Risk Factors, Patterns, and Outcomes of Late Recurrence after Liver Resection for Patients with Hepatocellular Carcinoma (Analysis of a Multicenter Cohort over 15 Years)

( Xin-fei Xu ),( Jiong-jie Yu ),( Ju-dong Li ),( Hao Xing ),( Jun Han ),( Zhen-li Li ),( Han Wu ),( Han Zhang ),( Jian-hong Zhong ),( Yi- Sheng Huang ),( Ya-hao Zhou ),( Ting-hao Chen ),( Hong Wang ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Late recurrence (> 2 years) after liver resection of hepatocellular carcinoma (HCC) is usually considered as multi-centric tumors or de novo cancer formation. We aimed to investigate risk factors, patterns and outcomes of late recurrence after HCC resection. Methods: From a multicenter database from 2001 to 2015, 734 patients who were alive and recurrence-free at 2 years after curative resection of initial HCC were enrolled into this retrospective study. Univariate and multivariate Cox-regression analysis were used to identify independent risk factors of late recurrence. Patterns, treatments and outcomes of late recurrence were investigated and analyzed. Results: During a median follow-up of 78.0 months after surgery, 303 patients (41.3%) developed late recurrence. Multivariate analysis revealed that cirrhosis, macroscopic vascular invasion, satellites, and tumor size > 5cm were independent risk factors of late recurrence. Among them, 273 (90.1%) were sole intrahepatic recurrence, 30 (9.9%) were concurrent intrahepatic and extrahepatic recurrence, and none of them was sole extrahepatic recurrence; 165 (54.4%) patients received curative treatments for recurrent HCC, including re-resection, transplantation and local ablation. Multivariate analysis showed regular postoperative surveillance and receiving curative treatments were two independent protective factors of prolonging survival for those patients with late recurrence. Conclusions: Late recurrence is correlated with cirrhosis and certain tumor-related characteristics of initial HCC. The patterns of late recurrence suggest that postoperative surveillance after 2 years of surgery could be adjusted and more targeted. Regular postoperative surveillance improves the probability to receive curative treatments again, yielding to better outcomes for patients with late recurrence.

A GPU-Accelerated Hydrodynamic Model for Urban Rainstorm Inundation Simulation: A Case Study in China

Hao Han,Jingming Hou,Zongxue Xu,Haixiao Jing,Jiahui Gong,Depeng Zuo,Bingyao Li,Shaoxiong Yang,Yongde Kang,Run Wang 대한토목학회 2022 KSCE JOURNAL OF CIVIL ENGINEERING Vol.26 No.3

Frequent urban rainstorm inundations can cause serious damages to human life and social economy. Reliable simulation of urban rainstorm inundation is an effective approach for performing flood risk analysis to reduce losses. In this work, a full 2D high-performance hydrodynamic model for urban rainstorm inundation simulation based on Graphic Processing Unit (GPU) was developed. The idealized V-shape catchment and sponge city district of Fengxi New City were selected as the study areas to assess performance of the model. The model was validated against analytical benchmark results of the idealized V-catchment test which show good agreement between the modelled flow and analytical solutions. The model was then applied to simulate actual urban rainstorm inundation process under measured rainfall. The results indicated that the model can be applied to high-resolution urban region simulations. Specifically, the validation results indicated that the proposed model had a good performance, with an accepted error of less than 15%. When applied to compute the Fengxi New city under design rainstorms with different annual return periods of 1, 5, 10, 20, 50, and 100 years, it was found that the model effectively evaluated the temporal and spatial variation process of urban inundation, and quantitatively investigated flood risks according to the water depth change. The model has been substantially accelerated on GPU to quickly predict urbaninundation. The accuracy and rapid simulation speed of the model were verified based on the actual study area. Therefore, the proposed model can help to predict the dynamic processes of urban flood inundation and thus reduce flood inundation disasters. This is essential for future optimal sponge urban construction planning in China.

Overexpression of EGFR Protein in Bruneian Lung Cancer Patients

Han, Yu Hao,Hamid, Mas R.W. Abdul,Telisinghe, Pemasiri Upali,Hussin, Juniadah Binti Haji,Mabruk, Mohamed Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.1

Background: Lung cancer is the leading cause of cancer death in Brunei Darussalam, accounting for almost 20% of the total. The epidermal growth factor receptor (EGFR) is a member of the erbB family of tyrosine kinase receptor proteins, which includes c-erbb2(HER2/neu), erb-B3, and erb-B4. EGFR overexpression is found in a third of all epithelial cancers, often associated with a poor prognosis. Materials and Methods: Protein expression of EGFR in 27 cases of lung cancer tissue samples and 9 cases of normal lung tissue samples was evaluated using an immunohistochemical approach. Results: The results demonstrated significant increase and overexpression of EGFR in Bruneian lung cancer tissue samples in comparison to normal lung tissue. However, there was no significant relationship between clinicopathologic variables (age and sex) of patients and EGFR protein expression. Conclusions: EGFR is overexpressed in Bruneian lung cancer patient tissue samples in comparison to normal lung tissue samples. This may indicate that EGFR protein over expression plays an important role in the genesis of this type of cancer in Brunei Darussalam.

Regulatory effect of peroxiredoxin 1 (PRDX1) on doxorubicin-induced apoptosis in triple negative breast cancer cells

Han Ying-Hao,Lian Xu-Dong,Lee Seung-Jae,Li Wei-Long,Sun Hu-Nan,Jin Mei-Hua,Kwon Taeho 한국응용생명화학회 2022 Applied Biological Chemistry (Appl Biol Chem) Vol.65 No.5

Patients with triple negative breast cancer (TNBC) lack the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2; thus, conventional hormone and targeted therapies have minimal effect on them. Therefore, clinical treatment of TNBC is still based on chemotherapy and supplemented by other methods. Doxorubicin (DOX), a common drug used in TNBC chemotherapy, has high affinity for cardiolipin, and the nematosomes are rich in cardiolipin; therefore, DOX has high mitochondria-targeting ability. DOX accumulates and plunders the electrons of nicotinamide adenine dinucleotide phosphate (NADPH) and cytochrome C in mitochondria to produce semiquinone DOX. Under the action of oxygen molecules, semiquinone DOX is reduced to DOX and reactive oxygen species (ROS) are generated. The accumulation of ROS can cause mitochondrial dysfunction and lead to mitochondrial dependent apoptosis. Bioinformatic analysis of samples from TNBC patients revealed that peroxiredoxin 1 (PRDX1) was highly expressed in TNBC tissues, and the poor prognosis of patients with high PRDX1 expression was considerably increased. Previous studies determined that DOX can upregulate the expression of the PRDX1 protein in the human TNBC cell line (MDA-MB-231). Thus, we speculate that PRDX1 plays an important role in the process of DOX-induced TNBC cell apoptosis. In this study, we aimed to explore the role of PRDX1 in the process of DOX-induced TNBC cell apoptosis. We found that PRDX1 deletion increased the sensitivity of MDA-MB-231 cells to DOX, which was mainly due to mitochondrial oxidative stress caused by intracellular ROS accumulation, leading to mitochondriadependent apoptosis. Deletion of PRDX1 promotes the PI3K/Akt signaling pathway to mediate the expression of GSK3β. Gsk3β is an upstream signal of mitochondria-dependent apoptosis, and is also an important target of ROS. PRDX1 participates in adriamycin-induced apoptosis of TNBC cells by regulating the expression level of GSK3β. Our findings present new insights to treat breast cancer and TNBC, outlines the clinical use of DOX, and provides a basic theory to develop PRDX1 gene function.

Identification of peroxiredoxin II and its related molecules as potential biomarkers of dermal mesenchymal stem cell homing using network analysis

Han Ying-Hao,Mao Ying-Ying,Feng Yao-Yuan,Xiang Hong-Yi,Sun Hu-Nan,Jin Mei-Hua,Kwon Taeho 한국응용생명화학회 2022 Applied Biological Chemistry (Appl Biol Chem) Vol.65 No.3

In this study, we performed RNA sequencing of Prx II +/+ and Prx II −/− dermal mesenchymal stem cells (DMSCs) to identify differentially expressed genes (DEGs). To explore the role of Prx II in DMSCs, we performed Gene Ontology analysis of the DEGs. The results showed that the DEGs were mainly involved in the biological processes of cell migration, intercellular adhesion, and coordination of the regulation of stem cell homing. Through the construction of protein–protein interaction network, four hub genes Cd274 , Ccl5 , Il1b , and Stat1 involved in cell adhesion and cell homing were screened. Quantitative reverse transcription PCR analysis showed that Cd274 , Ccl5 , Il1b , and Stat1 were down regulated in Prx II −/− DMSCs. miRwalk and Starbase databases were further used to screen the upstream molecules miRNA and lncRNA regulating hub gene. Prx II was found to be involved in the regulation of stem cell homing via the Tctn2/miR-351/Stat1/Il1b axis. Thus, we demonstrated that Prx II is a key molecule in the regulation of the homing ability of DMSCs. Our results provide a theoretical foundation for improving the homing ability of DMSCs by targeting Prx II.

Mechanisms of Cardiovascular Protection by Resveratrol

Han Dong Hao,Li Ren He 한국식품영양과학회 2004 Journal of medicinal food Vol.7 No.3

The phytoantitoxin, resveratrol, is a plant derived polyphenol with phytoestrogenic properties. Resveratrol protects the cardiovascular system by mechanisms that include defense against ischemic-reperfusion injury, promotion of vasorelaxation, protection and maintenance of intact endothelium, antiatherosclerotic properties, inhibition of LDL oxidation, suppression of platelet aggregation and estrogen like actions. The purpose of this article is to review the mechanisms of these effects.

Anti-inflammatory effect of hispidin on LPS induced macrophage inflammation through MAPK and JAK1/STAT3 signaling pathways

Han Ying-Hao,Chen Dong-Qin,Jin Mei-Hua,Jin Ying-Hua,Li Jing,Shen Gui-Nan,Li Wei-Long,Gong Yi-Xi,Mao Ying-Ying,Xie Dan-Ping,Lee Dong-Seok,Yu Li-Yun,Kim Sun-Uk,김지수,권태호,Cui Yu-Dong,Sun Hu-Nan 한국응용생명화학회 2020 Applied Biological Chemistry (Appl Biol Chem) Vol.63 No.3

Severe inflammatory reactions caused by macrophage activation can trigger a systemic immune response. In the present study, we observed the anti-inflammatory properties of hispidin on LPS induced RAW264.7 macrophage cells. Our results showed that hispidin treatment significantly reduced the production of cellular NO, IL-6 and reactive oxygen species (ROS) while has not inhibitory effect on TNF-α productions. Excitingly, hispidin treatment retains the phagocytosis ability of macrophages which enabling them to perform the function of removing foreign invaders. Signaling studies showed, hispidin treatment dramatic suppressed the LPS induced mitogen activated protein kinases (MAPK) and JAK/STAT activations. In conclusion, our findings suggest that hispidin may be a new therapeutic target for clinical treatment of macrophages-mediated inflammatory responses.

RNA sequencing reveals that Prx II gene knockout can down-regulate the allograft rejection of dermal mesenchymal stem cells

Han Ying-Hao,Mao Ying-Ying,Yu Nan-Nan,Jin Mei-Hua,Jin Ying-Hua,Wang Ai-Guo,Zhang Yong-Qing,Shen Gui-Nan,Cui Yu-Dong,Yu Li-Yun,Lee Dong-Seok,Jo Yu-Jin,Sun Hu-Nan,Kwon Jeongwoo,권태호 한국응용생명화학회 2020 Applied Biological Chemistry (Appl Biol Chem) Vol.63 No.3

In this study, we used RNA sequencing (RNA-seq) to analyze and compare bulk cell samples from wild-type (WT) dermal mesenchymal stem cells (DMSCs) (n = 3) and Prx II knockout DMSCs (n = 3). The purpose of the study was to elucidate the role of Prx II on allogeneic immune rejection of transplanted DMSCs. The results revealed differential expression of 472 genes (176 up-regulated and 296 down-regulated; p ≤ 0.05) between the PrxII+/+ (WT) and PrxII−/− sample groups. When highly regulated genes were categorized according to the Gene Ontology (GO) molecular function classification and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, the PrxII−/− samples showed a robust downward trend in allograft rejection. The study identified 43 all immunologically rejected differentially expressed genes, of which 41 showed lower expression in the PrxII−/− vs. PrxII+/+ (WT) samples. These findings suggest that Prx II gene knockout may down-regulate the allograft rejection that occurs during DMSCs transplantation and improve the survival rate of DMSCs in the host. This study provides a new perspective on the clinical treatment of stem cell transplantation.

An Experimental Study on Atomization Characteristics of Flash-boiling Swirl Spray Injected into Heated Convective Cross-flow for Urea-SCR system application

Hao Han,Woong Sup Yoon,Kwang Min Chun 한국자동차공학회 2012 한국자동차공학회 학술대회 및 전시회 Vol.2012 No.11

Urea-SCR, the selective catalytic reduction using urea as reducing agent, has been the most promising way to diminish NOx emissions originating from heavy duty vehicles. However, one of the shortcomings of Urea-SCR is NOx reduction performance degradation at low exhaust gas temperatures on account of ammonia slip and ammonia deposition. Therefore, in the present study, a new type of injection method is suggested which overcomes the shortcoming. The flashboiling atomization is one of the best means that improve the spray characteristics as finer droplets, shorter spray breakup length, and better distribution for enhancing the mixing of urea with exhaust gases. When liquid sheet is subjected to sufficient superheating (boiling) or pressure reduction (cavitation), it becomes formed bubbles. The subsequent growth of the bubbles drives the atomization process. In this experiment study, the injection temperature (dimensionless superheat degree) and crossflow temperature were varied. A high-speed photography technique and a laser-based optical technique (GSV, TSI Inc.) were used to characterize the breakup pattern and spray quality at the downstream of injection position. The spray breakup length and SMD distributions were measured as function of operating conditions. The experiment result proved that the atomization performance improved by flash-boiling swirl spray without being affected by exhaust gas temperatures.

Inhibitory effect of peroxiredoxin II (Prx II) on Ras–ERK–NF&kgr;B pathway in mouse embryonic fibroblast (MEF) senescence

Han, Ying-Hao,Kwon, Jeong-Hoon,Yu, Dae-Yeul,Moon, Eun-Yi Taylor Francis 2006 Free radical research Vol.40 No.11

<P>Intracellular reactive oxygen species (ROS) were attenuated by the expression of peroxiredoxin II (Prx II). Cellular senescence as judged by senescence-associated (SA)-&bgr;-galactosidase (Gal) positive cell formation was increased in Prx II-deficient mouse embryonic fibroblast (MEF). Ras expression was increased following passages. The level of Ras expression was higher in Prx II<SUP>− / − </SUP> MEF than wild type MEF. ERK activity was also augmented by the deletion of Prx II. SA-&bgr;-Gal-positive cell formation was reduced by PD98059, ERK inhibitor. Activated nuclear transcription factor, nuclear factor-kappaB (NF&kgr;B) by the deletion of Prx II was inhibited by the treatment with PD98059. In contrast, no changes in SA-&bgr;-Gal-positive cell formation were detected by NF&kgr;B inhibitor, <I>N</I>-alpha-tosyl-l-phenylalanyl chloromethyl ketone (TPCK). Collectively, results suggest that Prx II deletion activate Ras–ERK–NF&kgr;B pathways and cellular senescence in Prx II<SUP>− / − </SUP> MEF cells was mediated by ERK activation but not by NF&kgr;B activation.</P>