Cardiac cine magnetic resonance fingerprinting for combined ejection fraction,T1 and T2 quantification

This study introduces a technique called cine magnetic resonance fingerprinting (cine‐MRF) for simultaneous T₁, T₂ and ejection fraction (EF) quantification. Data acquired with a free‐running MRF sequence are retrospectively sorted into different cardiac phases using an external electrocardiogram (ECG) signal. A low‐rank reconstruction with a finite difference sparsity constraint along the cardiac motion dimension yields images resolved by cardiac phase. To improve SNR and precision in the parameter maps, these images are nonrigidly registered to the same phase and matched to a dictionary to generate T₁ and T₂ maps. Cine images for computing left ventricular volumes and EF are also derived from the same data. Cine‐MRF was tested in simulations using a numerical relaxation phantom. Phantom and in vivo scans of 19 subjects were performed at 3 T during a 10.9 seconds breath‐hold with an in‐plane resolution of 1.6 x 1.6 mm² and 24 cardiac phases. Left ventricular EF values obtained with cine‐MRF agreed with the conventional cine images (mean bias ?1.0%). Average myocardial T₁ times in diastole/systole were 1398/1391 ms with cine‐MRF, 1394/1378 ms with ECG‐triggered cardiac MRF (cMRF) and 1234/1212 ms with MOLLI; and T₂ values were 30.7/30.3 ms with cine‐MRF, 32.6/32.9 ms with ECG‐triggered cMRF and 37.6/41.0 ms with T₂‐prepared FLASH. Cine‐MRF and ECG‐triggered cMRF relaxation times were in good agreement. Cine‐MRF T₁ values were significantly longer than MOLLI, and cine‐MRF T₂ values were significantly shorter than T₂‐prepared FLASH. In summary, cine‐MRF can potentially streamline cardiac MRI exams by combining left ventricle functional assessment and T₁‐T₂ mapping into one time‐efficient acquisition.     

女性系统性红斑狼疮患者骨代谢异常的危险因素分析

摘要：目的 探讨骨代谢、骨密度与外周血淋巴细胞亚群的关系，初步探索免疫细胞在系统性红斑狼疮( systemic lupus erythematosus，SLE)骨代谢异常中的作用。方法 采用双能X线吸收法 （dual energy X-ray absorptiometry, DEXA ）检测SLE患者的骨密度，同日检测患者的外周血淋巴细胞亚群分布。结果 共纳入92名SLE女性患者，患者的平均年龄及病程分别为（42.1±14.1）岁、（84.4±73.0）个月。有62.0 %（n=57）患者存在骨代谢异常，其中44.6 %（n=41）患者为骨量减少，17.4 %（n=16）患者并发骨质疏松症，后者还包括9.8 %（n=9）发生脆性骨折的患者。全身骨密度最低值与年龄（r= –0.291，P=0.005）、病程（r=–0.239，P= 0.022）、绝经状态（r= –0.288，P=0.005）及碱性磷酸酶（r= –0.221，P= 0.033）均呈负相关。Logistics分析显示绝经状态（OR=13.0，P＜0.001，95% CI 3.43~49.5）、LDL-C（OR =5.74，P=0.002，95% CI 1.93~17.0）及外周血CD4+T细胞（OR =1.08，P = 0.025，95% CI 1.01~1.16）是骨代谢异常的影响因素，而年龄（OR=1.12，P＜0.001，95% CI 1.06~1.19）是骨质疏松的影响因素。结论 SLE患者骨代谢异常的发生率高，外周血淋巴细胞亚群分布可能与其发病存在相关性。     

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.     

血小板与淋巴细胞比率对胃癌预后影响的Meta分析

目的:探讨血小板与淋巴细胞比率(platelet-lymphocyte ratio,PLR)对胃癌患者预后评估的价值。方法:检索PubMed、Medline、Embase、Cochrane Library和中文数据库如中国期刊全文数据库(CNKI)、中国生物医学文献数据库(CBM)、万方数字化期刊全文数据库等,纳入关于PLR和胃癌患者预后关系的中英文文献,由2名研究者独立选择文献和提取数据资料并对纳入文献进行质量评估,采用Review Manager 5.3和Stata 15.1软件进行统计分析。结果:最终共纳入29项符合标准的研究,共计13696名胃癌患者。Meta分析结果显示治疗前高水平PLR的胃癌患者,其总生存期(overall survival,OS)明显缩短(HR=1.13,95%CI:1.03~1.24,P=0.01),但是与无病生存期(disease-free survival,DFS)(HR=1.19,95%CI:0.79~1.81,P=0.41)和无进展生存期(progression-free survival,PFS)(HR=1.10,95%CI:0.88~1.37,P=0.41)没有明显相关性。结论:治疗前高水平PLR是胃癌患者OS较短的重要临床预后指标,为临床医务工作人员评价胃癌患者的预后提供依据。但是仍需要更多大规模、多中心、更全面的实验研究进行验证。     

Osimertinib Improves Overall Survival in Patients With EGFR-Mutated NSCLC With Leptomeningeal Metastases Regardless of T790M Mutational Status

IntroductionOsimertinib, a third-generation EGFR tyrosine kinase inhibitor, efficiently penetrates the blood-brain barrier. This study explored whether treatment with osimertinib leads to improved overall survival (OS) for patients with EGFR-mutated NSCLC with leptomeningeal metastases (LM) compared with those not treated with osimertinib.MethodsFrom October 2008 to October 2019, patients with EGFR-mutated NSCLC and cytologically confirmed LM were retrospectively analyzed for OS according to osimertinib treatment and T790M mutational status. The OS was defined as the time from the diagnosis of LM to death.ResultsFor the 351 patients with LM included in the analysis, the median OS (mOS) was 8.1 months (95% confidence interval [CI]: 7.2–9.0). T790M mutation was detected in 88 of 197 patients tested, and a total of 110 patients were treated with osimertinib after LM. No difference in mOS according to T790M mutational status (10.1 mo [95% CI: 4.31–15.82] versus 9.0 [95% CI: 6.81–11.21], p = 0.936) was found. Nevertheless, patients treated with osimertinib had a superior OS of 17.0 months (95% CI: 15.13–18.94) compared with those not treated with osimertinib who had a mOS of 5.5 months (95% CI: 4.34–6.63), regardless of T790M mutational status (hazard ratio: 0.36 [95% CI: 0.28–0.47], p < 0.001). This was also considerably longer even than the mOS of 8.7 months (95% CI: 7.01–10.39) of those who were never treated with osimertinib but had first- or second-generation EGFR tyrosine kinase inhibitors.ConclusionsOsimertinib is a promising treatment option for EGFR-mutated NSCLC with LM regardless of T790M mutational status.     

羌活中的香豆素类成分及其抑制脂多糖诱导的RAW 264.7细胞NO生成活性的研究

目的研究羌活Notopterygium incisum的香豆素类成分及其抗炎活性。方法采用硅胶、HPLC等柱色谱方法进行分离纯化,通过质谱、核磁共振波谱数据鉴定化合物的结构;采用脂多糖(LPS)诱导的小鼠巨噬细胞RAW 264.7炎症反应模型,考察羌活中香豆素类成分对炎症反应模型一氧化氮(NO)生成的影响。结果从羌活甲醇提取物分离得到24个香豆素类化合物,分别鉴定为异欧前胡素(1)、川白芷素(2)、补骨脂素(3)、香柑内酯(4)、茵陈素(5)、欧芹酚(6)、5-去氢羌活醇(7)、环氧脱水羌活醇(8)、7″-O-甲基异羌活醇(9)、佛手柑素(10)、7-异戊烯氧基-6-甲氧基-香豆素(11)、栓翅芹烯醇(12)、羌活醇(13)、去甲呋喃羽叶芸香素(14)、异羌活醇(15)、蛇床夫内酯(16)、6-异戊烯氧基伞形花内酯(17)、紫花前胡苷元(18)、异虎耳草素(19)、紫花前胡苷(20)、前胡苷V(21)、前胡苷I(22)、印枳苷元-11-O-β-D-吡喃葡萄糖基-(1→6)-β-D-吡喃葡萄糖苷(23)、羌活苷(24)。化合物7～10、13和15抑制LPS诱导的RAW 264.7细胞NO生成活性最强,最大半数抑制浓度(IC_(50))值为8.50～35.12μmol/L。结论化合物7为新的天然产物,化合物17为首次从羌活中分离得到;C-5位上具有多烯烃结构的香豆素抑制LPS诱导的RAW 264.7细胞NO生成活性较强。     

红景天苷通过TLR4调控DC提高T细胞对肺癌3LL细胞的杀伤力

目的：探讨红景天苷（salidroside，SAL）对树突状细胞（dendritic cell，DC）表型及细胞毒性T细胞（cytotoxic T lympho‐cyte，CTL）抗肿瘤能力的影响。方法：选用Lewis肺癌细胞株3LL、野生型C57BL/6和TLR4-/-C57BL/6小鼠，获取小鼠骨髓来源的DC前体细胞，经过培养分化成未成熟DC，收获第6天的DC，经磁珠分选后获得纯度较高的CD11c+DC。将细胞分成PBS组、SAL组和脂多糖（lipopolysaccharide，LPS）组，培养48 h后用流式细胞术检测SAL体外对DC表面分子、吞噬功能、TLR4通路和对T细胞杀伤能力的影响。结果：与 PBS 组比较，SAL组DC的表面分子CD80、CD86、MHC Ⅱ表达水平显著升高（均 P<0.05）、吞噬功能显著下降（P<0.05）、TLR4 表达水平显著升高（P<0.01）；与野生型组比较，TLR4-/-组DC经SAL或LPS处理后，其表面分子CD80、CD86、MHC Ⅱ的表达水平显著降低（均P<0.05）；与PBS组比较，SAL组刺激活化的CTL对肺癌3LL细胞的杀伤效应显著升高（P<0.05）。结论：SAL可以通过调控TLR4诱导DC成熟，从而提高T细胞的杀伤能力     

PD-L1疫苗中引入不同免疫原性氨基酸对T细胞亚群分化的影响

为了比较内源性的3-硝基酪氨酸与非天然的4-硝基苯丙氨酸在PD-L1疫苗中的引入对T细胞亚群分化的影响，利用遗传密码扩充技术，将这两种免疫原性氨基酸分别引入到PD-L1疫苗的相同位点，获得具有3-硝基酪氨酸以及4-硝基苯丙氨酸的两种PD-L1突变体。用这两种突变体免疫小鼠，分析对小鼠脾脏T细胞亚群分化的影响。流式细胞术检测结果显示，4-硝基苯丙氨酸在PD-L1疫苗中的引入可促进Th1细胞的极化，同时降低Treg细胞的比例，3-硝基酪氨酸的引入对Th1细胞的极化无影响，同时能显著提高Treg和Th17细胞的比例。二者在PD-L1疫苗中的引入均能促进脾脏CD8⁺ T细胞的应答，其中含有4-硝基苯丙氨酸的PD-L1突变体应答效果更强。实验结果表明，与内源性的3-硝基酪氨酸在PD-L1疫苗中的引入相比，非天然的4-硝基苯丙氨酸更适合用于肿瘤疫苗的设计。     

五色培元固本膏对维持性血液透析患者细胞免疫功能的影响

目的:探讨五色培元固本膏对维持性血液透析(MHD)患者细胞免疫功能的影响。方法:90例MHD患者随机分为对照组和治疗组,两组血透方法相同。对照组给予一般治疗及血透治疗,治疗组在对照组基础上口服五色培元固本膏,连续治疗3个月; 20例健康志愿者作为正常组,三组观察时间均为3个月。治疗前后用流式细胞技术检测各组T细胞亚群表达水平,酶联免疫吸附法检测各组白介素-2(IL-2)和可溶性白介素-2受体(sIL-2R)蛋白表达水平。结果:治疗前与正常组比较,对照组与治疗组CD₄⁺、CD₄⁺/CD₈⁺和IL-2表达水平均明显下降,CD₈⁺和sIL-2表达水平均上升,差异有统计学意义(P<0.05)。治疗后,与对照组相比较,治疗组CD₄⁺、CD₄⁺/CD₈⁺、IL-2表达水平明显升高,CD₈⁺和sIL-2表达水平均降低,差异有统计学意义(P<0.05)。治疗组相较正常组CD₄⁺T淋巴细胞、CD₄⁺/CD₈⁺、IL-2表达水平,差异无统计学意义(P>0.05),CD₈⁺、sIL-2表达水平升高。结论:五色培元固本膏调节T淋巴细胞和IL-2表达改善MHD的细胞免疫功能。