Efficacy and Affecting Factors of 131I Thyroid Remnant Ablation After Surgical Treatment of Differentiated Thyroid Carcinoma

Purpose: Radioiodine (131I) thyroid remnant ablation is an important treatment of differentiated thyroid carcinoma (DTC) and various factors affecting its efficacy have been reported but not well defined. The aim of our study was to evaluate the efficacy and the affecting factors of 131I ablation after total or near-total thyroidectomy in a relative large DTC cohort.Methods: 261 DTC patients with negative thyroglobulin antibody received 100–200 mCi 131I for thyroid remnant ablation after total or near-total thyroidectomy between January 2012 and October 2015 in our hospital. The efficacy and affecting factors of 131I ablation therapy were retrospectively investigated.Results: The success rate of the first 131I thyroid remnant ablation was 65.90%. Univariate analysis demonstrated that larger tumor size, higher level of pre-ablation stimulated thyroglobulin (sTg), intermediate to high risk stratification for recurrence, and lymph node and distant metastases were associated with a lower success rate of the first 131I ablation (all p < 0.05). Multivariate logistic regression analysis showed that tumor size, pre-ablation sTg, and lymph node and distant metastases were independent factors affecting the efficacy of the first 131I ablation. Areas under receiver operating characteristic curves for sTg, sTg/TSH ratio, and tumor size to predict unsuccessful ablation were 0.831, 0.824, and 0.648, respectively. The threshold values were 4.595 ng/ml, 0.046 mg/IU, and 1.350 cm, respectively. The sensitivities were 95.51, 96.63, and 73.03% and the specificities were 64.54, 61.63, and 49.41%, respectively. The excellent response (ER) ratio of the successful group was significantly higher than that of the unsuccessful group.Conclusions: The efficacy of the first 131I thyroid remnant ablation after surgical treatment of DTC is well demonstrated, and tumor size, pre-ablation sTg, lymph node, and distant metastases are independent factors affecting its efficacy

Proteomic analysis of regenerating mouse liver following 50% partial hepatectomy

<p>Abstract</p> <p>Background</p> <p>Although 70% (or 2/3) partial hepatectomy (PH) is the most studied model for liver regeneration, the hepatic protein expression profile associated with lower volume liver resection (such as 50% PH) has not yet been reported. Therefore, the aim of this study was to determine the global protein expression profile of the regenerating mouse liver following 50% PH by differential proteomics, and thereby gaining some insights into the hepatic regeneration mechanism(s) under this milder but clinically more relevant condition.</p> <p>Results</p> <p>Proteins from sham-operated mouse livers and livers regenerating for 24 h after 50% PH were separated by SDS-PAGE and analyzed by nanoUPLC-Q-Tof mass spectrometry. Compared to sham-operated group, there were totally 87 differentially expressed proteins (with 50 up-regulated and 37 down-regulated ones) identified in the regenerating mouse livers, most of which have not been previously related to liver regeneration. Remarkably, over 25 differentially expressed proteins were located at mitochondria. Several of the mitochondria-resident proteins which play important roles in citric acid cycle, oxidative phosphorylation and ATP production were found to be down-regulated, consistent with the recently-proposed model in which the reduction of ATP content in the remnant liver gives rise to early stress signals that contribute to the onset of liver regeneration. Pathway analysis revealed a central role of c-Myc in the regulation of liver regeneration.</p> <p>Conclusions</p> <p>Our study provides novel evidence for mitochondria as a pivotal organelle that is connected to liver regeneration, and lays the foundation for further studies on key factors and pathways involved in liver regeneration following 50% PH, a condition frequently used for partial liver transplantation and conservative liver resection.</p

Deep functional analysis of synII, a 770-kilobase synthetic yeast chromosome

INTRODUCTION Although much effort has been devoted to studying yeast in the past few decades, our understanding of this model organism is still limited. Rapidly developing DNA synthesis techniques have made a “build-to-understand” approach feasible to reengineer on the genome scale. Here, we report on the completion of a 770-kilobase synthetic yeast chromosome II (synII). SynII was characterized using extensive Trans-Omics tests. Despite considerable sequence alterations, synII is virtually indistinguishable from wild type. However, an up-regulation of translational machinery was observed and can be reversed by restoring the transfer RNA (tRNA) gene copy number. RATIONALE Following the “design-build-test-debug” working loop, synII was successfully designed and constructed in vivo. Extensive Trans-Omics tests were conducted, including phenomics, transcriptomics, proteomics, metabolomics, chromosome segregation, and replication analyses. By both complementation assays and SCRaMbLE (synthetic chromosome rearrangement and modification by loxP -mediated evolution), we targeted and debugged the origin of a growth defect at 37°C in glycerol medium. RESULTS To efficiently construct megabase-long chromosomes, we developed an I- Sce I–mediated strategy, which enables parallel integration of synthetic chromosome arms and reduced the overall integration time by 50% for synII. An I- Sce I site is introduced for generating a double-strand break to promote targeted homologous recombination during mitotic growth. Despite hundreds of modifications introduced, there are still regions sharing substantial sequence similarity that might lead to undesirable meiotic recombinations when intercrossing the two semisynthetic chromosome arm strains. Induction of the I- Sce I–mediated double-strand break is otherwise lethal and thus introduced a strong selective pressure for targeted homologous recombination. Since our strategy is designed to generate a markerless synII and leave the URA3 marker on the wild-type chromosome, we observed a tenfold increase in URA3 -deficient colonies upon I- Sce I induction, meaning that our strategy can greatly bias the crossover events toward the designated regions. By incorporating comprehensive phenotyping approaches at multiple levels, we demonstrated that synII was capable of powering the growth of yeast indistinguishably from wild-type cells (see the figure), showing highly consistent biological processes comparable to the native strain. Meanwhile, we also noticed modest but potentially significant up-regulation of the translational machinery. The main alteration underlying this change in expression is the deletion of 13 tRNA genes. A growth defect was observed in one very specific condition—high temperature (37°C) in medium with glycerol as a carbon source—where colony size was reduced significantly. We targeted and debugged this defect by two distinct approaches. The first approach involved phenotype screening of all intermediate strains followed by a complementation assay with wild-type sequences in the synthetic strain. By doing so, we identified a modification resulting from PCRTag recoding in TSC10 , which is involved in regulation of the yeast high-osmolarity glycerol (HOG) response pathway. After replacement with wild-type TSC10 , the defect was greatly mitigated. The other approach, debugging by SCRaMbLE, showed rearrangements in regions containing HOG regulation genes. Both approaches indicated that the defect is related to HOG response dysregulation. Thus, the phenotypic defect can be pinpointed and debugged through multiple alternative routes in the complex cellular interactome network. CONCLUSION We have demonstrated that synII segregates, replicates, and functions in a highly similar fashion compared with its wild-type counterpart. Furthermore, we believe that the iterative “design-build-test-debug” cycle methodology, established here, will facilitate progression of the Sc2.0 project in the face of the increasing synthetic genome complexity. SynII characterization. ( A ) Cell cycle comparison between synII and BY4741 revealed by the percentage of cells with separated CEN2-GFP dots, metaphase spindles, and anaphase spindles. ( B ) Replication profiling of synII (red) and BY4741 (black) expressed as relative copy number by deep sequencing. ( C ) RNA sequencing analysis revealed that the significant up-regulation of translational machinery in synII is induced by the deletion of tRNA genes in synII. </jats:sec

Therapeutic potential of transplanted placental mesenchymal stem cells in treating Chinese miniature pigs with acute liver failure

<p>Abstract</p> <p>Background</p> <p>Stem cell-based therapy to treat liver diseases is a focus of current research worldwide. So far, most such studies depend on rodent hepatic failure models. The purpose of this study was to isolate mesenchymal stem cells from human placenta (hPMSCs) and determine their therapeutic potential for treating Chinese experimental miniature pigs with acute liver failure (ALF).</p> <p>Methods</p> <p>hPMSCs were isolated and analyzed for their purity and differentiation potential before being employed as the donor cells for transplantation. ALF models of Chinese experimental miniature pigs were established and divided into four groups: no cell transplantation; hPMSCs transplantation via the jugular vein; X-ray-treated hPMSCs transplantation via the portal vein; and hPMSCs transplantation via the portal vein. The restoration of biological functions of the livers receiving transplantation was assessed via a variety of approaches such as mortality rate determination, serum biochemical analysis, and histological, immunohistochemical, and genetic analysis.</p> <p>Results</p> <p>hPMSCs expressed high levels of CD29, CD73, CD13, and CD90, had adipogenic, osteogenic, and hepatic differentiation potential. They improved liver functions <it>in vivo </it>after transplantation into the D-galactosamine-injured pig livers as evidenced by the fact that ALT, AST, ALP, CHE, TBIL, and TBA concentrations returned to normal levels in recipient ALF pigs. Meanwhile, histological data revealed that transplantation of hPMSCs via the portal vein reduced liver inflammation, decreased hepatic denaturation and necrosis, and promoted liver regeneration. These ameliorations were not found in the other three groups. The result of 7-day survival rates suggested that hPMSCs transplantation via the portal vein was able to significantly prolong the survival of ALF pigs compared with the other three groups. Histochemistry and RT-PCR results confirmed the presence of transplanted human cells in recipient pig livers (Groups III, IV).</p> <p>Conclusions</p> <p>Our data revealed that hPMSCs could not only differentiate into hepatocyte-like cells <it>in vitro </it>and <it>in vivo</it>, but could also prolong the survival time of ALF pigs. Regarding the transplantation pathways, the left branch of the portal vein inside the liver was superior to the jugular vein pathway. Thus, hPMSCs transplantation through the portal vein by B-ultrasonography may represent a superior approach for treating liver diseases.</p

オンセイ ニンシキ ト アヤマリ ケンシュツ ノ キノウ オ ユウスル ジュウナンナ ゴガク ガクシュウ シエン システム

京都大学0048新制・課程博士博士(情報学)甲第15010号情博第369号新制||情||68(附属図書館)27460UT51-2009-R734京都大学大学院情報学研究科知能情報学専攻(主査)教授 河原 達也, 教授 奥乃 博, 教授 黒橋 禎夫, 教授 壇辻 正剛学位規則第4条第1項該当Doctor of InformaticsKyoto UniversityDA

Detect Overlapping Communities via Ranking Node Popularities

Detection of overlapping communities has drawn much attention lately as they are essential properties of real complex networks. Despite its influence and popularity, the well studied and widely adopted stochastic model has not been made effective for finding overlapping communities. Here we extend the stochastic model method to detection of overlapping communities with the virtue of autonomous determination of the number of communities. Our approach hinges upon the idea of ranking node popularities within communities and using a Bayesian method to shrink communities to optimize an objective function based on the stochastic generative model. We evaluated the novel approach, showing its superior performance over five state-of-the-art methods, on large real networks and synthetic networks with ground-truths of overlapping communities