Physiological and pathological functions of circular RNAs in the nervous system

Circular RNAs(circRNAs)are a class of covalently closed single-stranded RNAs that are expressed during the development of specific cells and tissues.CircRNAs play crucial roles in physiological and pathological processes by sponging microRNAs,modulating gene transcription,controlling the activity of certain RNA-binding proteins,and producing functional peptides.A key focus of research at present is the functionality of circRNAs in the nervous system and several advances have emerged over the last 2 years.However,the precise role of circRNAs in the nervous system has yet to be comprehensively reviewed.In this review,we first summarize the recently described roles of circRNAs in brain development,maturity,and aging.Then,we focus on the involvement of circRNAs in various diseases of the central nervous system,such as brain cancer,chronic neurodegenerative diseases,acute injuries of the nervous system,and neuropathic pain.A better understanding of the functionality of circRNAs will help us to develop potential diagnostic,prognostic,and therapeutic strategies to treat diseases of the nervous system.

肺癌组织中DNA聚合酶β基因突变的研究

背景与目的 DNA聚合酶β是参与DNA损伤修复的关键酶之一,国外有学者认为其编码基因Polb在30%的肿瘤中存在遗传突变,但受到所用标本量的限制,这一结论是否准确尚无定论。本研究基于基因测序技术,通过对69例肺癌患者组织标本的基因筛查,旨在明确DNA聚合酶β的基因突变在中国汉族人群肺癌患者中的发生频率。方法利用盐析法提取69例肺癌患者的癌及癌旁组织基因组DNA,并用于扩增Polb基因全部14个外显子区及启动子区。通过与NCBI数据库中野生型基因序列进行比对,系统分析肺癌组织中的Polb基因突变及其频率。结果相对于野生型,本研究共发现5种突变类型,其中3种(-196G>T,-188_-187insCGCCC,-168C>A)位于启动子区,2种(587C>G, 612A>T)位于外显子区,突变类型-188_-187insCGCCC和587C>G尚未见文献报道,后者可引起第196位氨基酸由苏氨酸突变为丝氨酸。另一方面,癌和癌旁组中均可检测到所有5种突变类型,提示这些突变并非肺癌组织所特有。结论肺癌组织中未发现特异性表达的Polb基因突变位点,Polb基因突变可能不是中国汉族肺癌患者的肿瘤标志物。

单操作孔胸腔镜胸腺扩大切除治疗重症肌无力:附45例报告

背景与目的胸腺切除已成为重症肌无力(myasthenia gravis, MG)治疗的重要组成部分,近年来,经电视胸腔镜(video-assisted thoracoscopic surgery, VATS)胸腺扩大切除得到广泛应用。传统VATS术式多需3个经肋间切口,本研究改良了手术入路和操作方式,现总结单操作孔VATS胸腺扩大切除治疗MG的效果。方法回顾性分析2017年7月-2018年12月北京医院胸外科应用单操作孔VATS行胸腺扩大切除术的45例MG患者资料,总结其手术安全性和疗效。结果本组45例均顺利完成胸腺扩大切除,无中转开胸、增加切口和围术期死亡,平均手术时间(141.3±39.2)min,平均术中出血量(64.2±45.5)m L,中位胸腔引流管留置时间3 d,平均胸腔引流量(890.4±439.1)m L,中位术后住院时间6 d。围术期并发症13例(28.9%),其中肌无力危象5例(11.1%),肺部并发症6例(13.3%),切口愈合不良4例(8.9%),房颤4例(8.9%),迟发性心包积血1例(2.2%)。中位随访时间18.5个月,统计术后1年的疗效,药物缓解1例(2.2%),微小症状表现18例(40.0%),改善23例(51.1%),无变化1例(2.2%),加重2例(4.4%)。结论单操作孔胸腔镜下胸腺扩大切除术治疗MG的手术安全性和疗效良好,围术期应注意预防肌无力危象、肺部并发症和切口并发症。

高级别胎儿型肺腺癌1例

胎儿型肺腺癌属极其罕见的肺恶性肿瘤,2011年由国际肺癌研究协会、美国胸科学会和欧洲呼吸学会共同制定的国际多学科肺腺癌新分类将胎儿型肺腺癌归为浸润性腺癌的变异型,并将其分为低级别、高级别两类,二者临床病理特点和生物学行为不尽相同。本文报道高级别胎儿型肺腺癌1例,并结合文献总结胎儿型肺腺癌的临床病理特点。

非小细胞肺癌免疫治疗生物标志物的研究进展

肺癌是全球死亡率最高的恶性肿瘤,非小细胞肺癌(non-small cell lung cancer,NSCLC)是其最常见的病理类型。近年来,免疫治疗给NSCLC的治疗带来划时代的变革,尤其是针对程序性死亡受体1(programmed cell death 1,PD-1)/程序性死亡配体1(programmed cell death ligand 1,PD-L1)的免疫检查点抑制剂(immune checkpoint inhibitors,ICIs),目前已被批准用于转移性NSCLC或部分局部晚期NSCLC患者的一线治疗和二线治疗。然而,仅15%-30%晚期NSCLC患者可以从免疫治疗中获得持续缓解和长期生存,如何探寻良好的生物标志物来有效地预测免疫治疗的疗效是当前面临的巨大挑战之一。本文对NSCLC免疫治疗疗效预测生物标志物的研究进展进行综述。

肺癌术后特发性肺纤维化急性加重抢救成功病例报道

特发性肺纤维化(idiopathic pulmonary fibrosis,IPF)是一种病因不明、慢性进行性、纤维化性间质性肺病,与肺癌关系密切,肺切除术后易出现IPF急性加重(acute exacerbation of IPF,AE-IPF),病情进展迅速,缺乏有效治疗,预后极差。本文报道1例肺癌术后AE-IPF典型病例,总结其诊治要点,以提高临床医师对肺癌手术后AE-IPF的重视。

The dominant driving force for supercontinent breakup: Plume push or subduction retreat?

Understanding the dominant force responsible for supercontinent breakup is crucial for establishing Earth＇s geodynamic evolution that includes supercontinent cycles and plate tectonics. Conventionally,two forces have been considered： the push by mantle plumes from the sub-continental mantle which is called the active force for breakup, and the dragging force from oceanic subduction retreat which is called the passive force for breakup. However, the relative importance of these two forces is unclear. Here we model the supercontinent breakup coupled with global mantle convection in order to address this question. Our global model features a spherical harmonic degree-2 structure, which includes a major subduction girdle and two large upwelling（superplume） systems. Based on this global mantle structure,we examine the distribution of extensional stress applied to the supercontinent by both subsupercontinent mantle upwellings and subduction retreat at the supercontinent peripheral. Our results show that：（1） at the center half of the supercontinent, plume push stress is ～3 times larger than the stress induced by subduction retreat;（2） an average hot anomaly of no higher than 50 K beneath the supercontinent can produce a push force strong enough to cause the initialization of supercontinent breakup;（3） the extensional stress induced by subduction retreat concentrates on a ～600 km wide zone on the boundary of the supercontinent, but has far less impact to the interior of the supercontinent. We therefore conclude that although circum-supercontinent subduction retreat assists supercontinent breakup, sub-supercontinent mantle upwelling is the essential force.

肺癌合并间质性肺病的外科治疗

背景与目的间质性肺病(interstitial lung disease,ILD)是一组主要累及肺间质和肺泡腔导致肺泡-毛细血管功能单位丧失的弥漫性肺疾病,常导致限制性通气功能障碍和弥散功能障碍。ILD基础上肺癌发病率增高,肺癌合并间质性肺病(lung cancer combined with ILD,LC-ILD)的手术风险明显增加。本研究旨在探讨LC-ILD外科治疗的安全性,总结围术期诊治经验。方法回顾性分析2012年1月-2019年12月北京医院胸外科收治的LC-ILD行肺切除术的患者资料,总结其临床表现、影像、病理、手术安全性、围术期并发症和诊治经验。结果本研究共纳入23例患者,男性20例(87.0%),平均年龄(69.1±7.8)岁,吸烟者19例(82.6%)。ILD类型包括特发性肺纤维化14例(60.9%)、特发性非特异性间质性肺炎7例(30.4%)、结缔组织病相关ILD 2例(8.7%)。肺癌病理包括腺癌7例(30.4%)、小细胞癌7例(30.4%)、鳞癌6例(26.1%)、小细胞癌混合鳞癌1例(4.3%)、大细胞癌2例(8.7%)。手术入路包括经电视胸腔镜16例(69.6%)和前外侧开胸7例(30.4%),切除方式包括肺叶切除13例(56.5%)、双肺叶切除1例(4.3%)和亚肺叶切除9例(39.1%)。术后90 d并发症11例(47.8%),其中肺部并发症8例(34.8%),ILD急性加重(acute exacerbation of ILD,AE-ILD)4例(17.4%),心房纤颤6例(26.1%),急性左心功能不全1例(4.3%)。术后90 d死亡2例(8.7%),死因均为AE-ILD。结论LC-ILD以合并症多、肺功能差的高龄患者居多,手术风险明显增高。术前应充分控制ILD病情,术中尽量降低手术创伤,术后应特别关注肺部并发症和AE-ILD。AEILD预后差,治疗难度大,糖皮质激素有助于改善病情,早诊早治是治疗关键。

An Efficient and Privacy-Preserving Data Aggregation Scheme Supporting Arbitrary Statistical Functions in IoT

The Internet of Things(IoT)has profoundly impacted our lives and has greatly revolutionized our lifestyle.The terminal devices in an IoT data aggregation application sense real-time data for the remote cloud server to achieve intelligent decisions.However,the high frequency of collecting user data will raise people concerns about personal privacy.In recent years,many privacy-preserving data aggregation schemes have been proposed.Unfortunately,most existing schemes cannot support either arbitrary aggregation functions,or dynamic user group management,or fault tolerance.In this paper,we propose an efficient and privacy-preserving data aggregation scheme.In the scheme,we design a lightweight encryption method to protect the user privacy by using a ring topology and a random location sequence.On this basis,the proposed scheme supports not only arbitrary aggregation functions,but also flexible dynamic user management.Furthermore,the scheme achieves faulttolerant capabilities by utilizing a future data buffering mechanism.Security analysis reveals that the scheme can achieve the desired security properties,and experimental evaluation results show the scheme's efficiency in terms of computational and communication overhead.

Preoperative prediction of lymph node metastasis using deep learning-based features

Lymph node involvement increases the risk of breast cancer recurrence.An accurate non-invasive assessment of nodal involvement is valuable in cancer staging,surgical risk,and cost savings.Radiomics has been proposed to pre-operatively predict sentinel lymph node(SLN)status;however,radiomic models are known to be sensitive to acquisition parameters.The purpose of this study was to develop a prediction model for preoperative prediction of SLN metastasis using deep learning-based(DLB)features and compare its predictive performance to state-of-the-art radiomics.Specifically,this study aimed to compare the generalizability of radiomics vs DLB features in an independent test set with dissimilar resolution.Dynamic contrast-enhancement images from 198 patients(67 positive SLNs)were used in this study.Of these subjects,163 had an in-plane resolution of 0.7×0.7 mm^(2),which were randomly divided into a training set(approximately 67%)and a validation set(approximately 33%).The remaining 35 subjects with a different in-plane resolution(0.78×0.78 mm^(2))were treated as independent testing set for generalizability.Two methods were employed:(1)conventional radiomics(CR),and(2)DLB features which replaced hand-curated features with pre-trained VGG-16 features.The threshold determined using the training set was applied to the independent validation and testing dataset.Same feature reduction,feature selection,model creation procedures were used for both approaches.In the validation set(same resolution as training),the DLB model outperformed the CR model(accuracy 83%vs 80%).Furthermore,in the independent testing set of the dissimilar resolution,the DLB model performed markedly better than the CR model(accuracy 77%vs 71%).The predictive performance of the DLB model outperformed the CR model for this task.More interestingly,these improvements were seen particularly in the independent testing set of dissimilar resolution.This could indicate that DLB features can ultimately result in a more generalizable model.

Two fully automated data-driven 3D whole-breast segmentation strategies in MRI for MR-based breast density using image registration and U-Net with a focus on reproducibility

Presence of higher breast density(BD)and persistence over time are risk factors for breast cancer.A quantitatively accurate and highly reproducible BD measure that relies on precise and reproducible whole-breast segmentation is desirable.In this study,we aimed to develop a highly reproducible and accurate whole-breast segmentation algorithm for the generation of reproducible BD measures.Three datasets of volunteers from two clinical trials were included.Breast MR images were acquired on 3T Siemens Biograph mMR,Prisma,and Skyra using 3D Cartesian six-echo GRE sequences with a fat-water separation technique.Two whole-breast segmentation strategies,utiliz-ing image registration and 3D U-Net,were developed.Manual segmentation was performed.A task-based analysis was performed:a previously developed MR-based BD measure,MagDensity,was calculated and assessed using automated and manual segmentation.The mean squared error(MSE)and intraclass correlation coefficient(ICC)between MagDensity were evaluated using the manual segmentation as a reference.The test-retest reproducibility of MagDensity derived from different breast segmentation methods was assessed using the difference between the test and retest measures(Δ_(2-1)),MSE,and ICC.The results showed that MagDensity derived by the registration and deep learning segmentation methods exhibited high concordance with manual segmentation,with ICCs of 0.986(95%CI:0.974-0.993)and 0.983(95%CI:0.961-0.992),respectively.For test-retest analysis,MagDensity derived using the regis-tration algorithm achieved the smallest MSE of 0.370 and highest ICC of 0.993(95%CI:0.982-0.997)when compared to other segmentation methods.In conclusion,the proposed registration and deep learning whole-breast segmentation methods are accurate and reliable for estimating BD.Both methods outperformed a previously developed algorithm and manual segmentation in the test-retest assessment,with the registration exhibiting superior performance for highly reproducible BD measurements.

ESTABLISHMENT OF VISIBLE ANIMAL METASTASIS MODELS FOR HUMAN NASOPHARYNGEAL CARCINOMA BASED ON A FAR-RED FLUORESCENT PROTEIN

Background and aims:The spectral properties of enhanced greenfluorescent protein(EGFP)used in current visualizable animal models for nasopharyngeal carcinoma(NPC)result in a limited imaging depth.Far-redfluorescent proteins have optimal spectral wavelengths that allow deep tissue penetration,thus are well-suited for the imaging of tumor growth and metastases in live animals.This study aims to establish an imageable animal model of NPC using far-redfluorescent proteins.Methods:Eukaryotic expression vectors of far-redfluorescent proteins,mLumin and Katushka S158A,were separately transfected into 5-8F NPC cells,and cell lines stably expressing the far-redfluorescent proteins were obtained.These cells were intraperitoneally or intravenously injected into mice,and their tumorigenic and metastatic potential were examined throughfluorescence imaging.Finally,factors affecting their tumorigenic ability were further assessed through testing side population(SP)cells proportion byflow cytometry.Results:NPC cell line with high tumorigenicity and metastasis(5-8F-mL2)was screened out,which stably expressed far-redfluorescent protein.Intraperitoneal and intravenous injection of 5-8F-mL2 cells resulted in an abdomen metastasis model and a lung metastasis model.In addition,NPC cell line without tumorigenicity(5-8F-Katushka S158A)was screened out.The percentage of SP cells between 5-8F-mL2 and 5-8F-Katushka S158A was found different,suggesting that the SP cell proportion may play a key role in the determination of cell tumorigenic ability.Conclusion:We successfully established animal models for NPC with high tumorigenicity and metastasis using a super-bright far-redfluorescent protein.Owing to the super-brightness and excellent wavelength parameters,these models may be applied as useful tools for intuitive and efficient monitoring of tumor growth and metastasis,as well as assessing the efficacy of nasopharyngeal cancer drugs.

MKK7-mediated phosphorylation of JNKs regulates the proliferation and apoptosis of human spermatogonial stem cells

BACKGROUND Human spermatogonial stem cells(SSCs)are the basis of spermatogenesis.However,little is known about the developmental regulatory mechanisms of SSC due to sample origin and species differences.AIM To investigates the mechanisms involved in the proliferation of human SSC.METHODS The expression of mitogen-activated protein kinase kinase 7(MKK7)in human testis was identified using immunohistochemistry and western blotting(WB).MKK7 was knocked down using small interfering RNA,and cell proliferation and apoptosis were detected by WB,EdU,cell counting kit-8 and fluorescenceactivated cell sorting.After bioinformatic analysis,the interaction of MKK7 with c-Jun N-terminal kinases(JNKs)was verified by protein co-immunoprecipitation and WB.The phosphorylation of JNKs was inhibited by SP600125,and the phenotypic changes were detected by WB,cell counting kit-8 and fluorescenceactivated cell sorting.RESULTS MKK7 is mainly expressed in human SSCs,and MKK7 knockdown inhibits SSC proliferation and promotes their apoptosis.MKK7 mediated the phosphorylation of JNKs,and after inhibiting the phosphorylation of JNKs,the phenotypic changes of the cells were similar to those after MKK7 downregulation.The expression of MKK7 was significantly downregulated in patients with abnormal spermatogenesis,suggesting that abnormal MKK7 may be associated with spermatogenesis impairment.CONCLUSION MKK7 regulates the proliferation and apoptosis of human SSC by mediating the phosphorylation of JNKs.

Robustness of radiomic features in magnetic resonance imaging: review and a phantom study

Radiomic analysis has exponentially increased the amount of quantitative data that can be extracted from a single image.These imaging biomarkers can aid in the generation of prediction models aimed to further personalized medicine.However,the generalizability of the model is dependent on the robustness of these features.The purpose of this study is to review the current literature regarding robustness of radiomic features on magnetic resonance imaging.Additionally,a phantom study is performed to systematically evaluate the behavior of radiomic features under various conditions(signal to noise ratio,region of interest delineation,voxel size change and normalization methods)using intraclass correlation coefficients.The features extracted in this phantom study include first order,shape,gray level cooccurrence matrix and gray level run length matrix.Many features are found to be non-robust to changing parameters.Feature robustness assessment prior to feature selection,especially in the case of combining multi-institutional data,may be warranted.Further investigation is needed in this area of research.

Exploring the impact of pericentric inversion ofchromosome 9 on fertility in sperm donors

Pericentric inversion of chromosome 9(inv[9])is a common chromosomal structural variant,but its impact on clinical outcomesremains debated.The screening criteria of sperm banks are rarely mentioned to individuals with inv(9).In this study,we evaluatedthe fertility of sperm donors with inv(9)who met eligibility criteria for sperm banks(inv[9]-eligible donors).From March 2004 toMay 2022,chromosomal analysis of 16124 sperm donors at CITIC-Xiangya Human Sperm Bank in Hunan Province(Changsha,China)found that 251(1.6%)had chromosome variations,with inv(9)being the most prevalent at 1.1%.All 169 inv(9)-eligibledonors were contacted to collect fertility outcome data,along with 206 eligible donors without inv(9)as controls.In addition,semen samples from inv(9)-eligible donors and eligible donors underwent assessments of sperm fluorescence in situ hybridization(FISH),mitochondrial membrane potential,DNA fragmentation index,acrosome integrity,reactive oxygen species(ROS),andsperm morphology.Results showed that inv(9)did not significantly increase reproductive risks overall.Despite detecting ROSlevel differences,the clinical impact may be insignificant.This study provides new data on the inv(9)population that can serveas a valuable reference for decision-making by sperm banks as well as for genetic counseling and clinical guidance for individualscarrying inv(9)variant.

Resonant Beam Communications:A New Design Paradigm and Challenges

Resonant beam communications (RBCom), which adopts oscillating photons between two separate retroreflectors for information transmission, exhibits potential advantages over other types of wireless optical communications (WOC). However, echo interference generated by the modulated beam reflected from the receiver affects the transmission of the desired information. To tackle this challenge, a synchronization-based point-to-point RBCom system is proposed to eliminate the echo interference, and the design for the transmitter and receiver is discussed. Subsequently,the performance of the proposed RBCom is evaluated and compared with that of visible light communications(VLC)and free space optical communications (FOC). Finally, future research directions are outlined and several implementation challenges of RBCom systems are highlighted.

为什么地球上超大陆的寿命变得越来越短了?

地球上的主要大陆地块在过去的20亿年间以来曾经三次聚合成一个超大陆,但一段时间以后又发生裂解.这种大陆地块的周期性聚合和裂解现象被称为超大陆旋回.地球通过超大陆旋回控制着地表的造山运动、成矿过程、大洋及超大洋的形成与闭合,甚至大气圈与生命圈的演化.但一个有趣的观察是,已知的由老到新的努纳(也称哥伦比亚)、罗迪尼亚(最早音译鲁迪尼亚)和盘古三个超大陆的寿命显示出一个逐渐递减的趋势,其分别为大约3亿年,2~2.5亿年和1.5亿年,反映出控制地球长期演化过程的某种重要的内在原因.本文通过超级电脑地球动力学三维建模发现,导致超大陆寿命不断减短的主要原因在于形成于超大陆内部的新的造山带的强度随着地球的年龄增大而逐渐减小,并进而提出这与地球的长期冷却过程有关.因为地幔温度随着地球年龄的增长在不断降低,上地幔岩石部分熔融的程度也在不断降低,因此造成新生造山带的岩石圈厚度不断减薄,强度降低.此外,沿新生造山带的岩浆底侵对板块缝合线及大断裂的岩浆缝合作用可能也会随之减弱.

Fundamental Limitation of Semantic Communications:Neural Estimation for Rate-Distortion

This paper studies the fundamental limit of semantic communications over the discrete memoryless channel.We consider the scenario to send a semantic source consisting of an observation state and its corresponding semantic state,both of which are recovered at the receiver.To derive the performance limitation,we adopt the semantic rate-distortion function(SRDF)to study the relationship among the minimum compression rate,observation distortion,semantic distortion,and channel capacity.For the case with unknown semantic source distribution,while only a set of the source samples is available,we propose a neural-network-based method by leveraging the generative networks to learn the semantic source distribution.Furthermore,for a special case where the semantic state is a deterministic function of the observation,we design a cascade neural network to estimate the SRDF.For the case with perfectly known semantic source distribution,we propose a general Blahut-Arimoto(BA)algorithm to effectively compute the SRDE.Finally,experimental results validate our proposed algorithms for the scenarios with ideal Gaussian semantic source and some practical datasets.

Advances in metabolomics of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease(COPD)is a chronic lung disease with limited airflow.COPD is charac-terized by chronic bronchitis and emphysema,and is often accompanied by malnutrition with fatigue,muscle weakness,and an increased risk of infection.Although the pulmonary function test is used as the gold crite-rion for diagnosing COPD,it is unable to identify early COPD or classify the subtypes,thereby impeding early intervention and the precise diagnosis of COPD.Recent evidence suggests that metabolic dysfunction,such as changes in lipids,amino acids,glucose,nucleotides,and microbial metabolites in the lungs and intestine,have a great potential for diagnosing COPD in the early stage.However,a comprehensive summary of these metabolites and their effects on COPD is still lacking.This review summarizes the metabolites that are changed in COPD and highlights some promising early diagnostic markers and therapeutic targets.We emphasize that intensified dietary management may be among the most feasible methods to improve metabolism in the body.

Influence of sperm morphology on pregnancy outcome and offspring in in vitro fertilization and intracytoplasmic sperm injection:a matched case-control study

Sperm morphology was once believed as one of the most predictive indicators of pregnancy outcome in assisted reproductive technology(ART).However,the impact of teratozoospermia on in vitro fertilization(IVF)/intracytoplasmic sperm injection(ICSI)outcomes and its offspring remains inconclusive.In order to evaluate the influence of teratozoospermia on pregnancy outcome and newborn status after IVF and ICSI,a retrospective study was conducted.This was a matched case-control study that included 2202 IVF cycles and 2574 ICSI cycles and was conducted at the Reproductive and Genetic Hospital of CITIC-Xiangya in Changsha,China,from June 2013 to June 2018.Patients were divided into two groups based on sperm morphology:teratozoospermia and normal sperm group.The pregnancy outcome and newborn outcome were analyzed.The results indicated that couples with teratozoospermia had a significantly lower optimal embryo rate compared to those with normal sperm morphology in IVF(P=0.007),while there were no statistically significant differences between the two groups in terms of the fertilization rate,cleavage rate,implantation rate,and pregnancy rate(all P>0.05).Additionally,teratozoospermia was associated with lower infant birth weight in multiple births after IVF.With regard to ICSI,there was no significant difference in both pregnancy outcome and newborn outcome between the teratozoospermia and normal groups(both P>0.05).Furthermore,no increase in the risk of birth defects occurred in the teratozoospermia group after IVF/ICSI.Consequently,we believe that teratozoospermia has limited predictive value for pregnancy outcomes in IVF/ICSI,and has little impact on the resulting offspring if multiple pregnancy is avoided.