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Mutation analysis of related genes in hamartoma polyp tissue of Peutz-Jeghers syndrome

World Journal of Gastroenterology 2020年第16期26卷 1926-1937页

作者： Zhi Zhang fu-xiao duan Guo-Li Gu Peng-Fei Yu Air Force Clinical College(Air Force Medical Center)of Anhui Medical University Beijing 100142China Department of General Surgery the General Hospital of Northern Theater Command PLAShenyang 110016Liaoning ProvinceChina Department of General Surgery Air Force Medical CenterPLABeijing 100142China

BACKGROUND Peutz-Jeghers syndrome(PJS)is a rare disease with clinical manifestations of pigmented spots on the lips,mucous membranes and extremities,scattered gastrointestinal polyps,and susceptibility to tumors.The clinical heterogeneity of PJS is obvious,and the relationship between clinical phenotype and genotype is still unclear.AIM To investigate the mutation status of hereditary colorectal tumor-associated genes in hamartoma polyp tissue of PJS patients and discuss its relationship with the clinicopathological data of PJS.METHODS Twenty patients with PJS were randomly selected for this study and were treated in the Air Force Medical Center(former Air Force General Hospital)PLA between 2008 and 2017.Their hamartoma polyp tissues were used for APC,AXIN2,BMPR1A,EPCAM,MLH1,MLH3,MSH2,MSH6,MUTYH,PMS1,PMS2,PTEN,SMAD4,and LKB1/STK11 gene sequencing using next-generation sequencing technology.The correlations between the sequencing results and clinical pathological data of PJS were analyzed.RESULTS Fourteen types of LKB1/STK11 mutations were detected in 16 cases(80.0%),of which 8 new mutations were found(3 types of frameshift deletion mutations:c.243delG,c.363_364delGA,and c.722delC;2 types of frameshift insertions:c.144_145insGCAAG,and c.454_455insC;3 types of splice site mutations:c.464+1G>T,c.464+1G>A,and c.598-1G>A);9 cases(45.0%)were found to have 18 types of heterozygous mutations in the remaining 13 genes except LKB1/STK11.Of these,MSH2:c.792+1G>A,MSH6:c.3689C>G,c.4001+13C>CTTAC,PMS1:c.46C>t,and c.922G>A were new mutations.CONCLUSION The genetic mutations in hamartoma polyp tissue of PJS are complex and diverse.Moreover,other gene mutations in PJS hamartoma polyp tissue were observed,with the exception of LKB1/STK11 gene,especially the DNA mismatch repair gene(MMR).Colorectal hamartoma polyps with LKB1/STK11 mutations were larger in diameter than those with other gene mutations.

关键词： Peutz-Jeghers syndrome STK11 gene LKB1 gene Sequencing Genetic analysis

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Must Peutz-Jeghers syndrome patients have the LKB1/STK11 gene mutation?A case report and review of the literature

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World Journal of Clinical Cases 2018年第8期6卷 224-232页

作者： fu-xiao duan Guo-Li Gu Hai-Rui Yang Peng-Fei Yu Zhi Zhang Department of General Surgery Air Force General Hospital of Chinese PLA

Peutz-Jeghers syndrome(PJS) is an autosomal dominant inherited disease, which is characterized by mucocutaneous pigmentation and multiple gastrointestinal hamartoma polyps. The germline mutation of LKB1/STK11 gene on chromosome 19 p13.3 is considered to be the hereditary cause of PJS. However, must a patient with PJS have the LKB1/STK11 gene mutation? We here report a case of a male patient who had typical manifestations of PJS and a definite family history, but did not have LKB1/STK11 gene mutation. By means of high-throughput sequencing technology, only mutations in APC gene(c.6662 T > C: p.Met2221 Thr) and MSH6 gene(c.3488 A > T: p.Glu1163 Val) were detected. The missense mutations in APC and MSH6 gene may lead to abnormalities in structure and function of their expression products, and may result in the occurrence of PJS. This study suggests that some other genetic disorders may cause PJS besides LKB1/STK11 gene mutation.

关键词： Peutz-Jeghers syndrome Gastrointestinal polyps High-throughput sequencing LKB1/STK11 APC MSH6 Hamartoma

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Must pilots permanently quit flying career after treatment for colorectal cancer?-Medical waiver for Air Force pilots with colorectal cancer: Three case reports

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World Journal of Clinical Cases 2020年第4期8卷 790-797页

作者： Guo-Li Gu fu-xiao duan Zhi Zhang Xue-Ming Wei Li Cui Bo Zhang Department of General Surgery Air Force Medical CenterPLABeijing 100142China Department of General Surgery the General Hospital of Northern Theater Command PLAShenyang 110016Liaoning ProvinceChina Department of Aviation Diseases Air Force Medical CenterPLABeijing 100142China Department of Medical Research Air Force Medical CenterPLABeijing 100142China

BACKGROUND Colorectal cancer(CRC)could seriously threaten the physical and mental health of pilots.Shall they end their flying after treatment of CRC?With this study,we investigated the possibility of a gradual medical waiver for such pilots to fly aircrafts again after treatment of CRC.CASE SUMMARY We analyzed the medical waiver and clinical data of 3 pilots with CRC,who had accepted the treatment at the Department of General Surgery,Air Force Medical Center(formerly,Air Force General Hospital)between 2013 and 2018.All 3 cases underwent a series of comprehensive treatment courses,including radical resection of CRC,sequential radiotherapy,and chemotherapy.The follow-up results were satisfactory.After passing through the high-risk period of recurrence and metastasis of CRC,they all were given a medical waiver for flying again.Medical observation showed that their flying operations were safe.CONCLUSION The CRC treatment shall follow the guidelines for diagnosis and treatment and should simultaneously protect the combating capabilities of pilots as much as possible.It is safe for pilots with CRC,who are continuously monitored under medical observation after passing through the high-risk period of recurrence and metastasis,to undertake military flight missions again.

关键词： Colorectal cancer Pilot Waiver Treatment Military medicine Aeromedicine Case report

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Accurate Distinction of Weak and Strong AC Grids for Emerging Hierarchical-Infeed LCC-UHVDC Systems

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CSEE Journal of Power and Energy Systems 2024年第2期10卷 772-777页

作者： Hao xiao Xianzhong duan Yi Zhang Department of Electrical and Computer Engineering University of ManitobaWinnipeg R3T 2N2ManitobaCanada State Key Laboratory of Advanced Electromagnetic Engineering and Technology Hubei Electric Power Security and High Efficiency Key LaboratorySchool of Electrical and Electronic EngineeringHuazhong University of Science and TechnologyWuhan 430074HubeiChina RTDS Technologies Inc. Winnipeg R3T 2E1ManitobaCanada

Distinction of weak and strong AC grids for emerging hierarchical-infeed LCC-UHVDC systems is important for planning and operation departments. However, accuracy of earlier distinction methods is limited as they were developed by empirical reasoning without rigorous theoretical analysis. Hence in this letter, hierarchical-infeed interactive effective short-circuit ratio (HIESCR) index is first used for strength evaluation of HIDC systems with complex inter-inverter interactions considered. Boundary HIESCR (BHIESCR) is also introduced in the proposed distinction method of weak and strong AC grids. That is, weak (or strong) AC grids are, respectively, identified when HIESCR is less (or greater) than BHIESCR. Second, it is shown BHIESCR remains almost unchanged as 3.0 versus various system parameters and rated operation variables based on rigorous theoretical analysis. This salient feature makes the proposed method more accurate than earlier methods. Finally, the proposed method is validated by simulations based on the PSCAD/EMTDC program.

关键词： Hierarchical-Infeedinteractive effective short-circuit ratio hierarchical-infeed LCC-UHVDC systems inter-inverter interactions strong AC grids weak AC grids

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Low-Complexity Reconstruction of Covariance Matrix in Hybrid Uniform Circular Array

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China Communications 2024年第3期21卷 66-74页

作者： fu Zihao Liu Yinsheng duan Hongtao Information School Communication University of ChinaBeijing 100024China Beijing Institute of Electronic System Engineering Beijing 100854China School of Electronic and Information Engineering Beijing Jiaotong UniversityBeijing 100044China Beijing Radio Monitoring Station of State Radio Monitoring Center(SRMC) Beijing 100037China

Spatial covariance matrix(SCM) is essential in many multi-antenna systems such as massive multiple-input multiple-output(MIMO). For multi-antenna systems operating at millimeter-wave bands, hybrid analog-digital structure has been widely adopted to reduce the cost of radio frequency chains.In this situation, signals received at the antennas are unavailable to the digital receiver, and as a consequence, traditional sample average approach cannot be used for SCM reconstruction in hybrid multi-antenna systems. To address this issue, beam sweeping algorithm(BSA) which can reconstruct the SCM effectively for a hybrid uniform linear array, has been proposed in our previous works. However, direct extension of BSA to a hybrid uniform circular array(UCA)will result in a huge computational burden. To this end, a low-complexity approach is proposed in this paper. By exploiting the symmetry features of SCM for the UCA, the number of unknowns can be reduced significantly and thus the complexity of reconstruction can be saved accordingly. furthermore, an insightful analysis is also presented in this paper, showing that the reduction of the number of unknowns can also improve the accuracy of the reconstructed SCM. Simulation results are also shown to demonstrate the proposed approach.

关键词： hybrid array millimeter-wave spatial covariance matrix uniform circular array

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High-throughput screening of single-atom catalysts confined in monolayer black phosphorus for efficient nitrogen reduction reaction

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Nano Research 2024年第4期17卷 2360-2367页

作者： xiao-Yan Li Manyi duan Pengfei Ou Department of Electrical and Computer Engineering University of TorontoTorontoOntario M5S 1A4Canada School of Physics and Electronic Engineering Sichuan Normal UniversityChengdu 610101China Department of Chemistry Northwestern UniversityEvanstonIL 60208USA

The discovery of metal-nitrogen centers as the active sites for electrolysis has aroused significant interest in utilizing single-atom catalysts for nitrogen reduction reaction(NRR).Properly designed nanostructured catalysts that strongly interact with nitrogen molecules(N_(2))can promote adsorption and activation,thereby resulting in efficient catalysts with high stability,activity,and selectivity.In this study,using density functional theory calculations,we selected monolayer black phosphorus(BP)as the substrate and screened a series of single-atom transition metals confined in tri-coordinated and tetra-coordinated active centers(without and with N dopants)to electro-catalyze NRR.As a result,we have identified two promising candidates(Hf_(1)-N_(1)P_(2)-1 and Tc_(1)-N_(4)),which exhibit not only low overpotentials of 0.56 and 0.49 V but also high thermodynamic and electrochemical stability,as well as good selectivity towards NRR over the competing hydrogen evolution reaction.We also demonstrate the ability of Hf_(1)-N_(1)P_(2)-1 and Tc_(1)-N_(4) to activate and hydrogenate N_(2) by donating electrons and regulating charge transfer.This study not only predicts new BP-based promising catalysts but also provides guidance for the rational design of high-performance NRR electrocatalysts under ambient conditions.

关键词： N_(2) electroreduction reaction single-atom catalysts black phosphorus density functional theory high-throughput calculations

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Joint Sample Position Based Noise Filtering and Mean Shift Clustering for Imbalanced Classification Learning

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Tsinghua Science and Technology 2024年第1期29卷 216-231页

作者： Lilong duan Wei Xue Jun Huang xiao Zheng School of Computer Science and Technology Anhui University of TechnologyMaanshan 243032China Institute of Artificial Intelligence Hefei Comprehensive National Science CenterHefei 230088China

The problem of imbalanced data classification learning has received much attention.Conventional classification algorithms are susceptible to data skew to favor majority samples and ignore minority samples.Majority weighted minority oversampling technique(MWMOTE)is an effective approach to solve this problem,however,it may suffer from the shortcomings of inadequate noise filtering and synthesizing the same samples as the original minority data.To this end,we propose an improved MWMOTE method named joint sample position based noise filtering and mean shift clustering(SPMSC)to solve these problems.Firstly,in order to effectively eliminate the effect of noisy samples,SPMsC uses a new noise filtering mechanism to determine whether a minority sample is noisy or not based on its position and distribution relative to the majority sample.Note that MWMOTE may generate duplicate samples,we then employ the mean shift algorithm to cluster minority samples to reduce synthetic replicate samples.Finally,data cleaning is performed on the processed data to further eliminate class overlap.Experiments on extensive benchmark datasets demonstrate the effectiveness of SPMsC compared with other sampling methods.

关键词： imbalanced data classification oversampling noise filtering clustering

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Control of fine particulate nitrate during severe winter haze in“2+26”cities

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Journal of Environmental Sciences 2024年第2期136卷 261-269页

作者： Chuang Qin xiao fu Tao Wang Jian Gao Jiaqi Wang Institute of Environment and Ecology Tsinghua Shenzhen International Graduate SchoolTsinghua UniversityShenzhen 518055China Department of Civil and Environmental Engineering Hong Kong Polytechnic UniversityHong Kong 99907China State Key Laboratory of Environmental Criteria and Risk Assessment Chinese Research Academy of Environmental SciencesBeijing 10084China

The“2+26”cities,suffering the most severe winter haze pollution,have been the key region for air quality improvement in China.Increasing prominent nitrate pollution is one of the most challenging environmental issues in this region,necessitating development of an effective control strategy.Herein,we use observations,and state-of-the-art model simulations with scenario analysis and process analysis to quantify the effectiveness of the future SO_(2)-NO_(X)-VOC-NH_(3) emission control on nitrate pollution mitigation in“2+26”cities.Focusing on a serious winter haze episode,we find that limited NO_(X)emission reduction alone in the short-term period is a less effective choice than VOC or NH_3emission reduction alone to decrease nitrate concentrations,due to the accelerated NO_(X)-HNO_(3)conversion by atmospheric oxidants and the enhanced HNO_(3)to NO_(3)^(-)partition by ammonia,although deep NO_(X)emission reduction is essential in the long-term period.The synergistic NH_(3) and VOC emission control is strongly recommended,which can counteract the adverse effects of nonlinear photochemistry and aerosol chemical feedback to decrease nitrate more.Such extra benefits will be reduced if the synergistic NH_(3) and VOC reduction is delayed,and thus reducing emission of multiple precursors is urgently required for the effective control of increasingly severe winter nitrate pollution in“2+26”cities.

关键词： Nitrate Winter haze pollution Emission reduction “2+26”cities

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New clinical trial design in precision medicine:discovery,development and direction

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1293-1321页

作者： xiao-Peng duan Bao-Dong Qin xiao-Dong Jiao Ke Liu Zhan Wang Yuan-Sheng Zang Department of Medical Oncology Changzheng HospitalNaval Medical UniversityShanghaiChina

In the era of precision medicine,it has been increasingly recognized that individuals with a certain disease are complex and different from each other.Due to the underestimation of the significant heterogeneity across participants in traditional"one-sizefits-all"trials,patient-centered trials that could provide optimal therapy customization to individuals with specific biomarkers were developed including the basket,umbrella,and platform trial designs under the master protocol framework.In recent years,the successive FDA approval of indications based on biomarker-guided master protocol designs has demonstrated that these new clinical trials are ushering in tremendous opportunities.Despite the rapid increase in the number of basket,umbrella,and platform trials,the current clinical and research understanding of these new trial designs,as compared with traditional trial designs,remains limited.The majority of the research focuses on methodologies,and there is a lack of in-depth insight concerning the underlying biological logic of these new clinical trial designs.Therefore,we provide this comprehensive review of the discovery and development of basket,umbrella,and platform trials and their underlying logic from the perspective of precision medicine.Meanwhile,we discuss future directions on the potential development of these new clinical design in view of the"Precision Pro","Dynamic Precision",and"Intelligent Precision".This review would assist trial-related researchers to enhance the innovation and feasibility of clinical trial designs by expounding the underlying logic,which be essential to accelerate the progression of precision medicine.

关键词： clinical approval successive

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Trace formula of the integro-differential operator on a quantum graph

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Applied Mathematics(A Journal of Chinese Universities) 2024年第2期39卷 311-318页

作者： WEI Li-xiao YANG Chuan-fu School of Mathematics and Statistics Nanjing University of Science and TechnologyNanjing 210094China.

In this paper we study the eigenvalue problem for integro-differential operators on a lasso graph.The trace formula of the operator is established by applying the residual technique in complex analysis.

关键词： integro-differential operators eigenvalue trace formula

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