右美托咪定联合舒芬太尼自控静脉镇痛对妇科腹腔镜手术患者术后镇痛效果 炎症细胞因子及早期恢复的影响

目的探讨右美托咪定联合舒芬太尼自控静脉镇痛(PCIA)对妇科腹腔镜手术患者术后镇痛效果、炎症细胞因子及早期恢复的影响。方法选择2019年9月—2020年9月在该院接受妇科腹腔镜手术的100例患者作为研究对象。采用随机数表法均分两组,各50例。对照组给予舒芬太尼镇痛,观察组给予右美托咪定联合舒芬太尼镇痛。比较两组术后恢复情况,分析两组术后镇痛,记录麻醉诱导前(T0)、术毕(T1)、术后6 h(T2)及术后24 h(T3)时白细胞介素-6(IL-6)、白细胞介素-10(IL-10)及肿瘤坏死因子-α(TNF-α)变化,统计两组术后不良反应发生情况。结果观察组呼唤睁眼时间、定向力恢复时间及首次肛门排气时间均短于对照组(均P<0.05),两组术后住院时间比较,差异无统计学意义(P>0.05);两组患者T1、T2及T3时的拉姆齐镇静评分(RSS)和数字疼痛分级法(NRS)评分逐渐下降,观察组T1和T2时的RSS评分明显高于对照组,而NRS评分低于对照组(P<0.05);两组患者T1、T2及T3时的IL-6、IL-10及TNF-α表达水平均高于T0时,且观察组患者T1、T2及T3时的IL-6、TNF-α表达水平均低于对照组,IL-10表达水平高于对照组(P<0.05);观察组术后不良反应发生率(6.00%)低于对照组的22.00%(P<0.05)。结论右美托咪定联合舒芬太尼PCIA可提高妇科腹腔镜手术患者术后镇痛效果,抑制炎性反应,促进术后早日恢复,减少不良反应发生,临床运用价值较高。     

细胞因子在分化型甲状腺癌诊疗中的应用进展北大核心

甲状腺癌是内分泌系统常见的恶性肿瘤之一,其发病率呈逐年上升趋势。甲状腺癌以分化型甲状腺癌(differentiated thyroid carcinoma, DTC)为主,尽管多数DTC患者经规范化治疗后预后良好,但由于部分肿瘤的病理类型侵袭性较高或肿瘤组织分化程度较低,病情进展迅速导致患者总生存时间显著缩短。近年来,有关炎症与肿瘤之间相关性的研究越来越多,炎性微环境的改变在肿瘤发病机制中的作用逐渐被证实,更多的证据表明细胞因子可作为肿瘤的良恶性鉴别、预后判断提示及诊疗方案选择等的重要参考依据。本文就部分细胞因子在DTC诊疗中的应用进展进行论述,旨在为DTC的诊疗与预后判断等提供参考依据。     

ArgD of Mycobacterium tuberculosis is a functional N-acetylornithine aminotransferase with moonlighting function as an effective immune modulator

Mycobacterium tuberculosis (M. tuberculosis) encodes an essential enzyme acetyl ornithine aminotransferase ArgD (Rv1655) of arginine biosynthetic pathway which plays crucial role in M. tuberculosis growth and survival. ArgD catalyzes the reversible conversion of N-acetylornithine and 2 oxoglutarate into glutamate-5-semialdehyde and L-glutamate. It also possesses succinyl diaminopimelate aminotransferase activity and can thus carry out the corresponding step in lysine biosynthesis. These essential roles played by ArgD in amino acid biosynthetic pathways highlight it as an important metabolic chokepoint thus an important drug target. We showed that M. tuberculosis ArgD rescues the growth of ΔargD E. coli grown in minimal media validating its functional importance. Phylogenetic analysis of M. tuberculosis ArgD showed homology with proteins in gram positive bacteria, pathogenic and non-pathogenic mycobacteria suggesting the essentiality of this protein. ArgD is a secretory protein that could be utilized by M. tuberculosis to modulate host innate immunity as its moonlighting function. In-silico analysis predicted it to be a highly antigenic protein. The recombinant ArgD protein when exposed to macrophage cells induced enhanced production of pro-inflammatory cytokines TNF, IL6 and IL12 in a dose dependent manner. ArgD also induced the increased production of innate immune effector molecule NOS2 and NO in macrophages. We also demonstrated ArgD mediated activation of the canonical NFkB pathway. Notably, we also show that ArgD is a specific TLR4 agonist involved in the activation of pro-inflammatory signaling for sustained production of effector cytokines. Intriguingly, ArgD protein treatment activated macrophages to acquire the M1 phenotype through the increased surface expression of MHCII and costimulatory molecules CD80 and CD86. ArgD induced robust B-cell response in immunized mice, validating its antigenicity potential as predicted by the in-silico analysis. These properties of M. tuberculosis ArgD signify its functional plasticity that could be exploited as a possible drug target to combat tuberculosis.     

Noscapine hydrochloride (benzyl-isoquinoline alkaloid) effectively prevents protein denaturation through reduction of IL-6, NF-kB,COX-2, Prostaglandin-E2 in rheumatic rats

Noscapine hydrochloride (benzyl-isoquinoline antitussive alkaloid) is an opium derivative and generally used as a cough suppressant. Numerous studies on noscapine hydrochloride have reported that it has potent anti-inflammatory activity. However, the mechanisms by which it exerts an anti-inflammatory function is not well understood. Protein denaturation is the primary step that leads to the organ destruction and permanent arthritic disability. The above-mentioned facts provided the ground to plan this study using different in-vitro and in-vivo approaches. RT-qPCR and ELISA assays were used to assess the inflammatory markers related to protein denaturation in complete adjuvant persuaded rheumatism in Sprague - Dawley rats. The results were collected as paw volume and body weight changes, arthritic scoring and serum antioxidant enzymes assays. These findings demonstrated that all doses of noscapine hydrochloride (10, 20 and 40 mg/kg) studied in this study, significantly (p < 0.001) decreased the protein denaturation by preventing the increase in levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), nuclear factor-kB (NF-kB), cyclooxygenase-2 (COX-2) and prostaglandin E2. Noscapine hydrochloride significantly reduced the paw volume (p < 0.001), arthritic scoring and reversed the body mass as compared to arthritic control diseased rats.     

Cytokine and LL-37 gene expression levels in Bartonella spp. seropositive and seronegative patients of a rheumatology clinic

PurposeThe variation in the immune response to Bartonella spp. infection in humans remains unclear. The present study compares the expression of selected interleukins, cytokines and cathelicidin (LL-37) in rheumatology clinic patients suffering from musculoskeletal symptoms with healthy blood donors. The patients had previously been tested for the presence of Bartonella henselae antibodies.MethodsGene expression of LL-37, interleukin (IL)-2, IL-4, IL-6, IL-12, interferon-(IFN)-γ, and tumor necrosis factor (TNF-α)-α was determined in blood samples using quantitative Polymerase Chain Reaction (qPCR). Statistical analysis was prepared with STATISTICA.ResultsStatistically significant differences in the mRNA levels of the tested cytokines (IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-12; p<0.0001) were observed between the healthy controls and patients; however, no difference was observed for LL37 mRNA (p ?= ?0.1974). No significant differences in mRNA expression were observed between IgG in anti-Bartonella seropositive and seronegative individuals (p>0.05). The only significant differences between the Bartonella spp. DNA positive and negative patients, indicated by PCR, were observed for TNF-α and IL-12 mRNA (p ?= ?0.0045 and p ?= ?0.0255, respectively).ConclusionA broadly similar immune response to the tested cytokines was observed among the participants irrespective of anti-Bartonella spp. IgG seropositivity. However, the Bartonella DNA-positive participants demonstrated significantly lower expression of IL-12 and TNF-α mRNA; this may indicate that these bacteria have a suppressive influence on the immune system.     

南星骨痛凝胶贴膏对兔膝骨关节炎关节形态及血清IL-1、TNF-α、MMP-13、TIMP-1表达的影响

目的观察南星骨痛凝胶贴膏对兔膝骨关节炎关节形态及血清IL-1、TNF-α、MMP-13、TIMP-1表达的影响,探讨南星骨痛凝胶贴膏治疗兔膝骨关节炎可能的作用机制。方法 18只健康6月龄新西兰兔随机分成3组:空白组(A组)、模型组(B组)、骨痛膏治疗组(C组). BC组用3%木瓜蛋白酶关节腔内注射造模后C组给予南星骨痛凝胶贴膏外敷,给药4周后,用Aloka Latheta LCT-200观察兔膝骨关节影像学改变、用ELISA法检测血清IL-1、TNF-α、MMP-13、TIMP-1含量。结果 C组兔膝关节病变程度较B组轻,C组兔血清中IL-1、TNF-α、MMP-13含量较B组降低(P<0. 05),TIMP-1含量较B组升高(P <0. 05)。结论南星骨痛凝胶贴膏能减轻兔膝关节骨关节炎病变程度,对关节软骨有保护作用,其作用机制可能与抑制炎症因子IL-1、TNF-α及MMP-13表达,增加TIMP-1表达有关。     

Gankyrin在炎症相关性癌症中的作用机制研究进展

慢性非可控性炎症是癌症发生发展的基本微环境。约1/4癌症病例的病因和发病机制与感染和慢性炎症相关。Gankyrin是一个重要的癌蛋白，它在多种恶性肿瘤中高表达，并在癌症发生发展中起着关键的作用。近期研究发现Gankyrin在结肠炎相关性结肠癌（colitis-associated cancer，CAC）和慢性肝炎向肝细胞肝癌（hepatocellular carcinoma，HCC）发展的过程中扮演着重要的角色。同时，Gankyrin与多种细胞因子以及炎症信号通路密切相关。本文对Gankyrin在炎症相关性癌症中的作用机制研究进展作一简要综述。