基于MRI影像组学构建PD-1/PD-L1抑制剂治疗dMMR/MSI-H直肠癌疗效的预测模型

目的:探讨MRI影像组学模型在程序性细胞死亡蛋白-1(PD-1)/程序性细胞死亡-配体1(PD-L1)抑制剂联合全程新辅助治疗(TNT)局部进展期直肠癌(LARC)的疗效预测价值。方法:收集河南中医药大学第一附属医院PD-1/PD-L1抑制剂联合TNT治疗的80例错配修复基因缺陷(dMMR)/微卫星高度不稳定(MSI-H)基因型中低位LARC患者的临床和影像资料。将入组患者按7∶3比例分为训练集和测试集,提取影像组学特征,从中筛选并构建影像组学模型。描绘影像组学模型的Rad-score与病理金标准之间的受试者工作特征(ROC)曲线,计算曲线下面积(AUC),并评价模型的诊断效能。采用决策曲线分析(DCA)计算风险阈值的范围,并评估临床获益情况。收集湖南省人民医院25例dMMR/MSI-H基因型LARC患者的影像资料作为外部验证集。结果:训练集、测试集及外部验证集三者之间的临床特征无统计学差异(P>0.05)。经过降维处理、t检验及一致性检验以及LASSO交叉验证后,筛选出一阶偏度特征和体积2个特征构建影像组学模型。训练集、测试集和外部验证集的影像组学预测模型ROC曲线的AUC、灵敏度、特异度、阳性预测值和阴性预测值分别为0.920、97.1%、85.7%、91.9%、94.7%;0.885、80.0%、88.9%、92.3%、72.7%;0.875、87.5%、88.9%、93.3%、80.0%。DCA曲线显示,当风险阈值范围为0%~82%时,采用影像组学模型预测LARC患者为病理完全缓解(pCR)的获益大于将所有患者都视为pCR或者无病理完全缓解(npCR)。结论:基于MRI影像组学构建的dMMR/MSI-H型局部进展期直肠癌PD-1/PD-L1抑制剂联合全程新辅助放化疗疗效预测模型,有较大潜力为不同基因分型的直肠癌患者制定个体化治疗策略提供量化依据。

帕金森病患者血清LCN2、PROS1水平变化及其与疾病分期、认知障碍的相关性

目的探讨帕金森病(PD)患者血清脂质运载蛋白2(LCN2)、蛋白S基因(PROS1)水平变化及其与疾病分期、认知障碍的相关性。方法选取2019年1月至2022年12月该院诊治的PD患者120例为研究对象(PD组),参考改良版Hoehn-Yahr分级(H-Y分级),分为早期PD组(0~1.5级,n=50),中期PD组(>1.5~3.0级,n=39),晚期PD组(>3.0~5.0级,n=31)。以同期健康体检的60例体检健康者为对照组。检测两组血清LCN2、PROS1水平。比较不同PD疾病分期PD患者血清LCN2、PROS1水平差异。Spearman秩相关分析血清LCN2、PROS1水平与简易智力状态检查量表(MMSE),蒙特利尔认知评估量表(MoCA)及H-Y分级的相关性。多因素Logistic回归分析影响PD患者认知功能障碍的相关因素。绘制受试者工作特征(ROC)曲线分析血清LCN2、PROS1水平对PD患者认知障碍的评估价值。结果PD组血清LCN2、PROS1水平分别为(97.47±11.28)μg/L、(77.52±8.69)μg/L,明显高于对照组(40.15±6.22)μg/L、(32.49±4.37)μg/L,差异均有统计学意义(t=36.641、37.783,均P<0.05)。晚期PD组血清LCN2、PROS1水平高于早期、中期PD组,差异均有统计学意义(均P<0.05)。认知障碍组PD患者病程、血清LCN2、PROS1、H-Y分级均高于认知正常组患者,而MoCA评分、MMSE评分低于认知正常组,差异均有统计学意义(P<0.05)。血清LCN2、PROS1水平与MoCA评分,MMSE评分呈负相关(r=-0.634、-0.489,均P<0.05),与H-Y分级呈正相关(r=0.467、0.625,均P<0.05)。血清LCN2、PROS1是影响PD患者认知功能障碍的相关危险因素。血清LCN2、PROS1单独及联合对PD患者认知功能障碍预测的曲线下面积(AUC)为0.905(95%CI:0.868~0.955),0.803(95%CI:0.764~0.849),0.836(95%CI:0.770~0.867),血清LCN2、PROS1联合检测AUC明显高于单独检测,差异具有统计学意义(Z=5.558,4.974,均P<0.001)。结论PD患者血清LCN2、PROS1水平升高,与PD疾病分期、认知障碍有关,两者联合检测对PD患者认知障碍具有较高的评估价值。

The Christian Doctrines of Salvation at the Earlier Stages of The Pilgrim's Progress

John Bunyan's The Pilgrim's Progress has been written to preach the Christian doctrines of salvation.Therefore its allegorical protagonists have gradually gone through four stages of development on the path to salvation.This paper is focused on the earlier two stages,that is,the repentance of sins and the temptations after conversion.

STAGE在C3I仿真测试系统中的应用

针对C3I系统面临的测试问题,提出一种将STAGE应用于C3I系统的仿真测试系统,并分析了STAGE的优点,介绍其组成结构、功能和STAGE在该系统中的应用。该系统已应用于某实际C3I系统的测试。

Microbiome changes in the gastric mucosa and gastric juice in different histological stages of Helicobacter pylori-negative gastric cancers

BACKGROUND The gastric microbiota in patients with gastric cancer(GC)has received increasing attention,but the profiling of the gastric microbiome through the histological stages of gastric tumorigenesis remains poorly understood,especially for patients with Helicobacter pylori-negative GC(HPNGC).AIM To characterize microbial profiles of gastric mucosa and juice for HPNGC carcinogenesis and identify distinct taxa in precancerous lesions.METHODS The 16S rRNA gene analysis was performed on gastric mucosa from 134 Helicobacter pylori-negative cases,including 56 superficial gastritis(SG),9 atrophic gastritis(AG),27 intestinal metaplasia(IM),29 dysplasia(Dys),and 13 GC cases,to investigate differences in gastric microbial diversity and composition across the disease stages.In addition,paired gastric mucosa and juice samples from 18 SG,18 IM,and 18 Dys samples were analyzed.α-Diversity was measured by Shannon and Chao1 indexes,andβ-diversity was calculated using partial least squares discrimination analysis(PLS-DA).Differences in the microbial composition across disease stages in different sample types were assessed using the linear discriminant analysis effect size.RESULTS The diversity and composition of the bacterial microbiota in the gastric mucosa changed progressively across stages of gastric carcinogenesis.The diversity of the gastric mucosa microbiota was found to be significantly lower in the IM and Dys groups than in the SG group,and the patients with GC had the lowest bacterial community richness(P<0.05).Patients with IM and those with Dys had similar gastric mucosa microbiota profiles with Ralstonia and Rhodococcus as the predominant genera.Microbial network analysis showed that there was increasing correlation strength between IM and Dys(|correlation threshold|≥0.5,P<0.05).GC and its precancerous lesions have distinguishable bacterial taxa;our results identified HPNGC-associated bacteria Streptococcaceae and Lactobacillaceae(P<0.05).Additionally,across precancerous lesion stages from AG to Dys in Helicobacter pylori-negative patients,Burkholderiaceae abundance continuously increased,while Streptococcaceae and Prevotellaceae abundance presented a continuous downward trend.Furthermore,the microbial diversity was higher in gastric juice(P<0.001)than in the mucosa,while PLS-DA revealed a statistically significant difference between the two groups(ANOSIM,P=0.001).A significant difference in the microbial structure was identified,with Proteobacteria being more prevalent in the gastric mucosa and Firmicutes being more abundant in gastric juice.CONCLUSION Our results provide insights into potential taxonomic biomarkers for HPNGC and its precancerous stages and assist in predicting the prognosis of IM and Dys based on the mucosal microbiota profile.

Partial improvement in performance of patients with severe Alzheimer's disease at an early stage of fornix deep brain stimulation

Deep brain stimulation is a therapy for Alzheimer＇s disease（AD） that has previously been used for mainly mild to moderate cases. This study provides the first evidence of early alterations in performance induced by stimulation targeted at the fornix in severe AD patients. The performance of the five cases enrolled in this study was scored with specialized assessments including the Mini-Mental State Examination and Clinical Dementia Rating, both before and at an early stage after deep brain stimulation. The burden of caregivers was also evaluated using the Zarit Caregiver Burden Interview. As a whole, the cognitive performance of patients remained stable or improved to varying degrees, and caregiver burden was decreased. Individually, an improved mental state or social performance was observed in three patients, and one of these three patients showed remarkable improvement in long-term memory. The conditions of another patient deteriorated because of inappropriate antipsychotic medications that were administered by his caregivers. Taken together, deep brain stimulation was capable of improving some cognitive aspects in patients with severe AD, and of ameliorating their emotional and social performance, at least at an early stage. However, long-term effects induced by deep brain stimulation in patients with severe AD need to be further validated. More research should focus on clarifying the mechanism of deep brain stimulation. This study was registered with ClinicalTrials.gov（NCT03115814） on April 14, 2017.

S100 calcium binding protein A6 and associated long noncoding ribonucleic acids as biomarkers in the diagnosis and staging of primary biliary cholangitis

BACKGROUND Primary biliary cholangitis(PBC)is a chronic and slowly progressing cholestatic disease,which causes damage to the small intrahepatic bile duct by immunoregulation,and may lead to cholestasis,liver fibrosis,cirrhosis and,eventually,liver failure.AIM To explore the potential diagnosis and staging value of plasma S100 calcium binding protein A6(S100A6)messenger ribonucleic acid(mRNA),LINC00312,LINC00472,and LINC01257 in primary biliary cholangitis.METHODS A total of 145 PBC patients and 110 healthy controls(HCs)were enrolled.Among them,80 PBC patients and 60 HCs were used as the training set,and 65 PBC patients and 50 HCs were used as the validation set.The relative expression levels of plasma S100A6 mRNA,long noncoding ribonucleic acids LINC00312,LINC00472 and LINC01257 were analyzed using quantitative reverse transcription-polymerase chain reaction.The bile duct ligation(BDL)mouse model was used to simulate PBC.Then double immunofluorescence was conducted to verify the overexpression of S100A6 protein in intrahepatic bile duct cells of BDL mice.Human intrahepatic biliary epithelial cells were treated with glycochenodeoxycholate to simulate the cholestatic environment of intrahepatic biliary epithelial cells in PBC.RESULTS The expression of S100A6 protein in intrahepatic bile duct cells was up-regulated in the BDL mouse model compared with sham mice.The relative expression levels of plasma S100A6 mRNA,log10 LINC00472 and LINC01257 were upregulated while LINC00312 was down-regulated in plasma of PBC patients compared with HCs(3.01±1.04 vs 2.09±0.87,P<0.0001;2.46±1.03 vs 1.77±0.84,P<0.0001;3.49±1.64 vs 2.37±0.96,P<0.0001;1.70±0.33 vs 2.07±0.53,P<0.0001,respectively).The relative expression levels of S100A6 mRNA,LINC00472 and LINC01257 were up-regulated and LINC00312 was down-regulated in human intrahepatic biliary epithelial cells treated with glycochenodeoxycholate compared with control(2.97±0.43 vs 1.09±0.08,P=0.0018;2.70±0.26 vs 1.10±0.10,P=0.0006;2.23±0.21 vs 1.10±0.10,P=0.0011;1.20±0.04 vs 3.03±0.15,P<0.0001,respectively).The mean expression of S100A6 in the advanced stage(III and IV)of PBC was up-regulated compared to that in HCs and the early stage(II)(3.38±0.71 vs 2.09±0.87,P<0.0001;3.38±0.71 vs 2.57±1.21,P=0.0003,respectively);and in the early stage(II),it was higher than that in HCs(2.57±1.21 vs 2.09±0.87,P=0.03).The mean expression of LINC00312 in the advanced stage was lower than that in the early stage and HCs(1.39±0.29 vs 1.56±0.33,P=0.01;1.39±0.29 vs 2.07±0.53,P<0.0001,respectively);in addition,the mean expression of LINC00312 in the early stage was lower than that in HCs(1.56±0.33 vs 2.07±0.53,P<0.0001).The mean expression of log10 LINC00472 in the advanced stage was higher than those in the early stage and HCs(2.99±0.87 vs 1.81±0.83,P<0.0001;2.99±0.87 vs 1.77±0.84,P<0.0001,respectively).The mean expression of LINC01257 in both the early stage and advanced stage were up-regulated compared with HCs(3.88±1.55 vs 2.37±0.96,P<0.0001;3.57±1.79 vs 2.37±0.96,P<0.0001,respectively).The areas under the curves(AUC)for S100A6,LINC00312,log10 LINC00472 and LINC01257 in PBC diagnosis were 0.759,0.7292,0.6942 and 0.7158,respectively.Furthermore,the AUC for these four genes in PBC staging were 0.666,0.661,0.839 and 0.5549,respectively.The expression levels of S100A6 mRNA,log10 LINC00472,and LINC01257 in plasma of PBC patients were decreased(2.35±1.02 vs 3.06±1.04,P=0.0018;1.99±0.83 vs 2.33±0.96,P=0.036;2.84±0.92 vs 3.69±1.54,P=0.0006),and the expression level of LINC00312 was increased(1.95±0.35 vs 1.73±0.32,P=0.0007)after treatment compared with before treatment using the paired t-test.Relative expression of S100A6 mRNA was positively correlated with log10 LINC00472(r=0.683,P<0.0001);serum level of collagen type IV was positively correlated with the relative expression of log10 LINC00472(r=0.482,P<0.0001);relative expression of S100A6 mRNA was positively correlated with the serum level of collagen type IV(r=0.732,P<0.0001).The AUC for the four biomarkers obtained in the validation set were close to the training set.CONCLUSION These four genes may potentially act as novel biomarkers for the diagnosis of PBC.Moreover,LINC00472 acts as a potential biomarker for staging in PBC.

Anodal transcranial direct current stimulation alleviates cognitive impairment in an APP/PS1 model of Alzheimer’s disease in the preclinical stage

Anodal transcranial direct current stimulation(AtDCS)has been shown to alleviate cognitive impairment in an APP/PS1 model of Alzheimer’s disease in the preclinical stage.However,this enhancement was only observed immediately after AtDCS,and the long-term effect of AtDCS remains unknown.In this study,we treated 26-week-old mouse models of Alzheimer’s disease in the preclinical stage with 10 AtDCS sessions or sham stimulation.The Morris water maze,novel object recognition task,and novel object location test were implemented to evaluate spatial learning memory and recognition memory of mice.Western blotting was used to detect the relevant protein content.Morphological changes were observed using immunohistochemistry and immunofluorescence staining.Six weeks after treatment,the mice subjected to AtDCS sessions had a shorter escape latency,a shorter path length,more platform area crossings,and spent more time in the target quadrant than sham-stimulated mice.The mice subjected to AtDCS sessions also performed better in the novel object recognition and novel object location tests than sham-stimulated mice.Furthermore,AtDCS reduced the levels of amyloid-β42 and glial fibrillary acidic protein,a marker of astrocyte activation,and increased the level of neuronal marker NeuN in hippocampal tissue.These findings suggest that AtDCS can improve the spatial learning and memory abilities and pathological state of an APP/PS1 mouse model of Alzheimer’s disease in the preclinical stage,with improvements that last for at least 6 weeks.

基于STM32的5段式S型交流伺服电机控制方法

在传统的加减速算法中,由于起点和终点的加速度不连续,易造成电机在运转过程中存在着冲击噪声和抖动现象。因此为实现交流伺服电机运行平稳,减少运行过程中的抖动和噪声,以及提高系统运行效率,减少系统运算量,提出了5段式S型加减速控制算法。同时将该S型控制算法改进后运用到STM32单片机上,以设计小型化、低成本的伺服控制器。采用位移和速度数组遍历查询的方式进行程序的设计,可实现电机速度、位移可调的加速启动、匀速运行和减速停止。为验证该控制器的可行性,将其运用到矿石分选实验平台上进行实际运行测试,利用上位机软件进行实时速度图像采集并对采集的图像进行分析。结果表明:该控制器可在较短时间内完成速度表计算和扫描,从实验平台上采集的图像中可以分析出运行过程中速度过渡较为平滑,电机运行平稳。

特定分布硅片曝光场的复合S型轨迹规划算法研究

为减小光刻机硅片台在步进扫描运动中的冲击和振荡,研究了一种S型轨迹规划算法。采用S型轨迹规划方法中的复合法,引入可调节的权重系数,兼顾时间和冲击两个因素,分别对步进运动、扫描运动加速段和扫描运动减速段进行研究。在对步进运动和扫描运动进行仿真分析的基础上,针对一种特定分布的曝光场进行“步进+扫描”综合仿真。仿真结果表明,相较于传统3阶轨迹规划,所研究的S型轨迹规划的加速度曲线更加平滑,不易激励柔性环节产生残余振动,可有效地减小冲击和振荡,保证光刻机硅片台在扫描曝光过程中的稳定性。

Unicentric Castleman's disease associated with end stage renal disease caused by amyloidosis

Castleman's disease(CD), also known as angiofolicular lymph node hyperplasia, is a rare heterogenous group of lymphoproliferative disorders. Histologically, it can be classified as hyaline vascular type, plasma cell type, or mixed type. Clinically two different subtypes of the CD are present: Unicentric and multicentric. Unicentric CD is generally asymptomatic and associated with hyaline vascular type, and its diagnoses depend on the localized lymphadenopathy on examination or imaging studies. However, multicentric CD presents with generalized lymphadenopathy and systemic symptoms including malaise, fever, night sweats, weight loss, and it is associated with the plasma cell type and mix type. Herein, we report a patient with unicentric CD of the plasma cell type without systemic symptoms, who developed end stage renal failure caused by amyloidosis 6 years after onset of CD.

Prey Predator Fishery Model with Stage Structure in Two Patchy Marine Aquatic Environment

In this paper, we propose and analyze a mathematical model to study the dynamics of a fishery resource system with stage structure in an aquatic environment that consists of two zones namely unreserved zone (fishing permitted) and reserved zone (fishing is strictly prohibited). In this model we introduce a stage structure in which predators are split into two kinds as immature predators and mature predators. It is assumed that immature predators cannot catch the prey and their foods are given by their parents (mature predators). It is also assumed that the fishing of immature predators prohibited in the unreserved zone and predator species are not allowed to enter inside the reserved zone. The local and global stability analysis has been specified. Biological and Bionomical equilibriums of the system are derived. Mathematical formulation of the optimal harvesting policy is given and its solution is derived in the equilibrium case by using Pontryagin’s maximum principle.

“Malaysia Has Certainly Benefited from China’s Prominence on the World Stage”——Exclusive Interview with See Chee Kong Leonard, Business Minister of Embassy of Malaysia in PRC

Relations between China and Malaysia have been developing steadily.Recently,See Chee Kong Leonard,Business Minister of Embassy of Malaysia in PRC,accepted an interview with Chinas Foreign Tradey and talked about the 45 years of economic and trade cooperation and achievements of the two countries.

Inheriting Good Tradition and Expanding Cooperation Fields for New Stage of Friendship:on FES President Beck 's Visit to China

At the invitation of the Chinese Association for International Understanding(CAFIU),a delegation headed by Mr.Kurt Beck,President of FriedrichEbert-Stiftung(FES),visited China from 17 to 20,October 2013.As his first visit to China since taking the office of FES President,President Beck aimed at keeping abreast of China’s political,economic and social development since the 18th National Congress of the CPC as well as renewing the Memorandum of Understanding between CAFIU and FES.

On with the Show China and the U.S.Tango Together on the World Stage

AS the world enters a new year,its largest developed nation and developing nation approach the 40th anniversary of the start of normalization process of diplomatic relations. Defined by dramatic twists and turns,the China-U.S. relationship has bounced back and forth from such optimistic events as the tentative contact during the Ping Pong Diplomacy of 1971,President Nixon’s visit in 1972,

2022年门源M_(S)6.9地震前地球物理场异常时空演化特征

1研究背景。由于印度板块与欧亚板块相互推挤影响,晚中新世以来青藏高原东北缘迅速抬升,地形变化与地质构造均异常复杂(沈旭章,2013)。历史上该区域发生多次6级以上强震,伴随孕震过程出现的地球物理场异常丰富且多样,异常数量及变化幅度能够客观反映区域应力变化的水平,其演化过程也受到孕震体物理、化学性质变化和地壳应力状态变化的控制(李丽,1999;苏维刚,2021)。

Innuovo: The NdFeB listed enterprise's first annual report is on the stage

On the evening of March 8th,Innuovo released its annual report,in which,business income grew steadily,and net profits soared a lot over the same period.The annual report on annual board of directors in 2017 is as follows:1.An overview In 2017,the trend of global economic recovery was obvious.