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NQO1 Mediates Lenvatinib Resistance by Regulating ROS-induced Apoptosis in Hepatocellular Carcinoma

Current Medical Science 2024年第1期44卷 168-179页

作者： wei XUE Ting WANG Wen-jing TIAN Si-qi PANG Hua-feng ZHANG wei-dong jia Department of General Surgery The First Affiliated Hospital of University of Science and Technology of ChinaDivision of Life Science and MedicineUniversity of Science and Technology of ChinaHefei 230027China Institute of Health and Medicine Hefei Comprehensive National Science CenterHefei 230601China The Chinese Academy of Sciences Key Laboratory of Innate Immunity and Chronic Disease School of Basic Medical SciencesDivision of Life Science and MedicineUniversity of Science and Technology of ChinaHefei 230027China

Objective Hepatocellular carcinoma(HCC)is the third leading cause of cancer-associated death *** a first-line drug for advanced HCC treatment,lenvatinib faces a significant hurdle due to the development of both intrinsic and acquired resistance among patients,and the underlying mechanism remains largely *** present study aims to identify the pivotal gene responsible for lenvatinib resistance in HCC,explore the potential molecular mechanism,and propose combinatorial therapeutic targets for HCC *** Cell viability and colony formation assays were conducted to evaluate the sensitivity of cells to lenvatinib and ***-Seq was used to determine the differences in transcriptome between parental cells and lenvatinib-resistant(LR)*** upregulated genes were analyzed by GO and KEGG ***,qPCR and Western blotting were employed to determine the relative gene expression ***,the intracellular reactive oxygen species(ROS)and apoptosis were detected by flow *** PLC-LR and Hep3B-LR were *** was a total of 116 significantly upregulated genes common to both LR cell *** GO and KEGG analyses indicated that these genes were involved in oxidoreductase and dehydrogenase activities,and reactive oxygen species ***,NAD(P)H:quinone oxidoreductase 1(NQO1)was highly expressed in LR cells,and was involved in the lenvatinib *** high expression of NQO1 decreased the production of ROS induced by lenvatinib,and subsequently suppressed the *** combination of lenvatinib and NQO1 inhibitor,dicoumarol,reversed the resistance of LR *** The high NQO1 expression in HCC cells impedes the lenvatinib-induced apoptosis by regulating the ROS levels,thereby promoting lenvatinib resistance in HCC cells.

关键词： hepatocellular carcinoma lenvatinib resistance NAD(P)H quinone oxidoreductase 1 reactive oxygen species apoptosis dicoumarol

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Clinical characteristics and mechanism of liver damage in patients with severe acute respiratory syndrome

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Hepatobiliary & Pancreatic Diseases International 2005年第1期4卷 60-63页

作者： Zhang Yang Min Xu Jun-Qing Yi wei-dong jia Guangzhou No.8 People's Hospital Guangzhou 510060 China. yangzhangz@***

BACKGROUND: Abnormal liver function was found in patients with severe acute respiratory syndrome (SARS). This study was undertaken to explore the clinical characteristics and mechanisms of liver damage.METHODS: The serial laboratory data of liver function test and hepatic histological examination from 168 patients with SARS were retrospectively analyzed.RESULTS: The abnormalities of serum alanine aminotransferase (ALT) were 52.5%, 71.8%, 85.7% and 85.2%. The average levels of ALT of the patients were 56.07+/-51.57 U/L, 86.46+/-69.93 U/L, 106.69+/-102.50 U/L and 111.32+/-160.24 U/L, and the average levels of serum albumin were 37.25+/-5.37 g/L, 35.82+/-4.74 g/L, 34.49+/-5.04 g/L, and 34.26+/-4.70 g/L, at the day of admission, the first week, second week, and third week after hospitalization, respectively. Significant correlation was not shown among liver damage, blood oxygen saturation (SaO2), degree of fever, and immune functional disorder in this study. Hepatic histological examination of 4 patients demonstrated that non-specific inflammation existed in the liver.CONCLUSIONS: Liver damage of patients with SARS usually occurs in the early stage of the disease with a high occurrence rate and a prolonged profile, which can be characterized by early, obvious decrease of albumin levels and slightly abnormal levels of ALT. The liver damage induced by SARS seems to be caused by SARS virus directly rather than by low SaO2 or high fever. Hepatotoxic drugs may play a role in increasing the severity of liver damage or prolonging the time of liver function recovery.

关键词： severe acute respiratory syndrome liver damage liver function

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Computed tomography-based radiomics to predict early recurrence of hepatocellular carcinoma post-hepatectomy in patients background on cirrhosis

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World Journal of Gastroenterology 2024年第15期30卷 2128-2142页

作者： Gui-Xiang Qian Zi-Ling Xu Yong-Hai Li jian-Lin Lu Xiang-Yi Bu Ming-Tong wei wei-dong jia Department of Hepatic Surgery Anhui Provincial HospitalThe First Affiliated Hospital of USTCDivision of Life Science and MedicineUniversity of Science and Technology of ChinaHefei 230001Anhui ProvinceChina Department of Hepatic Surgery Anhui Provincial Hospital Affiliated to Anhui Medical UniversityAnhui Medical UniversityHefei 230001Anhui ProvinceChina Department of Anorectal Surgery the First People’s Hospital of HefeiHefei 230001Anhui ProvinceChina

BACKGROUND The prognosis for hepatocellular carcinoma(HCC)in the presence of cirrhosis is unfavourable,primarily attributable to the high incidence of *** To develop a machine learning model for predicting early recurrence(ER)of posthepatectomy HCC in patients with cirrhosis and to stratify patients’overall survival(OS)based on the predicted risk of *** In this retrospective study,214 HCC patients with cirrhosis who underwent curative hepatectomy were *** feature selection was conducted using the least absolute shrinkage and selection operator and recursive feature elimination ***-radiologic features were selected through univariate and multivariate logistic regression *** machine learning methods were used for model comparison,aiming to identify the optimal *** model’s performance was evaluated using the receiver operating characteristic curve[area under the curve(AUC)],calibration,and decision curve ***,the Kaplan-Meier(K-M)curve was used to evaluate the stratification effect of the model on patient *** Within this study,the most effective predictive performance for ER of post-hepatectomy HCC in the background of cirrhosis was demonstrated by a model that integrated radiomics features and clinical-radiologic *** the training cohort,this model attained an AUC of 0.844,while in the validation cohort,it achieved a value of *** K-M curves illustrated that the combined model not only facilitated risk stratification but also exhibited significant discriminatory ability concerning patients’*** The combined model,integrating both radiomics and clinical-radiologic characteristics,exhibited excellent performance in HCC with *** K-M curves assessing OS revealed statistically significant differences.

关键词： Machine learning Radiomics Hepatocellular carcinoma Cirrhosis Early recurrence Overall survival Computed tomography Prognosis Risk factor Delta-radiomics

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Laparoscopic combined with thoracoscopic transdiaphragmatic hepatectomy for hepatitis B-related hepatocellular carcinoma located in segment VII or VIII

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Hepatobiliary & Pancreatic Diseases International 2020年第3期19卷 291-294页

作者： Yu Zhu Zhen-Yu Li Chun-Guo Wang Zhe-Ping Fang wei-dong jia Fa-Biao Zhang School of Medicine Shandong UniversityJinan 250012China Division of Liver Surgery The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Department of Hepatobiliary Surgery Taizhou Hospital of Zhejiang ProvinceWenzhou Medical UniversityTaizhou 317000China

Laparoscopic hepatectomy(LH)is considered a safe and effective method of treating liver cancer because of its relatively low level of trauma,bleeding,pain,and short hospital stay as compared with traditional open surgery[1].However,this is not ideal for tumors located in segment VII or VIII of the liver as these tumors are difficult to be exposed during laparoscopy,and the conversion rate is relatively high[2].Although it has been reported that the thoracoscopic transdiaphragmatic segment VII or VIII hepatectomy can obtain better visual field and operation space[3]。

关键词： hepatectomy Laparoscopic bleeding

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Evaluating microvascular invasion in hepatitis B virus-related hepatocellular carcinoma based on contrast-enhanced computed tomography radiomics and clinicoradiological factors

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World Journal of Gastroenterology 2024年第45期30卷 4801-4816页

作者： Zi-Ling Xu Gui-Xiang Qian Yong-Hai Li jian-Lin Lu Ming-Tong wei Xiang-Yi Bu Yong-Sheng Ge Yuan Cheng wei-dong jia Department of General Surgery Anhui Provincial Hospital Affiliated to Anhui Medical UniversityHefei 230001Anhui ProvinceChina Department of General Surgery Anhui Provincial HospitalThe First Affiliated Hospital of University of Science and Technology of ChinaDivision of Life Science and MedicineUniversity of Science and Technology of ChinaHefei 230001Anhui ProvinceChina Department of Anorectal Surgery The First People's Hospital of HefeiHefei 230001Anhui ProvinceChina

BACKGROUND Microvascular invasion(MVI)is a significant indicator of the aggressive behavior of hepatocellular carcinoma(HCC).Expanding the surgical resection margin and performing anatomical liver resection may improve outcomes in patients with ***,no reliable preoperative method currently exists to predict MVI status or to identify patients at high-risk group(M2).AIM To develop and validate models based on contrast-enhanced computed tomo-graphy(CECT)radiomics and clinicoradiological factors to predict MVI and identify M2 among patients with hepatitis B virus-related HCC(HBV-HCC).The ultimate goal of the study was to guide surgical *** A total of 270 patients who underwent surgical resection were retrospectively *** cohort was divided into a training dataset(189 patients)and a validation dataset(81)with a 7:3 *** features were selected using intra-class correlation coefficient analysis,Pearson or Spearman’s correlation analysis,and the least absolute shrinkage and selection operator algorithm,leading to the construction of radscores from CECT *** and multivariate analyses identified significant clinicoradiological factors and radscores associated with MVI and M2,which were subsequently incorporated into predictive *** models’performance was evaluated using calibration,discrimination,and clinical utility *** Independent risk factors for MVI included non-smooth tumor margins,absence of a peritumoral hypointensity ring,and a high radscore based on delayed-phase CECT *** MVI prediction model incorporating these factors achieved an area under the curve(AUC)of 0.841 in the training dataset and 0.768 in the validation *** M2 prediction model,which integrated the radscore from the 5 mm peritumoral area in the CECT arterial phase,α-fetoprotein level,enhancing capsule,and aspartate aminotransferase level achieved an AUC of 0.865 in the training dataset and 0.798 in the validation

关键词： Radiomics Contrast-enhanced computed tomography Hepatocellular carcinoma Microvascular invasion Hepatitis B virus

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Renewing urban large-scale topographical maps by using of Quick Bird panchromatic remote sensing images

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中国有色金属学会会刊：英文版 2005年第S1期15卷 164-167页

作者： SONG wei-dong, KANG jia-yin (Liaoning Technical University, Fuxin 123000, China)

Urban large-scale topographical maps can be renewed by means of overlapping the original digital line graph (DLG) and up-to-date remote sensitive images which have high precision and have been orthographically rectified precisely. Quick Bird panchromatic remote sensing image is used and an urban area with even terrain and dense buildings is selected as experimental area. Ground control points (GCPs) are selected on a new 1∶500 topographical map and multinomial model is applied for rectification. After rectification the absolute positional error of a single point of the image is less than 1m, therefore this method is suitable for renewing topographical maps of up to (1∶2 000) scale.

关键词： Quick Bird geometry rectification renewing of topographic maps

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Effect of octreotide on angiogenesis induced by hepatocellular carcinoma in vivo

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Hepatobiliary & Pancreatic Diseases International 2003年第3期2卷 404-409页

作者： wei-dong jia Ge-Liang Xu Hui-Chuan Sun Lu Wang Rong-Nang Xu Qiong Xue Department of General Surgery Anhui Provincial Hospital Hefei 230001 China. jwd@***

OBJECTIVE: To investigate the effect of somatostatin analogue octreotide on angiogenesis induced byhepatocellular carcinoma (HCC) in ***: LCI-D20 corneal micropocket model in nude mouse was used to dynamically observeangiogenesis under a stereoscopic zoom microscope and a digital camera system and to evaluate the effectof octreotide on angiogenesis. Male nude mice were subcutaneously implanted with LCI-D20 tumor tissuesfor tumor xenograft studies. Microvessel density in CD34-stained tumor sections was analyzed byimmunohistochemical SP ***: Tumor tissues from LCI-D20 implanted into the corneal micropocket induced *** animals received systemic octreotide treatment, angiogenesis response in the cornea of mice wasmoderate, the appearance of vascular buds was delayed, and the new capillaries were sparse and grewslowly. Compared with the control group, the neovascularization induced by HCC in the cornea of micewas markedly inhibited on day 7, 9, 12, 15, 18 and 21 after implantation in the octreotide-treated group(P<0.05). Systemic administration of octreotide produced a significant suppression of the growth ofLCI-D20. Immunohistochemical studies of tumor tissues revealed decreased microvessel density in theoctreotide-treated animals as compared with the controls (21.7±4.27 versus 31.8±3.87, P<0. 01).CONCLUSION: Somatostatin analogue octreotide is able to inhibit angiogenesis induced by HCC invivo and may provide a new approach to the treatment of HCC.

关键词： liver neoplasms neovascularization angiogenesis octreotide

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Alterations of FHIT Gene and P16 Gene in Nickel Transformed Human Bronchial Epithelial Cells

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Biomedical and Environmental Sciences 2006年第4期19卷 277-284页

作者： wei-dong JI jia-KUN CHEN jia-CHUN LU ZHONG-LIANG WU FEI YI SU-MEI FENG Institute for Chemical Carcinogenesis Guangzhou Medical College Guangzhou 510182 Guangdong China

Objective To study the alterations of FHIT gene and P16 gene in malignant transformed human bronchial epithelial cells induced by crystalline nickel sulfide using an immortal human bronchial epithelial cell line, and to explore the molecular mechanism of nickel carcinogenesis. Methods 16HBE cells were treated 6 times with different concentrations of NiS in vitro, and the degree of malignant transformation was determined by assaying the anchorage-independent growth and tumorigenicity. Malignant transformed cells and tumorigenic cells were examined for alterations of FHIT gene and P16 gene using RT-PCR, DNA sequencing, silver staining PCR-SSCP and Western blotting. Results NiS-treated cells exhibited overlapping growth. Compared wkh that of negative control cells, soft agar colony formation efficiency of NiS-treated cells showed significant increases （P〈0.01） and dose-dependent effects. NiS-treated cells could form tumors in nude mice, and a squamous cell carcinoma was confirmed by histopathological examination. No mutation of exon 2 and exons 2-3, no abnormal expression in pl6 gene and mutation of FHIT exons 5-8 and exons 1-4 or exons 5-9 were observed in transformed cells and tumorigenic cells. However, aberrant transcripts or loss of expression of the FHIT gene and Fhit protein was observed in transformed cells and tumorigenic cells. One of the aberrant transcripts in the FHIT gene was confirmed to have a deletion of exon 6, exon 7, exon 8, and an insertion of a 36 bp sequence replacing exon 6-8. Conclusions The FHIT gene rather than the P16 gene, plays a definite role in nickel carcinogenesis. Alterations of the FHIT gene induced by crystalline NiS may be a molecular event associated with carcinogen, chromosome fragile site instability and cell malignant transformation. FHIT may be an important target gene activated by nickel and other exotic carcinogens.

关键词： Crystalline nickel sulfide Human bronchial epithelial cell line Malignant transformation P16 gene FHIT gene

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Results of hip resurfacing for developmental dysplasia of the hip of Crowe type Ⅰ and Ⅱ

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Chinese Medical Journal 2008年第15期121卷 1379-1383页

作者： XU wei-dong LI jia ZHOU Zhen-hua WU Yue-song LI Ming Department of Orthopedics Changhai Hospital Affiliated to the Second Military Medical University Shanghai 200433 China

Background Recently, the new generation of metal-on-metal total hip resurfacing arthroplasty is well known for preserving the proximal femoral bone stock, minimizing the risk of postoperative dislocation using large femoral heads, and expecting low wear of metal-on-metal articulation for longer prosthesis survival. It also has the advantage in biomechanical loading in the proximal femur. The osteoarthritis secondary to developmental dysplasia of the hip （DDH） has been the most common reason for total hip arthroplasty. Most of the patients are young and active, who require improved range of motion of the hip besides relief of the pain, even expect to resume the ability to run and jump after the joint arthroplasty, thus to be allowed an active lifestyle. The objective of the current study was to evaluate the early outcome of resurfacing arthroplasty for the mild DDH cases （Crowe type Ⅰ and Ⅱ）. Methods Between September 2005 and May 2007, twenty-one consecutive patients （twenty-six hips） with the diagnosis of osteoarthritis secondary to DDH underwent metal-on-metal resurfacing arthroplasty. The average age at the time of surgery was 46.5 years （range, 37-59 years）. Six patients （28.6%） were male and fifteen （71.4%） were female. Clinical and radiographic results were observed. The follow-up was performed at 6 weeks, 3, 6, 9 months and then yearly. Results All patients were followed for a mean of 18 months （9-29 months）. During the follow-up period no complications, such as dislocation of hip joints, infection or femoral neck fracture occurred. The clinical outcomes, as rated with the Harris hip score, improved significantly compared with the preoperative ratings. The mean postoperative Harris hip score was 90.7, compared to 35.5 preoperatively. The radiographic analysis showed that all prostheses were fixed with no radiolucencies. All of the patients who had equal limb lengths preoperatively had equal lengths postoperatively. Of the nine patients with preoperative limb-

关键词： arthroplasty hip dislocation congenital

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多基地空时码探测信号设计及时反相关检测技术

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物理学报 2014年第5期63卷 194-202页

作者：生雪莉芦嘉凌青徐江董伟佳哈尔滨工程大学水声技术重点实验室哈尔滨150001 哈尔滨工程大学水声工程学院哈尔滨150001 复杂舰船系统仿真重点实验室北京100161

为实现浅海复杂环境下的多基地声纳多源目标回波分辨,本文设计了一种适用于多入多出垂直阵信道环境下的空时码探测信号,并针对倾斜垂直阵的多途子信道差异问题,提出了信号的时反相关检测技术.空时码探测信号采用伪随机信号调制,具有良... 详细信息

为实现浅海复杂环境下的多基地声纳多源目标回波分辨,本文设计了一种适用于多入多出垂直阵信道环境下的空时码探测信号,并针对倾斜垂直阵的多途子信道差异问题,提出了信号的时反相关检测技术.空时码探测信号采用伪随机信号调制,具有良好的正交性,能在抗子信道严重衰落的同时,分辨多源目标回波.垂直阵受水流冲击,呈倾斜状态时,其多途子信道不一致性会导致各子信道传递信号无法在接收端聚焦,使阵列增益受损,同时导致时延测量能力下降和信号判决错误率上升,为此本文设计了信道训练信号用以估计多途子信道环境,通过虚拟时间反转镜获得子信道不一致条件下的最佳匹配检测信号,实现对接收信号的时反相关检测.仿真结果表明,本文所设计的探测信号和检测方法,能够克服复杂的信道条件和多途子信道不一致性引起的检测问题,满足多基地声纳探测需求,实现多源目标回波分辨.

关键词：空时码探测信号时反相关检测多途子信道差异多源目标回波分辨

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