摘要：
Importance
Sorafenib is the first-line treatment for hepatocellular carcinoma with portal vein invasion; however, it has shown unsatisfactory survival benefit. Sorafenib plus hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin, fluorouracil, and leucovorin (FOLFOX) has shown promising results for these patients in a previous phase 2 study.
Objective
To investigate the efficacy and safety of sorafenib plus HAIC compared with sorafenib for hepatocellular carcinoma with portal vein invasion.
Design, Setting, and Participants
This randomized, open-label clinical trial enrolled 818 screened patients. Of the 818 participants, 247 with hepatocellular carcinoma and portal vein invasion were randomly assigned (1:1) via a computer-generated sequence to receive sorafenib plus HAIC or sorafenib. This trial was conducted at 5 hospitals in China and enrolled patients from April 1, 2016, to October 10, 2017, with a follow-up period of 10 months.
Interventions
Randomization to receive 400 mg sorafenib twice daily (sorafenib group) or 400 mg sorafenib twice daily plus HAIC (SoraHAIC group) (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, fluorouracil bolus 400 mg/m2 on day 1, and fluorouracil infusion 2400 mg/m2 for 46 hours, every 3 weeks).
Main Outcomes and Measures
The primary endpoint was overall survival by intention-to-treat analysis. Safety was assessed in patients who received at least 1 dose of study treatment.
Results
For 247 patients (median age, 49 years; range, 18-75 years; 223 men and 24 women), median overall survival was 13.37 months (95% CI, 10.27-16.46) in the SoraHAIC group vs 7.13 months (95% CI, 6.28-7.98) in the sorafenib group (hazard ratio [HR], 0.35; 95% CI, 0.26-0.48; P < .001). The SoraHAIC group showed a higher response rate than the sorafenib group (51 [40.8%] vs 3 [2.46%]; P < .001), and a longer median progression-free survival (7.03 [95% CI, 6.05-8.02] vs 2.6 [95% CI, 2.15-3.05] months; P < .001). Grade 3/4 adverse events that were more frequent in the SoraHAIC group than in the sorafenib group included neutropenia (12 [9.68%] vs 3 [2.48%]), thrombocytopenia (16 [12.9%] vs 6 [4.96%]), and vomiting (8 [6.45%] vs 1 [0.83%]).
Conclusions and Relevance
Sorafenib plus HAIC of FOLFOX improved overall survival and had acceptable toxic effects compared with sorafenib in patients with hepatocellular carcinoma and portal vein invasion.
Trial Registration
ClinicalTrials.gov identifier: NCT02774187
通讯机构：
[Tang, Chao-Ke] U;Univ South China, Inst Cardiovasc Dis, Hengyang 421001, Hunan, Peoples R China.
关键词：
Cholesterol transport system;Atherosclerosis;High-density lipoprotein
摘要：
Atherosclerosis, the pathological basis of most cardiovascular disease (CVD), is closely associated with cholesterol accumulation in the arterial intima. Excessive cholesterol is removed by the reverse cholesterol transport (RCT) pathway, representing a major antiatherogenic mechanism. In addition to the RCT, other pathways are required for maintaining the whole-body cholesterol homeostasis. Thus, we propose a working model of integrated cholesterol transport, termed the cholesterol transport system (CTS), to describe body cholesterol metabolism. The novel model not only involves the classical view of RCT but also contains other steps, such as cholesterol absorption in the small intestine, low-density lipoprotein uptake by the liver, and transintestinal cholesterol excretion. Extensive studies have shown that dysfunctional CTS is one of the major causes for hypercholesterolemia and atherosclerosis. Currently, several drugs are available to improve the CTS efficiently. There are also several therapeutic approaches that have entered into clinical trials and shown considerable promise for decreasing the risk of CVD. In recent years, a variety of novel findings reveal the molecular mechanisms for the CTS and its role in the development of atherosclerosis, thereby providing novel insights into the understanding of whole-body cholesterol transport and metabolism. In this review, we summarize the latest advances in this area with an emphasis on the therapeutic potential of targeting the CTS in CVD patients.
作者机构：
[He, Wei-Min; Cao, Zhong; Zhu, Qin] Changsha Univ Sci & Technol, Hunan Prov Key Lab Mat Protect Elect Power & Tran, Changsha 410114, Peoples R China.;[Lin, Ying-Wu] Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Peoples R China.;[Zhu, Qin] Hunan Univ Sci & Technol, Dept Chem, Xiangtan 411201, Peoples R China.
通讯机构：
[He, Wei-Min] C;Changsha Univ Sci & Technol, Hunan Prov Key Lab Mat Protect Elect Power & Tran, Changsha 410114, Peoples R China.
关键词：
Green chemistry;Dual role;Quinoline N-oxides;Alkynes;Water
摘要：
Herein we summarized some clean preparation examples to emphasize the concept of dual roles design (or named as "two birds one stone strategy") in green and sustainable chemistry. In those examples, the reactants and/or solvent play dual roles rendering a cleaner organic preparation process. Consequently, both the chemical waste and manufacturing cost could be reduced. (C) 2019 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.
期刊：
International Journal of Pharmaceutics,2018年535(1-2):253-260 ISSN：0378-5173
通讯作者：
Zheng, Xing;Tang, Guotao
作者机构：
[Wang, Zhe; Deng, Xiangping; Tang, Guotao; Zheng, Xing] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Inst Pharm & Pharmacol, Hengyang, Peoples R China.;[Ding, Jinsong; Zhou, Wenhu] Cent S Univ, Xiangya Sch Pharmaceut Sci, Changsha, Hunan, Peoples R China.;[Zheng, Xing; Tang, Guotao] Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Zheng, X; Tang, GT] U;Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China.
关键词：
pH-sensitive micelles;pH-sensitive release;release mechanism;targeted drug delivery system
摘要：
During the past decades, chemotherapy has been regarded as the most effective method for tumor therapy, but still faces significant challenges, such as poor tumor selectivity and multidrug resistance. The development of targeted drug delivery systems brings certain dramatic advantages for reducing the side effects and improving the therapeutic efficacy. Coupling a specific stimuli-triggered drug release mechanism with these delivery systems is one of the most prevalent approaches for targeted therapy. Among these approaches, pH-sensitive micelles are regarded as the most general strategy with advantages of increasing solubility of water-insoluble drugs, pH-sensitive release, high drug loading, etc. This review will focus on the potential of pH-sensitive micelles in tumor therapy, analyze four types of drug-loaded micelles and mechanisms of drug release and give an exhaustive collection of recent investigations. Sufficient understanding of these mechanisms will help us to design more efficient pH-sensitive drug delivery system to address the challenges encountered in targeted drug delivery systems for tumor therapy.
期刊：
Chemical Communications,2018年54(4):370-373 ISSN：1359-7345
通讯作者：
Shi, Weiqun
作者机构：
[Lan, Jianhui; Cao, Xingzhong; Yuan, Liyong; Chai, Zhifang; Shi, Weiqun; Tian, Ming] Chinese Acad Sci, Inst High Energy Phys, Lab Nucl Energy Chem, Beijing 100049, Peoples R China.;[Tian, Ming] Univ South China, Sch Chem & Chem Engn, Hengyang 421001, Hunan, Peoples R China.;[Wang, Xiaolin] China Acad Engn Phys, Inst Nucl Phys & Chem, Mianyang 621900, Sichuan, Peoples R China.;[Chai, Zhifang] Soochow Univ, Sch Radiol & Interdisciplinary Sci, Suzhou 215123, Peoples R China.;[Gibson, John K.] Lawrence Berkeley Natl Lab, Chem Sci Div, Berkeley, CA 94720 USA.
通讯机构：
[Shi, Weiqun] C;Chinese Acad Sci, Inst High Energy Phys, Lab Nucl Energy Chem, Beijing 100049, Peoples R China.
摘要：
The preliminary results described here show that the adsorbability of uranyl ions by a highly stable MOF UiO-66 can be drastically enhanced by tailoring the missing-linker defects in this MOF. The combination of defect-induced functionality improvement with the acid-resistant nature of UiO-66 substantiates the applicability of this material for actinide capture from acidic media.
作者机构：
[Wang Xiao-kang; Wang Jian-qiang; Tian Zhang-peng; Nie Ru-xin] Cent S Univ, Sch Business, Changsha 410083, Peoples R China.;[Wang Tie-li] Univ South China, Sch Management, Hengyang 421001, Peoples R China.
通讯机构：
[Wang Xiao-kang] C;Cent S Univ, Sch Business, Changsha 410083, Peoples R China.
关键词：
Best-worst method;Complex proportional assessment;Failure mode and effects analysis;Linguistic distribution assessment;Multi-granular linguistic
摘要：
The sustainability challenge is increasingly driving the adoption of supercritical water gasification (SCWG) technology to ensure the elimination and recovery of pollution produced by sewage sludge treatment (SST). Risk evaluation by failure mode and effects analysis (FMEA) plays a crucial role in guaranteeing the reliability and safety of SCWG systems. However, some limitations in existing FMEA methods need to be ameliorated. Multiple risk factors are involved in prioritizing risk levels for failure modes in SCWG systems, it is essential a multiple criteria decision making (MCDM) process, in which overall assessments of failure modes should be provided according to their performances from several points during a system operation period. Due to differences in knowledge backgrounds and experiences, FMEA team members prefer to utilize multi-granular linguistic term sets to express their assessments of system risk. A hybrid risk evaluation model by FMEA is exploited with multi-granular linguistic distribution assessments to suit practical case. Best-worst and maximizing derivation methods are adopted to determine subjective and objective combined weights for distinguishing the importance of risk factors. Complex proportional assessment method is used to prioritize failure modes for explicitly and effectively reflecting the risk level of each failure mode. The proposed model is applied in a practical case of an SCWG system used in SST. Results derived from comparative and sensitivity analyses fully demonstrate the reliability and validity of the model.
摘要：
To overcome the deficiencies of weak local search ability in genetic algorithms (GA) and slow global convergence speed in ant colony optimization (ACO) algorithm in solving complex optimization problems, the chaotic optimization method, multi-population collaborative strategy and adaptive control parameters are introduced into the GA and ACO algorithm to propose a genetic and ant colony adaptive collaborative optimization (MGACACO) algorithm for solving complex optimization problems. The proposed MGACACO algorithm makes use of the exploration capability of GA and stochastic capability of ACO algorithm. In the proposed MGACACO algorithm, the multi-population strategy is used to realize the information exchange and cooperation among the various populations. The chaotic optimization method is used to overcome long search time, avoid falling into the local extremum and improve the search accuracy. The adaptive control parameters is used to make relatively uniform pheromone distribution, effectively solve the contradiction between expanding search and finding optimal solution. The collaborative strategy is used to dynamically balance the global ability and local search ability, and improve the convergence speed. Finally, various scale TSP are selected to verify the effectiveness of the proposed MGACACO algorithm. The experiment results show that the proposed MGACACO algorithm can avoid falling into the local extremum, and takes on better search precision and faster convergence speed.
作者机构：
[Yu, B. X.; Hu, T.; Sun, Z. J.; Guo, R. P.; Ning, Z.; Wen, S. P.; Sun, G. X.; Ma, M. M.; Min, J.; Zhao, Ling; Ai, X. C.; Zhu, Z. A.; Xu, G. F.; Wang, K.; Heng, Y. K.; Ji, Q.; Zhang, J. W.; Rong, G.; Li, H. J.; Wang, Y. F.; Wang, L. L.; Jin, D. P.; Xiu, Q. L.; Lu, Y.; Ouyang, Q.; Sun, J. F.; Ji, X. B.; Zhang, J. Q.; Qian, S.; Wang, P.; Dong, M. Y.; Prasad, V.; Fang, S. S.; Chang, J. F.; Liu, Z. A.; Sun, S. S.; Fu, C. D.; Zhang, Y.; Lou, X. C.; Wang, Z. G.; Zhang, B. X.; Sun, X. H.; Cao, G. F.; Xu, J. J.; Wu, L. H.; Zhao, Y. B.; Gao, Q.; Zheng, J. P.; Zhang, B. Y.; Jiang, X. S.; Gu, M. H.; Lu, Y. P.; Dong, L. Y.; Zhao, G.; Wu, L. J.; Yuan, Y.; Wu, Z.; Fang, Y.; Luo, X. L.; Ji, X. L.; Li, H. B.; Zhuang, J.; Li, J. C.; Guo, A. Q.; Zhang, J. Y.; Guo, Y.; Wang, L. S.; Yin, J. H.; Jin, S.; Song, W. M.; Zhang, J. Z.; He, K. L.; Chen, G.; Chen, J. C.; Ablikim, M.; Liu, C. X.; Zhu, K.; Qin, X. S.; Liu, H. H.; Wang, W.; Bai, J. Z.; Zhao, J. Z.; Mao, Z. P.; Zhao, Q.; Lu, J. G.; Liu, P. L.; Chen, Y. B.; Niu, S. L.; Liu, J.; Wang, Z.; Liu, Fang; Zhao, J. Y.; Dong, J.; Zhang, C. C.; Zhang, D. H.; Guan, Y. H.; Yuan, C. Z.; Zhang, H. Y.; Chen, M. L.; Ma, T.; Hou, Z. L.; Sun, Y. Z.; Liu, B. J.; Min, T. J.; Zhu, K. J.; Liu, H. M.; Ma, H. L.; Ye, M.; Xie, Y. G.; Sheng, H. Y.; Song, X. Y.; Zou, B. S.; Chen, H. S.; Deng, Z. Y.; Ma, Q. M.; Wang, Z. Y.; Zhao, T. C.; Zhao, Q. W.; Cai, X.; Xu, L.; Zhang, Y. H.; Zhu, S.; An, F. F.; Zou, J. H.; Zhang, J. L.; Liu, J. Y.; Li, W. G.; Niu, X. Y.; Mo, X. H.; Zhou, L.; Fang, J.; Shen, X. Y.; Zhu, Y. S.; Li, X. N.; Ma, X. Y.; Hu, H. M.; Gong, W. X.; Wang, P. L.; Zhang, J.; Duan, P. F.; Hu, Y.; Kang, X. L.; Zhang, L.; Li, F.; Zhang, K.; Zhou, X. Y.; Tang, X.; Chen, X.; Yang, H. X.; Qin, Z. H.; Xiao, D.; Li, G.; Ping, R. G.; Qiu, J. F.; Zhao, J. W.; Zhang, J. J.; Dai, H. L.; Li, W. D.] Inst High Energy Phys, Beijing 100049, Peoples R China.;[Qi, H. R.; Li, Y. B.; Shen, C. P.] Beihang Univ, Beijing 100191, Peoples R China.;[Li, Lei] Beijing Inst Petrochem Technol, Beijing 102617, Peoples R China.;[Musiol, P.; Heinsius, F. H.; Pelizaeus, M.; Zhu, S. H.; Kopf, B.; Albrecht, M.; Holtmann, T.; Schnier, C.; Wiedner, U.; Held, T.] Ruhr Univ Bochum, D-44780 Bochum, Germany.;[Ke, B. C.; Briere, R. A.; Albayrak, O.; Bennett, J. V.] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA.
通讯机构：
[Ablikim, M.] I;Inst High Energy Phys, Beijing 100049, Peoples R China.
摘要：
Cervical cancer contributed the second highest number of deaths in female cancers, exceeded only by breast cancer, carrying high risks of morbidity and mortality. There was a great need and urgency in searching novel treatment targets and prognosis biomarkers to improve the survival rate of cervical cancer patients. Many long non-coding RNAs (lncRNAs) were emerging as pivotal regulators in various biological processes and took vitally an effect on the oncogenesis and progression of cervical cancer. In this review, we summarized the origin and overview function of lncRNAs; highlighted the roles of lncRNAs in cervical cancer in terms of prognosis and tumor progression, invasion and metastasis, apoptosis, and radio-resistance; and outlined the molecular mechanisms of lncRNAs in cervical cancer from the aspects of the interaction of lncRNAs with proteins/mRNAs (especially in HPV protein) and miRNAs, as well as RNA N-methyladenosine (m6A) methylation of lncRNAs. Meanwhile, the application of lncRNAs as biomarkers in cervical cancer prognosis and predictors for metastasis was also discussed. An overview of these researches will be valuable for broadening horizons into mechanisms, selection of meritorious biomarkers for diagnosis as well as prognosis, and future targeted therapy of cervical cancer.
作者机构：
[Yu, B. X.; Mao, Z. P.; Zhao, Q.; Lu, J. G.; Liu, Zhiqiang; Chen, Y. B.; He, M.; Hu, T.; Wang, Z.; Liu, Fang; Sun, Z. J.; Xue, Z.; Ning, Z.; Zhang, C. C.; Wen, S. P.; Sun, G. X.; Zhang, D. H.; Li, C. H.; Yuan, C. Z.; Min, J.; Zhang, H. Y.; Zhao, Ling; Chen, M. L.; Ma, T.; Zhu, Z. A.; Xu, G. F.; Wang, K.; Heng, Y. K.; Ji, Q.; Zhang, J. W.; Hou, Z. L.; Rong, G.; Li, Lei; Sun, Y. Z.; Liu, B. J.; Min, T. J.; Wang, Y. F.; Zhu, K. J.; Liu, H. M.; Li, Q. J.; Ma, H. L.; Wang, L. L.; Jin, D. P.; Xiu, Q. L.; Ye, M.; Xie, Y. G.; Sheng, H. Y.; Ouyang, Q.; Song, X. Y.; Ma, S.; Zou, B. S.; Chen, H. S.; Ji, X. B.; Zhang, J. Q.; Qian, S.; Wang, P.; Deng, Z. Y.; Ma, Q. M.; Dong, M. Y.; Fang, S. S.; Chang, J. F.; Wang, Z. Y.; Zhao, T. C.; Liu, Z. A.; Cai, X.; Lv, M.; Wu, N.; Zhang, Y. H.; Wang, Q. J.; An, F. F.; Ye, H.; Sun, S. S.; Fu, C. D.; Zhang, Y.; Lou, X. C.; Zou, J. H.; Wang, Z. G.; Zhang, J. L.; Jiang, L. L.; Zhang, B. X.; Zhang, X. J.; Lai, W.; Li, W. G.; Cao, G. F.; Mo, X. H.; Zhou, L.; Wu, L. H.; Fang, J.; Zhao, Y. B.; Huang, L.; Shen, X. Y.; Zheng, J. P.; Zhu, Y. S.; Li, X. N.; Zhang, B. Y.; Jiang, X. S.; Gu, M. H.; Lu, Y. P.; Dong, L. Y.; Ma, X. Y.; Hu, H. M.; Li, K.; Gong, W. X.; Dai, J. P.; Wang, P. L.; Zhao, G.; Wang, B.; Yuan, Y.; Wu, Z.; Chu, Y. P.; Luo, X. L.; Ji, X. L.; Li, H. B.; Zhuang, J.; Li, J. C.; Liu, Zhiqing; Zhang, S. H.; Li, F.; Zhang, J. Y.; Wang, L. S.; Jin, S.; Tang, X.; Song, W. M.; Yang, H. X.; Qin, Z. H.; Li, G.; Zhang, J. Z.; He, K. L.; Chen, G.; Ping, R. G.; Qiu, J. F.; Zhao, J. W.; Chen, J. C.; Ablikim, M.; Han, Y. L.; Liu, C. X.; Zhu, K.; Qin, X. S.; Dai, H. L.; Li, W. D.; Bai, J. Z.] Inst High Energy Phys, Beijing 100049, Peoples R China.;[Shen, C. P.] Beihang Univ, Beijing 100191, Peoples R China.;[Leyhe, M.; Wiedner, U.; Becker, J.; Pelizaeus, M.; Kopf, B.; Friedel, P.; Held, T.] Ruhr Univ Bochum, D-44780 Bochum, Germany.;[Briere, R. A.; Liu, C. L.; Albayrak, O.] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA.;[Yang, Y.; Liu, Feng; Huang, G. M.; Zhang, Zhenghao] Cent China Normal Univ, Wuhan 430079, Peoples R China.
通讯机构：
[Ablikim, M.] I;Inst High Energy Phys, Beijing 100049, Peoples R China.
作者：
Chalhoub, Boulos;Denoeud, France;Liu, Shengyi;Parkin, Isobel A. P.;Tang, Haibao;...
期刊：
Science,2014年345(6199):950-953 ISSN：0036-8075
通讯作者：
Chalhoub, B.
作者机构：
[Samans, Birgit; Snowdon, Rod J.] Department of Plant Breeding, Research Center for Biosystems, Land Use and Nutrition, Justus Liebig University, Heinrich-Buff-Ring 26-32, 35392 Giessen, Germany.;[Guan, Mei; Liu, Zhongsong; Guan, Chunyun] College of Agronomy, Hunan Agricultural University, Changsha 410128, China.;[Town, Christopher D.] J. Craig Venter Institute, Rockville, MD 20850, USA.;Center for Genomics and Biotechnology, Fujian Agriculture and Forestry, University, Fuzhou 350002, Fujian Province, China.;[Renault, Victor] Fondation Jean Dausset–Centre d’Étude du Polymorphisme Humain, 27 rue Juliette Dodu, 75010 Paris, France.
通讯机构：
[Boulos Chalhoub] I;[Isobel A. P. Parkin; David Edwards] A;[Yongming Zhou; Andrew G. Sharpe] N;[Wei Hua] K;[Andrew H. Paterson] P
摘要：
Oilseed rape (Brassica napus L.) was formed ~7500 years ago by hybridization between B. rapa and B. oleracea, followed by chromosome doubling, a process known as allopolyploidy. Together with more ancient polyploidizations, this conferred an aggregate 72× genome multiplication since the origin of angiosperms and high gene content. We examined the B. napus genome and the consequences of its recent duplication. The constituent An and Cn subgenomes are engaged in subtle structural, functional, and epigenetic cross-talk, with abundant homeologous exchanges. Incipient gene loss and expression divergence have begun. Selection in B. napus oilseed types has accelerated the loss of glucosinolate genes, while preserving expansion of oil biosynthesis genes. These processes provide insights into allopolyploid evolution and its relationship with crop domestication and improvement.
