NLR与MSI对急性NSTEMI短期预后判断价值

目的本研究旨在探讨校正休克指数(MSI)和中性粒细胞/淋巴细胞比值(NLR)在判断急性非ST段抬高型心肌梗死(NSTEMI)患者短期内可能出现不良预后的预测能力。方法研究组选择2020年3月到2021年9月期间,首次就诊急诊科明确诊断为急性非ST段抬高型心肌梗死的276例患者。通过快速急诊绿道监测血压与心率,并于急诊科10 min内抽取血常规、床旁心脏彩超等相关化验检查,依据监测及化验结果,研究小组计算了校正休克指数(MSI)和中性粒细胞/淋巴细胞比值(NLR),然后根据统计结果将患者分为2组:NLR≥5.0组(n=75)与NLR﹤5.0组(n=201);(2)MSI≥1.2组(n=57)与MSI<1.2组(n=219)。比较2组一般资料情况,发生不良心血管事件的比例,采用受试者ROC曲线下面积来评估NLR值和MSI值对NSTEMI院内不良心血管事件的预测能力。结果连续入选的276例NSTEMI患者中,发生不良心血管事件52例,占18.8%,心源性休克患者15例,占5.4%,恶性心律失常患者24例,占8.7%,死亡13例,占4.7%。NLR≥5.0与MSI≥1.2值组的心功能、收缩压(SBP)、舒张压(DBP)及心率(HR)分别与NLR<5.0与MSI<1.2组比较,差异有统计学意义(P<0.05);NLR≥5.0与MSI≥1.2组MACE发生率分别高于NLR<5.0组与MSI<1.2组(P<0.05)。此外,NLR和MSI的ROC曲线下面积分别为0.734和0.703,提示NLR和MSI均具有评价急性非ST段抬高型心肌梗死患者短期不良心血管事件发生能力。结论MSI与NLR是评估NSTEMI短期不良预后的两个简单的重要的易获得指标。

MSI-H/dMMR对BRAF V600E突变型的手术可切除结直肠癌患者的临床病理学特征及预后的影响

结直肠癌(colorectal cancer,CRC)是一种涉及多基因、多步骤累积的复杂疾病,具有高度的异质性。微卫星不稳定性(microsatellite instability,MSI)和BRAF基因突变是CRC分子特征中的两个关键指标。有研究[1-3]表明,MSI与错配修复系统(mismatch repair,MMR)的检测结果具有较好的一致性。

结直肠癌患者RAS、BRAF基因突变与MSI状态的相关性及其临床病理特征

目的:结直肠癌是人类最常见的恶行肿瘤之一,其发病率和病死率呈逐年上升趋势。本研究旨在分析结直肠癌患者大鼠肉瘤病毒癌基因(rat sarcoma viral oncogene,RAS)、鼠类肉瘤病毒癌基因同源物(V-Raf murine sarcoma viral oncogene homolog B,BRAF)突变与微卫星不稳定(microsatellite instability,MSI)状态相关性及其临床病理特征,为结直肠癌临床治疗及预后评估提供依据。方法:回顾性分析444例结直肠癌患者的临床病理资料,并提取肿瘤组织基因组DNA,采用荧光定量PCR法检测Kirsten大鼠肉瘤病毒癌基因同源物(Kirsten rat sarcoma viral oncogene homolog,KRAS)、Neuroblastoma大鼠肉瘤病毒癌基因同源物(neuroblastoma rat sarcoma viral oncogene homolog,NRAS)第2、3、4外显子及BRAF V600E突变;运用PCR-毛细血管电泳行MSI状态分析。结果:K(N)RAS基因突变184例(41.44%,184/444),其中KRAS突变173例(94.02%,173/184),NRAS突变11例(5.98%,11/184),K(N)RAS共突变3例。BRAF V600E突变21例(4.7%,21/444)。微卫星高度不稳定(microsatellite instability high,MSIH)48例(10.81%,48/444),微卫星低度不稳定(microsatellite instability low,MSI-L)和微卫星稳定(microsatellite stable,MSS)共396例(89.19%,396/444)。K(N)RAS基因突变右半结肠癌多于左半结肠癌,且黏液腺癌突变率高于单纯腺癌(均P<0.05)。K(N)RAS基因突变与患者性别、年龄、肿瘤大小、肉眼分型、组织学分化程度、淋巴结转移、病理分期均无关(均P>0.05)。女性BRAF V600E突变高于男性,低分化高于中分化(均P<0.05),BRAF V600E突变与患者发病年龄、肿瘤位置、大小、肉眼分型、组织学类型、淋巴结转移、病理分期均无关(均P>0.05)。发生MSI-H的患者中,右半结肠癌多于左半结肠癌,肿瘤直径≥4.5 cm病例多于直径更小病例,隆起型多于其他肉眼分型,黏液腺癌多于单纯腺癌,低分化多于高分化(均P<0.05),而与患者性别和年龄均无关(均P>0.05)。K(N)RAS突变与MSI-H发生无关(P>0.05),但RAS基因Gly位点突变与MSI-H发生相关(P<0.05)。携带RAS基因Gly位点突变的MSI-H结直肠癌患者男性多于女性,发病年龄无差异,右半结肠多于左半结肠,肉眼分型多为溃疡型,单纯腺癌比例高于黏液腺癌,多为中低分化,较多处于病理分期I~II期,常不伴淋巴结转移和BRAF V600E突变,Gly突变位点多为Gly12Ser/Asp突变。BRAF V600E突变与MSI-H发生有关(P<0.05)。与K(N)RAS突变型MSI-L/MSS结直肠癌比较,K(N)RAS突变型MSI-H结直肠癌较易发生于右半结肠,肿瘤直径≥4.5 cm的病例较多,组织学类型多为黏液腺癌,较少发生淋巴结转移,多处于病理分期I~II(均P<0.05);K(N)RAS突变型MSI-H结直肠癌与性别、年龄、肿瘤肉眼分型、组织学分化均无相关(均P>0.05)。与RAS野生型-MSI-L/MSS结直肠癌比较,RAS野生型-MSI-H结直肠癌多发生于右半结肠,肿瘤直径≥4.5 cm,多为溃疡型和隆起型,较多为黏液腺癌,且多为中低分化(均P<0.05),而RAS野生型-MSI-H结直肠癌与性别、年龄、淋巴结转移、病理分期均无关(均P>0.05)。结论:结直肠癌KRAS基因Gly位点突变、BRAF V600E突变与MSI-H发生相关;MSI-H-RAS基因Gly点突变结直肠癌患者有其独特的临床病理特征;RAS-MSI基因状态与临床病理特征相关;K(N)RAS、BRAF V600E、MSI检测有利于结直肠癌患者个体化治疗及预后评估。

纳武利尤单抗联合伊匹木单抗治疗MSI-H晚期结肠癌1例报道

本文报告1例晚期结肠癌患者,既往术后标本免疫组化结果提示错配修复完整(proficient mismatch repair, pMMR),予术后化疗等全身治疗后病情进展。随后行二代测序(next-generation sequencing, NGS)提示该患者微卫星高度不稳定(microsatellite instability-high, MSI-H)以及高水平的肿瘤突变负荷值(tumor mutation burden, TMB)。

基于MLWE和MSIS的可验证解密方案

两方安全计算中涉及的可验证解密技术可以应用在医疗研究数据共享、机构间合作进行模型训练等有隐私保护需求的现实场景中,有助于进一步打破数据孤岛、保障数据安全。但是目前已有的为基于格密码或其他后量子加密方案正确解密所构造的零知识证明的效率不高。面对这一现状,文中针对Kyber提出了一个基于模容错学习问题(MLWE)和模小整数解问题(MSIS)的可验证解密方案。首先,根据Kyber的加解密特性,在利用证明者和验证者所持数据构造相等关系时存在差异,该方案提出了一种利用误差估计结合Kyber的压缩函数,使证明者提供给验证者一部分所持数据的信息,从而消除差异的方法,进而提供可以用于验证的相等关系,把该关系与Dilithium签名方案无公钥压缩版本的框架相结合,构造非交互式零知识证明,将可验证解密问题转变为证明环中短向量满足的线性关系。其次,在理论上分析了方案的正确性、安全性、通信开销和计算复杂度,将方案的合理性和零知识性规约到MSIS困难假设,并提供了2组不同安全等级的建议参数设置。最后,通过编写C语言程序测试了所提方案的正确性和效率。实验结果与理论分析结果基本一致,与现有方案相比,所提方案在对单个密文的证明大小和证明时间上有显著优势,更加简洁、高效。

晚期dMMR/MSI-H肝内胆管细胞癌1例报告

胆道恶性肿瘤(biliary tract cancer,BTC)占所有消化系肿瘤的3%[1],在原发性肝胆恶性肿瘤发病率中占据第二位[2],肝内胆管癌(intrahepatic cholangiocarcinoma,ICCA)属于BTC的一种,我国BTC中仅有1.3%至10.0%患者表现为MSI-H,32.3%至42.86%患者表现为PD-L1阳性[3],因此MSI-H、PD-L1阳性的ICCA患者极具讨论价值。

Construction and validation of somatic mutation-derived long noncoding RNAs signatures of genomic instability to predict prognosis of hepatocellular carcinoma

BACKGROUND Long non-coding RNAs(LncRNAs)have been found to be a potential prognostic factor for cancers,including hepatocellular carcinoma(HCC).Some LncRNAs have been confirmed as potential indicators to quantify genomic instability(GI).Nevertheless,GI-LncRNAs remain largely unexplored.This study established a GI-derived LncRNA signature(GILncSig)that can predict the prognosis of HCC patients.AIM To establish a GILncSig that can predict the prognosis of HCC patients.METHODS Identification of GI-LncRNAs was conducted by combining LncRNA expression and somatic mutation profiles.The GI-LncRNAs were then analyzed for functional enrichment.The GILncSig was established in the training set by Cox regression analysis,and its predictive ability was verified in the testing set and TCGA set.In addition,we explored the effects of the GILncSig and TP53 on prognosis.RESULTS A total of 88 GI-LncRNAs were found,and functional enrichment analysis showed that their functions were mainly involved in small molecule metabolism and GI.The GILncSig was constructed by 5 LncRNAs(miR210HG,AC016735.1,AC116351.1,AC010643.1,LUCAT1).In the training set,the prognosis of high-risk patients was significantly worse than that of low-risk patients,and similar results were verified in the testing set and TCGA set.Multivariate Cox regression analysis and stratified analysis confirmed that the GILncSig could be used as an independent prognostic factor.Receiver operating characteristic curve analysis of the GILncSig showed that the area under the curve(0.773)was higher than the two LncRNA signatures published recently.Furthermore,the GILncSig may have a better predictive performance than TP53 mutation status alone.CONCLUSION We established a GILncSig that can predict the prognosis of HCC patients,which will help to guide prognostic evaluation and treatment decisions.

多队列MSI-X引擎设计与实现

智能网卡是业界和学术界的研究热点之一,Corundum基于FPGA提供了一种开源的智能网卡软件,获得了广泛应用,但存在着队列管理不够灵活,中断处理逻辑可伸缩性较差的问题。为此,该文在Corundum基础上实现了一种支持中断、轮询混合模式的MSI-X引擎,大幅提高了Corun⁃dum的多队列管理能力,并同时具备高性能吞吐能力。该文给出了MSI-X中断申请至中断事件处理的整个流程,实验表明,该设计在不影响吞吐性能的基础上,可支持2048个中断向量,支持中断向量和传输队列的多对多绑定,支持直接中断和间接中断,同时可通过动态缓冲区监测的方式降低中断触发频率。该设计在Xilinx FPGA平台上实现了MSI-X引擎,在智能网络虚拟化中具有广泛的应用前景。

基于RISC-V的MSI硬件辅助中断虚拟化设计

当前的RISC-V外部中断控制器PLIC无法直接处理MSI,在虚拟化环境下中断处理效率相对较低。基于RISC-V AIA协议,首次提出了一种RISC-V架构下MSI硬件辅助中断虚拟化设计。该设计可作为独立模块集成到RISC-V架构的处理器中,直接接收处理MSI。相较于PLIC,此设计具有更短的中断响应时间。并且在虚拟化场景下,相较于软件实现所需的数千个时钟周期,硬件辅助的中断虚拟化方案仅需6个时钟周期即可完成MSI的重映射,显著提升了MSI虚拟化的处理效率。

结直肠癌患者KRAS、NRAS、BRAF、HER2基因突变及MSI状态与临床特征的相关性分析

目的探讨结直肠癌患者的Kirsten大鼠肉瘤病毒癌基因同源物(KRAS)、神经母细胞瘤病毒癌基因RAS同源物(NRAS)、鼠类肉瘤滤过性毒菌致癌同源体B(BRAF)、人表皮生长因子受体2(HER2)基因突变及微卫星不稳定性(MSI)状态与临床病理特征之间的关系。方法收集2019年10月至2022年3月在该院接受治疗的226例结直肠癌患者的临床资料,采用二代测序技术检测KRAS、NRAS、BRAF、HER2基因突变情况和MSI状态,应用免疫组化法评估错配修复系统(MMR)状态,采用多因素Logistic回归分析KRAS、NRAS、BRAF、HER2与临床病理特征的关系。结果在226例结直肠癌患者中,KRAS基因突变频率为54.9%,NRAS基因突变频率为5.3%,BRAF基因突变频率为8.4%,HER2基因扩增突变频率为1.8%。黏液腺癌KRAS基因的突变频率高于普通腺癌(P<0.05),右半结肠癌KRAS基因突变的风险增加(OR=2.145,P=0.012)。而NRAS基因突变在左半结肠和直肠癌频率较高(P<0.05)。BRAF基因突变在低分化类型及微卫星高度不稳定(MSI-H)的结直肠癌中突变频率均较高(P<0.05),右半结肠BRAF基因突变的风险增加(OR=2.844,P=0.042)。HER2基因扩增突变表现肝肺等远处转移(P<0.05)。KRAS基因突变与NRAS、BRAF、HER2扩增突变是相互排斥的,差异有统计学意义(P<0.05)。MSI-H在右半结肠中的发生频率更高(P<0.05)。226例标本检出10例标本错配修复缺陷(dMMR)/MSI-H,8例标本dMMR/微卫生稳定,5例标本错配修复正常/MSI-H,dMMR和MSI-H之间存在中等程度的一致性(Kappa=0.575)。结论结直肠癌患者中,KRAS、NRAS、BRAF、HER2基因及MSI状态与临床病理特征有关,联合检测能够提供更准确、有效的数据,以指导患者的治疗临床用药和预后判断。

Wave nature of Rosensweig instability

The explicit analytical solution of Rosensweig instability spikes'shapes obtained by Navier-Stokes(NS)equation in diverse magnetic field H vertical to the flat free surface of ferrofluids are systematically studied experimentally and theoretically.After carefully analyzing and solving the NS equation in elliptic form,the force balanced surface equations of spikes in Rosensweig instability are expressed as cosine wave in perturbated magnetic field and hyperbolic tangent in large magnetic field,whose results both reveal the wave-like nature of Rosensweig instability.The results of hyperbolic tangent form are perfectly fitted to the experimental results in this paper,which indicates that the analytical solution is basically correct.Using the forementioned theoretical results,the total energy of the spike distribution pattern is calculated.By analyzing the energy components under different magnetic field intensities H,the hexagon-square transition of Rosensweig instability is systematically discussed and explained in an explicit way.

Theoretical analysis of the elastic Kelvin-Helmholtz instability in explosive weldings

By considering the joint effects of the Kelvin-Helmholtz(KH) and Rayleigh-Taylor(RT) instabilities, this paper presents an interpretation of the wavy patterns that occur in explosive welding. It is assumed that the elasticity of the material at the interface effectively determines the wavelength, because explosive welding is basically a solid-state welding process. To this end, an analytical model of elastic hydrodynamic instabilities is proposed, and the most unstable mode is selected in the solid phase. Similar approaches have been widely used to study the interfacial behavior of solid metals in high-energy-density physics. By comparing the experimental and theoretical results, it is concluded that thermal softening,which significantly reduces the shear modulus, is necessary and sufficient for successful welding. The thermal softening is verified by theoretical analysis of the increase in temperature due to the impacting and sliding of the flyer and base plates, and some experimental observations are qualitatively validated.In summary, the combined effect of the KH and RT instabilities in solids determines the wavy morphology, and our theoretical results are in good qualitative agreement with experimental and numerical observations.

Integrated chromosomal instability and tumor microbiome re define d prognosis-related subtypes of pancreatic cancer

Background:Pancreatic cancer is a common malignancy with poor prognosis and limited treatment.Here we aimed to investigate the role of host chromosomal instability(CIN)and tumor microbiome in the prognosis of pancreatic cancer patients.Methods:One hundred formalin-fixed paraffin-embedded(FFPE)pancreatic cancer samples were collected.DNA extracted from FFPE samples were analyzed by low-coverage whole-genome sequencing(WGS)via a customized bioinformatics workflow named ultrasensitive chromosomal aneuploidy detector.Results:Samples were tested according to the procedure of ultrasensitive chromosomal aneuploidy detector(UCAD).We excluded 2 samples with failed quality control,1 patient lost to follow-up and 6 dead in the perioperative period.The final 91 patients were admitted for the following analyses.Thirteen(14.3%)patients with higher CIN score had worse overall survival(OS)than those with lower CIN score.The top 20 microbes in pancreatic cancer samples included 15 species of bacteria and 5 species of viruses.Patients with high human herpesvirus(HHV)-7 and HHV-5 DNA reads exhibited worse OS.Furthermore,we classified 91 patients into 3 subtypes.Patients with higher CIN score(n=13)had the worst prognosis(median OS 6.9 mon);patients with lower CIN score but with HHV-7/5 DNA load(n=24)had worse prognosis(median OS 10.6 mon);while patients with lower CIN score and HHV-7/5 DNA negative(n=54)had the best prognosis(median OS 21.1 mon).Conclusions:High CIN and HHV-7/5 DNA load were associated with worse survival of pancreatic cancer.The novel molecular subtypes of pancreatic cancer based on CIN and microbiome had prognostic value.

Tendoscopic Surgery for Peroneal Tendons Instability: A Literature Review

Introduction: There has been a surge in the use of tendoscopic surgery for treating peroneal tendons instability. The novelty of this approach demanded a literature review of its indications, limitations, and clinical outcomes. Aim: a literature review of the clinical studies reporting on tendoscopic peroneal tendon stabilisation surgery along with its outcomes and complications. Methods: We carried out a comprehensive review of the literature up until September 2022 with an extensive search of the MEDLINE, Embase and Cochrane library databases. Results: Initial search resulted in 66 articles. Four duplicate articles were removed. Further 30 articles were excluded after title and abstract screening. Eight studies satisfied the inclusion criteria and were included in this review. Articles were analysed for outcomes and complications. Conclusion: The tendoscopic technique for peroneal tendon instability is an effective and safe surgical technique with very low failure rate. Levels of Evidence: Level IV.

Transverse mode-coupling instability with longitudinal impedance

Transverse mode-coupling instability(TMCI)is a dangerous transverse single-bunch instability that can lead to severe par-ticle loss.The mechanism of TMCI can be explained by the coupling of transverse coherent oscillation modes owing to the transverse short-range wakefield(i.e.,the transverse broadband impedance).Recent studies on future circular colliders,e.g.,FCC-ee,showed that the threshold of TMCI decreased significantly when both longitudinal and transverse impedances were included.We performed computations for the circular electron-positron collider(CEPC)and observed a similar phenom-enon.Systematic studies on the influence of longitudinal impedance on the TMCI threshold were conducted.We concluded that the imaginary part of the longitudinal impedance,which caused a reduction in the incoherent synchrotron tune,was the primary reason for the reduction in the TMCI threshold.Additionally,the real part of the longitudinal impedance assists in increasing the TMCI threshold.

Chronic Ankle Instability: Therapeutic Exercise and Data Analysis

Background and Objectives: Ankle injuries are the most common type of injury in healthy active individuals. If not treated properly, recurrent sprains can lead to a condition of chronic ankle instability (CAI). The present paper examines some subjects with a previous history of acute inversion ankle sprain who have developed a subsequent condition of instability, grouping them according to inclusion criteria and analyzing them through four field tests considered objective by the scientific literature: SEBT test, BEES test, TIBT test, SHT test. The data obtained were stored in order to compare them following a re-education protocol aimed at improving proprioception, balance, walking and strengthening the extrinsic and intrinsic muscles of the foot. per year. The subjects were then divided into two categories: subjects with CAI > 1 year and subjects with CAI ≤ 1 year. A protocol lasting 6 weeks was administered to both groups, trying to work on improving balance in single stance, improving static and dynamic stability, strengthening the gluteus medius and maximus (pelvis stabilizers) and strengthening of the intrinsic muscles of the foot. At the end of the protocol the subjects were all re-evaluated with the same field tests used previously and the data obtained were compared both with the pre-protocol data and with the data measured by the control subjects.

High-resolution reconstruction of the ablative RT instability flowfield via convolutional neural networks

High-resolution flow field data has important applications in meteorology,aerospace engineering,high-energy physics and other fields.Experiments and numerical simulations are two main ways to obtain high-resolution flow field data,while the high experiment cost and computing resources for simulation hinder the specificanalysis of flow field evolution.With the development of deep learning technology,convolutional neural networks areused to achieve high-resolution reconstruction of the flow field.In this paper,an ordinary convolutional neuralnetwork and a multi-time-path convolutional neural network are established for the ablative Rayleigh-Taylorinstability.These two methods can reconstruct the high-resolution flow field in just a few seconds,and further greatlyenrich the application of high-resolution reconstruction technology in fluid instability.Compared with the ordinaryconvolutional neural network,the multi-time-path convolutional neural network model has smaller error and canrestore more details of the flow field.The influence of low-resolution flow field data obtained by the two poolingmethods on the convolutional neural networks model is also discussed.

Parametric instability in the pure-quartic nonlinear Schrödinger equation

We study the nonlinear stage of modulation instability(MI)in the non-intergrable pure-quartic nonlinear Schrödinger equation where the fourth-order dispersion is modulated periodically.Using the three-mode truncation,we reveal the complex recurrence of parametric resonance(PR)breathers,where each recurrence is associated with two oscillation periods(PR period and internal oscillation period).The nonlinear stage of parametric instability admits the maximum energy exchange between the spectrum sidebands and central mode occurring outside the MI gain band.

A Study of Radiation-Induced Telomere Instability Using Multiplex Ligation-Dependent Probe Amplification (MLPA)

The integrity of the chromosomes for two WIL2-derived lymphoblastoid cell lines (TK6 and WTK1) in the presence and absence of ionizing radiation was analyzed by Multiplex Ligation-Dependent Probe Amplification (MLPA). The TK6 cell line has the native p53 tumor-suppressor gene, whereas WTK1 cells contain a p53 mutation. Each cell line was isolated pre- and post-irradiation (2 and 3 Gy) and analyzed by MLPA. The impact of irradiation on these two cell lines was investigated using probes that target specific regions on chromosomes associated with subtelomeric regions. Results indicate that WTK1 and TK6 are impacted differently after irradiation, and that each cell line presents its own unique MLPA profile. The most notable differences are the appearance of a number of probes in the post-irradiated MLPA profile that are not present in the controls, and two unique probe signals only seen in WTK1 cells. These results build on our previous studies that indicate how different human cell lines can be affected by radiation in significantly different ways depending on the presence or absence of wild type p53.

PD-1单抗治疗一例dMMR/MSI-H/TMB-H型结肠癌伴颅内转移瘤患者临床完全缓解

一例70岁男性患者,在接受右半肠癌根治性手术1年后出现了记忆丧失和认知功能下降的症状,头颅磁共振成像检查发现脑部肿块,手术后经病理检查确诊为结肠腺癌转移。原发灶及颅内转移瘤免疫组织化学检测均提示为错配修复缺陷。原发结肠肿瘤组织基因检测证实为微卫星高度不稳定伴有高肿瘤突变负荷,肿瘤突变负荷为77.7 muts/Mb。患者结肠癌根治术和颅内转移瘤术后均接受了辅助化疗,但在颅内转移瘤切除术和化疗结束后1个月颅内转移复发。患者接受帕博利珠单抗治疗后结果颅内转移瘤消退并达到临床完全缓解。