Early screening to identify and diagnose primary nasal tuberculosis in patients with tumor necrosis factor inhibitors

In this editorial,we comment on the article by Liu et al.Based on our analysis of a case report,we consider that early screening and recognition of primary nasal tuberculosis are crucial for patients undergoing treatment with tumor necrosis factor inhibitor(TNFi).While TNFi therapy increases the risk of reactivating latent tuberculosis,primary nasal tuberculosis remains rare due to the protective mechanisms of the nasal mucosa.Risk factors for primary nasal tuberculosis include minimally invasive nasal surgery,diabetes,and human immunodefi ciency virus.Patients with early symptoms such as nasal congestion,rhinorrhea,altered olfaction,epistaxis,or ulceration,and unresponsive to conventional antibiotics and antihistamines should undergo early rhinoscopy,possibly followed by repeated tissue biopsies and acid-fast bacilli culture when necessary.When diagnosis is challenging,it is essential to consider local tuberculosis epidemiology and the efficacy of diagnostic antituberculosis treatment.The preferred method for tuberculosis screening is the Interferon Gamma Release Assay,with a general recommendation for screening at 3 and 6 months after initial treatment and then every six months.However,the optimal frequency is not yet consensus-driven and may be increased in economically viable settings.

Tumor Necrosis Factor-Alpha (TNF)-308G/A and Interleukin 8(IL-8)-251C/T Polymorphisms in Pulmonary Tuberculosis Patients from Congo

Background: Tuberculosis (TB) is one of the world’s deadliest infectious diseases. Tumor necrosis factor-Alpha (TNF-α) and Interleukin 8 (IL-8) are involved in the pathogenesis of pulmonary TB (PTB). However, the contribution of polymorphisms of these cytokines to PTB susceptibility needed more investigation across geographic regions and ethnic groups. Purpose: The aim of this study was to investigate the association of the TNF-α-308 G/A and IL-8-251T/A polymorphisms with PTB risk in the Congolese population. Methods: This case-control study included 150 PTB patients and 160 control subjects. Blood samples were collected from all participants and were used for the TNF-α-308 G/A and IL-8-251T/A genotyping by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Odds ratios (OR) were calculated to estimate the potential polymorphism associations. A P level of Results: A significant difference was found between PTB patients and controls regarding the TNF-α-308AA genotype (P = 0.035) distribution. Moreover, this genotype was associated with risk to TB (OR = 7.19, 95% CI = 0.85 - 60.65, P = 0.035). The A allele was significantly more frequent in PTB patients than in controls, and was associated with risk to PTB (OR = 1.68, 95% CI = 1.05 - 2.68, P = 0.014). Regarding the IL-8-251T/A gene, TA and AA genotypes were significantly more frequent in PTB patients compared to controls, and were associated with increased risk to PTB (OR = 2.64, 95% CI = 0.97 - 7.18, P = 0.031 and OR = 3.0, 95% CI = 1.13 - 7.98, P = 0.014, respectively). However, the IL-8-251 A allele was not associated to PTB susceptibility (OR = 0.27, 95% CI = 0.15 - 0.44). Conclusion: TNF-α-308G/A and IL-8-251T/A polymorphisms may be associated to PTB susceptibility in the Congolese population, and the AA genotype of both cytokines could be a risk factor.

Study of tumor necrosis factor receptor in the inflammatory bowel disease

Ulcerative colitis(UC)and Crohn’s disease(CD)are part of Inflammatory Bowel Diseases(IBD)and have pathophysiological processes such as bowel necrosis and enteric neurons and enteric glial cells.In addition,the main inflammatory mediator is related to the tumor necrosis factor-alpha(TNF-α).TNF-αis a mediator of the intestinal inflammatory processes,thus being one of the main cytokines involved in the pathogenesis of IBD,however,its levels,when measured,are present in the serum of patients with IBD.In addition,TNF-αplays an important role in promoting inflammation,such as the production of interleukins(IL),for instance IL-1βand IL-6.There are two receptors for TNF as following:The tumor necrosis factor 1 receptor(TNFR1);and the tumor necrosis factor 2 receptor(TNFR2).They are involved in the pathogenesis of IBD and their receptors have been detected in IBD and their expression is correlated with disease activity.The soluble TNF form binds to the TNFR1 receptor with,and its activation results in a signaling cascade effects such as apoptosis,cell proliferation and cytokine secretion.In contrast,the transmembrane TNF form can bind both to TNFR1 and TNFR2.Recent studies have suggested that TNF-αis one of the main pro-inflammatory cytokines involved in the pathogenesis of IBD,since TNF levels are present in the serum of both patients with UC and CD.Intravenous and subcutaneous biologics targeting TNF-αhave revolutionized the treatment of IBD,thus becoming the best available agents to induce and maintain IBD remission.The application of antibodies aimed at neutralizing TNF-αin patients with IBD that induce a satisfactory clinical response in up to 60%of patients,and also induced long-term maintenance of disease remission in most patients.It has been suggested that anti-TNF-αagents inactivate the pro-inflammatory cytokine TNF-αby direct neutralization,i.e.,resulting in suppression of inflammation.However,anti-TNF-αantibodies perform more complex functions than a simple blockade.

Predictors and optimal management of tumor necrosis factor antagonist nonresponse in inflammatory bowel disease:A literature review

Tumor necrosis factor-α(TNF-α)antagonists,the first biologics approved for treating patients with inflammatory bowel disease(IBD),are effective for the induction and maintenance of remission and significantly improving prognosis.However,up to one-third of treated patients show primary nonresponse(PNR)to anti-TNF-αtherapies,and 23%-50%of IBD patients experience loss of response(LOR)to these biologics during subsequent treatment.There is still no recognized predictor for evaluating the efficacy of anti-TNF drugs.This review summarizes the existing predictors of PNR and LOR to anti-TNF in IBD patients.Most predictors remain controversial,and only previous surgical history,disease manifestations,drug concentrations,antidrug antibodies,serum albumin,some biologic markers,and some genetic markers may be potentially predictive.In addition,we also discuss the next steps of treatment for patients with PNR or LOR to TNF antagonists.Therapeutic drug monitoring plays an important role in treatment selection.Dose escalation,combination therapy,switching to a different anti-TNF drug,or switching to a biologic with a different mechanism of action can be selected based on the concentration of the drug and/or antidrug antibodies.

Joint Detection of Serum Vitamin D,Body Mass Index,and Tumor Necrosis Factor Alpha for the Diagnosis of Crohn’s Disease

Objective Vitamin D(VD)deficiency was reported to contribute to the progression of Crohn’s disease(CD)and affect the prognosis of CD patients.This study investigated the role of serum VD,body mass index(BMI),and tumor necrosis factor alpha(TNF-α)in the diagnosis of Crohn’s disease.Methods CD patients(n=76)and healthy subjects(n=76)were enrolled between May 2019 and December 2020.The serum 25-hydroxyvitamin D[25(OH)D]levels,BMI,and TNF-αlevels,together with other biochemical parameters,were assessed before treatment.The diagnostic efficacy of the single and joint detection of serum 25(OH)D,BMI,and TNF-αwas determined using receiver operating characteristic(ROC)curves.Results The levels of 25(OH)D,BMI,and nutritional indicators,including hemoglobin,total protein,albumin,and high-density lipoprotein cholesterol,were much lower,and the TNF-αlevels were much higher in the CD patients than in the healthy subjects(P<0.05 for all).The areas under the ROC curve for the single detection of 25(OH)D,BMI,and TNF-αwere 0.887,0.896,and 0.838,respectively,with the optimal cutoff values being 20.64 ng/mL,19.77 kg/m^(2),and 6.85 fmol/mL,respectively.The diagnostic efficacy of the joint detection of 25(OH)D,BMI,and TNF-αwas the highest,with an area under the ROC curve of 0.988(95%CI:0.968–1.000).Conclusion The joint detection of 25(OH)D,TNF-α,and BMI showed high sensitivity,specificity,and accuracy in CD diagnosis;thus,it would be effective for the diagnosis of CD in clinical practice.

Acute heart failure as an adverse event of tumor necrosis factor inhibitor therapy in inflammatory bowel disease:A review of the literature

Tumor necrosis factor inhibitors(anti-TNFs)are widely used therapies for the treatment of inflammatory bowel diseases(IBD);however,their administration is not risk-free.Heart failure(HF),although rare,is a potential adverse event related to administration of these medications.However,the exact mechanism of development of HF remains obscure.TNFαis found in both healthy and damaged hearts.Its effects are concentration-and receptor-dependent,promoting either cardio-protection or cardiomyocyte apoptosis.Experimental rat models with TNFαreceptor knockout showed increased survival rates,less reactive oxygen species formation,and improved diastolic left ventricle pressure.However,clinical trials employing anti-TNF therapy to treat HF had disappointing results,suggesting abolishment of the cardioprotective properties of TNFα,making cardiomyocytes susceptible to apoptosis and oxidation.Thus,patients with IBD who have risk factors should be screened for HF before initiating anti-TNF therapy.This review aims to discuss adverse events associated with the administration of anti-TNF therapy,with a focus on HF,and propose some approaches to avoid cardiac adverse events in patients with IBD.

Systematic review and meta-analysis on the association of tuberculosis in Crohn's disease patients treated with tumor necrosis factor-α inhibitors(Anti-TNFα)

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.

Tumor necrosis factor-alpha(TNF-α) in spotted halibut Verasper variegatus at the embryonic and metamorphic stages

As an aquatic fish,the spotted halibut Verasper variegatus is highly susceptible to bacterial and virus infections.Tumor necrosis factor-alpha(TNF-α)as a cytokine could control the inflammatory responses.The functions of TNF-αin many species have been widely studied,particularly in mammals.However,little is known about the TNF-αfunctions in V.variegatus.We first cloned and sequenced the TNF-αgene in V.variegatus(VvTNF-α).The two conserved cysteine residues,transmembrane sequence,Thr-Leu motif,and TNF family signature,as well as the TA-rich motifs of its proteins related to inflammatory responses had high similarity to those of the other teleost and mammalian TNF-α.The phylogenetic analysis showed that VvTNF-αwas consistent with TNF-αgenes of other vertebrates.The VvTNF-αtranscripts were extensively distributed in the peripheral blood leukocytes(PBLs),spleen,and gill,indicating that the VvTNF-αhad a role in immune function.Furthermore,treatment with pathogen-associated molecular patterns(PAMPs)could induce a rapid and significant increase of VvTNF-αin the PBLs,which reveals that VvTNF-αdoes participate in the host immune responses against bacterial and viral pathogens.We found that VvTNF-αhad an interesting expression pattern during metamorphosis,showing that the flatfish TNF-αmay have some novel functions during specific developmental stages.In addition,the 3 D structure prediction of VvTNF-αprovided an indication of how it is likely to interact with other proteins.Therefore,VvTNF-αhas multiple functions,and provides valuable information to explore novel functions of TNF-α.

SYNTHESIS AND EXPRESSION OF A GENE FOR HUMAN TUMOR NECROSIS FACTOR-ALPHA (TNF-α)

TNF-α was found originally In sera of Bacillus Calmette Guerln infected mice as a macrophage derived factor. It Is cytotoxlc for tumor cell and less or not toxic to normal cells in vitor. The gene for human TNF-α with E. coli-preferred codons has been designed according to the amino acid sequence deduced from the cDNA. The gene with 504 bp was divided into 27 oligonucleotide fragments having 30. to 40 nucleotides each. The solid phase phosphotriester method was used for the synthesis of these oligonucleotides. The 27 fragments were annealed to three segments and then linked by T4 DNA ligase. The entire gene was incorporated into plasmld PDR540 with Tac promoter which was used to transform E. coli 7118. The expressed protein was estimated by SDSPAGE with a molecular weight of 1. 7×104Da. The cytotoxlc activity of the product against L-929 cell was 1. 0×107units/ml culture.

The interleukin-1 receptor antagonist (IL-1-Ra) and soluble tumor necrosis factor receptor I (sTNF RI) in periodontal disease

The course and severity of periodontitis can be significantly affected by bacterial virulence as well as host immunity dysfunction. Periodontal tissue destruction has been proved to result from cascade of cytokines synthesized by reactive cells upon stimulation by pathogenic bacteria and lipopolysaccharides within their cell membranes. The clinical use of genetically programmed cells, producing substances blocking IL-1, based on recombinant IL-1 antagonist, as well as cytokines activating fibroblasts and osteoblasts to regenerate the destroyed periodontal tissue could prove alternative to the conventional treatment. Another cytokine of interest in respect to periodontitis ethiopathogenesis is soluble tumor necrosis factor receptor I (sTNF RI). Observation of soluble TNF receptors as physiologic inhibitors of TNF led to its administration in therapeutic process as well as in therapy selected cases of aggressive periodontitis.

Pro-inflammatory cytokine;tumor-necrosis factor-alpha (TNF-α) inhibits astrocytic support of neuronal survival and neurites outgrowth

Reactive astrogliosis has been implicated in the failure of axonal regeneration in adult mammalian Central Nervous System (CNS). It is our hypothesis that inflammatory cytokines act upon astrocytes to alter their biochemical and physical properties, which may in turn be responsible for the failure of neuronal regeneration. We have therefore examined the effect of tumor-necrosis factor-alpha (TNF-α) on the ability of astrocytes to support the survival of the cortical neurons and the growth of the neurites. Mouse astrocytes and cortical neuronal cultures were prepared. It was observed that when neurons were cultured in absence of astrocytes only a few of them grew and survived only for 5-6 days. These neurons had small cell bodies and few, short neurites. However, when the same numbers of neurons were cultured on the top of astrocytes, more neurons grew and survived up to 16-18 days. They had bigger cell bodies and many long branched neurites that formed anestamosing networks. The neurons then coalesced and the neurites formed thick bundles. When the same numbers of neurons were grown on the top of astrocytes pre-treated with TNF-α, few neurons survived up to 13 days. The neurites of the survived neurons were shorter than neurites of neurons grown on normal astrocytes and did not form bundles. In addition, TNF-α stimulated the expression of glial fibrillary acidic protein (GFAP) by astrocytes. These results support that the pro-inflammatory cytokine, TNF-α modulates the gliosis and that the astrocytic cell supports neuronal survival and neurite outgrowth.

Recombination Mutant Human Tumor Necrosis Factor Combined with Chemotherapy in the Treatment of Advanced Cancer

Objective: Past studies showed that tumor necrosis factor (TNF) assisted anti-tumor treatment and intensified the sensitivity of chemotherapy. However its clinical application has been curbed because of its low purity, high dosage, and strong toxicity. The objective of present study is to evaluate the therapeutic effects and adverse reactions of recombinant mutant human tumor necrosis factor (rmhTNF) combined with chemotherapy in patients with advanced malignant tumor. Methods: 105 patients with advanced malignant tumor were randomly divided into trial group, 69 patients, and control group, 36 patients. rmhTNF was injected intramuscularly to the trial group at a dose of 4×106 U/m2, from the 1st to 7th days, the 11th to 17th days combined with chemotherapy course. The chemotherapy plan was as follows: CAP for patients with the NSCLC; FAM for patients with gastric cancer; FC for patients with colorectal cancer. One treatment cycle lasted for 21 days and two cycles were scheduled. The control group was given only the same chemotherapy as the trial group. Results: In the trial group there was 1 CR case and 12 PR cases, and the response rate was 13/69 (18.84%); in the control group 1 PR case, the response rate 1/36 (2.78%). The response rate in the trial group was significantly higher than that in the control group (P=0.022). The response rate for NSCLC in the trial group was 8/17 (47.06%), and 1/6 (16.67%) in the control group. The response rates for gastric cancer and colorectal cancer in the trial groups also were higher than those in the control groups. After the treatment the KPS was 89.00±9.92 in the trial group, and 84.17±8.84 in the control group, with a significant difference between the two groups (P=0.028). The adverse reactions of rmhTNF injection included: pain in the injection area, chill, hardening and swelling and redness in the injection area, fever, ostealgia and myosalgia, and cold-like symptoms. All these adverse reactions were mild and bearable. Conclusion: The administration of rmhTNF in combination with general chemotherapy is an effective and secure means in treating advanced malignant tumor.

清燥救肺汤联合痰热清注射液防治放射性肺损伤的临床疗效及对免疫指标、IL-2和TNF-α表达的影响

目的探讨清燥救肺汤联合痰热清注射液防治放射性肺损伤的临床疗效及对免疫指标、白细胞介素-2(interleukin-2,IL-2)和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)表达的影响。方法选择2020年9月~2022年12月在唐山市人民医院放化科接受胸部三维适形放射治疗的肺癌患者100例,随机分为对照组和治疗组各50例。对照组采用单纯放疗,治疗组在对照组基础上给予清燥救肺汤联合痰热清注射液。放疗结束后3个月比较两组近期疗效、放射性肺炎和不良反应发生情况,及放疗前与放疗结束后3个月生存质量、免疫指标、IL-2和TNF-α水平变化。结果治疗组近期有效率高于对照组(P<0.05)。2组放疗结束后3个月卡氏功能状态(karnofsky performance status,KPS)评分高于放疗前(P<0.05);治疗组放疗结束后3个月KPS评分改善情况优于对照组(P<0.05)。2组放疗结束后3个月中医证候积分均低于放疗前(P<0.05);治疗组放疗结束后3个月中医证候积分改善优于对照组(P<0.05)。治疗组患者放疗结束后3个月CD3+、CD4+和CD4+/CD8+高于放疗前(P<0.05),改善情况优于对照组(P<0.05),对照组患者放疗结束后3个月CD3+、CD4+/CD8+较放疗前无明显变化(P>0.05)。2组患者放疗结束后3个月血清IL-2水平高于放疗前,而TNF-α水平低于放疗前(P<0.05);治疗组患者放疗结束后3个月血清IL-2水平和TNF-α水平改善情况均优于对照组(P<0.05)。2组不良反应发生情况比较差异无统计学意义(P>0.05)。结论清燥救肺汤联合痰热清注射液可明显降低放射性肺炎发生率,改善部分免疫指标水平,减轻细胞炎性反应。

Chemerin、TNF-α在妊娠期糖尿病患者母血、脐血及脐带组织中的表达

目的测定Chemerin及肿瘤坏死因子(TNF-α)在妊娠期糖尿病(GDM)患者及胎儿中的表达水平,探讨Chemerin在GDM及胎儿发育中的作用。方法选择2016年8月至2017年11月产检并分娩的53例GDM孕妇为GDM组,选择同期产检并分娩的59例正常孕妇为正常妊娠组(NGT组)。酶联免疫吸附法测定2组患者血清中Chemerin及TNF-α的水平。实时荧光定量PCR和免疫印迹法测定脐带组织中Chemerin及TNF-αmRNA和蛋白的表达。结果2组母体血清Chemerin水平差异无统计学意义(P>0.05),GDM组脐血Chemerin明显高于NGT组(P<0.01)。2组母血Chemerin水平均明显低于脐血(P<0.01)。与NGT组母体血清中TNF-α水平相比,GDM组母体TNF-α明显升高(P<0.01)。2组脐血TNF-α水平差异无统计学意义(P>0.05)。GDM组母血TNF-α明显高于脐血(P<0.01),而NGT组母血TNF-α与脐血差异无统计学意义(P>0.05)。脐带组织中Chemerin mRNA在GDM组的表达水平明显高于NGT组(P<0.05),TNF-αmRNA在GDM组的表达水平明显高于NGT组(P<0.05)。Chemerin的蛋白表达在2组间差异无统计学意义(P>0.05),TNF-α蛋白在GDM组的表达明显高于NGT组(P<0.05)。相关性分析表明,GDM组中脐血血清Chemerin与TNF-α水平呈负相关(P<0.05);2组TNF-αmRNA及蛋白的表达均与新生儿体重呈正相关(P<0.05)。结论胎儿发育受到宫内炎症状态的调节,GDM患者脐血Chemerin可通过TNF-α间接发挥作用。

外周血sIL-2R、CD4^(+)/CD8^(+)、TNF-α对初治活动性肺结核老年患者化疗疗效的评估价值

目的探讨外周血可溶性白细胞介素2受体(sIL-2R)、CD4^(+)淋巴细胞百分比/CD8^(+)淋巴细胞百分比比值(下称CD4^(+)/CD8^(+))、肿瘤坏死因子-α(TNF-α)对初治活动性肺结核老年患者化疗疗效的评估价值。方法将2019年12月至2022年12月该院收治的102例初治活动性肺结核老年患者纳入研究作为观察组,另选取102例年龄≥60岁且同期于该院体检的健康者作为对照组。比较两组外周血sIL-2R、TNF-α、CD4^(+)/CD8^(+)水平并分析sIL-2R、TNF-α、CD4^(+)/CD8^(+)间的相关性。观察组均采用2HRZE/4HR抗结核治疗方案,比较观察组治疗前、治疗1个月、治疗6个月时不同疗效患者外周血sIL-2R、TNF-α、CD4^(+)/CD8^(+);分析sIL-2R、CD4^(+)/CD8^(+)、TNF-α水平与疗效的相关性;采用受试者工作特征(ROC)曲线分析各指标用于老年患者化疗疗效评估的效能。结果观察组sIL-2R、TNF-α水平高于对照组,而CD4^(+)/CD8^(+)低于对照组,差异均有统计学意义(P<0.05)。观察组sIL-2R、TNF-α与CD4^(+)/CD8^(+)呈负相关(P<0.05),sIL-2R与TNF-α呈正相关(P<0.05)。治疗1个月、治疗6个月时显效患者sIL-2R、TNF-α水平低于有效患者,而后者又低于无效患者,显效患者CD4^(+)/CD8^(+)高于有效患者,而后者又高于无效患者,差异均有统计学意义(P<0.05)。sIL-2R、TNF-α水平与疗效呈负相关(P<0.05),CD4^(+)/CD8^(+)与疗效呈正相关(P<0.05)。ROC曲线分析显示,治疗1个月、6个月时sIL-2R、CD4^(+)/CD8^(+)、TNF-α联合用于评估疗效的曲线下面积(AUC)明显大于各时间点单项指标用于评估的AUC(P<0.05),而且治疗6个月时各指标联合评估的AUC大于治疗1个月(P<0.05)。结论初治活动性肺结核老年患者sIL-2R、CD4^(+)/CD8^(+)、TNF-α水平与患者疗效密切相关,将以上指标联合用于评估患者化疗疗效具有一定参考价值。

脱离低压低氧环境对高原肺动脉高压大鼠肺血管重建和TNF-α表达的影响

目的 探究脱离低压低氧环境对高原肺动脉高压大鼠肺血管重建和肿瘤坏死因子-α(TNF-α)表达的影响。方法 取120只Wistar大鼠随机分为对照组、高海拔组(10、20、30天)、低海拔组(10、20、30、90天)。测定各组肺动脉压力和右心室肥厚指标,采用HE染色观察大鼠肺组织病理变化,评估肺血管重建程度[肺小动脉管壁厚度/外径百分比(WT%)和管壁面积/总面积百分比(WA%)],免疫组化法检测肺组织切片中TNF-α的表达。结果 与对照组比较,高海拔组大鼠平均肺动脉压(mPAP)、右心室肥厚指数(RVHI)、WT%、WA%、肺组织TNF-α表达均升高;与高海拔30天组比较,低海拔组大鼠mPAP、RVHI、WT%、WA%、肺组织TNF-α表达均降低;且随时间延长,变化更为显著(P<0.05)。随造模时间延长,肺血管管壁厚度呈逐步增厚,管腔逐步变小;以高海拔地区造模30天为低海拔组参考,随着返低海拔地区时间延长,肺血管管壁厚度呈逐步变薄,管腔逐步变大。结论 脱离低压低氧环境后,高原肺动脉高压大鼠右心室肥厚和肺血管重建改善,肺组织TNF-α表达降低。

Uptake of bacterial lipopolysaccharide and expression of tumor necrosis factor α mRNA in isolated rat intrahepatic bile duct epithelial cells *

AIM To study the uptake of bacterial lipopolysaccharides (LPS) and expression of tumor necrosis factor α mRNA (TNF α mRNA) with cultured rat intrahepatic bile duct epithelial cells.

血清铁蛋白、IL-6、TNF-α表达水平与高炎症表型急性呼吸窘迫综合征患者病情严重程度及早期预后的相关性

目的 分析血清铁蛋白(SF)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)表达水平与高炎症表型急性呼吸窘迫综合征(ARDS)患者病情严重程度及早期预后的相关性。方法 回顾性选取2020年1月至2022年12月在北京市昌平区医院就诊的高炎症表型ARDS患者124例为研究对象。根据临床诊断结果分为轻度组(n=29)、中度组(n=51)、重度组(n=44)。根据入院治疗1个月后患者情况将其分为存活组(n=83)、死亡组(n=41)。检测并比较各组SF、IL-6、TNF-α表达水平变化,并分析高炎症表型ARDS中SF、IL-6、TNF-α表达水平与病情严重程度、早期预后的相关性。结果 轻度组SF、IL-6、TNF-α表达水平分别为(127.41±13.57)μg/L、(65.24±10.04) pg/mL、(43.17±8.26) ng/mL,均低于中度组[(241.55±17.03)μg/L、(127.05±12.19) pg/mL、(71.82±9.05) ng/mL]和重度组[(378.34±20.04)μg/L、(186.73±15.25) pg/mL、(104.50±11.46) ng/mL],中度组SF、IL-6、TNF-α表达水平均低于重度组,差异均有统计学意义(P<0.05)。存活组SF、IL-6、TNF-α表达水平分别为(156.25±9.06)μg/L、(71.52±11.36) pg/mL、(51.60±7.92) ng/mL,均低于死亡组[(419.72±23.64)μg/L、(216.82±13.51) pg/mL、(161.25±12.36) ng/mL],差异均有统计学意义(P<0.05)。Pearson相关性分析结果显示,SF、IL-6、TNF-α水平表达与高炎症表型ARDS患者病情严重程度、早期预后均呈正相关(r=0.424、0.516、0.460,r=0.503、0.602、0.437;P<0.05)。结论 高炎症表型ARDS患者均伴有严重炎症反应,且SF、IL-6、TNF-α表达水平与病情严重程度、早期预后均呈正相关,需密切监测指标变化,可为病情严重程度、早期预后评估提供一定依据。

齐刺环跳穴干预坐骨神经损伤大鼠海马IL-1β、IL-6、TNF-α及GFAP表达影响的实验研究

目的 通过观察齐刺环跳穴对坐骨神经损伤大鼠海马白细胞介素-1β(Interleukin-1β,IL-1β)、白细胞介素-6(Interleukin-6,IL-6)、肿瘤坏死因子-α(Tumor Necrosis Factor-alpha, TNF-α)及胶质纤维酸性蛋白(Glial Fibrillary Acidic Protein, GFAP)表达的影响,探讨齐刺环跳穴治疗坐骨神经痛的中枢镇痛机制。方法 60只SD大鼠随机分为假手术组、模型组、齐刺组、单刺组及药物组,每组12只,采用钳夹法制备大鼠坐骨神经损伤模型。造模第2天开始进行针刺及药物干预,连续14 d。观察各组大鼠干预前后坐骨神经功能指数(Sciatic nerve Function Index, SFI)、热缩足反射潜伏期(Paw Withdrawal Latency, PWL)的变化,ELISA法检测海马组织IL-1β、IL-6、TNF-α蛋白表达水平,实时定量PCR法及免疫组化法检测海马组织GFAP表达水平。结果 干预前,与假手术组比较,其余各组大鼠PWL值、SPI值显著降低(P<0.01),与模型组比较,齐刺组干预后大鼠PWL值、SPI值显著改善(P<0.01)。ELISA法、RT-PCR法及免疫组化检测结果显示,模型组、齐刺组、单刺组、药物组IL-1β、IL-6、TNF-α、GFAP表达较假手术组显著升高(P<0.01);与模型组相比,齐刺组、单刺组、药物组IL-1β、IL-6、TNF-α、GFAP表达显著下降,齐刺组表达低于单刺组及药物组(P<0.01)。结论 齐刺环跳穴缓解坐骨神经痛的镇痛机制可能与下调海马炎症因子表达,抑制星形胶质细胞活化,从而降低中枢痛觉敏化程度有关。

脊柱结核术后TLR-4、TNF-α、IL-6、IL-17的变化及与预后的相关性研究

目的分析脊柱结核术后Toll样受体(TLR)-4、肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6、IL-17的变化及与预后的相关性。方法选择2021年1月—2022年12月收治的60例接受手术治疗的脊柱结核患者作为观察组,另选60例非脊柱结核且行脊柱手术的患者作为对照组(部分病例由基金项目中合作医院提供)。检测两组患者血清及病灶组织TLR-4、TNF-α、IL-6、IL-17表达水平。根据观察组患者术后6个月的预后情况,分为预后良好组和预后不良组,比较两组术前及术后6个月的血清TLR-4、TNF-α、IL-6、IL-17表达水平,使用Pearson相关性分析评价脊柱结核患者术前血清TLR-4、TNF-α、IL-6、IL-17表达水平与术后6个月改良巴氏指数(MBI)量表评分的关系,受试者工作特征(ROC)曲线分析术后血清TLR-4、TNF-α、IL-6联合IL-17对脊柱结核术后预后不良的预测效能。结果观察组术前血清及病灶组织的TLR-4、TNF-α、IL-6、IL-17表达水平均高于对照组,差异均有统计学意义(P<0.05);预后不良组术前血清TLR-4、TNF-α、IL-6、IL-17表达水平均高于预后良好组,差异均有统计学意义(P<0.05);术后6个月,预后良好组血清TLR-4、TNF-α、IL-6、IL-17表达水平较术前明显降低,与预后不良组比较,差异均有统计学意义(P<0.05);经Pearson相关性分析,脊柱结核患者术前血清TLR-4、TNF-α、IL-6、IL-17表达水平与术后6个月MBI量表评分呈负相关(P<0.05);经ROC曲线分析,术前血清TLR-4、TNF-α、IL-6联合IL-17预测脊柱结核术后预后不良的ROC曲线下面积为0.921。结论脊柱结核术后血清TLR-4、TNF-α、IL-6、IL-17较术前明显降低,与预后密切相关,术前血清TLR-4、TNF-α、IL-6联合IL-17预测预后不良的效能较好,值得临床予以重视。