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.     

Correlation of 3-T MRI and CT findings with patient symptoms and treatment outcome in radiofrequency ablation of osteoid osteoma

ObjectiveThe aim of this prospective study was to evaluate pre- and post-treatment MRI and CT findings of osteoid osteoma (OO) patients treated with radiofrequency thermo-ablation (RFTA) and to compare these findings with visual analog scale (VAS) scores.MethodsSixteen patients (4 females and 12 males; mean age of 18.87 ± 8.75 years (range: 8–37)) with OO were examined with CT and MRI, at baseline and at an average of 3 months following the procedure. On pre- and post-procedural CT and MRIs, OO-related findings were recorded. Treatment success was evaluated with VAS scores.ResultsBaseline VAS scores were 8 or 9 and follow-up scores were 0 or 1, indicating no early recurrences.Nidus diameters decreased significantly after the procedure (p = 0.027, p = 0.002, and p = 0.002; and p = 0.001, p = 0.001, p = 0.001 for AP, ML and CC nidus diameters for CT and MRI, respectively).The mean nidus volume were significantly decreased after the procedure (p = 0.001, for CT and MRI).On post-procedural images, cortical thickening, the signal intensity and contrast enhancement of the nidus and the extent of periostitis were significantly decreased (p = 0.019, p = 0.001, p = 0.001 and p = 0.034, respectively). There was no significant change in nidus calcification, perinidal cortical and intramedullary sclerosis, periosteal reaction, bone deformity, bone marrow and soft tissue edema, joint effusion and synovitis after the procedure (p = 0.253, p = 0.062, p = 0.245, p = 1, p = 1, p = 0.429, p = 0.371, p = 0.625, p = 1).ConclusionAlthough the changes in imaging findings may be helpful in early follow-up of OO patients treated with RFTA, these changes alone cannot be used with accuracy in predicting treatment response.Level of EvidenceLevel IV, Therapeutic Study.     

MiR-222 promotes the progression of polycystic ovary syndrome by targeting p27 Kip1

Polycystic ovary syndrome (PCOS) is one of the most complex and common reproductive and endocrinologic disorders in the child-bearing age of women. Recently, miR-222 were reported to be associated with the etiology of PCOS. However, the function of miR-222 during the pathogenesis of PCOS remains unclear. In the present study, we aimed to investigate the role of miR-222 in PCOS. Firstly, miR-222 expression was examined by quantitative real-time PCR (qRT-PCR) in PCOS. The effects of miR-222 on proliferation, apoptosis and cell cycle in KGN cells were analyzed by CCK-8 assay and flow cytometry analysis, respectively. In addition, bioinformatics analysis was used to predict the target genes of miR-222, and dual-luciferase reporter assay was applied to verified the interaction between miR-222 and p27 Kip1 in KGN cells. Moreover, the expressions of p27 Kip1 in KGN cells treated with miR-222 mimics or miR-222 inhibitor were evaluated by qRT-PCR and western blot assays. The results showed that the expression of miR-222 was remarkably upregulated in PCOS tissues compared with corresponding normal tissues. In the gain-of-function and loss-of-function assays, we revealed that miR-222 mimics significantly promoted cell proliferation, while miR-222 inhibitor induced cell apoptosis and cell cycle arrested. Furthermore, p27 Kip1 was identified as a target gene of miR-222, and could be negatively regulated by miR-222 mimics in KGN cells. In conclusion, our findings suggested that miR-222 may promote the progression of PCOS by targeting p27 Kip1.     

222Rn-220Rn分辨探测器参加国际比对结果分析

目的 提高²²²Rn与²²⁰Rn的累积测量水平,保证测量结果的准确性与可靠性。方法 采用中国疾病预防控制中心辐射防护与核安全医学所的氡课题组（以下简称本实验室）改进的LD-P型²²²Rn-²²⁰Rn分辨探测器参加日本放射线医学综合研究所（NIRS）组织的²²²Rn-²²⁰Rn累积探测器国际比对。将²²²Rn-²²⁰Rn分辨探测器寄往日本,在NIRS的²²²Rn室和²²⁰Rn室进行不同条件下的比对,暴露结束后再寄回本实验室进行蚀刻与分析,测量结果告知NIRS。最后NIRS将²²²Rn与²²⁰Rn暴露参考值回馈本实验室。结果 在高²²²Rn和低²²²Rn条件下,测量值与NIRS提供的参考值的相对百分偏差（RPD）分别为-12.0%、-11.8%;变异系数（COV）分别为3.0%、6.2%。在高²²⁰Rn和低²²⁰Rn条件下,测量值与NIRS提供的参考值的相对百分偏差（RPD）分别为-0.8%、-8.0%;变异系数（COV）分别为6.7%、4.5%。结论 本次比对LD-P型探测器²²²Rn与²²⁰Rn的测量结果均为NIRS规定的Ι级结果（PRD<10%）,比对结果较好。     

MicroRNA-222对肺腺癌细胞增殖、迁移和侵袭的影响

摘要：目的  探讨microRNA-222（miR-222）对肺腺癌细胞增殖、迁移和侵袭的影响。方法  将miR-222和对照分别转染入肺腺癌细胞系A549进行活细胞计数法试剂盒（CCK-8）增殖实验、Transwell迁移及Matrigel侵袭实验,观察miR-222对肺腺癌细胞增殖、迁移和侵袭的影响。运用荧光素酶报告实验、实时荧光定量聚合酶链反应（qRT-PCR）及Western blot验证miR-222靶向下调ETS1的过程。结果  CCK-8增殖实验,Transwell迁移及Matrigel侵袭实验发现,与对照组相比miR-222能够促进肺腺癌细胞增殖、迁移和侵袭。荧光素酶报告实验、qRT-PCR及Western blot实验发现,miR-222可以靶向下调ETS1的表达,且ETS1参与调节上述过程。结论  miR-222通过靶向下调ETS1,促进肺腺癌细胞增殖、迁移和侵袭。

     

乳腺肿瘤患者血清miRNA-222、miRNA-21检测的临床意义

目的 探讨血清miRNA-222、miRNA-21水平对于乳腺肿瘤患者的临床意义。方法 选择经病理确诊并分类的35例乳腺癌患者和32例乳腺良性肿瘤患者;同时选35例女性健康体检者作为对照。采用RT-PCR的方法测定所有受试者的血清miRNA-222、miRNA-21的相对表达水平,分析血清miRNA-222、miRNA-21在乳腺肿瘤疾病上的临床意义。结果 乳腺癌组与乳腺良性肿瘤组血清miRNA-222水平无差异(P>0.05),但两者均高于对照组(P <0.05);乳腺癌组血清miRNA-21水平与对照组比较差异有统计学意义(P <0.05),乳腺癌组miRNA-21表达水平高于乳腺良性肿瘤组(P <0.05),但乳腺良性肿瘤组和对照组之间无差异(P>0.05)。血清miRNA-21区分乳腺肿瘤良恶性的曲线下面积为0.693,P值为0.020,最大约登指数为0.295,诊断临界值为0.693,灵敏度为85.71%,特异度为43.75%;miRNA-222的曲线下面积为0.465,<0.5,且P>0.05,说明miRNA-222对于诊断乳腺恶性病变不具有统计学意义。有淋巴结转移乳腺癌患者的miRNA-222、miRNA-21表达水平高于无淋巴结转移乳腺癌患者,差异有统计学意义(P <0.05)。按照年龄、肿瘤直径、ER、PR、HER-2分组比较乳腺癌患者的miRNA-222、miRNA-21表达水平,差异无统计学意义(P>0.05)。结论 血清miRNA-222、miRNA-21水平检测对乳腺肿瘤的诊断有一定的临床指导意义。     

Radon-222 and related activities in surface waters of the English Lake District

Activities of radon-222 in selected surface waters of the English Lake District have been determined. Very wide variations were observed. The activity present in lakes and streams depends on the nature of the bedrock or sediment, the presence of faulting, the degree of turbulence, and the supply of fresh water from tributaries and ground waters. Radium-226 and uranium-238 activities were found to be comparable but in no case was it found that radon-222 is significantly supported by dissolved radium-226.