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Liver cancer is one of the most prevalent malignant tumors worldwide. According to the staging criteria of Barcelona Clinic Liver Cancer, clinical guidelines provide tutorials to clinical management of liver cancer at their individual stages. However, most patients diagnosed with liver cancer are at advanced stage, thereby, many researchers conduct investigations on targeted therapy, aiming to improve the overall survival of these patients. To date, small molecule-based targeted therapies are highly recommended (fist-line: Sorafenib and Lenvatinib; second-line: Regorafenib and Cabozantinib) by current clinical guidelines of American Society of Clinical Oncology, European Society for Medical Oncology, and National Comprehensive Cancer Network. Herein, we summarize the small molecule-based targeted therapies in liver cancer, including the approved and preclinical therapies as well as the therapies under clinical trials, and introduce their history of discovery, clinical trials, indications, and molecular mechanisms. For drug resistance, the revealed mechanisms of action and the combination therapies are also discussed. In fact, the known small molecule-based therapies still have limited clinical benefits to liver cancer patients. Therefore, we analyze the current status and give our ideas for the urgent issues and future directions in this field, suggesting the clues for novel techniques in liver cancer treatment.
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OBJECTIVE: To assess the practical and health economical values of non-invasive prenatal test (NIPT) in Changsha Municipal Public Welfare Program. METHODS: A retrospective analysis was carried out on 149 165 women undergoing NIPT test from April 9, 2018 to December 31, 2019. For pregnant women with high risks, invasive prenatal diagnosis and follow-up of pregnancy outcome were conducted. The cost-benefit of NIPT for Down syndrome was analyzed. RESULTS: NIPT was carried out for 149 165 pregnant women and succeeded in 148 749 cases (99.72%), for which outcome were available in 148 538 (99.86%). 90% of pregnant women from the region accepted the screening with NIPT. 415 (0.27%) were diagnosed as high risk. Among these, 381 (91.81%) accepted amniocentesis, which led to the diagnosis of 212 cases of trisomy 21 (PPV=85.14%), 41 cases with trisomy 18 (PPV=48.81%) and 10 cases with trisomy 13 (PPV=20.83%). The sensitivity and specificity of NIPT for trisomy 21, trisomy 18 and trisomy 13 were (97.70%, 99.98%), (97.62%, 9.97%) and (100%, 99.97%), respectively. In addition, 213 and 30 cases were diagnosed with sex chromosomal aneuploidies (PPV=46.2%) and other autosomal anomalies (PPV=16.57%), respectively. For Down syndrome screening, the cost and benefit of the project was 120.79 million yuan and 1,056.95 million yuan, respectively. The cost-benefit ratio was 1: 8.75, and safety index was 0.0035. CONCLUSION: NIPT is a highly accurate screening test for trisomy 21, which was followed by trisomy 18 and sex chromosomal aneuploidies, while it was less accurate for other autosomal aneuploidies. The application of NIPT screening has a high health economical value.
Assuntos
Teste Pré-Natal não Invasivo , Aneuploidia , Análise Custo-Benefício , Feminino , Humanos , Gravidez , Estudos Retrospectivos , Síndrome da Trissomía do Cromossomo 18/diagnóstico , Síndrome da Trissomía do Cromossomo 18/genéticaRESUMO
A fuzzy adaptive tracking control scheme is studied for a family of uncertain systems with immeasurable system states. The controller takes up few computation and transmission resources to achieve prescribed boundaries of the dynamic and steady-state performance indicators. Compared with the existing schemes, the low computational complexity is reflected in the following two points: (1) a fuzzy state observer is introduced, where only the estimation of states are incorporated into the input space of fuzzy logic systems (FLSs). (2) The problem of complexity explosion can be avoided without utilizing additional command filters or auxiliary dynamic surface control techniques. In addition, using the event-triggered control scheme, the data in the transmission is significantly reduced. Finally, the effectiveness of the scheme is fully verified by simulation.
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This paper is devoted to the prescribed performance control (PPC) for a class of strict-feedback nonlinear systems with input saturation constraints. With the help of an improved tuning function, the system can achieve the desired steady-state and transient performance in the pre-designed time. A new error transformation function is introduced, which has inherent robustness, so it does not need to use any approximation technique or calculate the analytical derivative. Compared with the relevant results, the proposed scheme has the same lower complexity, but better transient and steady-state performance, although there exists uncertain nonlinearity and uncertain disturbances in the system. Finally, the correctness of the above algorithm is verified by simulation experiments.
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The problem of event-triggered prescribed performance control for a class of uncertain nonlinear systems with unknown control directions and faults is investigated. Compared with the existing methods, a new set of error transformation functions is defined for the first time. Although no approximate structure is adopted, prescribed performance control (PPC) and event triggered control (ETC) are realized simultaneously for the nonlinear system considered in this paper for the first time. The proposed control scheme can guarantee that all closed-loop signals are bounded, and the tracking error, as well as all state errors, converges within the adjustable constraint functions. Finally, two simulation experiments verify the effectiveness of the proposed algorithm.