Optimization of 2-phenylaminoimidazo[4,5-h]isoquinolin-9-ones: orally active inhibitors of lck kinase

The tyrosine kinase p56lck (lck) is essential for T cell activation; thus, inhibitors of lck have potential utility as autoimmune agents. Our initial disclosure of a new class of lck inhibitors based on the phenylaminoimidazoisoquinolin-9-one showed reasonable cellular activity but did not work in vivo upon oral administration. Our current work highlights the further use of rational drug design and molecular modeling to produce a series of lck inhibitors that demonstrate cellular activity below 100 nM and are as efficacious as cyclosporin A in an in vivo mouse model of anti-CD3-induced IL-2 production.     

PCR法从痰液中快速检测结核分枝杆菌

目的：建立一种从痰液中检测结核分枝杆菌简便,快速且灵敏的方法。方法;用碱液化,水洗和Ｔｒｉｔｏｎ Ｘ－１００热裂解法从痰液中制备结核分枝杆菌ＤＮＡ,进行ＰＣＲ反应,并将该方法同其它几种方法进行比较。结果：该方法同抗酸性染色镜检法有显差异,同酚／氯仿法具有的灵敏度,结论：用该方法从痰液中检测结核分枝杆菌具有灵敏,简便和快速等特点。     

Efficient detection of a biomarker for infant jaundice by a europium(iii)-organic framework luminescence sensor

Efficient detection of excess bilirubin in human serum and urine is highly important for the early diagnosis of infant jaundice. A highly stable Eu(iii)-based microporous framework with bent {Eu(COO)} chains interconnected by pairs of T-shaped 4,4′-(4,4′-bipyridine-2,6-diyl)dibenzoate (bpydb²⁻) linkers, {[Eu(H₂O)(HCOO)(bpydb)]·solvent}_n (1), was solvothermally synthesized and used as a chemical sensor for bilirubin response under clinically-applicable visible-light excitation. Due to the significant synergetic effect of the inner filter effect and photoinduced electron transfer, 1 can effectively probe trace amounts of bilirubin in aqueous solution through fluorescence decay with a strong quenching constant of 6.40 × 10⁴ M⁻¹ and low detection limit of 1.75 μM. More importantly, a portable test paper made from 1 was further developed to achieve qualitative, naked-eye visualized differentiation for the biomarker in clinical applications. These interesting findings highlight the importance of the π-conjugated antenna ligand for clinically applicable Ln-MOF sensors.

A Eu(iii)–MOF sensor with intense red luminescence can effectively probe bilirubin in water through fluorescence decay, and can be fabricated into portable test papers to achieve visualized detection of bilirubin.     

免疫毒素去除T细胞在异基因造血干细胞移植中的应用

观察应用免疫毒素部分去除T细胞(TCD)的方法进行人类白细胞抗原／混合淋巴细胞培养(HLA/MLC)不相合异基因造血干细胞移植的临床疗效。采用蓖麻免疫毒素部分去T细胞对13例恶性血液病患者行HLA-MLC配型不相合的造血干细胞移植，其中慢性髓性白血病(CP1)6例；急性淋巴细胞白血病CR1 1例，CR2 1例，复发1例；急性髓性白血病CR1 2例，CR2 1例；骨髓增生异常综合征转化成急性髓性白血病M4型(CR1)1例。结果表明：13例患者中8例成功植入，其中2例发生Ⅱ度急性移植物抗宿主病(aGVHD)，2例发生Ⅲ-Ⅳ度aGVHD。随访8-90个月，2例发生Ⅲ-Ⅳ度aGvHD患者早期死亡，另有1例患者死于迟发感染，其余5例均无病存活至今。5例未植活的患者中4例回输同一供者外周血造血干细胞后3例未植入，1例植活，但死于移植相关合并症；1例再次行同基因造血干细胞移植成功并无病存活至今。结论：采用蓖麻免疫毒素部分去T细胞的方法行HLA/MLC配型不相合的异基因造血干细胞移植可减少重度aGVHD的发生，但移植早期排斥率(HVG)较高，临床应用效果有待进一步评估。     

Effects of Low-Dose Glucocorticoid Prophylaxis on Chronic Graft-versus-Host Disease and Graft-versus-Host Disease–Free,Relapse-Free Survival after Haploidentical Transplantation: Long-Term Follow-Up of a Controlled,Randomized Open-Label Trial

This long-term follow-up study evaluated the effects of corticosteroid prophylaxis on graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) based on a controlled open-label randomized trial in which 228 allotransplant recipients were categorized as low risk (n?=?83, group A) or high risk; patients at high risk were randomly assigned to receive (n?=?72, group B) or not receive (n?=?73, group C) low-dose methylprednisolone prophylaxis. The cumulative incidences of chronic GVHD, relapse, nonrelapse mortality, leukemia-free survival, overall survival, and GRFS were 60%, 19%, 16%, 68%, 73%, and 46%, respectively, in all cases. Compared with the patients in group C, the cases in group B experienced a lower cumulative incidence of moderate to severe chronic GVHD (42% versus 20%; P = .010), herpes zoster infection (28% versus 12%; P = .010), pulmonary infections (42% versus 21%; P = .040), and osteonecrosis of the femoral head (ONFH; 16% versus 6%; P = .045) as well as better GRFS (59% versus 33%; P = .017). Factors associated with GRFS included total dose of corticosteroid used in the first 100days after transplantation (hazard ratio, 1.547; P?=?.015) and platelet recovery (hazard ratio, 1.456; P?=?.037). Our results suggest that low-dose glucocorticoid prophylaxis reduces GVHD and thus reduces the total dose of steroids, which might contribute to lower incidence of infections and ONFH and a superior GRFS, indicating that higher steroid doses are harmful. Reducing the total dose is of course beneficial. (ClinicalTrials.gov number, NCT01607580.)     

不同类型眼眶假瘤病理特征分析

目的讨论不同病理类型眼眶炎性假瘤的临床表现及病理图像特点。方法28例眼眶炎性假瘤病例．均经手术切除肿瘤，常规HE病理切片检查确诊。收集每例临床资料。结果根据显微镜下图像特点，本组有5种类型的眼眶炎性假瘤。结论不同类型的眼眶炎性假瘤在病理切片图像及临床表现方面各有明显特点。     

Inhibition of histamine release from human mast cells by natural chymase inhibitors

AIM: To investigate the ability of natural chymase inhibitors to modulate histamine release from human mast cells.METHODS: Enzymatically dispersed cells from human lung, tonsil, and skin were challenged with anti-IgE or calcium ionophore A23187 in the absence or presence of the natural chymase inhibitors secretory leukocyte protease inhibitor (SLPI) and α1-antitrypsin, then histamine release was determined. RESULTS: IgE-dependent histamine release from lung, tonsil, and skin mast cells were inhibited by up to 70 %, 61%, and 62 %, respectively following incubation with α1-antitrypsin (5000 nmol/L). SLPI 5000 nmol/L was also able to inhibit anti-IgE-dependent histamine released from lung, tonsil and skin mast cells by up to approximately 72 %, 67 %, and 58 %,respectively. While neither α1-antitrypsin nor SLPI by themselves altered histamine release from lung, tonsil and skin mast cells, they were able to inhibit calcium ionophore-induced histamine release from lung and tonsil mast cells. CONCLUSION: Both α1-antitrypsin and SLPI could potently inhibit IgE-dependent and calcium ionophoreinduced histamine release from dispersed human lung, tonsil, and skin mast cells in a concentration-dependent manner, which suggested that they were likely to play a protective role in mast cell associated diseases including allergy.     

细胞间粘附分子-2在妊娠期高血压疾病患者的动态变化和临床意义

目的:探讨细胞间粘附分子-2(ICAM-2)在正常妊娠妇女和妊娠期高血压疾病患者血浆中的变化及其临床意义。方法:研究对象包括25例妊娠期高血压疾病患者(其中子痫前期13例、妊娠期高血压12例)、24例正常妊娠妇女和25例正常未孕妇女,应用酶联免疫吸附试验(ELISA)测定研究对象妊娠早、中、晚三期血浆中的ICAM-2水平。结果:与未孕组比较,正常妊娠组孕中晚期ICAM-2明显高于未孕组,差异有统计学意义(P<0.05),与正常妊娠组比较,妊娠期高血压组妊娠三期中ICAM-2水平差异有统计学意义(P<0.05),子痫前期组妊娠三期ICAM-2明显高于正常妊娠组,差异均具有统计学意义(P<0.01)。结论:外周血中ICAM-2水平变化与妊娠期高血压疾病密切相关,随着病情加重ICAM-2值明显升高,ICAM-2对预测子痫前期的发生、发展及终止妊娠时机的选择有重要作用;ICAM-2值在正常妊娠中不随孕龄的增长而升高,可能预示不良妊娠结局。     

老年核性及皮质性白内障晶状体上皮细胞中bFGF及α-SMA的表达

目的 比较老年核性及皮质性白内障晶状体上皮细胞(lens epithelia cells,LEC)中碱性成纤维细胞生长因子(basic fibroblast growth factor,bFGF)及α-平滑肌肌动蛋白(alpha smooth muscle actin,α-SMA)的表达,探讨其在老年性白内障发展中的作用.方法 按照老年核性与皮质性白内障诊断标准将患者分为2组,每组36眼(男女比例1:1) ,于白内障超声乳化术中截取其前囊膜(含LEC),用免疫组织化学的方法 检测出每组LEC中bFGF及α-SMA 的表达,对阳性细胞进行计数,2组间卡方检验作统计学分析.结果 晶状体囊膜下上皮细胞中bFGF和α-SMA的阳性表达主要分布在囊膜周边部,越近中央区,其表达越弱;老年核性白内障组LEC中bFGF的表达水平显著高于皮质性白内障组(平均阳性细胞率分别为61.33%和2.13%),差异有显著统计学意义(χ2=14.06,P＜0.01);老年核性白内障组LEC α-SMA的表达水平亦高于皮质性白内障组(平均阳性细胞率分别为32.21%和5.04%),差异有统计学意义(χ2=4.43,P＜0.05).结论 老年核性白内障较皮质性白内障有更多的LEC以增生和分化为主.     

冷应激大鼠肾上腺差异表达基因的克隆

目的 分离常温生活ＳＤ大鼠和－１０℃冷应激４ｈ大鼠肾上腺的差异表达基因。方法 取同一祖父母的近效系Ⅲ组ＳＤ大鼠,将实验组在－１０℃冷应激４ｈ,取大鼠肾上腺采用ｍＲＮＡ差异展示技术分离差异表达条带。将差异条带克隆、测共分离出差异条带１６２条,５９条为新表达的差异片段,４７条为高表达的差异带１６２条,５９条为新表达的差异片段,４７条为高表达的差异片段,３６条为弱表达的差异片段,２０条为实验组未表达条带