical therapy is often poor. Anti-tumor necrosis factor therapy has revolutionised the treatment of CD. We present a patient with pyloric ste...Gastroduodenal Crohn’s disease (CD) is rare and the response to standard medical therapy is often poor. Anti-tumor necrosis factor therapy has revolutionised the treatment of CD. We present a patient with pyloric stenosis associated with CD which improved with Adalimumab therapy. We recommend considering antitumor necrosis factor therapy in symptomatic gastroduodenal CD.展开更多
Tumor necrosis factor (TNF) has certain radioprotective effect on host tissue and is capable of enhancing the antitumor effect of radiotherapy. In addition, the transcriptional regulation of the promoter region of Eg...Tumor necrosis factor (TNF) has certain radioprotective effect on host tissue and is capable of enhancing the antitumor effect of radiotherapy. In addition, the transcriptional regulation of the promoter region of Egr 1 gene is activated by ionizing radiation. So we fused Egr 1 promoter with hTNF α cDNA, and resultantly constructed a double copy and radiationin ducible retroviral vector named as pETDC. After packaged with Psi 2 and Crip cells in vitro, the hTNF recombinant retroviruses were in the titers of 4×10 5 CFU/ml. By infection of murine fibroblast cell line NIH3T3 and murine melanoma cell line B16.F10 with the recombinant retroviruses and followed by G418 resistant selection, two positive clones secreting TNF at the levels of 2.1 ng/ml and 1.1 ng/ml respectively were generated. After exposure to 20 Gy ionizing radiation, TNF secre tions from the two positive clones were elevated to 13.8 ng/ml (6.6 fold) and 5.7 ng/ml (5.2 fold) respectively. Furthermore, hTNF α expression in pETDC transfected cells was confirmed by RT PCR. These data provide an experimental bases for the application of TNF gene therapy combined with local radiotherapy in cancer patients.展开更多
Radio genetic therapy which combines gene therapy with radiotherapy has shown promising results in cancer treatment. In this study, an oncolytic adenovirusbased gene therapy system regulated by radiation was construct...Radio genetic therapy which combines gene therapy with radiotherapy has shown promising results in cancer treatment. In this study, an oncolytic adenovirusbased gene therapy system regulated by radiation was constructed to improve the cancer curative effect. This gene therapy system incorporated the radiation-inducible early growth response gene(Egr-1) promoter and the anticancer gene tumor necrosis factor-related apoptosis-inducing ligand(TRAIL). To confirm the antitumor effect of Ad-ET combined with^12C^(6+)tion irradiation, the survival and apoptosis fraction of tumor cells HT1080 and normal cells MRC-5 in combination treatment were detected by CCK-8 assay and FACS analysis. Then the expression levels of TRAIL gene and protein were tested by real-time PCR and western blotting. The results show that^12C^(6+)tion irradiation could induce cell growth inhibition and apoptosis by activating the TRAIL gene expression in tumor cells, while exhibiting no obvious toxicity to the normal lung cell line MRC-5. Theresults also demonstrate that use of an oncolytic adenovirusbased radiation-inducible gene therapy system together with^12C^(6+)tion irradiation could cause synergistic antitumor effect specifically in tumor cells but not in normal cells. The results indicate that the novel radio genetic therapy could potentiate radiation treatment by improving the safety and efficiency of monotherapy, and provide theoretical support for clinical application of combination treatment.展开更多
Psoriasis is a chronic, immune-mediated, inflammatory disease with a high prevalence in the general population (2%). The anti-tumor necrosis factor receptor etanercept is Food and Drug Administration (FDA) approved fo...Psoriasis is a chronic, immune-mediated, inflammatory disease with a high prevalence in the general population (2%). The anti-tumor necrosis factor receptor etanercept is Food and Drug Administration (FDA) approved for the treatment of moderate-to-severe plaque psoriasis. Both continuous and interrupted etanercept therapy is effective and well-tolerated. This report <strong>aims</strong> to document a new case presentation of psoriasis on intermittent etanercept injection throughout 36 weeks with long-lasting sustained efficacy and no risk factor. <strong>Case Report</strong>: A 39-year-old adult male patient with long-standing chronic plaque psoriasis for 15 years duration without joint involvement started loading dose treatment of etanercept injection in whom due to his work circumstances not taken maintenance therapy and showed-up at the clinic after 36 weeks from first induction therapy when partial relapse of psoriatic lesions appear in last week with continued improvement when reintroducing loading treatment on followed-up over the next 36 weeks. <strong>Conclusion</strong>: Intermittent etanercept therapy considers effective for 36 weeks with prolonging sustained efficacy and without adverse effect.展开更多
文摘Anti-tumour necrosis factor α(anti-TNFα) therapy is an established treatment in inflammatory bowel disease.However, this treatment is associated with high costs and the possibility of severe adverse events representing a true challenge for patients, clinicians and health care systems.Consequently, a crucial question is raised namely if therapy can be stopped once remission is achieved and if so, how and in whom.Additionally, in a real-life clinical setting, discontinuation may also be considered for other reasons such as the patient's preference, pregnancy, social reasons as moving to countries or continents with less access, or different local policy or reimbursement.In contrast to initiation of anti-TNFα therapy guidelines regarding stopping of this treatment are missing.As a result, the decision of discontinuation is still a challenging aspect in the use of anti-TNFα therapy.Currently this is typically based on an estimated, case-by-case, benefit-risk ratio.This editorial is intended to provide an overview of recent data on this topic and shed light on the proposed drug withdrawal strategies.
基金ThisprojectwassupportedbyagrantfromNationalNaturalSciencesFoundationofChina (No 30 170 94 5 )
文摘To explore a new method for the therapy of the avascular necrosis of the femoral head, the recombinant plasmid pCD-hVEGF 165 was mixed with collagen and was implanted in the necrotic femoral head The expression of vascular endothelial growth factor (VEGF) was detected by RNA dot hybridization and immunohistochemical method The repair of the femoral head was observed by histological method The results showed that the expression of VEGF was detectable in the femoral head treated with VEGF gene Angiogenesis in these femoral heads was more abundant than the control Bone repairing was augmented in the femoral head treated with VEGF gene The results suggest that angiogenesis in bone tissue could be augmented by gene transfection of VEGF and bone repairing would be accelerated accordingly
文摘AIM To study the innate immune function in ulcerative colitis(UC) patients who fail to respond to anti-tumor necrosis factor(TNF) therapy.METHODS Effects of anti-TNF therapy, inflammation and medications on innate immune function were assessed by measuring peripheral blood mononuclear cell(PBMC) cytokine expression from 18 inflammatory bowel disease patients pre- and 3 mo post-anti-TNF therapy. Toll-like receptor(TLR) expression and cytokine production post TLR stimulation was assessed in UC "responders"(n = 12) and "non-responders"(n = 12) and compared to healthy controls(n = 12). Erythrocyte sedimentation rate(ESR) and C-reactive protein(CRP) levels were measured in blood to assess disease severity/activity and inflammation. Pro-inflammatory(TNF, IL-1β, IL-6), immuno-regulatory(IL-10), Th1(IL-12, IFNγ) and Th2(IL-9, IL-13, IL-17A) cytokine expression was measured with enzyme-linked immunosorbent assay while TLR cellular composition and intracellular signalling was assessed with FACS.RESULTS Prior to anti-TNF therapy, responders and nonresponders had similar level of disease severity and activity. PBMC's ability to respond to TLR stimulation was not affected by TNF therapy, patient's severity of the disease and inflammation or their medication use. At baseline, non-responders had elevated innate but not adaptive immune responses compared to responders(P < 0.05). Following TLR stimulation, nonresponders had consistently reduced innate cytokine responses to all TLRs compared to healthy controls(P < 0.01) and diminished TNF(P < 0.001) and IL-1β(P < 0.01) production compared to responders. This innate immune dysfunction was associated with reduced number of circulating plasmacytoid dendritic cells(p DCs)(P < 0.01) but increased number of CD4+ regulatory T cells(Tregs)(P = 0.03) as well as intracellular accumulation of IRAK4 in non-responders following TLR-2,-4 and-7 activation(P < 0.001). CONCLUSION Reduced innate immunity in non-responders may explain reduced efficacy to anti-TNF therapy. These serological markers may prove useful in predicting the outcome of costly anti-TNF therapy.
文摘Objective: The aim of the study is to assess the risk of post-operative outcome in rheumatoid arthritis (RA) patients continuing versus stopping combination therapy of methotrexate (MTX) and hydroxychloroquine (HCQ) or tumor necrosis factor α inhibitors (TNF) prior to surgery. Methods: Using the United States Veterans Affairs (VA) databases, we identified surgical procedures in a 17-year cohort of RA patients. Among those patients, those on MTX + HCQ or MTX + TNF were identified. Post-operative outcome variables include infection, length of post-operative hospital stay and death. Results: We identified a total of 29,708 surgeries in RA patients. Among them, we identified the most recent elective surgeries without pre-operative infection in 16,174 patients. There were 783 and 550 patients on MTX + HCQ and MTX + TNF, respectively. The rates of post-op infection were 5% and 4% for the MTX + HCQ and MTX + TNF continuing medication groups, respectively, similar to the general RA population (5%). Sensitivity analyses at various time points of discontinuation combination therapies prior to surgery did not show significant change in terms of infection. Conclusions: The prevalence of adverse outcome is low. The proportion of post-operative infection in continuing and discontinuing medicine groups is similar for both MTX + HCQ and MTX + TNF. While we were unable to formally compare proportions of post-operative infection among the two groups, these preliminary findings do not support the hypothesis that continuing either MTX + TNF or MTX + HCQ combination during perioperative period increases post-operative infection compared with discontinuation prior to therapy.
文摘Objective: To explore the clinical efficacy of neurogrowth factor in the treatment of gingival pain and swelling in patients with dental pulp necrosis after root canal therapy and the effect on the serum inflammatory cytokines. Methods: A total of 156 patients with gingival pain and swelling after root canal therapy due to dental pulp necrosis were included in the study and randomized into the control group (n=78) and teh treatment group (n=78). The patients in the control group were given metronidazole tablets. On the above basis, the patients in the treatment group were given local injection of neurogrowth factors. 10-day treatment was regarded as one course, and the patients were continuously treated for 2 courses. The improvement of clinical symptoms before and after treatment in the two groups was evaluated. Gingival sulcus index and serum inflammatory cytokines before and after treatment in the two groups were detected and compared. Results: When compared with before treatment, the periodontal soft tissue swelling, tooth mobility, and periapical pain scores after treatment in the two groups were significantly reduced, and those in the treatment group were significantly lower than those in the control group. When compared with before treatment, the gingival sulcus bleeding index 1 and 2 courses after treatment in the two groups was significantly reduced, and that 2 courses after treatment was significantly lower than that after 1 course treatment. The gingival sulcus bleeding index 1 and 2 courses after treatment in the treatment group was significantly lower than that in the control group. When compared with before treatment, the serum IL-8 and IL-6 levels after treatment in the two groups, and TNF-α level after treatment in the treatment group were significantly reduced, and the above indicators in the treatment group were significantly lower than those in the control group. Conclusions: The neurogrowth factors in the treatment of gingival pain and swelling in patients with dental pulp necrosis after root canal therapy can effectively improve the clinical symptoms, and inhibit the inflammatory reaction, with a significant efficacy.
文摘Ulcerative jejunoileitis is an uncommon clinical syndrome consisting of abdominal pain,weight loss associated with diarrhea,and multiple inflammatory ulcerations and strictures of the small bowel.Ulcerative jejunoileitis can complicate established celiac disease or develop in patients de novo.Increased levels of tumor necrosis factor-alpha(TNF-α) in the small intestine of patients with untreated celiac disease are associated with a role in the immune pathogenesis of this disorder.No specific therapy has been shown to change the course of ulcerative jejunoileitis.We report a case of severe ulcerative jejunoileitis previously unresponsive to traditional therapies,including high dose corticosteroids and cyclosporine.The patient had a dramatic resolution of symptoms and a complete normalization of endoscopic findings after anti-TNF-α monoclonal antibody,infliximab(Remicade).
基金Supported by The student’s grant from the Foundation for Medical University of Lodz
文摘AIM:To investigate the correlation between the appearance of skin lesions and concentration of interleukin(IL)-17A,IL-23 and interferon-γ(IFN-γ)in Crohn’s disease(CD)patients during anti-tumor necrosis factor-α(TNF-α)therapy METHODS:A prospective study included 30 adult patients with CD of Caucasian origin(19 men and 11women;mean age±SD 32.0±8.6 years)during biological therapy with anti-TNF-αantibodies from January2012 to March 2013.Eighteen patients were treated with infliximab,seven with adalimumab and five withcertolizumab.Inclusion criteria were exacerbation of the underlying disease,Crohn’s Disease Activity Index over 300 and the ineffectiveness of previously used non-biological therapies.Patients with a history of psoriasis,atopic dermatitis and other autoimmune skin lesions were excluded from the study.The control group consisted of 12 healthy subjects.A diagnostic survey was carried out,blood tests and careful skin examination were performed,and the serum levels of IL-17,IL-23 and IFN-γwere measured using an enzyme-linked immunosorbent assays technique.Dermatoses that have developed in the course of biological therapy in patients who had no pre-existing skin lesions of similar character were qualified as skin lesions induced by antiTNF-αtherapy.RESULTS:Skin manifestations occurred in 18 of CD patients during the anti-TNF-αtherapy(60%),in the average time of 10.16±3.42 mo following the beginning of the 52-wk treatment cycle.Skin lesions observed in CD patients during biological therapy included psoriasiform lesions(44.4%),and eczema forms lesions(22.2%).In CD patients with drug induced skin lesions significantly higher levels of hemoglobin(13.3±1.5 g/dL vs 10.8±1.9 g/dL,P=0.018)and hematocrit(39.9%±4.5%vs 34.3%±5.4%,P=0.01),as well as a significantly lower level of platelets(268±62×103/μL vs 408±239×103/μL,P=0.046)was observed compared with CD patients without skin manifestations.The concentrations of IL-17A and IL-23in CD patients with skin lesions developed under antiTNF-αtherapy were significantly higher compared to those in patients without lesions(IL-17A:39.01±7.03pg/mL vs 25.71±4.90 pg/mL,P=0.00004;IL-23:408.78±94.13 pg/mL vs 312.15±76.24 pg/mL,P=0.00556).CONCLUSION:Skin lesions in CD patients during bio-logical therapy may result from significantly increased concentrations of IL-17A and IL-23,which are strongly associated with TNF-α/Th1 immune pathways.
文摘INTRODUCTIONAs stated in the author’s previous articles,severe acute pancreatitis is a multifacetted diseasewith rapid and sometimes fulminating onset and mayresult in many serious complications or even death iftreatment is improper or delayed.Therapeuticmeasures must be directed against these
文摘INTRODUCTIONThe strongest evidence that H.pylori infection isthe cause of peptic ulcer is that treatment withantibiotics as the only regimen,is not only effectivefor the clearance and eradication of the infection,but more importantly for the healing of the ulcer orthe remission of gastric lymphoma.However,it isstill a matter of controversy and research as to
基金Shenzhen Science and Technology Project(No.201103061)
文摘Objective:To investigate the interference and expression of human glial cell line-derived neurotrophic factor(hCDNF) and soluble TNF alpha(sTMFRⅠ) receptor genes in neural stem cells and to evaluate the roles of these proteins in the genetic treatment of spinal cord injury.Methods:Full-length of GDNF cDNA(538 bp) and sTMFRⅠcDNA(504 bp) were inserted into the early 1 region of adenovirus genomic DNA respectively and were immediated by the human cytomegalovirus(gene promoter/enhancer). These adenoviruses were propagated in HEK293 cells via homologous recombination for 7-10 days in vivo,then they were used to infect human neural stem ceils.The infection and expression of gene were tested under immunofluorescence.ELISA and Westem-blot after 48 hours.Results:Almost all the cultured cells showed the nestin immunofluorescence positive staining,which was the characteristics of neural stem cell.A great quantity of EGFP and KFP were observed in neural stem cells,which indicated the expression of GDNF and sTMFRⅠ.After transfection of GDNF and sTMFRⅠgenes,many neural stem cells show GFAP and tubulin immunofluorescence positive staining,which meant that most neural stem cells differentiated into neuron at that condition.Conclusions:The infective efficiency of adenovirus is greatly acceptable to neural stem cell,thus adenovirus provide a useful vector for exogenous GDNF and sTMFRⅠgenes expressing in neural stem cells,which is useful for differentiation of neural stem cell.
文摘Gastroduodenal Crohn’s disease (CD) is rare and the response to standard medical therapy is often poor. Anti-tumor necrosis factor therapy has revolutionised the treatment of CD. We present a patient with pyloric stenosis associated with CD which improved with Adalimumab therapy. We recommend considering antitumor necrosis factor therapy in symptomatic gastroduodenal CD.
文摘Tumor necrosis factor (TNF) has certain radioprotective effect on host tissue and is capable of enhancing the antitumor effect of radiotherapy. In addition, the transcriptional regulation of the promoter region of Egr 1 gene is activated by ionizing radiation. So we fused Egr 1 promoter with hTNF α cDNA, and resultantly constructed a double copy and radiationin ducible retroviral vector named as pETDC. After packaged with Psi 2 and Crip cells in vitro, the hTNF recombinant retroviruses were in the titers of 4×10 5 CFU/ml. By infection of murine fibroblast cell line NIH3T3 and murine melanoma cell line B16.F10 with the recombinant retroviruses and followed by G418 resistant selection, two positive clones secreting TNF at the levels of 2.1 ng/ml and 1.1 ng/ml respectively were generated. After exposure to 20 Gy ionizing radiation, TNF secre tions from the two positive clones were elevated to 13.8 ng/ml (6.6 fold) and 5.7 ng/ml (5.2 fold) respectively. Furthermore, hTNF α expression in pETDC transfected cells was confirmed by RT PCR. These data provide an experimental bases for the application of TNF gene therapy combined with local radiotherapy in cancer patients.
基金National Magnetic Confinement Fusion Science Program of China(No.2014GB112006)National Natural Science Foundation of China(No.11305204)Natural Science Foundation of Anhui Province of China(No.1508085SME220)
文摘Radio genetic therapy which combines gene therapy with radiotherapy has shown promising results in cancer treatment. In this study, an oncolytic adenovirusbased gene therapy system regulated by radiation was constructed to improve the cancer curative effect. This gene therapy system incorporated the radiation-inducible early growth response gene(Egr-1) promoter and the anticancer gene tumor necrosis factor-related apoptosis-inducing ligand(TRAIL). To confirm the antitumor effect of Ad-ET combined with^12C^(6+)tion irradiation, the survival and apoptosis fraction of tumor cells HT1080 and normal cells MRC-5 in combination treatment were detected by CCK-8 assay and FACS analysis. Then the expression levels of TRAIL gene and protein were tested by real-time PCR and western blotting. The results show that^12C^(6+)tion irradiation could induce cell growth inhibition and apoptosis by activating the TRAIL gene expression in tumor cells, while exhibiting no obvious toxicity to the normal lung cell line MRC-5. Theresults also demonstrate that use of an oncolytic adenovirusbased radiation-inducible gene therapy system together with^12C^(6+)tion irradiation could cause synergistic antitumor effect specifically in tumor cells but not in normal cells. The results indicate that the novel radio genetic therapy could potentiate radiation treatment by improving the safety and efficiency of monotherapy, and provide theoretical support for clinical application of combination treatment.
文摘Psoriasis is a chronic, immune-mediated, inflammatory disease with a high prevalence in the general population (2%). The anti-tumor necrosis factor receptor etanercept is Food and Drug Administration (FDA) approved for the treatment of moderate-to-severe plaque psoriasis. Both continuous and interrupted etanercept therapy is effective and well-tolerated. This report <strong>aims</strong> to document a new case presentation of psoriasis on intermittent etanercept injection throughout 36 weeks with long-lasting sustained efficacy and no risk factor. <strong>Case Report</strong>: A 39-year-old adult male patient with long-standing chronic plaque psoriasis for 15 years duration without joint involvement started loading dose treatment of etanercept injection in whom due to his work circumstances not taken maintenance therapy and showed-up at the clinic after 36 weeks from first induction therapy when partial relapse of psoriatic lesions appear in last week with continued improvement when reintroducing loading treatment on followed-up over the next 36 weeks. <strong>Conclusion</strong>: Intermittent etanercept therapy considers effective for 36 weeks with prolonging sustained efficacy and without adverse effect.