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Computed tomography-based radiomic model for the prediction of neoadjuvant immunochemotherapy response in patients with advanced gastric cancer
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作者 Jun Zhang Qi Wang +8 位作者 Tian-Hui Guo Wen Gao Yi-Miao Yu Rui-Feng Wang Hua-Long Yu Jing-Jing Chen ling-ling sun Bi-Yuan Zhang Hai-Ji Wang 《World Journal of Gastrointestinal Oncology》 SCIE 2024年第10期4115-4128,共14页
BACKGROUND Neoadjuvant immunochemotherapy(nICT)has emerged as a popular treatment approach for advanced gastric cancer(AGC)in clinical practice worldwide.However,the response of AGC patients to nICT displays significa... BACKGROUND Neoadjuvant immunochemotherapy(nICT)has emerged as a popular treatment approach for advanced gastric cancer(AGC)in clinical practice worldwide.However,the response of AGC patients to nICT displays significant heterogeneity,and no existing radiomic model utilizes baseline computed tomography to predict treatment outcomes.AIM To establish a radiomic model to predict the response of AGC patients to nICT.METHODS Patients with AGC who received nICT(n=60)were randomly assigned to a training cohort(n=42)or a test cohort(n=18).Various machine learning models were developed using selected radiomic features and clinical risk factors to predict the response of AGC patients to nICT.An individual radiomic nomogram was established based on the chosen radiomic signature and clinical signature.The performance of all the models was assessed through receiver operating characteristic curve analysis,decision curve analysis(DCA)and the Hosmer Lemeshow goodness-of-fit test.RESULTS The radiomic nomogram could accurately predict the response of AGC patients to nICT.In the test cohort,the area under curve was 0.893,with a 95%confidence interval of 0.803-0.991.DCA indicated that the clinical application of the radiomic nomogram yielded greater net benefit than alternative models.CONCLUSION A nomogram combining a radiomic signature and a clinical signature was designed to predict the efficacy of nICT in patients with AGC.This tool can assist clinicians in treatment-related decision-making. 展开更多
关键词 Gastric cancer Radiomics Computed tomography Neoadjuvant immunochemotherapy Machine learning IMMUNOLOGY
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Preoperative perineural invasion in rectal cancer based on deep learning radiomics stacking nomogram: A retrospective study
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作者 Zhi-Chun Zhao Jia-Xuan Liu ling-ling sun 《Artificial Intelligence in Medical Imaging》 2024年第1期1-12,共12页
BACKGROUND The presence of perineural invasion(PNI)in patients with rectal cancer(RC)is associated with significantly poorer outcomes.However,traditional diagnostic modalities have many limitations.AIM To develop a de... BACKGROUND The presence of perineural invasion(PNI)in patients with rectal cancer(RC)is associated with significantly poorer outcomes.However,traditional diagnostic modalities have many limitations.AIM To develop a deep learning radiomics stacking nomogram model to predict preoperative PNI status in patients with RC.METHODS We recruited 303 RC patients and separated them into the training(n=242)and test(n=61)datasets on an 8:2 scale.A substantial number of deep learning and hand-crafted radiomics features of primary tumors were extracted from the arterial and venous phases of computed tomography(CT)images.Four machine learning models were used to predict PNI status in RC patients:support vector machine,k-nearest neighbor,logistic regression,and multilayer perceptron.The stacking nomogram was created by combining optimal machine learning models for the arterial and venous phases with predicting clinical variables.RESULTS With an area under the curve(AUC)of 0.964[95%confidence interval(CI):0.944-0.983]in the training dataset and an AUC of 0.955(95%CI:0.900-0.999)in the test dataset,the stacking nomogram demonstrated strong performance in predicting PNI status.In the training dataset,the AUC of the stacking nomogram was greater than that of the arterial support vector machine(ASVM),venous SVM,and CT-T stage models(P<0.05).Although the AUC of the stacking nomogram was greater than that of the ASVM in the test dataset,the difference was not particularly noticeable(P=0.05137).CONCLUSION The developed deep learning radiomics stacking nomogram was effective in predicting preoperative PNI status in RC patients. 展开更多
关键词 Rectal cancer Perineural invasion Radiomics Deep learning Machine learning
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Tongxinluo promotes endothelium-dependent arteriogenesis to attenuate diabetic peripheral arterial disease
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作者 Jiao-Jiao Gu Yun-Long Hou +10 位作者 Yi-Hui Yan Jie Li Ya-Ru Wei Kun Ma Xiao-Qi Wang Jie-Han Zhang Dan-Dong Wang Cui-Ru Li Dong-Qi Li ling-ling sun Huai-Lin Gao 《World Journal of Diabetes》 SCIE 2023年第3期234-254,共21页
BACKGROUND Peripheral arterial disease(PAD)has become one of the leading causes of disability and death in diabetic patients.Restoring blood supply to the hindlimbs,especially by promoting arteriogenesis,is currently ... BACKGROUND Peripheral arterial disease(PAD)has become one of the leading causes of disability and death in diabetic patients.Restoring blood supply to the hindlimbs,especially by promoting arteriogenesis,is currently the most effective strategy,in which endothelial cells play an important role.Tongxinluo(TXL)has been widely used for the treatment of cardio-cerebrovascular diseases and extended for diabetes-related vascular disease.AIM To investigate the effect of TXL on diabetic PAD and its underlying mechanisms.METHODS An animal model of diabetic PAD was established by ligating the femoral artery of db/db mice.Laser Doppler imaging and micro-computed tomography(micro-CT)were performed to assess the recovery of blood flow and arteriogenesis.Endothelial cell function related to arteriogenesis and cellular pyroptosis was assessed using histopathology,Western blot analysis,enzyme-linked immunosorbent assay and real-time polymerase chain reaction assays.In vitro,human vascular endothelial cells(HUVECs)and human vascular smooth muscle cells(VSMCs)were pretreated with TXL for 4 h,followed by incubation in high glucose and hypoxia conditions to induce cell injury.Then,indicators of HUVEC pyroptosis and function,HUVECVSMC interactions and the migration of VSMCs were measured.RESULTS Laser Doppler imaging and micro-CT showed that TXL restored blood flow to the hindlimbs and enhanced arteriogenesis.TXL also inhibited endothelial cell pyroptosis via the reactive oxygen species/nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3/Caspase-1/GSDMD signaling pathway.In addition,TXL restored endothelial cell functions,including maintaining the balance of vasodilation,acting as a barrier to reduce inflammation,and enhancing endothelial-smooth muscle cell interactions through the Jagged-1/Notch-1/ephrin-B2 signaling pathway.Similar results were observed in vitro.CONCLUSION TXL has a pro-arteriogenic effect in the treatment of diabetic PAD,and the mechanism may be related to the inhibition of endothelial cell pyroptosis,restoration of endothelial cell function and promotion of endothelial cell-smooth muscle cell interactions. 展开更多
关键词 Diabetic peripheral arterial disease ARTERIOGENESIS Endothelial cell Inflammation PYROPTOSIS
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Factors associated with gastrointestinal stromal tumor rupture and pathological risk:A single-center retrospective study
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作者 Jia-Zheng Liu Zhong-Wen Jia ling-ling sun 《World Journal of Radiology》 2023年第12期350-358,共9页
BACKGROUND Gastrointestinal stromal tumor(GIST)is a rare gastrointestinal mesenchymal tumor with potential malignancy.Once the tumor ruptures,regardless of tumor size and mitotic number,it can be identified into a hig... BACKGROUND Gastrointestinal stromal tumor(GIST)is a rare gastrointestinal mesenchymal tumor with potential malignancy.Once the tumor ruptures,regardless of tumor size and mitotic number,it can be identified into a high-risk group.It is of great significance for the diagnosis,treatment,and prognosis of GIST if non-invasive examination can be performed before surgery to accurately assess the risk of tumor.AIM To identify the factors associated with GIST rupture and pathological risk.METHODS A cohort of 50 patients with GISTs,as confirmed by postoperative pathology,was selected from our hospital.Clinicopathological and computed tomography data of the patients were collected.Logistic regression analysis was used to evaluate factors associated with GIST rupture and pathological risk grade.RESULTS Pathological risk grade,tumor diameter,tumor morphology,internal necrosis,gas-liquid interface,and Ki-67 index exhibited significant associations with GIST rupture(P<0.05).Gender,tumor diameter,tumor rupture,and Ki-67 index were found to be correlated with pathological risk grade of GIST(P<0.05).Multifactorial logistic regression analysis revealed that male gender and tumor diameter≥10 cm were independent predictors of a high pathological risk grade of GIST[odds ratio(OR)=11.12,95%confidence interval(95%CI):1.81-68.52,P=0.01;OR=22.96,95%CI:2.19-240.93,P=0.01].Tumor diameter≥10 cm,irregular shape,internal necrosis,gas-liquid interface,and Ki-67 index≥10 were identified as independent predictors of a high risk of GIST rupture(OR=9.67,95%CI:2.15-43.56,P=0.01;OR=35.44,95%CI:4.01-313.38,P<0.01;OR=18.75,95%CI:3.40-103.34,P<0.01;OR=27.00,95%CI:3.10-235.02,P<0.01;OR=4.43,95%CI:1.10-17.92,P=0.04).CONCLUSION Tumor diameter,tumor morphology,internal necrosis,gas-liquid,and Ki-67 index are associated with GIST rupture,while gender and tumor diameter are linked to the pathological risk of GIST.These findings contribute to our understanding of GIST and may inform non-invasive examination strategies and risk assessment for this condition. 展开更多
关键词 Gastrointestinal stromal tumors Imaging findings Tumor rupture Pathological risk grades
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FLT3-ITD突变的急性髓系白血病免疫表型及临床特征分析 被引量:2
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作者 孙玲玲 孙佳英 杨威 《中国现代医学杂志》 CAS 2019年第12期58-62,共5页
目的讨论FLT3-ITD突变的急性髓系白血病(AML)的免疫表型及临床特征。方法回顾性分析2015年6月—2017年6月中国医科大学附属第四医院收治的FLT3-ITD+及FLT3-ITD-AML组患者的免疫表型、临床资料,并对两组患者化疗后临床结局及生存状况进... 目的讨论FLT3-ITD突变的急性髓系白血病(AML)的免疫表型及临床特征。方法回顾性分析2015年6月—2017年6月中国医科大学附属第四医院收治的FLT3-ITD+及FLT3-ITD-AML组患者的免疫表型、临床资料,并对两组患者化疗后临床结局及生存状况进行比较。结果FLT3-ITD+AML组患者CD56、CD33、CD11b及CD7表达高于FLT3-ITD-AML组(P<0.05),而CD34、CD117表达低于FLT3-ITD-AML组(P<0.05)。与FLT3-ITD-AML组患者比较,FLT3-ITD+AML组患者外周血白细胞计数及骨髓原始细胞比例升高(P<0.05),而血红蛋白及血小板计数比较,差异无统计学意义(P>0.05);FLT-ITD-AML组患者总反应率高于FLT3-ITD+AML组(P<0.05);FLT3-ITD-AML组患者无病生存率和总生存率高于FLT3-ITD+AML组(P<0.05)。FLT3-ITD+AML组患者完全缓解患者CD56、CD34、CD11b、CD7、CD33及CD117的表达水平低于未缓解患者(P<0.05)。结论FLT3-ITD+AML患者白血病细胞抗原表达紊乱,外周血白细胞及骨髓原始细胞高,完全缓解率低,预后差,是AML预后不良因素。AML患者早期检测FLT3-ITD突变及免疫分型对于指导治疗、判断预后具有重要临床意义。 展开更多
关键词 白血病 免疫表型分型 预后
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Survival trends in gastric cancer patients of Northeast China 被引量:13
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作者 HaoZhang ling-ling sun +4 位作者 Yan-Li Meng Guang-Yu Song Jing-Jing Hu PingLu BinJi 《World Journal of Gastroenterology》 SCIE CAS CSCD 2011年第27期3257-3262,共6页
AIM: To describe survival trends in patients in Northeast China diagnosed as gastric cancer. METHODS: A review of all inpatient and outpatient records of gastric cancer patients was conducted in the First Affiliated H... AIM: To describe survival trends in patients in Northeast China diagnosed as gastric cancer. METHODS: A review of all inpatient and outpatient records of gastric cancer patients was conducted in the First Affiliated Hospital of China Medical University. All the gastric cancer patients who satisfied the inclusion criteria from January 1, 1980 through December 31, 2003 were included in the study. The main outcomes were based on median survival and 3-year and 5-year survival rates, by decade of diagnosis. RESULTS: From 1980 through 2003, the median survival for patients with gastric cancer (n = 1604) increased from 33 mo to 49 mo. The decade of diagnosis was not significantly associated with patient survival for gastric cancer (P = 0.084 for overall survival, and P = 0.150 for 5-year survival); however, the survival rate of the 2000s was remarkably higher than that of the 1980s (P = 0.019 for overall survival, and P = 0.027 for 5-year survival).CONCLUSION: There was no significant difference of survival among each period; however, the survival rate of the 2000s was remarkably higher than that of the 1980s. 展开更多
关键词 Survival trends Gastric cancer Northeast China
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Protective effect and mechanism of ginsenoside Rg1 on H2O2 induced hippocampal neurons aging due to down-regulate NOX2 mediated NLRP1 inflammasome activation in vitro 被引量:1
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作者 Tan-zhen XU Ya-li CHEN +4 位作者 Xiao-yan SHEN ling-ling sun Bi-qiong ZHANG Da-ke HUANG Wei-zu LI 《中国药理学与毒理学杂志》 CAS CSCD 北大核心 2018年第4期321-321,共1页
OBJECTIVE To explore the protective effects and mechanisms of Ginsenoside Rg1(Rg1) on H_2O_2-induced hippocampal neurons aging in vitro.METHODS The primary culture hippo.campal neurons(7 d) were randomly placed into s... OBJECTIVE To explore the protective effects and mechanisms of Ginsenoside Rg1(Rg1) on H_2O_2-induced hippocampal neurons aging in vitro.METHODS The primary culture hippo.campal neurons(7 d) were randomly placed into six groups:normal control group,H_2O_2(200 μM) treat.ment group,and H_2O_2+Rg1(1,5 and 10μM) groups.The neurons were with Rg1(1,5 and 10 μmol·L^(-1))for 6 h.H_2O_2(200 μmol · L-1) was added to the medium and incubate for 18 h.The Dihydroethidium(DHE) staining was performed for ROS production assessment.The LDH release and Hoechst 33258 were performed to examine the neuronal damage and apoptosis.The immunoblot was used to deter.mine the expression of β-Gal,NOX2,p22 phox,p47 phox,NLRP-1,ASC and Caspase-1 in hippocampal neurons.The ELISA was performed to detect the levels of IL-1β and IL-18 released in the supernatant in hippocampal neurons.RESULTS Rg1(5 and 10 μmol·L^(-1)) significantly reduced the ROS production,attenuated H_2O_2-induced neuronal damage and apoptosis(P<0.05,P<0.01).The immunoblot results showed that Rg1(5 and 10 μmol·L^(-1)) treatment significantly decreased the expression of β-Gal,NOX2,p22 phox,p47 phox,NLRP-1,ASC and Caspase-1 in hippocampal neurons(P<0.05,P<0.01).Additionally,Rg1(5 and 10 μmol·L^(-1)) treatment significantly decreased IL-1β and IL-18 release in the supernatant.CONCLUSION The protective effect of Rg1 in H_2O_2-induced hippocampal neurons aging may be due to inhibit NOX2-NLRP1 activation. 展开更多
关键词 人参皂甙 海马神经体 治疗方法 临床分析
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2+0 CYP21A2 deletion carrier—a limitation of the genetic testing and counseling:A case report
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作者 Na Xi Xiao Song +4 位作者 Xue-Yan Wang Sheng-Fang Qin Guan-Nan He ling-ling sun Xi-Min Chen 《World Journal of Clinical Cases》 SCIE 2021年第23期6789-6797,共9页
BACKGROUND CYP21A2 gene mutations may all cause reduction or loss of 21-hydroxylase activity,leading to development of congenital adrenal hyperplasia(CAH)with different clinical phenotypes.For families with CAH childr... BACKGROUND CYP21A2 gene mutations may all cause reduction or loss of 21-hydroxylase activity,leading to development of congenital adrenal hyperplasia(CAH)with different clinical phenotypes.For families with CAH children,genetic testing of the parents and genetic counseling are recommended to assess the risk of recurrence.CASE SUMMARY We report a case of CAH with a high suspicion before delivery.The risk of the child suffering from CAH during the pregnancy had been underestimated due to the deviation of genetic counseling and genetic testing results.Our report confirmed a CYP21A2 homozygous deletion in this case,CYP21A2 heterozygous deletion in the mother,and a rare 2+0 CYP21A2 deletion in the father.CONCLUSION It is important to analyze the distribution of CYP21A2 gene in the two alleles of parents of children with CAH. 展开更多
关键词 CYP21A2 gene mutations Congenital adrenal hyperplasia PREGNANCY Genetic counseling Genetic testing Pathogenic point mutations Alleles
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Extraosseous spinal epidural plasmocytoma associated with multiple myeloma: Two case reports
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作者 Jiu-Fa Cui ling-ling sun +1 位作者 Hua Liu Chuan-Ping Gao 《World Journal of Clinical Cases》 SCIE 2021年第11期2555-2561,共7页
BACKGROUND Multiple myeloma is a malignant hematological disease characterized by proliferation of monoclonal plasma cells mainly in the bone marrow.Extraosseous epidural plasmacytoma associated with myeloma arises fr... BACKGROUND Multiple myeloma is a malignant hematological disease characterized by proliferation of monoclonal plasma cells mainly in the bone marrow.Extraosseous epidural plasmacytoma associated with myeloma arises from lymphoid tissue in the epidural space without focal vertebral involvement,and is rare.CASE SUMMARY A 52-year-old woman was diagnosed with kappa subtype nonsecretory multiple myeloma and presented with bilateral arm weakness 11 mo after completing multiple courses of chemotherapy.Spinal magnetic resonance imaging(MRI)showed a posterior C7–T3 epidural mass with spinal cord compression.After five courses of chemotherapy,follow-up MRI showed resolution of cord compression.A 54-year-old man presented with paraplegia 15 mo after a diagnosis of IgD kappa subtype multiple myeloma and completing multiple courses of chemotherapy.He underwent Th11 and L1 laminectomies for tumor resection because MRI showed an epidural mass causing cord compression.Histopathologic examination was consistent with IgD multiple myeloma.The patients have currently survived for 33 mo and 19 mo,respectively.CONCLUSION Isolated extraosseous epidural plasmacytoma associated with multiple myeloma without bony involvement is difficult to diagnose by imaging.Definitive diagnosis requires pathological and immunohistochemical examination. 展开更多
关键词 PLASMOCYTOMA MYELOMA EXTRAOSSEOUS SPINE Magnetic resonance imaging Case report
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Design of ternary D flip-flop with pre-set and pre-reset functions based on resonant tunneling diode literal circuit 被引量:4
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作者 Mi LIN Wei-feng LV ling-ling sun 《Journal of Zhejiang University-Science C(Computers and Electronics)》 SCIE EI 2011年第6期507-514,共8页
The problems existing in the binary logic system and the advantages of multiple-valued logic (MVL) are introduced. A literal circuit with three-track-output structure is created based on resonant tunneling diodes (RTD... The problems existing in the binary logic system and the advantages of multiple-valued logic (MVL) are introduced. A literal circuit with three-track-output structure is created based on resonant tunneling diodes (RTDs) and it has the most basic memory function. A ternary RTD D flip-flop with pre-set and pre-reset functions is also designed, the key module of which is the RTD literal circuit. Two types of output structure of the ternary RTD D flip-flop are optional: one is three-track and the other is single-track; these two structures can be transformed conveniently by merely adding tri-valued RTD NAND, NOR, and inverter units after the three-track output. The design is verified by simulation. Ternary flip-flop consists of an RTD literal circuit and it not only is easy to understand and implement but also provides a solution for the algebraic interface between the multiple-valued logic and the binary logic. The method can also be used for design of other types of multiple-valued RTD flip-flop circuits. 展开更多
关键词 Resonant tunneling diode (RTD) Ternary logic Literal circuit D flip-flop
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The most robust design for digital logics of multiple variables based on neurons with complex-valued weights 被引量:2
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作者 Wei-feng LU Mi LIN ling-ling sun 《Journal of Zhejiang University-Science A(Applied Physics & Engineering)》 SCIE EI CAS CSCD 2009年第2期184-188,共5页
Neurons with complex-valued weights have stronger capability because of their multi-valued threshold logic. Neurons with such features may be suitable for solution of different kinds of problems including associative ... Neurons with complex-valued weights have stronger capability because of their multi-valued threshold logic. Neurons with such features may be suitable for solution of different kinds of problems including associative memory,image recognition and digital logical mapping. In this paper,robustness or tolerance is introduced and newly defined for this kind of neuron ac-cording to both their mathematical model and the perceptron neuron's definition of robustness. Also,the most robust design for basic digital logics of multiple variables is proposed based on these robust neurons. Our proof procedure shows that,in robust design each weight only takes the value of i or -i,while the value of threshold is with respect to the number of variables. The results demonstrate the validity and simplicity of using robust neurons for realizing arbitrary digital logical functions. 展开更多
关键词 Complex-valued weights Multi-valued neurons (MVNs) Digital logic Robust design
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Quantitative Evaluation of the Compatibility Effects of Aidi Injection on the Treatment of Hepatocellular Carcinoma Using Targeted Metabolomics:A New Strategy on the Mechanism Study of an Anticancer Compound in Traditional Chinese Medicine 被引量:3
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作者 Ran Liu Lin-Lin Zhu +4 位作者 Chun-Yu Yu Ya-Ping Shuai ling-ling sun Kai-Shun Bi Qing Li 《World Journal of Traditional Chinese Medicine》 2021年第1期111-119,共9页
Objective:Compound traditional Chinese medicine(CTCM)with the application of compatibility from multiple active ingredients with multiple-specific targets can achieve a synergistic effect on cancer therapy.This study ... Objective:Compound traditional Chinese medicine(CTCM)with the application of compatibility from multiple active ingredients with multiple-specific targets can achieve a synergistic effect on cancer therapy.This study is aimed to observe the compatibility effects of Aidi injection on the treatment of hepatocellular carcinoma and to explore the mechanism of CTCM.Methods:Aidi injection is a clinical compound prescription containing Mylabris,Ginseng,Astragalus,and Acanthopanax,which can inhibit tumor growth and induce apoptosis.In this study,the anticancer activity of Aidi injection,as well as its disassembled and combined compositions,had been evaluated by varying levels of polyamine biomarkers on human hepatoma Hep-G2 cells detected using ultrahigh-performance liquid chromatography-tandem mass spectrometry.Results:According to the different variations in polyamine levels,it was revealed that Mylabris and Ginseng had an antitumor effect,while Astragalus acted as an assistant and Acanthopanax had weak anticancer activity.The increased level of polyamines in Hep-G2 cells had been found in HL-7702 cells.On combining Mylabris and Ginseng,polyamine levels went close to the normal level,which was even more marked when Astragalus was added.Aidi injection acted like the combination of Mylabris,Ginseng,and Astragalus.Conclusions:This study established a quantitative evaluation of the compatibility effects of Aidi injection based on polyamine biomarkers and evaluated the consistency of its anticancer effect,providing a manner to research the efficacy evaluation of CTCM.Moreover,the correlation between polyamine metabolism and anticancer activity can be used in anticancer drug screening. 展开更多
关键词 Compatibility effects evaluation compound traditional Chinese medicine hepatocellular carcinoma polyamine biomarker
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An efficient PSP-based model for optimized cross-coupled MOSFETs in voltage controlled oscillator
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作者 Li-heng LOU ling-ling sun +1 位作者 Jun LIU Hai-jun GAO 《Journal of Zhejiang University-Science C(Computers and Electronics)》 SCIE EI 2013年第3期205-213,共9页
This paper proposes an efficient PSP-based model for cross-coupled metal-oxide-semiconductor field-effect transistors(MOSFETs) with optimized layout in the voltage controlled oscillator(VCO).The model employs a PSP ch... This paper proposes an efficient PSP-based model for cross-coupled metal-oxide-semiconductor field-effect transistors(MOSFETs) with optimized layout in the voltage controlled oscillator(VCO).The model employs a PSP charge model to characterize the bias-dependent extrinsic capacitance instead of numerical functions with strong non-linearity.The simulation convergence is greatly improved by this method.An original scheme is developed to extract the parameters of the PSP charge model based on S-parameters measurement.The interconnection parasitics of the cross-coupled MOSFETs are modeled based on vector fitting.The model is verified with an LC VCO design,and exhibits excellent convergence during simulation.The results show improvements as high as 60.5% and 61.8% in simulation efficiency and accuracy,respectively,indicating that the proposed model better characterizes optimized cross-coupled MOSFETs in advanced radio frequency(RF) circuit design. 展开更多
关键词 Layout optimizing Modeling PSP Charge model Cross-coupled Metal-oxide-semiconductor(MOS) Voltage controlled oscillator(VCO)
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