针刺调控α7nAchR激活胆碱能抗炎通路的研究现状

胆碱能抗炎通路是一条神经免疫通路,主要依靠乙酰胆碱与巨噬细胞及其他细胞表面上的α7nAchR相结合抑制促炎因子的合成与释放,从而防止组织损伤。α7nAchR是胆碱能递质的主要受体,在胆碱能抗炎通路中起关键作用。针刺治疗有明确的抗炎作用,其作用机制可能与调控α7nAchR激活胆碱能抗炎通路有关。近年来虽然国内外学者对针刺抗炎机制进行了大量研究,然而针刺抗炎的作用机制目前仍不明确。该文从胆碱能抗炎通路概述、α7nAchR结构及功能、α7nAchR的分布、α7nAchR在胆碱能抗炎通路的作用、针刺调控α7nAchR激活胆碱能抗炎通路的机制等方面对针刺调控α7nAchR激活胆碱能抗炎通路进行分析总结,为今后探究针刺抗炎作用机制提供借鉴思路和科学依据。     

New immunosuppressive agents in transplantation

Immunosuppressive agents have enabled the development of allogenic transplantation during the last 40 years, allowing considerable improvement in graft survival. However, several issues remain such as the nephrotoxicity of calcineurin inhibitors, the cornerstone of immunosuppressive regimens and/or the higher risk of opportunistic infections and cancers. Most immunosuppressive agents target T cell activation and may not be efficient enough to prevent allo-immunization in the long term. Finally, antibody mediated rejection due to donor specific antibodies strongly affects allograft survival.Many drugs have been tested in the last decades, but very few have come to clinical use. The most recent one is CTLA4-Ig (belatacept), a costimulation blockade molecule that targets the second signal of T cell activation and is associated with a better long term kidney function than calcineurin inhibitors, despite an increased risk of acute cellular rejection.The research of new maintenance long-term immunosuppressive agents focuses on costimulation blockade. Agents inhibiting CD40-CD40 ligand interaction may enable a good control of both T cells and B cells responses. Anti-CD28 antibodies may promote regulatory T cells. Agents targeting this costimulation pathways are currently evaluated in clinical trials.Immunosuppressive agents for ABMR treatment are scarce since anti-CD20 agent rituximab and proteasome inhibitor bortezomib have failed to demonstrate an interest in ABMR. New drugs focusing on antibodies removal (imlifidase), B cell and plasmablasts (anti-IL-6/IL-6R, anti-CD38…) and complement inhibition are in the pipeline, with the challenge of their evaluation in such a heterogeneous pathology.     

两种技术修复肘关节恐怖三联征中外侧副韧带复合体的疗效比较

目的比较穿骨隧道缝合固定和锚钉固定修复肘关节恐怖三联征中外侧副韧带复合体（lateral collateral ligament complex，LCLC）损伤的疗效。方法回顾分析 2012 年 6 月—2018 年 1 月收治的 50 例肘关节恐怖三联征患者临床资料，其中 22 例采用锚钉固定（锚钉组）、28 例采用穿骨隧道缝合固定（穿骨隧道组）修复 LCLC。两组患者性别、年龄、骨折侧别、受伤至入院时间以及冠状突骨折、桡骨头骨折及肘关节恐怖三联征分型等一般资料比较，差异均无统计学意义（P>0.05）。记录并比较两组手术时间、术中出血量、骨折愈合时间以及并发症发生情况，末次随访时 Mayo 肘关节评分系统（MEPS）、关节活动度、Broberg-Morrey 分级。 结果两组患者均顺利完成手术，手术时间及术中出血量比较差异均无统计学意义（P>0.05）。 患者均获随访，穿骨隧道组随访时间为（24.43±6.84）个月，锚钉组为（21.55±6.16）个月，差异无统计学意义（t=1.534，P=0.132）。X 线片复查示，两组冠状突及桡骨头骨折均愈合，愈合时间组间比较差异无统计学意义（P>0.05）。末次随访时，两组肘关节屈伸活动度、旋转活动度、MEPS 评分、Broberg-Morrey 分级比较，差异均无统计学意义（P>0.05）。随访期间患者均无肘关节再脱位或不稳发生，穿骨隧道组并发症发生率为 28.57%（8/28）、锚钉组为 27.27%（6/22），差异无统计学意义（χ²=2.403，P=0.121）。 结论治疗肘关节恐怖三联征时，采用穿骨隧道固定或锚钉固定修复 LCLC 均可获得满意疗效。     

Nano-curcumin therapy,a promising method in modulating inflammatory cytokines in COVID-19 patients

BackgroundAs an ongoing worldwide health issue, Coronavirus disease 2019 (COVID–19) has been causing serious complications, including pneumonia, acute respiratory distress syndrome (ARDS), and multi-organ failure. However, there is no decisive treatment approach available for this disorder, which is primarily attributed to the large amount of inflammatory cytokine production. We aimed to identify the effects of Nano-curcumin on the modulation of inflammatory cytokines in COVID-19 patients.MethodForty COVID-19 patients and 40 healthy controls were recruited and evaluated for inflammatory cytokine expression and secretion. Subsequently, COVID-19 patients were divided into two groups: 20 patients receiving Nano-curcumin and 20 patients as the placebo group. The mRNA expression and cytokine secretion levels of IL-1β, IL-6, TNF-α and IL‐18 were assessed by Real‐time PCR and ELISA, respectively.ResultOur primary results indicated that the mRNA expression and cytokine secretion of IL-1β, IL-6, TNF-α, and IL-18 were increased significantly in COVID-19 patients compared with healthy control group. After treatment with Nano-curcumin, a significant decrease in IL-6 expression and secretion in serum and in supernatant (P = 0.0003, 0.0038, and 0.0001, respectively) and IL-1β gene expression and secretion level in serum and supernatant (P = 0.0017, 0.0082, and 0.0041, respectively) was observed. However, IL-18 mRNA expression and TNF-α concentration were not influenced by Nano-curcumin.ConclusionNano-curcumin, as an anti-inflammatory herbal based agent, may be able to modulate the increased rate of inflammatory cytokines especially IL-1β and IL-6 mRNA expression and cytokine secretion in COVID-19 patients, which may cause an improvement in clinical manifestation and overall recovery.     

Extended criteria for liver transplantation in hepatocellular carcinoma. A retrospective,multicentric validation study in Belgium

BackgroundRecent studies indicate that a group of patients with cirrhosis receiving a liver transplantation for hepatocellular cancer (HCC) beyond the Milan Criteria (MC) can achieve a similar outcome compared to patients within these criteria. This study aims to investigate the value of the Asan critera (AC), up-to-7 criteria (UT7), French alpha-foetoprotein (AFP) model and Metroticket 2.0 (MT2.0) model compared to the MC.Methods526 patients transplanted for non-metastatic HCC were analyzed. Patient groups within and beyond MC and extended criteria were determined according to radiological assessment and AFP value at listing.ResultsOverall survival (OS) and recurrence (RR) rates were similar between patients within MC and all extended criteria. Five-year OS within MC was 71.3% compared to 70.9% for AC, 71.4% for UT7, 69.7% for AFP-model and 71.0% for MT2.0 criteria. Five-year RR within MC was 12.3% compared to 13.5% for AC, 13.0% for UT7, 14.3% for AFP-model and 13.2% for MT2.0 criteria. Patients beyond MC but within the extended criteria had tendency towards higher recurrence.ConclusionsAll validated extended criteria (AC, UT7, AFP-model and MT2.0) could be proposed as alternatives to the MC with similar outcome. Prospective data are awaited to assess recurrence beyond MC.     

Clinical effectiveness and radial artery remodeling assessment via very-high-frequency ultrasound/ultra biomicroscopy after applying slender 7Fr sheath for transradial approach in left main bifurcation disease

Abstract

Objective

To explore the clinical effect and radial remodeling of transradial slender 7?Fr sheath for left main bifurcation disease (LM bifurcation).     

光叶决明中1个新的二聚苯丙素类化合物

目的对决明属植物光叶决明Cassia floribunda茎叶的化学成分进行研究。方法运用硅胶、MCI、RP-18、TLC、HPLC等多种色谱技术进行分离纯化,根据理化性质和波谱数据鉴定化合物的结构。结果从光叶决明90%乙醇提取物中分离得到18个化合物,分别鉴定为决明顺反二聚苯丙素(1)、反式对羟基肉桂酸乙酯(2)、shonanin(3)、邻苯二甲酸二丁酯(4)、1,6,8-三羟基-3-甲基蒽醌(5)、2,5-二甲基-7-羟基-色原酮(6)、2-(2′-羟丙基)-5-甲基-7-羟基色酮(7)、4′,7-二羟基-5-甲氧基黄酮(8)、柯伊利素(9)、山柰酚(10)、芹菜素(11)、3-甲氧基槲皮素(12)、6-demethoxycapillarisin(13)、7,4′-二羟基黄酮(14)、木犀草素(15)、butin(16)、甘草素(17)和圣草酚(18)。结论化合物1为新的苯丙素类化合物;化合物2～18均为首次从该植物中分离得到,其中,化合物2～4、8、9、11、13、14、16～18为首次从决明属植物中分离得到。     

脑脊液ctDNA对非小细胞肺癌脑膜转移患者的临床价值

背景与目的肺癌脑膜转移病死率极高。循环肿瘤DNA（circulating tumor DNA, ctDNA）已被证实含有肿瘤的基因组改变信息，并已被用于监测肿瘤的进展和对治疗的响应。对于存在脑膜转移瘤的患者，由于血脑屏障等因素的存在，外周血ctDNA不能反映脑部病灶的信息，此时脑脊液ctDNA作为检测样本能更好地体现颅内肿瘤的基因状态，指导临床对颅内病灶的靶向治疗。本研究旨在探究脑脊液ctNDA用于监测非小细胞肺癌（non-small cell lung cancer, NSCLC）脑膜转移的可行性以及脑脊液ctDNA检测对NSCLC脑膜转移的临床价值。方法入组NSCLC脑膜转移患者21例，通过二代基因测序技术对患者的脑脊液及外周血样本进行基因检测，并进行脑脊液细胞学病理学检测和头颅核磁共振增强检查。结果入组21例患者脑脊液中均检测到ctDNA。脑脊液ctDNA检测的灵敏性在脑膜转移诊断方面优于细胞学（P < 0.001）。脑脊液的基因突变检出率及基因突变丰度均高于血浆（P < 0.001）。脑脊液具有独特的基因谱。6例动态检测的患者中，脑脊液中ctDNA丰度变化均同时或早于临床疾病变化出现，可及时揭示耐药机制和监测复发趋势。结论脑脊液ctDNA检出率高于细胞学及影像学；脑脊液ctDNA检测可展现脑膜转移病灶特有的突变图谱；脑脊液ctDNA动态监测对肺癌患者临床疗效具有提示意义。