Analyses of data of patients with Thrombotic Microangiopathy in the WAA registry

Thrombotic Microangiopathy (TMA) is a histopathological feature of various diseases including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome.The aim of this study was to investigate the outcome and prognostic variables of TMA-patients.

Materials and methods

Data were consecutively retrieved from the WAA-apheresis registry (www.waa-registry.org) during 2003–2009. Included were all 120 patients (1237 procedures) who suffered from various forms of TMA, as registered by the ICD-10 code M31.1. Besides registry data, more extensive information was retrieved from the latest 64 patients. Adverse events of the TMA patients were compared to those of the other patients in the registry.

Results

The mean age was 46 years (range 11–85 years, 57% women). In 72% therapeutic apheresis was due to an acute indication while a long-term indication was present in 28%. Plasma exchange was performed by centrifugation and filtration technique (95% and 4%, respectively), and immunoadsorption in 1% of the patients. Only fresh frozen plasma was used as replacement fluid in 69% of procedures. Adverse events were more frequent than in the general apheresis population (10% versus 5%, RR 1.9, CI 1.6–2.3). No death occurred due to apheresis treatment. Three percent of the procedures were interrupted. Bronchospasm and/or anaphylactic shock were present in two patients and one patient suffered from TRALI. At admission 26% were bedridden and needed to be fed. The risk of dying during the treatment period was significantly higher if the patient also suffered from a compromising disease, such as cancer. There was an inverse correlation between the ADAMTS13 level and the antibody titer (r = −0.47, p = 0.034).

Conclusions

Patients with TMA have an increased risk for moderate and severe AE compared to the general apheresis population. Many patients were severely ill at admission. The prognosis is worse if the patient also has a severe chronic disease. Even slightly increased ADAMTS13-antibody titers seem to have a negative impact on the ADAMTS13 levels.     

Gene polymorphism of IL-6 and MMP-3 decreases passive range of motion after rotator cuff repair

Objectives: Post-operative stiffness is common after rotator cuff repair, given the difference in susceptibility and severity, the genetic factors may be involved. Interleukin 6 (IL-6) and Matrix metalloproteinases 3 (MMP-3) were previous found as key cytokines in the pathologies of adhesive capsulitis. The present study aims to investigate whether variants within the IL-6 and MMP-3 gene contributed to post-operative stiffness in a Chinese Han population. Methods: A total of 188 patients diagnosed with rotator cuff tears treated with mini-open surgery were enrolled in this study, among which 87 patients were diagnosed as post-operative stiffness and the remaining 101 patients as controls. All subjects were genotyped for IL-6 and MMP-3 SNPs. Results: The rs1800796 of IL-6 and rs679620 of MMP-3 were found significantly associated with increased susceptibility and severity of post-operative stiffness. Conclusion: The rs1800796 SNP of IL-6 and rs650108 SNP of MMP-3 were associated with increased risk of post-operative stiffness susceptibility and severity. This finding can be used in guiding the rehabilitation procedure after rotator cuff surgery, in another word, those with the genetic susceptibility factors should receive a more radical rehabilitation procedure and those without the susceptibility factors can be more conservative.     

Pro-Apoptotic Activity of 4-Isopropyl-2-(1-Phenylethyl) Aniline Isolated from Cordyceps bassiana

Cordyceps species including Cordyceps bassiana are a notable anti-cancer dietary supplement. Previously, we identified several compounds with anti-cancer activity from the butanol fraction (Cb-BF) of Cordyceps bassiana. To expand the structural value of Cb-BF-derived anti-cancer drugs, we employed various chemical moieties to produce a novel Cb-BF-derived chemical derivative, KTH-13-amine-monophenyl [4-isopropyl-2-(1-phenylethyl) aniline (KTH-13-AMP)], which we tested for anti-cancer activity. KTH-13-AMP suppressed the proliferation of MDA-MB-231, HeLa, and C6 glioma cells. KTH-13-AMP also dose-dependently induced morphological changes in C6 glioma cells and time-dependently increased the level of early apoptotic cells stained with annexin V-FITC. Furthermore, the levels of the active full-length forms of caspase-3 and caspase-9 were increased. In contrast, the levels of total forms of caspases-3, caspase-8, caspase-9, and Bcl-2 were decreased in KTH-13-AMP treated-cells. We also confirmed that the phosphorylation of STAT3, Src, and PI3K/p85, which is linked to cell survival, was diminished by treatment with KTH-13-AMP. Therefore, these results strongly suggest that this compound can be used to guide the development of an anti-cancer drug or serve as a lead compound in forming another strong anti-proliferative agent.     

Hyperpolarized [1,3‐13C2]ethyl acetoacetate is a novel diagnostic metabolic marker of liver cancer

An increased prevalence of liver diseases such as hepatitis C and nonalcoholic fatty liver results in an augmented incidence of the most common form of liver cancer, hepatocellular carcinoma (HCC). HCC is most often found in the cirrhotic liver and it can therefore be challenging to rely on anatomical information alone when diagnosing HCC. Valuable information on specific cellular metabolism can be obtained with high sensitivity thanks to an emerging magnetic resonance (MR) technique that uses ¹³C labeled hyperpolarized molecules. Our interest was to explore potential new high contrast metabolic markers of HCC using hyperpolarized ¹³C‐MR. This work led to the identification of a class of substrates, low molecular weight ethyl‐esters, which showed high specificity for carboxyl esterases and proved in many cases to possess good properties for signal enhancement. In particular, hyperpolarized [1,3‐¹³C₂]ethyl acetoacetate (EAA) was shown to provide a metabolic fingerprint of HCC. Using this substrate a liver cancer implanted in rats was diagnosed as a consequence of an ～4 times higher metabolic substrate‐to‐product ratio than in the surrounding healthy tissue, (p = 0.009). Unregulated cellular uptake as well as cosubstrate independent enzymatic conversion of EAA, made this substrate highly useful as a hyperpolarized ¹³C‐MR marker. This could be appreciated by the signal‐to‐noise (SNR) obtained from EAA, which was comparable to the SNR reported in a literature liver cancer study with state‐of‐the‐art hyperpolarized substrate, [1‐¹³C]pyruvate. Also, the contrast‐to‐noise (CNR) in the EAA based metabolic ratio images was significantly improved compared with the CNR in equivalent images reported using [1‐¹³C]pyruvate.     

An engineered TIMP2-based and enediyne-integrated fusion protein for targeting MMP-14 shows potent antitumor efficacy

Recent studies have shown that MMP-14 is highly expressed in a panel of human solid tumors and poses as a potential molecular target for anticancer drugs. Currently, major strategies for targeted therapeutics have mainly focused on the use of antibody or ligand-based agents. For seeking an alternative approach, it is of interest to employ endogenous proteins as drug delivery carriers. Considering the facts that TIMP2, the tissue inhibitor of metalloproteinase 2, shows specific interaction with MMP-14 and that Lidamycin (LDM), an extremely potent cytotoxic antitumor antibiotic, consists of an apoprotein (LDP) and a highly active enediyne (AE); we designed and prepared a TIMP2-based and enediyne-integrated fusion protein LDP(AE)-TIMP2 by DNA recombination and molecular reconstitution consecutively. Furthermore, the MMP-14 binding attributes of the active fusion protein were determined and its therapeutic efficacy against human esophageal carcinoma KYSE150 xenograft and human fibrosarcoma HT1080 xenograft models in nude mice was investigated. It is suggested that TIMP2, the endogenous and MMP-14 binding protein, might serve as a guided carrier for targeted therapeutics.     

Expression of DDX27 contributes to colony-forming ability of gastric cancer cells and correlates with poor prognosis in gastric cancer

Previously, we have reported that gain at chromosome 20q13 is the most common genomic copy number aberration in gastric cancer (GC) (29/30 cases), and that among the genes located in this region, we have identified DDX27, whose expression level shows the highest correlation with genomic copy number, as a candidate therapeutic target for GC. Here, we analyzed the clinicopathological significance of DDX27 using immunohistochemistry and studied its functions using knockdown assays. We found that DDX27 was frequently upregulated in GC tissues (98 of 140 cases, 70%), and significantly associated with venous invasion and liver metastasis. Furthermore, multivariate analysis of GC patients showed that high expression of DDX27 was independently associated with poorer prognosis. In functional assays, knockdown of DDX27 reduced the ability of GC cells to form colonies both on conventional plates and soft agar, but had little effect on their invasiveness. We also found that knockdown of DDX27 reduced the viability of GC cells through inhibition of cell cycle progression independently of apoptosis. Interestingly, DDX27 depletion induced accumulation of TP53 in a TP53 wild-type cell line, AGS, but not in a TP53-deleted cell line, 44As3, although DDX27 knockdown commonly reduced the viability of both, indicating the TP53-dependent and independent cell cycle control of DDX27. Thus, our results suggest that expression of DDX27 contributes to colony formation by GC cells through cell cycle control and may be a potential therapeutic target for GC patients with chromosome gain at 20q13.     

阿帕替尼联合TP方案化疗对非小细胞肺癌患者肿瘤标志物、MMP-9及MMP-2水平的影响

目的 探讨阿帕替尼联合TP方案化疗对非小细胞肺癌患者肿瘤标志物、MMP-9及MMP-2水平的影响.方法 将86例非小细胞肺癌患者根据随机数字表法分为对照组与观察组,各43例.对照组给予TP方案化疗,观察组在对照组基础上给予阿帕替尼.比较两组的临床效果.结果 观察组的治疗总有效率高于对照组(P<0.05).治疗后,两组的...     

牙槽突裂植骨前后上颌扩弓对上颌牙槽骨位移影响的三维有限元分析

目的模拟比较牙槽突裂植骨前后上颌扩弓对上颌牙槽骨位移影响。方法在已建立的植骨前上颌骨有限元模型上，采用ANSYS软件模拟牙槽突裂植骨，形成植骨后上颌骨模型。在2组模型上分别施加相同上颌扩弓力，观察比较牙槽骨区域三维方向位移形变情况。结果三维方向位移量比较，植骨前扩弓组均显著大于植骨后扩弓组（P<0.05）。水平向位移：植骨前扩弓，由前向后牙槽骨区域位移量逐渐降低；植骨后扩弓，由前向后牙槽骨区域位移量逐渐升高；植骨前后扩弓健侧牙槽骨位移量均显著大于患侧（P<0.05）。垂直向位移：植骨前后扩弓，牙槽骨前内侧均向下移动，牙槽骨后外侧均向上移动。矢状向位移：植骨前扩弓，牙槽骨前内侧向前移动，后外侧向后移动，植骨后扩弓移动趋势相反。结论单侧完全性唇腭裂患者植骨前扩弓三维方向移动均较植骨后明显，植骨前扩弓建议扩弓器适当向后移动，植骨后扩弓建议扩弓器适当向前移动并配合前牵引治疗，同时治疗中需警惕不对称扩弓及前牙开的发生。     

天然罗汉松二萜体外抗登革病毒活性研究

登革病毒(dengue virus,DENV)是造成热带和亚热带地区登革热和登革出血热季节性大爆发的蚊媒病原体,可导致严重威胁生命的疾病,因此亟需研发DENV疫苗和药物.本研究发现从石栗枝叶中分离的罗汉松型二萜(3α,5β,10α)-13-methoxypodocarpa-8,11,13-triene-3,12-dio...