AIM To perform a meta-analysis on the risk of developing Mycobacterium tuberculosis(TB) infection in Crohn's disease(CD) patients treated with tumor necrosis factoralpha(TNFα) inhibitors.METHODS A meta-analysis o...AIM To perform a meta-analysis on the risk of developing Mycobacterium tuberculosis(TB) infection in Crohn's disease(CD) patients treated with tumor necrosis factoralpha(TNFα) inhibitors.METHODS A meta-analysis of randomized, double-blind, placebocontrolled trials of TNFα inhibitors for treatment of CD in adults was conducted. Arcsine transformation of TB incidence was performed to estimate risk difference. A novel epidemiologically-based correction(EBC) enabling inclusions of studies reporting no TB infection cases in placebo and treatment groups was developed to estimate relative odds.RESULTS Twenty-three clinical trial studies were identified, including 5669 patients. Six TB infection cases were reported across 5 studies, all from patients receiving TNFα inhibitors. Eighteen studies reported no TB infection cases in placebo and TNFα inhibitor treatment arms. TB infection risk was significantly increased among patients receiving TNFα inhibitors, with a risk difference of 0.028(95%CI: 0.0011-0.055). The odds ratio was 4.85(95%CI: 1.02-22.99) with EBC and 5.85(95%CI: 1.13-30.38) without EBC.CONCLUSION The risk of TB infection is higher among CD patients receiving TNFα inhibitors. Understanding the immunopathogenesis of CD is crucial, since using TNFα inhibitors in these patients could favor mycobacterial infections, particularly Mycobacterium avium subspecies paratuberculosis, which ultimately could worsen their clinical condition.展开更多
It remains controversial whether tumor necrosis factor（TNF）-α antagonism is effective for asthma.This meta-analysis was performed to evaluate efficacy of TNF-α antagonism in treatment of patients with asthma.MEDLI...It remains controversial whether tumor necrosis factor（TNF）-α antagonism is effective for asthma.This meta-analysis was performed to evaluate efficacy of TNF-α antagonism in treatment of patients with asthma.MEDLINE,EMBASE,LILACS,and CINAHL databases were searched for English-language studies published through January 3,2010.Randomized-controlled trials comparing TNF-α antagonism with control therapy were selected.For each report,data were extracted in relation to the outcomes analyzed：asthma exacerbation,asthma quality of life questionnaire scores,and forced expiratory volume in 1 second.Four assessable trials were identified including 641 patients with asthma.TNF-α antagonism therapy was superior to control therapy in preventing exacerbations in asthmatics [pooled odds ratio 0.52（95% confidence interval 0.29-0.88）,P=0.02]however,there was a nonsignificant reduction in asthma quality of life questionnaire scores [0.23（0 to 0.47）,P=0.05],forced expiratory volume in 1 second [0.03,（-0.14 to 0.10）,P=0.74] when analyzed using standardized mean differences.TNF-α antagonism was superior to control chemotherapy in terms of asthma exacerbation,but not asthma quality of life questionnaire scores or forced expiratory volume in 1 second.展开更多
AIM To perform a meta-analysis of observational studies on inflammatory markers levels and occurrence of colorectal adenoma.METHODS Pub Med and EMBASE databases were searched until March 2016 for the articles reportin...AIM To perform a meta-analysis of observational studies on inflammatory markers levels and occurrence of colorectal adenoma.METHODS Pub Med and EMBASE databases were searched until March 2016 for the articles reporting on the circulating levels of inflammatory markers, including: C-reactive protein(CRP), interleukin-6(IL-6), and tumor necrosis factor-alpha(TNF-a) and risk of colorectal adenoma. Random-effects models were used to calculate summary odds ratios(ORs) with 95%CIs for the highest vs lowest category of exposure. Heterogeneity was assessed by using the Q test and I2 statistic. Subgroup analyses were also performed to test for potential source of heterogeneity.RESULTS A total of 14 case-control studies were included. Ten studies on CRP including a total of 3350 cases and 4168 controls showed non-significant summary(OR = 1.23, 95%CI: 0.98-1.54; I2 = 54%, P heterogeneity = 0.01) in the general analysis, but significant increased odds when considering only advanced adenoma(OR = 1.59, 95%CI: 1.09-2.32; I2 = 44%, P heterogeneity = 0.15). Subgroup and stratified analyses revealed a potential influence of smoking status and aspirin use on the association between CRP levels and colorectal adenoma. Five studies examined the association between circulating levels of TNF-a and colorectal adenoma risk, including a total of 1,568 cases and 2,832 controls. The summary OR for the highest vs the lowest category of exposure was 1.00(95%CI: 0.77-1.29). The relationship between circulating IL-6 levels and colorectal adenoma risk was investigated in 7 studies including a total of 1936 cases and 3611 controls. The summary OR for the highest vs the lowest category of exposure was 1.19(95%CI: 0.92-1.55).CONCLUSION Summary of current evidence suggests a positive association of CRP levels and advanced colorectal adenoma risk. The role of potential confounding factors should be further evaluated.展开更多
Background Numerous studies have described the association between polymorphisms in the tumor necrosis factor （TNF） gene and risk of endometriosis.However,the results remain controversial.Here we reviewed studies re...Background Numerous studies have described the association between polymorphisms in the tumor necrosis factor （TNF） gene and risk of endometriosis.However,the results remain controversial.Here we reviewed studies reporting the association between TNF gene polymorphisms and endometriosis risk in Asians.Methods PubMed and Embase were searched.Twelve case-control studies assessing the role of multiple TNF gene polymorphisms in endometriosis were included.If no less than two articles evaluated one variant,meta-analysis was conducted; otherwise,narrative analysis was chosen.A fixed-or random-effects model was employed according to the heterogeneity among studies.The strength of the association between TNF gene polymorphisms and endometriosis risk was assessed by odds ratios and 95％ confidence intervals.Results For TNF-α-238G＞A,-308G＞A,-857C＞T,and-863C＞A,no significant associations were identified from all genetic models.For TNF-α-850T＞C,results from one study showed that patients harboring the heterozygote TC were less susceptible to endometriosis than patients harboring the homozygote TT.For TNF-α-1031T＞C,a mild increase in endometriosis risk was found in the Asian population.Meta-analysis from two studies found that the TNF-β ＋252＞G polymorphism had a protective effect in Chinese individuals.Due to the limitations of the included studies,it is necessitated to perform more studies to elucidate the possible roles of TNF gene polymorphisms in the pathogenesis of endometriosis.Conclusions TNF-α-1031T＞C and TNF-β ＋252A＞G were significantly associated with the risk of endometriosis in Asian and Chinese populations,respectively.To further evaluate these associations,more large-scale,rigorously designed studies are needed.展开更多
目的探讨改良俯卧位通气对清醒病毒性肺炎患者呼吸循环、康复指标、并发症的影响。方法选取2021年8月—2023年6年就诊的134例病毒性肺炎,按照随机数字表法分为研究组、对照组,各67例,对照组采用常规俯卧位通气,研究组采用改良俯卧位通...目的探讨改良俯卧位通气对清醒病毒性肺炎患者呼吸循环、康复指标、并发症的影响。方法选取2021年8月—2023年6年就诊的134例病毒性肺炎,按照随机数字表法分为研究组、对照组,各67例,对照组采用常规俯卧位通气,研究组采用改良俯卧位通气。比较2组康复指标、血气指标[氧合指数(PaO_(2)/FiO_(2))、动脉血二氧化碳分压(PaCO_(2))、动脉血氧分压(PaO_(2))、血氧饱和度(SpO_(2))]、血流动力学指标[心率(HR)、中心静脉压(CVP)、平均动脉压(MAP)]、呼吸功能指标[平台压(Pplat)、气道峰压(Ppeak)、平均气道压(Pmean)]、炎症指标[白细胞介素-6(IL-6)、粒细胞-巨噬细胞集落刺激因子(GM-CSF)、肿瘤坏死因子-α(TNF-α)]、并发症及压力性损伤发生率。结果研究组住院时间短于对照组(P<0.05);2组俯卧2、4、8、12、16 h PaCO_(2)、PaO_(2)、PaO_(2)/FiO_(2)、SpO_(2),以及俯卧24、36 h时Ppeak、Pmean、Pplat、GM-CSF、IL-6、TNF-α均较俯卧前得以明显改善(P<0.05),但2组间比较差异无统计学意义(P>0.05);2组组间、组内不同时间点CVP、MAP、HR比较,差异无统计学意义(P>0.05);研究组并发症总发生率2.99%(2/67)低于对照组11.94%(8/67),压力性损伤发生率2.99%(2/67)低于对照组13.43%(9/67)(P<0.05)。结论在清醒病毒性肺炎患者中,改良俯卧位通气可达到与常规俯卧位通气相近的辅助治疗效果,能改善机体氧合功能、呼吸循环功能,降低并发症及压力性损伤发生风险,加速病情康复。展开更多
目的:急性肾损伤是临床常见危重症之一,存活患者的肾脏远期预后不容乐观。文章系统评价细胞外囊泡对急性肾损伤动物模型的有效性,希望为临床试验提供启发。方法:检索PubMed、Embase、Web of Science、Cochrane Library、万方、维普、中...目的:急性肾损伤是临床常见危重症之一,存活患者的肾脏远期预后不容乐观。文章系统评价细胞外囊泡对急性肾损伤动物模型的有效性,希望为临床试验提供启发。方法:检索PubMed、Embase、Web of Science、Cochrane Library、万方、维普、中国知网和中国生物医学文献数据库中有关细胞外囊泡治疗急性肾损伤临床前研究的相关文章,检索时间为各数据库建立至2022-08-01,由2名研究人员独立提取数据,对文献采用SYRCLE动物实验偏倚风险评估表进行质量评价。采用RevMan 5.4和Stata 14.0软件对血肌酐、尿素氮、肿瘤坏死因子α、肾小管管状坏死与肾小管管型等结局指标进行Meta分析。结果:(1)共纳入19篇随机对照动物实验,包括399只啮齿动物,其中细胞外囊泡治疗组啮齿动物169只,对照组啮齿动物168只,干细胞治疗组啮齿动物62只。(2)Meta分析结果显示:与动物模型对照组相比,细胞外囊泡组血肌酐水平(SMD=-5.41,95%CI:-6.95至-3.88,P<0.001)、尿素氮水平(SMD=-4.57,95%CI:-5.94至-3.20,P<0.001)、肿瘤坏死因子α水平(SMD=-2.15,95%CI:-2.63至-1.68,P<0.001)明显降低,肾小管管状坏死(SMD=-6.15,95%CI:-9.66至-2.64,P=0.001)与肾小管管型(SMD=-3.33,95%CI:-4.17至-2.49,P=0.001)明显减少;细胞外囊泡组与间充质干细胞治疗组在改善血肌酐(SMD=-1.23,95%CI:-2.80-0.35,P=0.127)及尿素氮(SMD=-0.34,95%CI:-2.19-1.50,P=0.715)水平方面无显著差异。结论:细胞外囊泡有助于改善急性肾损伤动物模型的血肌酐和尿素氮水平,可显著降低肿瘤坏死因子α水平,并且减少肾小管管状坏死与肾小管管型,这些基础研究证据为下一步开展临床试验提供重要参考。展开更多
目的评价不同药物治疗方案用于儿童川崎病(KD)的疗效和安全性,为临床治疗提供循证参考。方法计算机检索the Cochrane Library、Medline、Embase、CINAHL、Web of Science、ProQuest、Google学术、中国知网、万方数据、百度学术数据库和...目的评价不同药物治疗方案用于儿童川崎病(KD)的疗效和安全性,为临床治疗提供循证参考。方法计算机检索the Cochrane Library、Medline、Embase、CINAHL、Web of Science、ProQuest、Google学术、中国知网、万方数据、百度学术数据库和世界卫生组织国际临床试验注册平台、ClinicalTrials.gov,收集在标准静脉注射免疫球蛋白(IVIG)疗法基础上给予糖皮质激素或环孢素或肿瘤坏死因子α(TNF-α)抑制剂(试验组)对比标准IVIG疗法(对照组)的随机对照试验(RCT),检索时限为建库至2023年2月28日。筛选文献、提取资料、评价文献质量后,采用Stata 14.2软件进行网状Meta分析。结果共纳入10项RCT,共计1323例患儿;涉及6种干预措施,分别为标准IVIG疗法、糖皮质激素疗法、环孢素疗法、TNF-α抑制剂疗法、补救性糖皮质激素疗法和补救性TNF-α抑制剂疗法。网状Meta分析结果显示,使用糖皮质激素疗法患儿的4~8周冠状动脉瘤(CAA)发生率显著低于使用标准IVIG疗法和TNF-α抑制剂疗法患儿,使用补救性糖皮质激素疗法、补救性TNF-α抑制剂疗法患儿的4~8周CAA发生率均较使用糖皮质激素疗法患儿显著升高;其他干预措施间比较,差异均无统计学意义(P>0.05);该发生率的网状Meta排序由低到高为糖皮质激素疗法<环孢素疗法<标准IVIG疗法<补救性TNF-α抑制剂疗法<补救性糖皮质激素疗法<TNF-α抑制剂疗法。使用环孢素疗法患儿的初始IVIG抵抗发生率显著低于使用标准IVIG疗法患儿;其他干预措施间比较,差异均无统计学意义(P>0.05);该发生率的网状Meta排序由低到高为环孢素疗法<糖皮质激素疗法<TNF-α抑制剂疗法<标准IVIG疗法。各干预措施间的不良反应发生率比较,差异均无统计学意义(P>0.05);该发生率的网状Meta排序由低到高为补救性TNF-α抑制剂疗法<TNF-α抑制剂疗法<标准IVIG疗法<糖皮质激素疗法<环孢素疗法。结论初始阶段给予糖皮质激素可显著减少KD患儿4~8周CAA的发生风险,给予环孢素可显著改善初始IVIG抵抗,在补救阶段使用TNF-α抑制剂的不良反应发生率可能最低。展开更多
The kinetic analysis of the interaction between tumor necrosis factor(TNF) and its monoclonal antibody was performed by surface plasmon resonance(SPR) technique. The monoclonal antibody was immobilized to the surface ...The kinetic analysis of the interaction between tumor necrosis factor(TNF) and its monoclonal antibody was performed by surface plasmon resonance(SPR) technique. The monoclonal antibody was immobilized to the surface of CM5 sensor chip by amine coupling. TNF at different concentrations was injected across the mAb immobilized surface. The interaction was recorded in real time and could be seen on the sensorgram. One cycle, including association, dissociation and regeneration, lasted no more than 15 min . The interaction results was evaluated using 1∶1 Langmuir binding model. The kinetic rate constants were calculated to be: k a=1.68×10 3 L·mol -1 ·s -1 , k d=1.73×10 -4 s -1 , and the affinity constants K A=9.7×10 6 L·mol -1 , K D=1.03×10 -7 mol·L -1 . The χ \+2 was 3.47, which showed that the interaction is consistent with the 1∶1 model. We can see from the results that although there are two binding sites in one mAb molecule, TNF reacts with each site in an independent and noncooperative manner.展开更多
文摘AIM To perform a meta-analysis on the risk of developing Mycobacterium tuberculosis(TB) infection in Crohn's disease(CD) patients treated with tumor necrosis factoralpha(TNFα) inhibitors.METHODS A meta-analysis of randomized, double-blind, placebocontrolled trials of TNFα inhibitors for treatment of CD in adults was conducted. Arcsine transformation of TB incidence was performed to estimate risk difference. A novel epidemiologically-based correction(EBC) enabling inclusions of studies reporting no TB infection cases in placebo and treatment groups was developed to estimate relative odds.RESULTS Twenty-three clinical trial studies were identified, including 5669 patients. Six TB infection cases were reported across 5 studies, all from patients receiving TNFα inhibitors. Eighteen studies reported no TB infection cases in placebo and TNFα inhibitor treatment arms. TB infection risk was significantly increased among patients receiving TNFα inhibitors, with a risk difference of 0.028(95%CI: 0.0011-0.055). The odds ratio was 4.85(95%CI: 1.02-22.99) with EBC and 5.85(95%CI: 1.13-30.38) without EBC.CONCLUSION The risk of TB infection is higher among CD patients receiving TNFα inhibitors. Understanding the immunopathogenesis of CD is crucial, since using TNFα inhibitors in these patients could favor mycobacterial infections, particularly Mycobacterium avium subspecies paratuberculosis, which ultimately could worsen their clinical condition.
基金supported by a grant from National Science Fund for Distinguished Young Scholars (No. 30925032)by grants from National Natural Sciences Foundation of China (No. 30872343 and No. 30770648)
文摘It remains controversial whether tumor necrosis factor（TNF）-α antagonism is effective for asthma.This meta-analysis was performed to evaluate efficacy of TNF-α antagonism in treatment of patients with asthma.MEDLINE,EMBASE,LILACS,and CINAHL databases were searched for English-language studies published through January 3,2010.Randomized-controlled trials comparing TNF-α antagonism with control therapy were selected.For each report,data were extracted in relation to the outcomes analyzed：asthma exacerbation,asthma quality of life questionnaire scores,and forced expiratory volume in 1 second.Four assessable trials were identified including 641 patients with asthma.TNF-α antagonism therapy was superior to control therapy in preventing exacerbations in asthmatics [pooled odds ratio 0.52（95% confidence interval 0.29-0.88）,P=0.02]however,there was a nonsignificant reduction in asthma quality of life questionnaire scores [0.23（0 to 0.47）,P=0.05],forced expiratory volume in 1 second [0.03,（-0.14 to 0.10）,P=0.74] when analyzed using standardized mean differences.TNF-α antagonism was superior to control chemotherapy in terms of asthma exacerbation,but not asthma quality of life questionnaire scores or forced expiratory volume in 1 second.
文摘AIM To perform a meta-analysis of observational studies on inflammatory markers levels and occurrence of colorectal adenoma.METHODS Pub Med and EMBASE databases were searched until March 2016 for the articles reporting on the circulating levels of inflammatory markers, including: C-reactive protein(CRP), interleukin-6(IL-6), and tumor necrosis factor-alpha(TNF-a) and risk of colorectal adenoma. Random-effects models were used to calculate summary odds ratios(ORs) with 95%CIs for the highest vs lowest category of exposure. Heterogeneity was assessed by using the Q test and I2 statistic. Subgroup analyses were also performed to test for potential source of heterogeneity.RESULTS A total of 14 case-control studies were included. Ten studies on CRP including a total of 3350 cases and 4168 controls showed non-significant summary(OR = 1.23, 95%CI: 0.98-1.54; I2 = 54%, P heterogeneity = 0.01) in the general analysis, but significant increased odds when considering only advanced adenoma(OR = 1.59, 95%CI: 1.09-2.32; I2 = 44%, P heterogeneity = 0.15). Subgroup and stratified analyses revealed a potential influence of smoking status and aspirin use on the association between CRP levels and colorectal adenoma. Five studies examined the association between circulating levels of TNF-a and colorectal adenoma risk, including a total of 1,568 cases and 2,832 controls. The summary OR for the highest vs the lowest category of exposure was 1.00(95%CI: 0.77-1.29). The relationship between circulating IL-6 levels and colorectal adenoma risk was investigated in 7 studies including a total of 1936 cases and 3611 controls. The summary OR for the highest vs the lowest category of exposure was 1.19(95%CI: 0.92-1.55).CONCLUSION Summary of current evidence suggests a positive association of CRP levels and advanced colorectal adenoma risk. The role of potential confounding factors should be further evaluated.
文摘Background Numerous studies have described the association between polymorphisms in the tumor necrosis factor （TNF） gene and risk of endometriosis.However,the results remain controversial.Here we reviewed studies reporting the association between TNF gene polymorphisms and endometriosis risk in Asians.Methods PubMed and Embase were searched.Twelve case-control studies assessing the role of multiple TNF gene polymorphisms in endometriosis were included.If no less than two articles evaluated one variant,meta-analysis was conducted; otherwise,narrative analysis was chosen.A fixed-or random-effects model was employed according to the heterogeneity among studies.The strength of the association between TNF gene polymorphisms and endometriosis risk was assessed by odds ratios and 95％ confidence intervals.Results For TNF-α-238G＞A,-308G＞A,-857C＞T,and-863C＞A,no significant associations were identified from all genetic models.For TNF-α-850T＞C,results from one study showed that patients harboring the heterozygote TC were less susceptible to endometriosis than patients harboring the homozygote TT.For TNF-α-1031T＞C,a mild increase in endometriosis risk was found in the Asian population.Meta-analysis from two studies found that the TNF-β ＋252＞G polymorphism had a protective effect in Chinese individuals.Due to the limitations of the included studies,it is necessitated to perform more studies to elucidate the possible roles of TNF gene polymorphisms in the pathogenesis of endometriosis.Conclusions TNF-α-1031T＞C and TNF-β ＋252A＞G were significantly associated with the risk of endometriosis in Asian and Chinese populations,respectively.To further evaluate these associations,more large-scale,rigorously designed studies are needed.
文摘目的探讨改良俯卧位通气对清醒病毒性肺炎患者呼吸循环、康复指标、并发症的影响。方法选取2021年8月—2023年6年就诊的134例病毒性肺炎,按照随机数字表法分为研究组、对照组,各67例,对照组采用常规俯卧位通气,研究组采用改良俯卧位通气。比较2组康复指标、血气指标[氧合指数(PaO_(2)/FiO_(2))、动脉血二氧化碳分压(PaCO_(2))、动脉血氧分压(PaO_(2))、血氧饱和度(SpO_(2))]、血流动力学指标[心率(HR)、中心静脉压(CVP)、平均动脉压(MAP)]、呼吸功能指标[平台压(Pplat)、气道峰压(Ppeak)、平均气道压(Pmean)]、炎症指标[白细胞介素-6(IL-6)、粒细胞-巨噬细胞集落刺激因子(GM-CSF)、肿瘤坏死因子-α(TNF-α)]、并发症及压力性损伤发生率。结果研究组住院时间短于对照组(P<0.05);2组俯卧2、4、8、12、16 h PaCO_(2)、PaO_(2)、PaO_(2)/FiO_(2)、SpO_(2),以及俯卧24、36 h时Ppeak、Pmean、Pplat、GM-CSF、IL-6、TNF-α均较俯卧前得以明显改善(P<0.05),但2组间比较差异无统计学意义(P>0.05);2组组间、组内不同时间点CVP、MAP、HR比较,差异无统计学意义(P>0.05);研究组并发症总发生率2.99%(2/67)低于对照组11.94%(8/67),压力性损伤发生率2.99%(2/67)低于对照组13.43%(9/67)(P<0.05)。结论在清醒病毒性肺炎患者中,改良俯卧位通气可达到与常规俯卧位通气相近的辅助治疗效果,能改善机体氧合功能、呼吸循环功能,降低并发症及压力性损伤发生风险,加速病情康复。
文摘The kinetic analysis of the interaction between tumor necrosis factor(TNF) and its monoclonal antibody was performed by surface plasmon resonance(SPR) technique. The monoclonal antibody was immobilized to the surface of CM5 sensor chip by amine coupling. TNF at different concentrations was injected across the mAb immobilized surface. The interaction was recorded in real time and could be seen on the sensorgram. One cycle, including association, dissociation and regeneration, lasted no more than 15 min . The interaction results was evaluated using 1∶1 Langmuir binding model. The kinetic rate constants were calculated to be: k a=1.68×10 3 L·mol -1 ·s -1 , k d=1.73×10 -4 s -1 , and the affinity constants K A=9.7×10 6 L·mol -1 , K D=1.03×10 -7 mol·L -1 . The χ \+2 was 3.47, which showed that the interaction is consistent with the 1∶1 model. We can see from the results that although there are two binding sites in one mAb molecule, TNF reacts with each site in an independent and noncooperative manner.
