DNA damage response-related immune activation signature predicts the response to immune checkpoint inhibitors: from gastrointestinal cancer analysis to pan-cancer validation

Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) cancer.Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts.Results: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer.Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.

细针穿刺细胞学检查以及BRAF、RAS基因突变筛查对甲状腺癌的诊断价值分析

目的:评估甲状腺细针穿刺细胞学检查(FNAC)以及BRAF、RAS基因突变筛查对甲状腺癌的诊断价值。方法:回顾性分析2022年1月至2022年12月,在本院门诊或住院行FNAC的甲状腺结节患者共计597例,其中25例因标本不满意予以剔除,282例患者进行了BRAF/RAS基因检测,227例进行了手术治疗。以术后病理结果为金标准,分析FNAC、BRAF、RAS,以及联合检测诊断甲状腺癌的敏感性、特异性和诊断准确率。结果:分析FNAC诊断为非典型病变、且术后病理为甲状腺恶性肿瘤的患者,BRAF/RAS基因的阳性率为42.9%,其中超声TI-RADS分类4B以上的亚组,BRAF的阳性率69.2%,但差异无统计学意义(P=0.116)。单独应用FNAC对甲状腺癌的敏感性为82.8%、特异性为100.0%,联合BRAF基因检测,其敏感性可提高到89.3%、特异性为96.6%,诊断的准确率由82.8%提升到85.9%。结论:在甲状腺结节患者中,通过超声TI-RADS分类筛查出高危患者(尤其是4B及以上的),联合FNAC和BRAF基因检测,可提高甲状腺癌的诊断率。

Comparison of growth and nutrient uptake capacities of three dominant species of Qinhuangdao green tides

Since 2015, green tides have been blooming in offshore waters of Qinhuangdao, with serious impacts on the local ecological environment and tourism. Ulva australis, Bryopsis plumosa, and U. prolifera are the dominant species of Qinhuangdao green tides, following a sequential succession pattern. Ulva prolifera is the dominant species,with the highest biomass and the greatest influence on the local ecological environment. To study the reason of green tide dominant species succession and U. profilera became the dominant species with the largest biomass,we compared and analyzed the growth and nutrient uptake capacity of the three algae. The results showed that temperature significantly affects the growth of the three species. Within the temperature range of the experimental setup, the optimum temperature for the growth of U. australis, B. plumosa and U. profilera is10℃, 15℃, and 20–25℃, respectively. Combined with the temperature variation trend during green tide bloom development, we believe that temperature is the key environmental factor for the succession of the dominant species. Ulva prolifera has a higher growth rate than U. australis and B. plumosa under the same nitrate,ammonium, and phosphate levels. Significant differences in the maximum absorption rate(R_(max)) and R_(max)/Ks(the relationship between uptake rate and substrate concentration) values indicated that U. prolifera had an apparent competitive advantage over U. australis and B. plumosa regarding nutrient uptake. Therefore, the strong growth and nutrient uptake capacities of U. prolifera might be the main reason for becoming the dominant species with the largest biomass in Qinhuangdao green tides.

Development of Henoch-Schoenlein purpura in a child with idiopathic hypereosinophilia syndrome with multiple thrombotic onset: A case report

BACKGROUND The incidence of pulmonary embolism(PE) in children is low, but its mortality is high. Hypereosinophilic syndrome(HES) is a group of diseases caused by an abnormal increase in eosinophilic granulocytes resulting in multiple-organ dysfunction. The urgent event of thromboembolism in the pulmonary region provoked by eosinophils in idiopathic HES(IHES) is relatively unusual. This article reports a case of IHES with multiple PEs and left leg venous thrombosis as the first manifestation. One month later, the patient developed Henoch-Schonlein purpura(HSP), which is very rare.CASE SUMMARY We report the case of a 12-year-old boy who was admitted to the hospital with dyspnea, left leg pain, and aggravation. He had bilateral PE and left leg venous embolism with mild eosinophilia. Low-molecular-weight heparin and urokinase were given. At the same time, the interventional department was contacted about filter implantation, followed by urokinase thrombolysis. The left leg thrombus was aspirated under ultrasound guidance. He was discharged from the hospital on rivaroxaban. One month later, he developed a rash on both legs and ankle pain consistent with HSP, with severe eosinophilia and motor and sensory disturbances. The patient was diagnosed with IHES with multiple embolisms complicated by HSP after excluding other causes of the eosinophil elevation. After glucocorticoid treatment, the symptoms were relieved, but the patient later developed purpura nephritis.CONCLUSION We report a rare and life-threatening case of IHES with multiple embolisms associated with HSP.A mild elevation of eosinophils early in the disease leads to difficulties in diagnosis and delayed treatment.

Earthquake, Volcano and Earth Rotation Harmonics

Earthquake prediction is considered impossible for there is no scientific way to find the date and time, the location, and the magnitude of an earthquake. A new idea is introduced in this paper—earth rotation harmonics triggered natural volcano and earthquake. With earth rotation harmonics response model for a location, it could be possible to calculate the earthquake date and time, and the magnitude. Properties of earth rotation harmonics triggered earthquake are discussed and verified with earthquake data from USGS website. Also, both earth tide and ocean tide effects on earthquake are discussed and verified with earthquake data—tides did not trigger the natural earthquake, they only affect the earthquake activities and time.

高含量RAP和RAS混合料混合及扩散情况的定量评价

由于再生沥青路面(RAP)和再生沥青瓦(RAS)的老化,新旧胶结料在拌和过程和后续扩散中会出现均匀性问题。该文采用改进的分级提取方法来提取胶结料,并通过凝胶渗透色谱(GPC)的大分子尺寸百分比(LMS%)对其进行逐层定量分析。结果表明:未活化的RAP胶结料可均匀分布于由基质和RAP骨料组成的胶结料混合体系中,表明高含量RAP胶结料的均匀性问题不大。而当使用RAS时,胶结料的扩散速率明显变慢,表明高含量RAS胶结料的均匀性问题仍待解决。

一种结合时刻表调整的列车节能驾驶优化方法

为了降低高速列车在连续站间运行的能耗,以区间运行能耗和运行时间为目标建立列车驾驶策略优化模型,采用基于模拟退火的粒子群算法PSO-SA进行求解,得到每个运行区间的能耗-时间Pareto解集,并通过最小二乘法拟合得到每个区间相应的Pareto曲线。在此基础上,提出一种时刻表优化调整方法,在始发站至终点站总运行时分确定的前提下,基于KKT(Karush-Kuhn-Tucker)条件调整每个站间运行时分,给出最优的站间运行时分组合和最佳的区间运行策略。以CRH2A高速列车在镇江南—昆山南区间实际运行数据为基础进行仿真验证,结果表明:通过区间最优工况求解和多站间运行时分调整优化,列车在多站间的总运行能耗降低了17.6%,验证了模型和算法的有效性。

基于移动闭塞时空占用带模型的高速列车追踪运行优化

针对移动闭塞系统下高速列车站间追踪优化问题,根据固定闭塞系统的闭塞时间阶梯模型,建立移动闭塞的时空占用带优化模型。首先将列车站间运行过程进行分解,获取影响列车区间运行过程8个阶段的4个关键速度(出站咽喉速度、站间巡航速度、惰行末速度、进站咽喉速度)。然后根据列车车站发车追踪间隔、列车区间追踪间隔和列车车站到达追踪间隔三种场景,分析列车最小追踪间隔。在此基础上,根据移动闭塞时空占用带上下限分析列车追踪过程,建立以能耗和运行时间为性能指标的列车追踪运行优化问题,采用量子进化算法优化列车的发车间隔和站间追踪策略。最后,以CRH380AL型动车组为原型,选取武广线赤壁北—岳阳东段为仿真线路区间,验证了移动闭塞时空占用带模型和量子进化算法的有效性。

An Optimal Feed Interpolator Based on G^2 Continuous Bézier Curves for High-Speed Machining of Linear Tool Path

A numerical control (NC) tool path of digital CAD model is widely generated as a set of short line segments in machining. However, there are three shortcomings in the linear tool path, such as discontinuities of tangency and curvature, huge number of line segments, and short lengths of line segments. These disadvantages hinder the development of high speed machining. To smooth the linear tool path and improve machining efficiency of short line segments, this paper presents an optimal feed interpolator based on G^2 continuous Bézier curves for the linear tool path. First, the areas suitable for fitting are screened out based on the geometric characteristics of continuous short segments (CSSs). CSSs in every area are compressed and fitted into a G^2 Continuous Bézier curve by using the least square method. Then a series of cubic Bézier curves are generated. However, the junction between adjacent Bézier curves is only G^0 continuous. By adjusting the control points and inserting Bézier transition curves between adjacent Bézier curves, the G^2 continuous tool path is constructed. The fitting error is estimated by the second-order Taylor formula. Without iteration, the fitting algorithm can be implemented in real-time environment. Second, the optimal feed interpolator considering the comprehensive constraints (such as the chord error constraint, the maximum normal acceleration, servo capacity of each axis, etc.) is proposed. Simulation and experiment are conducted. The results shows that the proposed method can generate smooth path, decrease the amount of segments and reduce machining time for machining of linear tool path. The proposed research provides an effective method for high-speed machining of complex 2-D/3-D profiles described by short line segments.

2型糖尿病患者糖化血红蛋白水平与骨代谢的关系

【目的】探讨2型糖尿病(T2DM)患者体内骨代谢情况及其与糖化血红蛋白(HbA1C)水平的相关性。【方法】回顾性分析2019年6月至2020年6月在华东师范大学附属芜湖医院内分泌科住院的T2DM患者的临床资料(n=92),包括一般情况、生化指标及25-(OH)维生素D、β胶原特殊序列(CROSSL)、总Ⅰ型胶原氨基延长肽(T-PINP)、骨钙素(OSTEOC)等骨代谢指标,左侧股骨颈骨密度(T-Score)。按照HbA1C水平分为3组(血糖良好组、血糖一般组、血糖不佳组),并将3组上述相关数据进行比较。【结果】与血糖控制不佳组比较,血糖良好组和血糖一般组患者血清25-(OH)维生素D、T-PINP、T-Score明显升高(P<0.05)。25-(OH)维生素D是骨质疏松的保护因素,HbA1C、空腹血糖是骨质疏松的危险因素。【结论】血糖控制不良的T2DM患者的骨吸收增加,髋骨骨密度下降。临床工作中需加强干预措施,重视骨质疏松的防治。

HbA1c、LDL-C与2型糖尿病下肢动脉血管病变的相关性

目的:探讨糖化血红蛋白(glycosylated hemoglobin,HbA1c)、低密度脂蛋白胆固醇(lowdensity lipoprotein cholesterol,LDL-C)与2型糖尿病(type 2 diabetes mellitus,T2DM)患者下肢动脉血管病变(lower extremity arterial disease,LEAD)的相关性。方法:选取2018年5月至2021年5月华东师范大学附属芜湖医院收治的T2DM患者96例,根据双下肢彩超是否有斑块将患者分为单纯T2DM组(n=47)与T2DM合并LEAD组(n=49)。比较两组血清HbA1c、LDL-C等指标差异,对HbA1c、LDL-C水平与双下肢血管病变的相关性进行多元逐步回归分析,采用受试者工作特征(receiver operating characteristic,ROC)曲线评价HbA1c、LDL-C对LEAD的诊断能力。结果:两组空腹血糖、HbA1c、总胆固醇、三酰甘油、LDL-C水平差异均有统计学意义(t=-3.345、5.022、-2.721、-2.494、2.462,均P<0.05)。多元逐步回归分析显示:血清HbA1c、LDL-C水平与T2DM患者发生LEAD相关(t=-3.823、-2.493,P<0.05)。ROC曲线分析显示:HbA1c的ROC曲线下面积为0.680,诊断LEAD的敏感度为60.0%,特异度为70.6%;LDL-C的ROC曲线下面积为0.727,敏感度为61.2%,特异度为76.5%。结论:T2DM合并LEAD患者血清HbA1c、LDL-C水平显著增高,HbA1c、LDL-C有望作为LEAD的诊断指标。

The green tide in Yingkou,China in summer 2021 was caused by a subtropical alga——Ulva meridionalis(Ulvophyceae,Chlorophyta)

The large-scale green tide caused by Ulva has occurred successively in the Yellow Sea since 2007,and new events of green tide also continued to appear in nearby sea areas,indicating an undergoing rapid development of occurrence patterns for harmful macroalgal blooms(HMBs)along coastal China.In August 2021,a green tide occurred for the first time in Bayuquan sea area of Yingkou city,Liaoning Province in the Bohai Sea.In this study,morphological and molecular approaches were used to identify the causative species as U.meridionalis,an alien subtropical alga previously found to dominate green tides in the South China Sea.According to the hydrological data of Bayuquan in summer 2021,combined with morphological and developmental observations for this alga,we hypothesized that the disturbance caused by the typhoon In-Fa might have detached the local U.meridionalis from substrates,especially for those thalli with poorly developed holdfasts,and the ensuing wave-free period with unusually high temperature,which fell in the reported optimum growth temperature for U.meridionalis,might have provided the favorable conditions for the final bloom of the floating seaweeds.This is the first report on the bloom of subtropical U.meridionalis in the north temperate sea zone,indicating that the ecological risk of causing green tides in the future by this rapidly spreading species deserves high attention.

Quantitative dual-energy computed tomography texture analysis predicts the response of primary small hepatocellular carcinoma to radiofrequency ablation

Background:Radiofrequency ablation(RFA)is one of the effective therapeutic modalities in patients with hepatocellular carcinoma(HCC).However,there is no proper method to evaluate the HCC response to RFA.This study aimed to establish and validate a clinical prediction model based on dual-energy com-puted tomography(DECT)quantitative-imaging parameters,clinical variables,and CT texture parameters.Methods:We enrolled 63 patients with small HCC.Two to four weeks after RFA,we performed DECT scanning to obtain DECT-quantitative parameters and to record the patients’clinical baseline variables.DECT images were manually segmented,and 56 CT texture features were extracted.We used LASSO al-gorithm for feature selection and data dimensionality reduction;logistic regression analysis was used to build a clinical model with clinical variables and DECT-quantitative parameters;we then added texture features to build a clinical-texture model based on clinical model.Results:A total of six optimal CT texture analysis(CTTA)features were selected,which were statis-tically different between patients with or without tumor progression(P<0.05).When clinical vari-ables and DECT-quantitative parameters were included,the clinical models showed that albumin-bilirubin grade(ALBI)[odds ratio(OR)=2.77,95%confidence interval(CI):1.35-6.65,P=0.010],λAP(40-100 keV)(OR=3.21,95%CI:3.16-5.65,P=0.045)and IC AP(OR=1.25,95%CI:1.01-1.62,P=0.028)were asso-ciated with tumor progression,while the clinical-texture models showed that ALBI(OR=2.40,95%CI:1.19-5.68,P=0.024),λAP(40-100 keV)(OR=1.43,95%CI:1.10-2.07,P=0.019),and CTTA-score(OR=2.98,95%CI:1.68-6.66,P=0.001)were independent risk factors for tumor progression.The clinical model,clinical-texture model,and CTTA-score all performed well in predicting tumor progression within 12 months after RFA(AUC=0.917,0.962,and 0.906,respectively),and the C-indexes of the clinical and clinical-texture models were 0.917 and 0.957,respectively.Conclusions:DECT-quantitative parameters,CTTA,and clinical variables were helpful in predicting HCC progression after RFA.The constructed clinical prediction model can provide early warning of potential tumor progression risk for patients after RFA.

Activation of phospholipase D activity in transforming growth factor-beta-induced cell growth inhibition

Cells regulate phospholipase D (PLD) activity in response to numerous extracellular signals. Here, we investigated the involvement of PLD activity in transforming growth factor-β(TGF-β1)-mediated growth inhibition of epithelial cells. TGFβ1 inhibits the growth of MDCK, Mv1Lu, and A-549 cells. In the presence of 0.4 % butanol, TGF-β1 induces an increase in the formation of phosp hat idylbutanol, a unique product catalyzed by PLD. TGF-β1 also induces an increase in phosphatidic acid (PA) level in A-549 and MDCK cells. TGF-β1 induces an increase in the levels of DAG labeled with [~3H]-myristic acid in A-549 and MDCK cells but not in Mv1Lu cells- No increase of DAG was observed in cells prelabeled with [~3H]-arachidonic acid.The data presented suggest that PLD activation is involved in the TGF-β1-induced cell growth inhibition.

Disposing Status and Control Countermeasures of Pesticide Packaging Wastes in Tobacco Producing Area in Yunnan Province

Pesticide packaging wastes pose a serious hazard to the agricultural production environment and the quality of agricultural products. The investigation for 2 consecutive years in Jietou Region of Tengchong County, a major tobacco planting area in Yunan, showed that： ① More than 80% of the pesticides purchased by farmers were used for tobacco cultivation, which was 4 times that of conventional crops planting, and most of the packaging materials were plastic bags; ② The main way for farmers to dispose plastic bags was to burn or discard them in the field garbage collection baskets; ③ In combination with field surveys, an average of 4.54 pieces of pesticide packaging wastes were scattered around every 667 m^2 of tobacco field. In addition, the number reduced significantly after carrying out pesticide packaging wastes recycling and control project at the local smoke station. At the same time, the average number of pesticide packaging wastes in the field collection baskets increased. Therefore, it can effectively control pesticide packaging wastes by changing the type of pesticide packaging, encouraging the establishment of recycling system and strengthening the cognitive training of farmers.

Screening and evaluation for soybean resistance to Phakopsora pachyrhyzi in Glycine soja

Soybean rust caused by Phakopsora pachyrhizy is an important disease of soybean, and yield losses are very common in humid growing regions. Most commercial cultivars are susceptible and the disease is usually managed with fungicides. Resistance breeding is the most effective in controlling the disease. In this study, detached - leaf assay and greenhouse inoculation were used to screen 200 Glycine soja accessions for resistance to Phakopsora pachyrhizi in China. Most of the accessions were susceptible, and W8214 was the only accession that demonstrated RB resistance to Phakopsora pachyrhizy. The further repeated tests confirmed the resistance in W8214.

Streamlined whole-genome genotyping through NGS-enhanced thermal asymmetric interlaced(TAIL)-PCR

Whole-genome genotyping(WGG)stands as a pivotal element in genomic-assisted plant breeding.Nevertheless,sequencing-based approaches for WGG continue to be costly,primarily owing to the high expenses associated with library preparation and the laborious protocol.During prior development of foreground and background integrated genotyping by sequencing(FBI-seq),we discovered that any sequence-specific primer(SP)inherently possesses the capability to amplify a massive array of stable and reproducible non-specific PCR products across the genome.Here,we further improved FBI-seq by replacing the adapter ligated by Tn5 transposase with an arbitrary degenerate(AD)primer.The protocol for the enhanced FBI-seq unexpectedly mirrors a simplified thermal asymmetric interlaced(TAIL)-PCR,a technique that is widely used for isolation of flanking sequences.However,the improved TAIL-PCR maximizes the primer-template mismatched annealing capabilities of both SP and AD primers.In addition,leveraging of next-generation sequencing enhances the ability of this technique to assay tens of thousands of genome-wide loci for any species.This cost-effective,user-friendly,and powerful WGG tool,which we have named TAIL-PCR by sequencing(TAIL-peq),holds great potential for widespread application in breeding programs,thereby facilitating genome-assisted crop improvement.

早孕期胎儿腹壁缺损的超声诊断

目的探讨早孕期胎儿腹壁缺损的超声图像特征及临床诊断价值。方法收集2019年1月至2021年12月湖北省妇幼保健院早孕期产前超声诊断和引产后病理证实的胎儿腹壁缺损病例77例,对其超声声像图与生后病理检查进行对比分析。结果77例早孕期腹壁缺损胎儿中,脐膨出47例,超声表现为胎儿脐部见腹腔器官向外膨出,外有包膜覆盖,脐带附于包块的顶端;腹裂19例,超声表现为胎儿脐部见腹腔器官向外膨出,漂浮于羊水中,无包膜覆盖,腹壁缺损多位于脐部右侧;体蒂异常7例,超声主要特征为腹壁(或胸腹壁)缺损伴器官外翻、脊柱侧弯、肢体畸形、脐带短;羊膜带综合征3例,主要超声特征为羊水中可见漂浮的光带黏附于胎儿,并出现与光带相关的肢体、腹壁等截断畸形;泄殖腔畸形1例,超声主要特征是脐膨出、脊柱侧弯、膀胱显示不清。2例脐膨出漏诊。本组早孕期腹壁缺损超声诊断率为97.4%(75/77)。结论早孕期胎儿腹壁缺损超声声像图表现看似简单,均为向外膨出的包块,但腹壁缺损可能为包含多器官畸形的疾病,早孕期超声具有较高的诊断价值。

The First High-quality Reference Genome of Sika Deer Provides Insights into High-tannin Adaptation

Sika deer are known to prefer oak leaves,which are rich in tannins and toxic to most mammals;however,the genetic mechanisms underlying their unique ability to adapt to living in the jungle are still unclear.In identifying the mechanism responsible for the tolerance of a highly toxic diet,we have made a major advancement by explaining the genome of sika deer.We generated the first high-quality,chromosome-level genome assembly of sika deer and measured the correlation between tannin intake and RNA expression in 15 tissues through 180 experiments.Comparative genome analyses showed that the UGT and CYP gene families are functionally involved in the adaptation of sika deer to high-tannin food,especially the expansion of the UGT family 2 subfamily B of UGT genes.The first chromosome-level assembly and genetic characterization of the tolerance to a highly toxic diet suggest that the sika deer genome may serve as an essential resource for understanding evolutionary events and tannin adaptation.Our study provides a paradigm of comparative expressive genomics that can be applied to the study of unique biological features in non-model animals.

不对称配位操纵电子再分布实现高电流密度下电催化水氧化

作为目前最有前景的绿氢生产方式,电解水技术被研究者广泛关注.其中,电催化析氧反应(oxygen evolution reaction,OER)作为电解水的半反应,由于其缓慢的四电子转移步骤而成为电解水器件的能量瓶颈.高效的OER催化电极设计是解决该问题的有效方式.本文分析了OER催化剂中氧原子介导的电子重排与活性位点配位不对称性之间的构效关系.通过自发氧化还原反应,将镍离子引入到泡沫镍(NF)表面的FeWO_(4)中,以此破坏FeWO_(4)晶格中FeO_(6)八面体的对称性,并基于此调节Fe位点的电子结构.结构调控促进了钨酸盐适度重构成为具有高OER活性的羟基氧化物.在碱性环境中,具有不对称配位Fe位点的Fe_(0.53)Ni_(0.47)WO_(4)/NF自支撑电极在10 mA cm^(-2)的电流密度下,可获得170 mV的超低过电势,并在1000 mA cm^(-2)的高电流密度下可维持稳定500 h.这种新型OER催化电极为高活性电催化系统的设计提供了新的见解.