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Detecting genetic hypermutability of gastrointestinal tumor by using a forensic STR kit

Anqi Chen, Suhua Zhang, Jixi Li, Chaoneng Ji, Jinzhong Chen, Chengtao Li

《医学前沿(英文)》 2020年 第14卷 第1期   页码 101-111 doi: 10.1007/s11684-019-0698-4

摘要: Growing evidence suggests that somatic hypermutational status and programmed cell death-1 overexpression are potential predictive biomarkers indicating treatment benefits from immunotherapy using immune checkpoint inhibitors. However, biomarker-matched trials are still limited, and many of the genomic alterations remain difficult to target. To isolate the potential somatic hypermutational tumor from microsatellite instability low/microsatellite stability (MSI-L/MSS) cases, we employed two commercial kits to determine MSI and forensic short tandem repeat (STR) alternations in 250 gastrointestinal (GI) tumors. Three types of forensic STR alternations, namely, allelic loss, Aadd, and Anew, were identified. 62.4% (156/250) of the patients with GI exhibited STR alternation, including 100% (15/15) and 60% (141/235) of the microsatellite high instability and MSI-L/MSS cases, respectively. 30% (75/250) of the patients exhibited STR instability with more than 26.32% (26.32%–84.21%) STR alternation. The cutoff with 26.32% of the STR alternations covered all 15 MSI cases and suggested that it might be a potential threshold. Given the similar mechanism of the mutations of MSI and forensic STR, the widely used forensic identifier STR kit might provide potential usage for identifying hypermutational status in GI cancers.

关键词: mismatch repair protein deficiency (MMR-D)     microsatellite instability (MSI)     short tandem repeats (STR)     gastrointestinal tumor     hypermutability    

Expression status of GATA3 and mismatch repair proteins in upper tract urothelial carcinoma

Yue Wang, Jinxia Zhang, Yunfan Wang, Shufang Wang, Yu Zhang, Qi Miao, Fei Gao, Huiying He

《医学前沿(英文)》 2019年 第13卷 第6期   页码 730-740 doi: 10.1007/s11684-019-0687-7

摘要: GATA binding protein 3 (GATA3) and mismatch repair (MMR) deficiency contribute to the development of urothelial carcinoma. However, the combined expression of GATA3 and microsatellite instability (MSI) in upper tract urothelial carcinoma (UTUC) and its prognostic value have not been investigated. Here, we immunohistochemically stained GATA3 and MMR proteins in 108 UTUC samples. GATA3 was positive in 74 cases, and its expression was significantly lower than in adjacent benign urothelium ( <0.001). Loss of GATA3 expression was statistically associated with adverse clinicopathologic parameters, such as advanced stage, lymphovascular invasion, neural invasion, lymph node metastasis, and extensive necrosis. Cancer-specific survival (CSS, =0.028) and disease-free survival (DFS, =0.024) were significantly shorter in patients with GATA3 negative tumors than in patients with GATA3 positive tumors. The absence of MMR proteins was observed in 8.3% of the cases, and focal staining was identified in 13.0%. When using “lax criteria” which resulted in counting cases as negative where MMR staining was in fact focally positive (<5%), we found that GATA3 was inversely associated with MSI ( =0.005). Moreover, GATA3 /microsatellite stability (MS) tumors were correlated with advanced pT stage ( <0.001) and poor outcome ( =0.019 for CSS, =0.016 for DFS) compared with GATA3 /MSI ones. The GATA3 /MSI cases had unfavorable clinical outcomes compared with GATA3 /MSI cases ( =0.008 for CSS, =0.023 for DFS). This finding raises a question as to whether GATA3 interacts with MSI through the TGF- signaling pathway and regulates UTUC progression.

关键词: upper tract urothelial carcinoma     GATA binding protein 3     mismatch repair     microsatellite instability     prognosis    

Novel polymorphic EST-based microsatellite marker isolation and characterization from

Manosh Kumar BISWAS,Peng CHEN,Mohamed Hamdy AMAR,Xiuxin DENG

《农业科学与工程前沿(英文)》 2015年 第2卷 第1期   页码 60-65 doi: 10.15302/J-FASE-2015048

摘要: Novel simple sequence repeat (SSR) markers were developed to evaluate their utility for genetic diversity and breeding studies of and related species. A total of 108 primer pairs were characterized by PCR amplification experiments. Among these, 61 were polymorphic and transferable to other citrus species. The number of alleles per locus ranged from 2 to 6, with an average of 2.37 alleles per locus. The expected heterozygosity and observed heterozygosity ranged from 0 to 0.83 and 0 to 1.00, respectively. These novel polymorphic SSR markers will be useful for citrus cultivar identification and evaluation as well as breeding studies.

关键词: microsatellite     polymorphism     Poncirus trifoliata    

Combustion instability detection using the wavelet detail of pressure fluctuations

JI Junjie, LUO Yonghao

《能源前沿(英文)》 2008年 第2卷 第1期   页码 116-120 doi: 10.1007/s11708-008-0019-0

摘要: A combustion instability detection method that uses the wavelet detail of combustion pressure fluctuations is put forward. To confirm this method, combustion pressure fluctuations in a stoker boiler are recorded at stable and unstable combustion with a pressure transducer. Daubechies one-order wavelet is chosen to obtain the wavelet details for comparison. It shows that the wavelet approximation indicates the general pressure change in the furnace, and the wavelet detail magnitude is consistent with the intensity of turbulence and combustion noise. The magnitude of the wavelet detail is nearly constant when the combustion is stable, however, it will fluctuate much when the combustion is unstable.

关键词: comparison     wavelet approximation     pressure transducer     general pressure     consistent    

海底不稳定性研究进展及展望

高伟健,李伟

《中国工程科学》 2023年 第25卷 第3期   页码 109-121 doi: 10.15302/J-SSCAE-2023.03.010

摘要:

海底不稳定性及次生海底地质灾害广泛存在于海洋之中,对海岸港口设施、海洋钻井平台、海底管道光缆等海底基础建设颇具威胁。但目前对海底不稳定性的成因机制与主控因素仍知之甚少,为加深对海底不稳定性的认识,本文回顾了海底不稳定性研究进展,梳理了海底不稳定性及次生海底地质灾害的主要类别、全球分布情况和地球物理识别特征,归纳了目前海底不稳定性研究的定量分析方法,进一步分析了其成因机制、控制因素及工程地质灾害风险,探讨了海底陆坡失稳演化过程试验模拟技术的适用范畴与技术瓶颈。最后,从海底不稳定性的致灾机理研究、多源数据智能分析和海底失稳立体监测3 个维度提出了未来海底不稳定性研究的发展方向与对策建议,以期为海底不稳定性的模拟、预测和预警等工作提供指导性建议。

关键词: 海底不稳定性;海底地质灾害;成因机制;风险评估;不稳定性分析    

表面张力作用下柱形胶体的弹性失稳

黄殿武,乔玲,汪时机

《中国工程科学》 2007年 第9卷 第4期   页码 50-54

摘要:

采用弹性理论研究了圆柱形胶体在表面张力作用下的弹性失稳问题;利用能量泛函变分的方法导出 了发生弹性失稳的非经典边界条件,得到了失稳的判据方程。分析判据方程发现,弹性失稳与圆柱体的半径、 内禀尺度和失稳波长相关。

关键词: 柱形胶体     弹性失稳     内禀尺度     表面效应    

工程饱和介质中漩涡光的调制不稳定性 Review

D.G. Pires, N.M. Litchinitser

《工程(英文)》 2022年 第17卷 第10期   页码 31-43 doi: 10.1016/j.eng.2022.04.022

摘要:

光束在水下环境、雾、云或生物组织等混浊介质中的传播在科学和技术中有着越来越重要的应用,包括生物成像、水下和自由空间通信技术。虽然这些应用在传统上依赖于常规的线性偏振高斯光束,但光具有许多未被发掘的自由度,如自旋角动量(SAM)和轨道角动量(OAM)。本文提出了具有“旋转”自由度的复杂光束在工程化非线性胶体介质中的非线性光-物质相互作用。利用变分法和摄动法,我们考虑了非圆柱光学涡旋、椭圆光学涡旋和高阶贝塞尔光束在时间上的积分(HOBBIT),来预测这些光束演化的动力学行为和稳定性。这些结果可应用于许多强散射环境下涉及光透射的情况。

关键词: Optical vortex     Orbital angular momentum     Modulation instability     Turbid media    

Molecular classification and precision therapy of cancer: immune checkpoint inhibitors

null

《医学前沿(英文)》 2018年 第12卷 第2期   页码 229-235 doi: 10.1007/s11684-017-0581-0

摘要:

On May 23, 2017, the US Food and Drug Administration (FDA) approved a treatment for cancer patients with positive microsatellite instability-high (MSI-H) markers or mismatch repair deficient (dMMR) markers. This approach is the first approved tumor treatment using a common biomarker rather than specified tumor locations in the body. FDA previously approved Keytruda for treatment of several types of malignancies, such as metastatic melanoma, metastatic non-small-cell lung cancer, recurrent or metastatic head and neck cancer, refractory Hodgkin lymphoma, and urothelial carcinoma, all of which carry positive programmed death-1/programmed death-ligand 1 biomarkers. Therefore, indications of Keytruda significantly expanded. Several types of malignancies are disclosed by MSI-H status due to dMMR and characterized by increased neoantigen load, which elicits intense host immune response in tumor microenvironment, including portions of colorectal and gastric carcinomas. Currently, biomarker-based patient selection remains a challenge. Pathologists play important roles in evaluating histology and biomarker results and establishing detection methods. Taking gastric cancer as an example, its molecular classification is built on genome abnormalities, but it lacks acceptable clinical characteristics. Pathologists are expected to act as “genetic interpreters” or “genetic translators” and build a link between molecular subtypes with tumor histological features. Subsequently, by using their findings, oncologists will carry out targeted therapy based on molecular classification.

关键词: molecular classification     precision medicine     pembrolizumab     PD-1/PD-L1     MSI-H    

Underlying mechanism of the hydrothermal instability of Cu

Nadeen Al-Janabi,Abdullatif Alfutimie,Flor R. Siperstein,Xiaolei Fan

《化学科学与工程前沿(英文)》 2016年 第10卷 第1期   页码 103-107 doi: 10.1007/s11705-015-1552-0

摘要: Water induced decomposition of Cu (BTC) (BTC= benzene-1,3,5-tricarboxylate) metal-organic framework (MOF) was studied using dynamic water vapour adsorption. Small-angle X-ray scattering, Fourier transform infrared spectroscopy and differential scanning calorimetry analyses revealed that the underlying mechanism of Cu (BTC) MOF decomposition under humid streams is the interpenetration of water molecules into Cu-BTC coordination to displace organic linkers (BTC) from Cu centres.

关键词: hydrothermal stability     metal-organic framework (MOF)     open metal sites (OMSs)     dynamic water vapour adsorption    

MSI/LOH and extron expression of the FHIT gene in gastric carcinoma

XIAO Yuping, MAO Lili, HAN Chengbo, LI Jinyi, XU Lei, XIN Yan

《医学前沿(英文)》 2007年 第1卷 第1期   页码 99-103 doi: 10.1007/s11684-007-0019-1

摘要: We detected loss of heterozygosity (LOH) and microsatellite instabilities (MSI), as well as extron expression of the fragile histidine triad (FHIT) gene in gastric carcinoma (GC), in order to evaluate their association with clinicopathological processes in gastric carcinogenesis. LOH and MSI of the FHIT were detected by using PCR at 4 microsatellite loci: D3S 1300, D3S 4103, D3S 1481, D3S 1234 in cancer tissues from 50 patients with primary GC, with normal mucosa acting as matched controls. FHIT transcripts were detected by nested RT-PCR in 30 cases of GC and their products were sequenced. Results show that the average frequencies of LOH and MSI of the FHIT gene in GC were 32.4% and 26.4%, respectively. There was no correlation between LOH and MSI of the FHIT gene in GC and the histological characteristics of gastric carcinoma (Bormann s or Lauren s classification). LOH of the FHIT gene in GC was related to depth invasiveness, and its frequency in GC where serosa was penetrated was significantly higher than that in GC without serosa penetration (73.5% 37.5%, <0.05). The frequency of MSI in GC without lymph node metastasis was significantly higher than that in GC with lymph node metastasis (66.7% 34.3%, <0.05). Aberrant transcripts were found in 11/30 GC tissues. Sequencing analysis of the aberrant fragments found a RT-PCR product missing exons 5 7 in one case of GC, and another product missing exons 4 7. Four of 10 (40.0%) cases of primary GC showed absent or decreased expression of the FHIT protein as compared to their matched normal tissues. The findings in this study suggest that LOH and MSI of FHIT gene may induce aberrant extron expression, which might play a role in gastric carcinogenesis.

Mechanisms and impacts of chromosomal translocations in cancers

null

《医学前沿(英文)》 2012年 第6卷 第3期   页码 263-274 doi: 10.1007/s11684-012-0215-5

摘要:

Chromosomal aberrations have been associated with cancer development since their discovery more than a hundred years ago. Chromosomal translocations, a type of particular structural changes involving heterologous chromosomes, have made a critical impact on diagnosis, prognosis and treatment of cancers. For example, the discovery of translocation between chromosomes 9 and 22 and the subsequent success of targeting the fusion product BCR-ABL transformed the therapy for chronic myelogenous leukemia. In the past few decades, tremendous progress has been achieved towards elucidating the mechanism causing chromosomal translocations. This review focuses on the basic mechanisms underlying the generation of chromosomal translocations. In particular, the contribution of frequency of DNA double strand breaks and spatial proximity of translocating loci is discussed.

关键词: DNA double strand breaks     chromosomal translocations     genomic instability     spatial proximity     carcinogenesis    

p-Cresyl sulfate promotes the formation of atherosclerotic lesions and induces plaque instability by

null

《医学前沿(英文)》 2016年 第10卷 第3期   页码 320-329 doi: 10.1007/s11684-016-0463-x

摘要:

Coronary atherosclerosis is a major complication of chronic kidney disease. This condition contributes to the increased mortality in dialysis patients. p-Cresyl sulfate (PCS) is a prototype of protein-bound uremic toxins that cannot be efficiently removed through routine dialysis procedures. In the present study, ApoE−/− mice that underwent 5/6 nephrectomy were randomly divided into two groups, namely, vehicle-treated group (n = 20) and PCS-treated group (n = 20). Mice were sacrificed for en face and immunohistological analyses after 8 or 24 weeks of high-fat diet. Rat aortic vascular smooth muscle cells (VSMCs) were treated with phosphate buffer solution or 500 µmol/L PCS for in vitro evaluation. PCS-treated mice were observed to suffer increased atherosclerotic lesions after eight weeks of PCS administration. Moreover, 24 weeks of PCS administration also markedly increased the vulnerability index of aortic plaques. PCS was also observed to facilitate the migration and proliferation of VSMCs during the progression of the disease. Moreover, PCS disturbed the balance between matrix metalloproteinases and tissue inhibitor of metalloproteinases within the plaques. Thus, PCS played a vital role in promoting atherogenesis and disturbing the stability of formed plaques probably by targeting VSMCs.

关键词: p-cresyl sulfate     atherosclerosis     plaque stability     vascular smooth muscle cell    

Aerodynamic stability evolution tendency of suspension bridges with spans from 1000 to 5000 m

《结构与土木工程前沿(英文)》 doi: 10.1007/s11709-023-0980-z

摘要: Aerodynamic instability owing to aerostatic and flutter-related failures is a significant concern in the wind-resistant design of long-span suspension bridges. Based on the dynamic characteristics of suspension bridges with spans ranging from 888 to 1991 m, we proposed fitted equations for increasing spans and base frequencies. Finite element models of suspension bridges with increasing span from 1000 to 5000 m were constructed. The structural parameters were optimized to follow the fitted tendencies. To analyze the aerodynamic instability, streamlined single-box section (SBS), lattice truss section (LTS), narrow slotted section (NSS), and wide slotted section (WSS) were considered. We performed three-dimensional (3-D) full-mode flutter analysis and nonlinear aerostatic instability analysis. The flutter critical wind speed continuously decreases with span growth, showing an unlimited approaching phenomenon. Regarding aerostatic instability, the instability wind speed decreases with span to approximately 3000 m, and increases when the span is in the range of 3000 to 5000 m. Minimum aerostatic instability wind speed with SBS or LTS girder would be lower than observed maximal gust wind speed, indicating the probability of aerostatic instability. This study proposes that suspension bridge with span approximately 3000 m should be focused on both aerostatic instability and flutter, and more aerodynamic configuration optimistic optimizations for flutter are essential for super long-span suspension bridges with spans longer than 3000 m.

关键词: suspension bridge     super long-span     finite element model     aerodynamic instability     aerodynamic configuration    

Stability of an annular viscous liquid jet in compressible gases with different properties inside and outside of the jet

Chunji YAN, Maozhao XIE,

《能源前沿(英文)》 2010年 第4卷 第2期   页码 198-204 doi: 10.1007/s11708-009-0054-5

摘要: A spatial linear instability analysis is conducted on an annular viscous liquid jet injected into compressible gases and a three-dimensional model of the jet is developed. The model takes into account differences between the velocities, densities of the gases inside and outside of the liquid jet. Theoretical analysis reveals that there exist 9 dimensionless parameters controlling the instability of the liquid jet. Numerical computations reveal some basic characteristics in the breakup and atomization process of the liquid jet as well as influences of these relevant parameters. Major observations and findings of this study are as follows. The Mach number plays a destabilizing role and the inner Mach number has a greater effect on the jet instability than the outer Mach number. The Reynolds number always tends to promote the instabilities of the liquid jet, but its influence is very limited. The Weber number and the gas-to-liquid density ratio also have unstable effects and can improve the atomization of liquid jets. Furthermore, the effects of the Weber number and gas-to-liquid density ratio on the maximum growth rates of axisymmetric and non-axisymmetric disturbances and corresponding dominant wave numbers are manifested in a linear way, while that of the Mach number is non-linear. The effect of Reynolds on the maximum growth rates is non-linear, but the dominant wavenumber is almost not affected by the Reynolds number.

关键词: liquid jet     dominant wave number     compressibility     instability    

Emergent limited perioperative transesophageal echocardiography: should new guidelines exist for limited echocardiography training for anesthesiologists?

null

《医学前沿(英文)》 2012年 第6卷 第3期   页码 332-337 doi: 10.1007/s11684-012-0212-8

摘要:

Bedside limited echocardiography, or focused cardiac ultrasound, continues to gain popularity in many emergency rooms, intensive care units, and operating rooms as a rapid method of assessing unstable patients. Effective monitoring of cardiovascular function in conditions like cardiac arrest or near-arrest is the crucial step to guide successful resuscitative efforts. Transesophageal echocardiography (TEE) has emerged as one of the preferred cardiac diagnostic and monitoring modalities in the intraoperative setting due to the fact that it is less invasive than many other monitors, is immediately accessible, and allows for continuous real-time monitoring of cardiac function. However, the minimum training requirements needed for the anesthesia provider to obtain the competency, knowledge, and skills for basic certification in perioperative TEE far exceed those developed for other medical specialties. We believe there is an urgent need to develop (1) practical guidelines for emergent perioperative TEE use for anesthesiologists and (2) a requisite educational curriculum to teach the basic skills necessary to aid in the diagnosis and treatment of cardiac arrest or near-arrest scenarios. The measures elucidated in this report summarize the efforts of the Department of Anesthesiology at the University of Florida in establishing the necessary steps to make this process not only practical, but accessible to all trainees. We hope that these collective efforts will provide more trainees the confidence in utilizing TEE to aid in establishing a diagnosis in critical situations.

关键词: transesophageal echocardiography     curriculum     competency training     hemodynamic instability    

标题 作者 时间 类型 操作

Detecting genetic hypermutability of gastrointestinal tumor by using a forensic STR kit

Anqi Chen, Suhua Zhang, Jixi Li, Chaoneng Ji, Jinzhong Chen, Chengtao Li

期刊论文

Expression status of GATA3 and mismatch repair proteins in upper tract urothelial carcinoma

Yue Wang, Jinxia Zhang, Yunfan Wang, Shufang Wang, Yu Zhang, Qi Miao, Fei Gao, Huiying He

期刊论文

Novel polymorphic EST-based microsatellite marker isolation and characterization from

Manosh Kumar BISWAS,Peng CHEN,Mohamed Hamdy AMAR,Xiuxin DENG

期刊论文

Combustion instability detection using the wavelet detail of pressure fluctuations

JI Junjie, LUO Yonghao

期刊论文

海底不稳定性研究进展及展望

高伟健,李伟

期刊论文

表面张力作用下柱形胶体的弹性失稳

黄殿武,乔玲,汪时机

期刊论文

工程饱和介质中漩涡光的调制不稳定性

D.G. Pires, N.M. Litchinitser

期刊论文

Molecular classification and precision therapy of cancer: immune checkpoint inhibitors

null

期刊论文

Underlying mechanism of the hydrothermal instability of Cu

Nadeen Al-Janabi,Abdullatif Alfutimie,Flor R. Siperstein,Xiaolei Fan

期刊论文

MSI/LOH and extron expression of the FHIT gene in gastric carcinoma

XIAO Yuping, MAO Lili, HAN Chengbo, LI Jinyi, XU Lei, XIN Yan

期刊论文

Mechanisms and impacts of chromosomal translocations in cancers

null

期刊论文

p-Cresyl sulfate promotes the formation of atherosclerotic lesions and induces plaque instability by

null

期刊论文

Aerodynamic stability evolution tendency of suspension bridges with spans from 1000 to 5000 m

期刊论文

Stability of an annular viscous liquid jet in compressible gases with different properties inside and outside of the jet

Chunji YAN, Maozhao XIE,

期刊论文

Emergent limited perioperative transesophageal echocardiography: should new guidelines exist for limited echocardiography training for anesthesiologists?

null

期刊论文