Approximately 1 in 8 women will develop breast cancer during their lifetime and the risk factors include age, family history, and reproductive factors. In women with a family history of breast cancer, there is a propo...Approximately 1 in 8 women will develop breast cancer during their lifetime and the risk factors include age, family history, and reproductive factors. In women with a family history of breast cancer, there is a proportion in which a gene mutation can be the cause of the predisposition for breast cancer. A careful assessment of family and clinical history should be performed in these women in order to determine if a genetic counseling referral is indicated. In cases of hereditary breast cancer, genetic testing with a multigene panel can identify specific genetic mutations in over 100 genes. The most common genes mutated in hereditary breast cancer are the high-penetrance BRCA1 and BRCA2 genes. In addition, other mutations in high-penetrance genes in familial cancer syndromes and mutations in DNA repair genes can cause hereditary breast cancer. Mutations in low-penetrance genes and variants of uncertain signifcance may play a role in breast cancer development, but the magnitude and scope of risk in these cases remain unclear, thus the clinical utility of testing for these mutations is uncertain. In women with high-penetrance genetic mutations or lifetime risk of breast cancer 〉 20%, risk-reducing interventions, such as intensive screening, surgery, and chemoprevention, can decrease the incidence and mortality of breast cancer.展开更多
Objective:To study the clinical effects of multigene combination test to guide chemotherapy combined with targeted therapy in patients with advanced gastrointestinal tumors.Methods:The samples were selected from 60 pa...Objective:To study the clinical effects of multigene combination test to guide chemotherapy combined with targeted therapy in patients with advanced gastrointestinal tumors.Methods:The samples were selected from 60 patients with advanced gastrointestinal tumors admitted to our hospital from March 2019 to July 2020,and were divided into a study group and a control group using a random number table model;patients in the control group did not undergo genetic testing and FOLLOX4+PD-1 chemotherapy,while patients in the study group underwent TYMS,ERCC1,EGFR,and KRAS and VEGF gene expression levels test,and the sensitive treatment plan was determined based on the test results,and the clinical indexes were compared between the two groups.Results:By comparing the total effective rate,survival time,and time to disease progression of chemotherapy in the two groups,the study group has a significant advantage(P<0.05).Conclusion:The combination of chemotherapy and targeted therapy for advanced gastrointestinal tumor patients can improve the efficiency of chemotherapy and prolong the time of disease progression and survival,which is worthy of comprehensive promotion.展开更多
Microorganisms are often likened to complex production workshops.In Saccharopolyspora spinosa(S.spinosa),the biosynthesis of spinosad is a production line within its intricate workshop.Optimizing the entire production...Microorganisms are often likened to complex production workshops.In Saccharopolyspora spinosa(S.spinosa),the biosynthesis of spinosad is a production line within its intricate workshop.Optimizing the entire production environment and reducing unnecessary metabolic flow is essential to increasing spinosad yield.Pyruvate serves as a crucial precursor for spinosad biosynthesis.Previous studies revealed that the pyc gene is highly expressed in the gluconeogenic pathway,leading to a pyruvate shunt.By downregulating pyc,we enhanced spinosad yield,although the improvement was below expectations.We speculated that most of the accumulated pyruvate following the pyc knockdown entered some synthetic pathways unrelated to spinosad.Through metabolic pathway and qRT-PCR analyses,we found that the expression levels of gltA1 and atoB3 within the pyruvate metabolic tributary,including the TCA cycle and ethylmalonyl-CoA pathway,were significantly increased in the pyc knockdown strain.The combined knockdown of these three genes optimized the spinosad production line,increasing its yield to 633.1±38.6 mg/L,representing a 199.4%increase.This study identifies three key genes for optimizing spinosad biosynthesis and offers insights into gene screening and the efficient construction of Spinosad-producing strains.展开更多
Understanding scale-up effects on the hydrodynamics of a liquid-solid circulating fluidized bed(LSCFB)unit requires both experimental and theoretical analysis.We implement multigene genetic programming(MGGP)to investi...Understanding scale-up effects on the hydrodynamics of a liquid-solid circulating fluidized bed(LSCFB)unit requires both experimental and theoretical analysis.We implement multigene genetic programming(MGGP)to investigate the solid holdup and distribution in three LSCFB systems with different heights.In addition to data obtained here,we also use a portion of data sets of LSCFB systems developed by Zheng(1999)and Liang et al.(1996).Model predictions are in good agreement with the experimental data in both radial and axial directions and at different normalized superficial liquid and solid velocities.The radial profiles of the solid holdup are approximately identical at a fixed average cross-sectional solid holdup for the three LSCFB systems studied.Statistical performance indicators including the mean absolute percentage error(6.19%)and correlation coefficient(0.985)are within an acceptable range.The results suggest that a MGGP modeling approach is suitable for predicting the solid holdup and distribution of a scaled-up LSCFB system.展开更多
文摘Approximately 1 in 8 women will develop breast cancer during their lifetime and the risk factors include age, family history, and reproductive factors. In women with a family history of breast cancer, there is a proportion in which a gene mutation can be the cause of the predisposition for breast cancer. A careful assessment of family and clinical history should be performed in these women in order to determine if a genetic counseling referral is indicated. In cases of hereditary breast cancer, genetic testing with a multigene panel can identify specific genetic mutations in over 100 genes. The most common genes mutated in hereditary breast cancer are the high-penetrance BRCA1 and BRCA2 genes. In addition, other mutations in high-penetrance genes in familial cancer syndromes and mutations in DNA repair genes can cause hereditary breast cancer. Mutations in low-penetrance genes and variants of uncertain signifcance may play a role in breast cancer development, but the magnitude and scope of risk in these cases remain unclear, thus the clinical utility of testing for these mutations is uncertain. In women with high-penetrance genetic mutations or lifetime risk of breast cancer 〉 20%, risk-reducing interventions, such as intensive screening, surgery, and chemoprevention, can decrease the incidence and mortality of breast cancer.
文摘Objective:To study the clinical effects of multigene combination test to guide chemotherapy combined with targeted therapy in patients with advanced gastrointestinal tumors.Methods:The samples were selected from 60 patients with advanced gastrointestinal tumors admitted to our hospital from March 2019 to July 2020,and were divided into a study group and a control group using a random number table model;patients in the control group did not undergo genetic testing and FOLLOX4+PD-1 chemotherapy,while patients in the study group underwent TYMS,ERCC1,EGFR,and KRAS and VEGF gene expression levels test,and the sensitive treatment plan was determined based on the test results,and the clinical indexes were compared between the two groups.Results:By comparing the total effective rate,survival time,and time to disease progression of chemotherapy in the two groups,the study group has a significant advantage(P<0.05).Conclusion:The combination of chemotherapy and targeted therapy for advanced gastrointestinal tumor patients can improve the efficiency of chemotherapy and prolong the time of disease progression and survival,which is worthy of comprehensive promotion.
基金supported by funding from the National Natural Science Foundation of China(31770106,32200062)the Natural Science Foundation of Hunan Province(2024JJ5258).
文摘Microorganisms are often likened to complex production workshops.In Saccharopolyspora spinosa(S.spinosa),the biosynthesis of spinosad is a production line within its intricate workshop.Optimizing the entire production environment and reducing unnecessary metabolic flow is essential to increasing spinosad yield.Pyruvate serves as a crucial precursor for spinosad biosynthesis.Previous studies revealed that the pyc gene is highly expressed in the gluconeogenic pathway,leading to a pyruvate shunt.By downregulating pyc,we enhanced spinosad yield,although the improvement was below expectations.We speculated that most of the accumulated pyruvate following the pyc knockdown entered some synthetic pathways unrelated to spinosad.Through metabolic pathway and qRT-PCR analyses,we found that the expression levels of gltA1 and atoB3 within the pyruvate metabolic tributary,including the TCA cycle and ethylmalonyl-CoA pathway,were significantly increased in the pyc knockdown strain.The combined knockdown of these three genes optimized the spinosad production line,increasing its yield to 633.1±38.6 mg/L,representing a 199.4%increase.This study identifies three key genes for optimizing spinosad biosynthesis and offers insights into gene screening and the efficient construction of Spinosad-producing strains.
基金support provided by King Abdulaziz City for Science and Technology(KACST)through the Science&Technology Unit at King Fahd University of Petroleum&Minerals(KFUPM)for funding of this work,project No.NSTIP#13-WAT96-04,as part of the National Science,Technology and Innovation Plan.
文摘Understanding scale-up effects on the hydrodynamics of a liquid-solid circulating fluidized bed(LSCFB)unit requires both experimental and theoretical analysis.We implement multigene genetic programming(MGGP)to investigate the solid holdup and distribution in three LSCFB systems with different heights.In addition to data obtained here,we also use a portion of data sets of LSCFB systems developed by Zheng(1999)and Liang et al.(1996).Model predictions are in good agreement with the experimental data in both radial and axial directions and at different normalized superficial liquid and solid velocities.The radial profiles of the solid holdup are approximately identical at a fixed average cross-sectional solid holdup for the three LSCFB systems studied.Statistical performance indicators including the mean absolute percentage error(6.19%)and correlation coefficient(0.985)are within an acceptable range.The results suggest that a MGGP modeling approach is suitable for predicting the solid holdup and distribution of a scaled-up LSCFB system.