Association between Helicobacter pylori infection,mismatch repair,HER2 and tumor-infiltrating lymphocytes in gastric cancer

BACKGROUND The influence of Helicobacter-pylori(H.pylori)infection and the characteristics of gastric cancer(GC)on tumor-infiltrating lymphocyte(TIL)levels has not been extensively studied.Analysis of infiltrating-immune-cell subtypes as well as survival is necessary to obtain comprehensive information.AIM To determine the rates of deficient mismatch-repair(dMMR),HER2-status and H.pylori infection and their association with TIL levels in GC.METHODS Samples from 503 resected GC tumors were included and TIL levels were evaluated following the international-TILs-working-group recommendations with assessment of the intratumoral(IT),stromal(ST)and invasive-border(IB)compartments.The density of CD3,CD8 and CD163 immune cells,and dMMR and HER2-status were determined by immunohistochemistry(IHC).H.pylori infection was evaluated by routine histology and quantitative PCR(qPCR)in a subset of samples.RESULTS dMMR was found in 34.4%,HER2+in 5%and H.pylori-positive in 55.7%of samples.High IT-TIL was associated with grade-3(P=0.038),while ST-TIL with grade-1(P<0.001),intestinal-histology(P<0.001)and no-recurrence(P=0.003).dMMR was associated with high TIL levels in the ST(P=0.019)and IB(P=0.01)compartments,and STCD3(P=0.049)and ST-CD8(P=0.05)densities.HER2-was associated with high IT-CD8(P=0.009).H.pylorinegative was associated with high IT-TIL levels(P=0.009)when assessed by routine-histology,and with high TIL levels in the 3 compartments(P=0.002-0.047)and CD8 density in the IT and ST compartments(P=0.001)when assessed by qPCR.A longer overall survival was associated with low IT-CD163(P=0.003)and CD8/CD3(P=0.001 in IT and P=0.002 in ST)and high IT-CD3(P=0.021),ST-CD3(P=0.003)and CD3/CD163(P=0.002).CONCLUSION TIL levels were related to dMMR and H.pylori-negativity.Low CD8/CD3 and high CD163/CD3 were associated with lower recurrence and longer survival.

Comprehensive analysis of gene mutations and mismatch repair in Chinese colorectal cancer patients

BACKGROUND RAS,BRAF,and mismatch repair(MMR)/microsatellite instability(MSI)are crucial biomarkers recommended by clinical practice guidelines for colorectal cancer(CRC).However,their characteristics and influencing factors in Chinese patients have not been thoroughly described.AIM To analyze the clinicopathological features of KRAS,NRAS,BRAF,and PIK3CA mutations and the DNA MMR status in CRC.METHODS We enrolled 2271 Chinese CRC patients at the China-Japan Friendship Hospital.MMR proteins were tested using immunohistochemical analysis,and the KRAS/NRAS/BRAF/PIK3CA mutations were determined using quantitative polymerase chain reaction.Microsatellite status was determined using an MSI detection kit.Statistical analyses were conducted using SPSS software and logistic regression.RESULTS The KRAS,NRAS,BRAF,and PIK3CA mutations were detected in 44.6%,3.4%,3.7%,and 3.9% of CRC patients,respectively.KRAS mutations were more likely to occur in patients with moderate-to-high differentiation.BRAF mutations were more likely to occur in patients with right-sided CRC,poorly differentiated,or no perineural invasion.Deficient MMR(dMMR)was detected in 7.9% of all patients and 16.8% of those with mucinous adenocarcinomas.KRAS,NRAS,BRAF,and PIK3CA mutations were detected in 29.6%,1.1%,8.1%,and 22.3% of patients with dMMR,respectively.The dMMR was more likely to occur in patients with a family history of CRC,aged<50 years,right-sided CRC,poorly differentiated histology,no perineural invasion,and with carcinoma in situ,stage I,or stage II tumors.CONCLUSION This study analyzed the molecular profiles of KRAS,NRAS,BRAF,PIK3CA,and MMR/MSI in CRC,identifying key influencing factors,with implications for clinical management of CRC.

Tislelizumab in previously treated,locally advanced unresectable/metastatic microsatellite instability-high/mismatch repair-deficient solid tumors

Objective:The open-label,phase II RATIONALE-209 study evaluated tislelizumab(anti-programmed cell death protein 1 antibody)as a tissue-agnostic monotherapy for microsatellite instability-high(MSI-H)/mismatch repair-deficient(dMMR)tumors.Methods:Adults with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR solid tumors were enrolled.Patients received tislelizumab 200 mg intravenously every 3 weeks.Objective response rate(ORR;primary endpoint),duration of response(DoR),and progression-free survival(PFS)were assessed by independent review committee(Response Evaluation Criteria in Solid Tumors v1.1).Results:Eighty patients were enrolled and treated;75(93.8%)patients had measurable disease at baseline.Most had metastatic disease and received at least one prior therapy for advanced/metastatic disease(n=79;98.8%).At primary analysis(data cutoff July 8,2021;median follow-up 15.2 months),overall ORR[46.7%;95%confidence interval(95%CI),35.1−58.6;one-sided P<0.0001]and ORR across tumor-specific subgroups[colorectal(n=46):39.1%(95%CI,25.1–54.6);gastric/gastroesophageal junction(n=9):55.6%(95%CI,21.2−86.3);others(n=20):60.0%(95%CI,36.1−80.9)]were significantly greater with tislelizumab vs.a prespecified historical control ORR of 10%;five(6.7%)patients had complete responses.Median DoR,PFS,and overall survival were not reached with long-term follow-up(data cutoff December 5,2022;median follow-up 28.9 months).Tislelizumab was well tolerated with no unexpected safety signals.Treatment-related adverse events(TRAEs)of grade≥3 occurred in 53.8%of patients;7.5%of patients discontinued treatment due to TRAEs.Conclusions:Tislelizumab demonstrated a significant ORR improvement in patients with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.

Spatial Mismatch of Tourism Resources and Tourism Economy:A Case Study of Ice and Snow Tourism in Altay Region

The coordinated development of tourism resources and tourism economy is vital improve the quality and efficiency of regional tourism.Taking the ice and snow tourism in Altay region as an example,this study constructed an evaluation indicator system and used the methods of gravity center model,spatial mismatch index model and obstacle degree model to calculate the spatial mismatch index and influencing factors of ice and snow tourism resources and tourism economy in Altay region as a whole and in each county and city.It found in the study period:(i)the ice and snow tourism resources and tourism economy in Altay region was synchronous in the development of time sequence,while the spatial distribution pattern was characterized by regional imbalance;(ii)at the macro scale,the spatial mismatch degree of the ice-snow tourism resource center and the tourism economic center in Altay region was gradually reduced,but they were always separated from the spatial geometric center of Altay region;(iii)at the micro scale,the spatial mismatch index of counties and cities in Altay region was mainly negative mismatch,and the types of spatial mismatch changed in different degrees;(iv)the factors showed certain spatial differentiation characteristics in different counties of Altay region,and there were some differences in the obstacles of different mismatch level areas,and the economic basis was the most frequent obstacle in different mismatch level areas of Altay region.

Impacts of Model Mismatch and Array Scale on Channel Estimation for XL-HRIS-Aided Systems

Extremely large-scale hybrid reconfigurable intelligence surface(XL-HRIS),an improved version of the RIS,can receive the incident signal and enhance communication performance.However,as the RIS size increases,the phase variations of the received signal across the whole array are nonnegligible in the near-field region,and the channel model mismatch,which will decrease the estimation accuracy,must be considered.In this paper,the lower bound(LB)of the estimated parameter is studied and the impacts of the distance and signal-tonoise ratio(SNR)on LB are then evaluated.Moreover,the impacts of the array scale on LB and spectral efficiency(SE)are also studied.Simulation results verify that even in extremely large-scale array systems with infinite SNR,channel model mismatch can still limit estimation accuracy.However,this impact decreases with increasing distance.

Impact of human leukocyte antigen mismatching on outcomes of liver transplantation:A meta-analysis

AIM:To assess the effect of human leukocyte antigen(HLA) mismatching on liver graft outcome and acute rejection from a meta-analysis of available cohort studies.METHODS:Articles in PubMed/MEDLINE,EMBASE and the Cochrane database from January 1970 to June 2009,including non-English literature identified in these databases,were searched.Only studies comparing HLA or sub-phenotype matching with mismatching were extracted.The percentage of graft survival was extracted by "Engauge Digitizer" from survival curves if the raw data were not displayed.A meta-analysis was performed when at least 3 studies provided data.RESULTS:Sixteen studies met the inclusion criteria.A lower number of HLA mismatches(0-2 vs 3-6) did reduce the incidence of acute rejection(relative risk:0.77,P = 0.03).The degree of HLA mismatching(0-2 vs 3-6) had no significant effect on 1-year [hazard ratio(HR):1.04,P = 0.68] and 5-year(HR:1.09,P = 0.38) graft survival.In sub-phenotype analysis,the degree of HLA-A,B and DR mismatching(0 vs 1-2) had no significant effect on 1-year and 5-year graft survival,either.The HRs and P-values were 0.95,0.71(HLA-A,1-year);1.06,0.60(HLA-A,5-year);0.77,0.16(HLA-B,1-year);1.07,0.56(HLA-DR,1-year);1.18,0.23(HLADR,5-year),respectively.CONCLUSION:The results of this systematic review imply that good HLA compatibility can reduce the incidence of acute rejection in spite of having no influence on graft outcomes.To obtain a short recovery time and minimize rejection post transplantation,HLA matching studies should be considered before the operation.

Channel Mismatching in Sidelobe Canceler: Limitations and Remedies

After a brief recall of the Sidelobe Canceler (SLC) working principle, including the derivation of a general formula for the Cancellation Ratio (CR), the effects of channel mismatching are investigated. In particular, curves providing CRvalues as a function of amplitude and phase channel mismatching, radar bandwidth, and jammer direction of arrival (JDOA) are provided for the cases of one and two auxiliary antennas. Subsequently, a time -space processor for performance restoration is analyzed in detail. In addition to the above mentioned quantities, the attainable CR value is expressed as a function of the space-time processor parameters. The contribution of the paper is related to the derivation of a number of mathematical equations of CR for several cases of practical interest for the radar engineer. In addition, several curves are presented to assist design of SLC systems.

Integral sliding mode control of time-delay systems with mismatching uncertainties

A linear matrix inequality （LMI）-based sliding surface design method for integral sliding mode control of uncertain time- delay systems with mismatching uncertainties is proposed. The uncertain time-delay system under consideration may have mis- matching norm bounded uncertainties in the state matrix as well as the input matrix, A sufficient condition for the existence of a sliding surface is given to guarantee asymptotic stability of the full order slJdJng mode dynamics. An LMI characterization of the slid- ing surface is given, together with an integral sliding mode control law guaranteeing the existence of a sliding mode from the initial time. Finally, a simulation is given to show the effectiveness of the proposed method.

多模核磁MISMATCH技术在超时间窗急性大动脉闭塞性脑梗死患者治疗中的指导作用

目的 探讨多模核磁MISMATCH技术在超时间窗急性大动脉闭塞性脑梗死患者治疗中的指导作用。方法 选取2019年1月—2023年3月于天水市第一人民医院经多模核磁磁共振扩散加权成像(diffusion weighted imaging, DWI)-动脉自旋标记(arterial spin labeling, ASL)、DWI-液体衰减反转恢复(fluid attenuated inversion recovery, FLAIR)、DWI-磁敏感加权技术(magnetic sensitivity weighting technology, SWI)的MISMATCH技术进行筛选的超时间窗(发病时间在6~24 h)急性大动脉闭塞性脑梗死经血管内介入治疗患者44例作为研究组,同时选取在本中心超时间窗内(发病时间在6~24 h)未经多模核磁DWI-ASL、DWI-FLAIR、DWI-SWI的MISMATCH技术进行筛选的急性大动脉闭塞性脑梗死经血管内介入治疗患者43例作为对照组。研究组超时间窗患者术前均予以核磁共振扫描筛选出DWI-ASL/DWI-FLAIR/DWI-SWI其中存在MISMATCH且磁共振血管成像(magnetic resonance angiography, MRA)发现有大血管闭塞。两组患者都进行血管内介入治疗,治疗后血管血流均达到改良的脑梗死分级系统(modified treatment in cerebral ischemia, mTICI)分级2b/3级,观察两组患者的治疗获益和预后情况。结果 研究组术后90 d功能独立率(改良Rankin评分量表评分0~3分)为59.09%,高于对照组的37.21%,差异有统计学意义(χ^(2)=4.170,P<0.05)。研究组与对照组术后90 d病死率分别为25.00%与46.51%,研究组明显低于对照组,差异有统计学意义(P<0.05)。两组患者术后7 d美国国立卫生研究院卒中量表评分均低于术前,且研究组低于对照组,差异有统计学意义(P<0.05)。研究组术后72 h症状性颅内出血与非症状性颅内出血发生率分别为22.73%、34.09%,对照组分别为44.19%、55.81%,研究组明显低于对照组,差异有统计学意义(P<0.05)。结论 经过多模核磁DWI-ASL、DWI-FLAIR、DWI-SWI的MISMATCH技术筛选出的超时间窗急性大动脉闭塞性脑梗死符合血管内治疗患者获益优于未经多模核磁DWI-ASL、DWI-FLAIR、DWI-SWI的MISMATCH技术进筛选的时间窗内急性大动脉闭塞性脑梗死患者获益,临床结局和安全性方面更好。

A polarization mismatched p-GaN/p-Al_(0.25)Ga_(0.75)N/p-GaN structure to improve the hole injection for GaN based micro-LED with secondary etched mesa

A low hole injection efficiency for InGaN/GaN micro-light-emitting diodes(μLEDs) has become one of the main bottlenecks affecting the improvement of the external quantum efficiency(EQE) and the optical power. In this work, we propose and fabricate a polarization mismatched p-GaN/p-Al_(0.25)Ga_(0.75)N/p-GaN structure for 445 nm GaN-based μLEDs with the size of 40 × 40 μm^(2), which serves as the hole injection layer. The polarization-induced electric field in the p-GaN/p-Al_(0.25)Ga_(0.75)N/p-GaN structure provides holes with more energy and can facilitate the non-equilibrium holes to transport into the active region for radiative recombination. Meanwhile, a secondary etched mesa for μLEDs is also designed, which can effectively keep the holes apart from the defected region of the mesa sidewalls, and the surface nonradiative recombination can be suppressed. Therefore, the proposed μLED with the secondary etched mesa and the p-GaN/p-Al_(0.25)Ga_(0.75)N/p-GaN structure has the enhanced EQE and the improved optical power density when compared with the μLED without such designs.

Lexical Mismatching in Chinese Students＇ EFL Writing

This paper attempts at an in-depth exploration of lexical mismatching, a pattern of vocabulary errors. In this paper, errors per se were collected from 107 writing samples of Chinese college students, and then investigated from a variety of linguistic perspectives. Traditional theoretical approaches, i.e. CA and EA, are incorporated in the source analysis for a more comprehensive interpretation. Hopefully, the findings of the study will shed lights on lexical instruction and acquisition in the field of SLA.

A tunable adaptive detector for distributed targets when signal mismatch occurs

Aiming at the problem of detecting a distributed target when signal mismatch occurs,this paper proposes a tunable detector parameterized by an adjustable parameter.By adjusting the parameter,the tunable detector can achieve robust or selective detection of mismatched signals.Moreover,the proposed tunable detector,with a proper tunable parameter,can provide higher detection probability compared with existing detectors in the case of no signal mismatch.In addition,the proposed tunable detector possesses the constant false alarm rate property with the unknown noise covariance matrix.

Measurement of the cavity-loaded quality factor in superconducting radio-frequency systems with mismatched source impedance

The accurate measurement of parameters such as the cavity-loaded quality factor(Q_(L))and half bandwidth(f_(0.5))is essential for monitoring the performance of superconducting radio-frequency cavities.However,the conventional"field decay method"employed to calibrate these values requires the cavity to satisfy a"zero-input"condition.This can be challenging when the source impedance is mismatched and produce nonzero forward signals(V_(f))that significantly affect the measurement accuracy.To address this limitation,we developed a modified version of the"field decay method"based on the cavity differential equation.The proposed approach enables the precise calibration of f_(0.5) even under mismatch conditions.We tested the proposed approach on the SRF cavities of the Chinese Accelerator-Driven System Front-End Demo Superconducting Linac and compared the results with those obtained from a network analyzer.The two sets of results were consistent,indicating the usefulness of the proposed approach.

Role of intelligent/interactive qualitative and quantitative analysisthree-dimensional estimated model in donor-recipient size mismatch following deceased donor liver transplantation

BACKGROUND Donor-recipient size mismatch(DRSM)is considered a crucial factor for poor outcomes in liver transplantation(LT)because of complications,such as massive intraoperative blood loss(IBL)and early allograft dysfunction(EAD).Liver volumetry is performed routinely in living donor LT,but rarely in deceased donor LT(DDLT),which amplifies the adverse effects of DRSM in DDLT.Due to the various shortcomings of traditional manual liver volumetry and formula methods,a feasible model based on intelligent/interactive qualitative and quantitative analysis-three-dimensional(IQQA-3D)for estimating the degree of DRSM is needed.AIM To identify benefits of IQQA-3D liver volumetry in DDLT and establish an estimation model to guide perioperative management.METHODS We retrospectively determined the accuracy of IQQA-3D liver volumetry for standard total liver volume(TLV)(sTLV)and established an estimation TLV(eTLV)index(eTLVi)model.Receiver operating characteristic(ROC)curves were drawn to detect the optimal cut-off values for predicting massive IBL and EAD in DDLT using donor sTLV to recipient sTLV(called sTLVi).The factors influencing the occurrence of massive IBL and EAD were explored through logistic regression analysis.Finally,the eTLVi model was compared with the sTLVi model through the ROC curve for verification.RESULTS A total of 133 patients were included in the analysis.The Changzheng formula was accurate for calculating donor sTLV(P=0.083)but not for recipient sTLV(P=0.036).Recipient eTLV calculated using IQQA-3D highly matched with recipient sTLV(P=0.221).Alcoholic liver disease,gastrointestinal bleeding,and sTLVi>1.24 were independent risk factors for massive IBL,and drug-induced liver failure was an independent protective factor for massive IBL.Male donor-female recipient combination,model for end-stage liver disease score,sTLVi≤0.85,and sTLVi≥1.32 were independent risk factors for EAD,and viral hepatitis was an independent protective factor for EAD.The overall survival of patients in the 0.85<sTLVi<1.32 group was better compared to the sTLVi≤0.85 group and sTLVi≥1.32 group(P<0.001).There was no statistically significant difference in the area under the curve of the sTLVi model and IQQA-3D eTLVi model in the detection of massive IBL and EAD(all P>0.05).CONCLUSION IQQA-3D eTLVi model has high accuracy in predicting massive IBL and EAD in DDLT.We should follow the guidance of the IQQA-3D eTLVi model in perioperative management.

用于多通道单分子定位的高精度图像配准方法

单分子定位技术可以绕过光学系统的衍射限制,在生物样品的单粒子追踪和超分辨显微成像中得到了广泛应用.多通道单分子定位采用多个成像通道,可以实现对不同目标的同时追踪或多色超分辨成像,也可以提升单粒子追踪的轴向深度或实现更高的定位精度和密度.但各通道图像间的差异会影响协同定位或定量分析,因此图像配准是其图像数据预处理的关键环节;且由于单分子定位精度高,其对多通道图像配准精度的要求也很高.现有技术一般采用基于控制点的配准方法,且多采用复杂而精密的方式来获取基准物网格图像用于定位得到控制点对,以实现高精度图像配准,对样品或实验设备要求高,难以直接推广.为此,本文基于局部非线性变换和误匹配点剔除,发展了一种可以直接采用随机分布荧光珠样品作为基准物的高精度图像配准方法,通过在特征匹配和变换模型参数估计的过程中对控制点进行监测和迭代筛选,以剔除因单分子定位不准确或精度差而导致未精确匹配的控制点对,从而消除以随机分布荧光珠样品作为基准物时对于控制点准确获取和精确匹配所带来的不良影响,同时采用基于局部加权平均的二阶多项式拟合进行变换模型参数估计,以更好地适用于不同通道间存在局部非线性形变的情形.结果表明,采用该方法只需要3次迭代,就可以将未准确定位和精确匹配的控制点对找到并剔除,从而实现更准确的变换模型参数估计,将配准精度提高一个数量级,在图像局部非线性形变情况严重的正交像散双通道单分子定位成像系统中实现了约6 nm的配准精度.

黄河流域(山东段)工业用地错配时空格局与应对策略

以黄河流域(山东段)9个设区市所辖77个区县为研究单元,利用2011—2020年山东省供地信息库中的工业用地供应数据,以及同期工业经济统计数据,分析黄河流域(山东段)工业用地供应与工业利润总额时空变化特征,通过空间错配指数分析工业用地错配时空格局,并从科学配置、存量挖潜、提质增效和层级协同4个方面提出应对策略。研究对于实现黄河流域(山东段)土地资源高效利用与聚集区域高质量发展具有重要意义。

Can a global mean sea-level rise reduce the Last Interglacial model-data mismatch in East Asia?

末次间冰期有着丰富的重建和模拟资料,为研究未来温暖气候提供了一个理想的参考.然而,关于末次间冰期的东亚气候,模拟与重建的结果间长期存在着不匹配的情况,模拟结果普遍较重建结果更为冷干。本研究利用挪威地球系统模式(NorESM1-F),探讨了在末次间冰期模拟试验中纳入全球平均海平面上升能否减少模式-数据的不匹配.该试验结果表明,海平面上升情况下东亚地区会产生一定的增温增湿效应,但不足以消除模式-数据不匹配.基于这些结果,作者探讨了其它可能造成不匹配的因素以供进一步研究.

供需视角下雨洪调节关键区识别及规划策略研究

雨洪调节服务供需测度对识别易涝区域、合理配置自然资源、优化雨洪安全格局具有重要意义。目前的研究多从供给或需求单一角度聚焦中心城区雨洪调节能力,而全域尺度雨洪调节服务供需测度实证研究较少,雨洪调节服务供需空间分布特征和影响供需平衡的关键驱动因子有待探究。以湖北省通城县为例,通过SCS-CN模型量化县域生态空间雨洪调节服务供给能力,利用洪水脆弱性指数评估社会经济对雨洪调节服务的需求水平,进而识别县域雨洪调节服务供需空间分布特征及失衡关键区域;结合斯皮尔曼相关系数分析和冗余分析,探究影响供需失衡的关键因子,并考虑人口密度和建设用地面积对雨洪调节服务供需的影响,从“宏观-中观-微观”3个尺度构建雨洪安全格局。研究结果表明:①县域内雨洪调节服务供需空间存在显著的分异情况,因此需要从整体角度构建和优化雨洪安全格局;②中心建成区是雨洪调节服务供需失衡最严重的区域,需要采取雨洪安全管控和修复措施;③县域内雨洪调节服务供需失衡的关键影响因子是人口密度,与雨洪灾害风险等级呈负相关。研究成果可为识别雨洪调节服务供需失衡区域以及优化国土空间规划体系下多尺度雨洪安全格局提供量化支持和依据。

中国省域旅游竞争力与旅游网络关注度空间错位研究

正确把握中国省域旅游竞争力与旅游网络关注度的错位关系,对推动区域旅游高质量发展大有裨益。基于新发展理念构建旅游竞争力评价指标体系,采用重力模型、空间错位指数综合考察2011—2020年中国省域旅游竞争力与旅游网络关注度的空间错位特征及影响因素。结果表明:①研究期内中国省域旅游竞争力与旅游网络关注度均呈增长趋势且具有明显的空间分异性,旅游竞争力重心呈集聚分布态势,旅游网络关注度重心则随时间波动变化,大致位于旅游竞争力重心的西南方向;②中国省域旅游竞争力与旅游网络关注度空间错位格局由东至西呈现出正向错位向负向错位逐渐过渡的分布特征,正向高错位区由东部沿海省域向中部省域延伸,负向高错位区主要分布在西部特色旅游地与热门网红城市;③旅游资源禀赋、经济社会发展、政府政策导向、网络环境等多种因素综合作用促成旅游竞争力与旅游网络关注度的空间错位格局。