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.

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.

The influence of gradient mismatches on mechanical properties and microstructure of 2219-T6 aluminum alloy VP-TIG joints

In this paper,6 mm thick 2219-T6 aluminum alloy was joined by means of variable polarity tungsten-arc welding( VP-TIG) and the influence of gradient mismatches on VP-TIG joints is investigated. The average tensile strength of the joints reduces 32%,53% and 59%,when the mismatch of the joint was 0. 635 mm,1. 44 mm,1. 83 mm,respectively.Incomplete penetration,additional bending moment( Ma) and decrease of effective load region area are considered to explain this phenomenon. The fracture location of tensile specimens occurred at the weld zone( WZ) close to partial melt zone( PMZ),corresponding to a sharp decline of microhardness from PMZ to WZ. The original position of fracture is found at weld toe,where incomplete penetration forms due to the introduction of gradient mismatches.

Analysis of Effects of System Mismatches on the Performance of Adaptive Generalized Sidelobe Canceller and Compensation Methods

The effect of system mismatches on an adaptive linear constrained generalized sidelobe canceller （LC-GSC） is discussed in this paper. Based on the array gain index, two classic system mismatches, the direction of arrival （DOA） mismatch and the mismatches arising from array disturbance, are studied, respectively. To obtain the effective methods for compensating for the system mismatches, we analyze the performance of the improved LC-GSC with the diagonal loading and additional constraints （such as the directional constraints and derivative constraints）. The computer simulations show that the techniques of diagonal loading and additional constraints can effectively compensate for the system mismatches. The loss of array gains can be controlled within 3 dB in the presence of 20% of array disturbances or DOA mismatch when the signal-to-noise ratio is less than 10 dB. The analysis illustrates that the proposed compensation methods are valid and feasible.

Raman spectroscopic study of G-A mismatches

G-A mismatches are non-canonical base pairs that widely occur in native nucleic acids. They have been found to be functionally important in adopting unusual structures. In this paper, G-A mispairing was studied by Raman spectral characterization of Polyadenylic acid （PolyA）, Polyguanylic acid （PolyG） and their equimolar mixture in solution of 0.08 mol/L Na^＋, pH7.0. The experiment showed the following three results. （1） At the experimental conditions used in the present work, PolyA and G A complexes existed as single-stranded and double-stranded helix of A form, respectively. And PolyG mainly occurred to be anti-parallel quadruplex conformers. （2） The formation of G A complexes, on one hand strengthened parts of base stacking interactions especially for PolyG, leading to Raman hypochromism effect with some corresponding bands shifting, and on the other hand weakened other base stacking interactions especially for PolyA to a certain degree. During this process, the backbone of PolyG underwent a significant change, but PolyA still conserved its main chain conformation. （3） The formation of G A complexes was stabilized by two interbase hydrogen- bond interactions （i.e. N6H2（A）-N3 （G） and N7 （A）--N2H2（G）） and a third hydrogen bond between O2^＋ （G） and N6 （A）. The third hydrogen bond was responsible for the remarkable changes of PolyG backbone conformation.

Effects of Emotional State on Processing Conceptual Mismatches: ERPs in a Picture-Sentence Matching Task

Event-related potential (ERP) studies demonstrated that emotional state immediately affects the processing of different linguistic mismatches (e.g., semantic and syntactic mismatches) in sentences. Furthermore, mood has been shown to impact discourse processing. In these studies, a strong expectancy was evoked by a linguistic context. In the present study, a strong expectancy was induced by a visual (non-linguistic) context paired with a sentence. A spatial array was followed by a sentence that matched (□○—The square stands in front of the circle) or mismatched the picture (intra-dimensional mismatch: □○—The square stands behind the circle;extra-dimensional mismatch: □○—The square stands above the circle). The main question was whether mood effects on the processing of visually induced expectancies are similar or different from mood effects on the processing of linguistically induced expectancies. To this aim, we presented conceptual (mis)matches that differed in saliency: intra-dimensional vs. extra-dimensional mismatches which are both reported to elicit an N2b/N400 and P600, reflecting reanalysis. EEG was recorded while participants read for comprehension. Mood (happy vs. sad) was effectively induced by film clips. Neither for N2b/N400 nor for P600, an interaction between mood and match was observed. Thus, in contrast with studies investigating the effects of pure linguistic mismatches (linguistic context paired with unexpected lexical item), mood did not modulate the processing of conceptual mismatches. However, a main effect of match revealed different ERP patterns for the two mismatches. While an increase in N2b/ N400 occurred for the intra-dimensional and extra-dimensional mismatches, a P600 only occurred to the extra-dimensional (more salient) mismatches. This finding is taken as support that being in an emotional state (positive or negative mood) influences processes of reanalysis. That is, when being in an emotional state, a reanalysis (monitoring) process is exclusively triggered by salient mismatches.

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。

DIGITAL BACKGROUND CALIBRATION OF CAPACITOR MISMATCHES AND HARMONIC DISTORTION IN PIPELINED ADC

A correlation-based digital background calibration algorithm for pipelined Analog-to- Digital Converters (ADCs) is presented in this paper. The merit of the calibration algorithm is that the main errors information, which include the capacitor mismatches and residue amplifier distortion, are extracted integrally. A modified 1st pipelined stage is adopted to solve the signal overflow caused by the Pseudo-random Noise (PN) sequences. Behavioral simulation results verify the effectiveness of the algorithm. It improves the Signal-to-Noise-plus-Distortion Ratio (SNDR) and Spurious-Free-Dynamic-Range (SFDR) of the pipelined ADC from 41.8 dB to 78.3 dB and 55.6 dB to 98.6 dB, respectively, which is comparable to the prior arts.

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.

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.

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.

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。

不同良恶性结直肠肿瘤患者PMS2、P53的表达情况及其与预后的相关性

目的:分析良恶性结直肠肿瘤患者错配修复蛋白(PMS2)、P53的表达情况及其与预后的相关性。方法:根据肿瘤的良恶性不同将113例结直肠肿瘤患者分为结直肠腺瘤组(n=55),结直肠癌组(n=58),所有患者均切除病理组织。通过免疫组化法检测PMS2、P53阳性表达率。分析PMS2、P53与临床特征的关系、预后的相关性,采用Logistic回归分析预后的影响因素。结果:与结直肠腺瘤组相比,结直肠癌组PMS2阳性率较低,P53阳性率较高(P<0.05)。PMS2与分化程度、淋巴结转移、发病位置、临床分期均呈负相关关系(P<0.05),P53与分化程度、淋巴结转移、发病位置、临床分期均呈正相关(P<0.05)。与预后良好患者相比,预后不良患者PMS2阳性率较低,P53阳性率较高(P<0.05)。PMS2与预后负相关,P53与预后正相关(P<0.05)。多因素Logistic回归模型显示,分化程度、淋巴结转移、发病位置、临床分期、PMS2、P53为影响结直肠癌预后的危险因素。随访3年,54例结直肠癌患者3年生存率为81.48%(44/54),PMS2阳性表达患者生存率高于PMS2阴性表达患者(χ^(2)=6.965,P=20.011),P53阳性表达患者生存率低于P53阴性表达患者(χ^(2)=5.429,P=20.020)。结论:在结直肠癌组织中,PMS2阳性表达率较低,P53阳性表达率较高,PMS2、P53与患者预后相关,是导致预后不良的影响因素。

子宫内膜癌组织中dMMR蛋白和miRNA Let-7表达水平及临床价值的研究

目的探讨子宫内膜癌(endometrial carcinoma,EC)中微小RNA Let-7(miRNA Let-7)表达水平与DNA错配修复(DNA mismatch repair,dMMR)蛋白表达缺失的关系及意义。方法选取2016年5月~2022年12月在江苏省连云港市妇幼保健院行根治性手术切除的子宫内膜癌患者74例,分别用免疫组织化学法检测dMMR蛋白(包括MLH1,PMS2,MSH2,MSH6)的表达、实时荧光定量聚合酶链反应(qRT-PCR)检测miRNA Let-7的相对表达量,按照dMMR蛋白表达情况,将EC患者分为表达完整组(n=43)和表达缺失组(n=31),采用Logistic多因素回归分析与dMMR蛋白缺失相关的危险因素、绘制受试者工作特征(receiver operating characteristic,ROC)曲线评估相关因素的预测价值。结果74例EC病例中,miRNA Let-7的表达水平在肌层浸润<1/2组显著高于肌层浸润≥1/2组,差异具有统计学意义(t=1.79,P=0.04);dMMR蛋白表达的缺失率为41.89%,且年龄<55岁组和miRNA Let-7低表达组(<0.715)患者中的dMMR蛋白缺失率高于≥55岁组和miRNA Let-7高表达组(≥0.715),差异具有统计学意义(χ2=3.92,4.50,均P<0.05);Logistic多因素回归分析结果显示miRNA Let-7表达水平是发生dMMR表达缺失的独立危险因素(P=0.012);Spearman相关分析表明,miRNA Let-7的表达水平与dMMR蛋白缺失呈明显负相关(r=-0.247,P=0.034);ROC曲线分析结果显示,miRNA Let-7表达水平对于预测EC患者中发生dMMR蛋白的缺失具有一定的价值,其AUC为0.737,最佳临界值为0.77,敏感度和特异度分别为0.651,0.806。结论子宫内膜癌患者中miRNA Let-7的表达水平与dMMR蛋白缺失具有相关性,也是发生dMMR蛋白缺失的危险因素,有望为预测dMMR的表达缺失提供帮助。

基于自适应字典校正的稀疏恢复STAP算法

空时自适应处理(Space-Time Adaptive Processing,STAP)技术在时间维(脉冲维)和空间维(阵元维)联合进行信号处理,以实现动目标检测功能。但是,传统STAP技术的计算复杂度非常高,而且在优化处理信号过程中需要大样本的支撑,在实际的工作场景中,杂波环境复杂易变,不易获取足够多的独立同分布样本,因此杂波抑制效果较差。稀疏恢复空时自适应处理(Sparse Recovery Space-Time Adaptive Processing,SR-STAP)算法可以利用很少的训练样本实现杂波抑制,但大多数SR-STAP算法的计算量巨大,运行速度慢,算法实时性不高。此外,SRSTAP算法需要对连续空时二维平面进行离散化处理,将空时二维平面划分为很多细小的网格,由于真实的杂波在空时平面上是连续分布的,同时考虑雷达接收信号中噪声、系统参数误差等因素的影响,真实杂波点与离散化网格点之间一定存在着偏差,会造成网格失配现象,导致SR-STAP算法杂波抑制性能下降。针对此问题,本文提出了基于自适应字典校正的稀疏恢复STAP算法。该算法首先通过子空间投影法筛选出与杂波最相关的原子;然后围绕选定原子由粗到细进行自适应局部网格划分,按照局部网格迭代选优准则,不断调整选择局域内的最优原子,直到满足迭代终止条件,以匹配真实的杂波点;最后利用选定的最优原子对应的空时导向矢量构造杂波子空间,更新噪声子空间上与杂波子空间正交的投影矩阵得到STAP权值。仿真实验表明,所提算法与传统SR-STAP算法相比,具有更高的稀疏恢复精度,更快的运行速度,改善了STAP性能。