ctDNA在转移性去势抵抗性前列腺癌诊断中的应用现状

转移性去势抵抗性前列腺癌(metastatic castration-resistant prostate cancer,mCRPC)是不可治愈的,严重威胁着男性患者的 健康,也是人类恶性肿瘤治疗的一个重要难题。循环肿瘤DNA( circulating tumor DNA,ctDNA)是 一种非侵入性、可重复的评估肿 瘤基因组的工具,具有全面了解恶性肿瘤的潜力,在mCRPC中也进行了深入研究。本文将对ctDNA在mCRPC中的检测情况,以 及用于mCRPC患者监测及对耐药性机制等相关研究现状进行综述,并提出对未来可能有参考价值的研究方向。

Dynamic phase assembled terahertz metalens for reversible conversion between linear polarization and arbitrary circular polarization

If a metalens integrates the circular polarization(CP)conversion function,the focusing lens together with circular-polariz-ing lens(CPL)in traditional cameras may be replaced by a metalens.However,in terahertz(THz)band,the reported metalenses still do not obtain the perfect and strict single-handed CP,because they were constructed via Pancharatnam-Berry phase so that CP conversion contained both left-handed CP(LCP)and right-handed CP(RCP)components.In this paper,a silicon based THz metalens is constructed using dynamic phase to obtain single-handed CP conversion.Also,we can rotate the whole metalens at a certain angle to control the conversion of multi-polarization states,which can simply manipulate the focusing for incident linear polarization(LP)THz wave in three polarization conversion states,in-cluding LP without conversion,LCP and RCP.Moreover,the polarization conversion behavior is reversible,that is,the THz metalens can convert not only the LP into arbitrary single-handed CP,but also the LCP and RCP into two perpen-dicular LP,respectively.The metalens is expected to be used in advanced THz camera,as a great candidate for tradi-tional CPL and focusing lens group,and also shows potential application in polarization imaging with discriminating LCP and RCP.

Novel ACTG1 mutation causing autosomal dominant non-syndromic hearing impairment in a Chinese family

γ -actin （ACTG1） gene is a cytoplasmic nonmuscle actin gene, which encodes a major cytoskeletal protein in the sensory hair cells of the cochlea. Mutations in ACTG1 were found to cause autosomal dominant, progressive, sensorineural hearing loss linked to the DFNA 20/26 locus on chromosome 17q25.3 in European and American families, respectively. In this study, a novel missense mutation （c.364A〉G; p.I122V） co-segregated with the affected individuals in the family and did not exist in the unaffected family members and 150 unrelated normal controls. The alteration of residue Ile122 was predicted to damage its interaction with actin-binding proteins, which may cause disruption of hair cell organization and function. These findings strongly suggested that the I122V mutation in ACTG1 caused autosomal dominant non-syndromic hearing impairment in a Chinese family and expanded the spectrum of ACTG1 mutations causing hearing loss.

Effectiveness of ozonated saline in the treatment of VX2 tumors in rabbits

Objective To investigate the efficacy, safety, and associated mechanisms of injected ozonated saline in the treatment of VX2 tumors. Methods A total of 90 rabbits bearing VX2 tumors on their left hind legs were randomly divided into three groups. The control group(A) received normal saline, while groups B and C received 20 μg/mL and 40 μg/mL O_3/O_2 ozonated saline, respectively. Rabbits were anesthetized and 2 mL of blood was drawn directly from the heart to measure serum concentrations of interleukin(IL-6) and tumor necrosis factor(TNF-α). The skin covering the VX2 tumor was cut in each rabbit and the maximum and vertical diameters of the tumors were measured under direct visualization. Several milliliters of saline, saline pre-treated with 20 μg/mL O_3/O_2, or saline pre-treated with 40 μg/mL O_3/O_2 were directly injected into the tumors of groups A, B, and C, respectively(injection volume(milliliter) =1/2 volume of the tumor, V = 1/2ab^2). On days 4, 8 and 12 following treatment, 10 rabbits were randomly selected from each group for blood sample collection, and serum IL-6 and TNF-α were measured. The tumor growth rate was calculated by measuring the maximum and vertical diameters of the VX2 tumors under direct visualization. All selected rabbits were euthanized and the tumors, livers, and lungs were removed for pathological examination. The tumor necrosis rate was calculated by cutting the tumors into half along the longitudinal axis and measuring the maximum diameters of the intratumoral necrotic regions. Results The average tumor volume in the three groups increased to different degrees at each time point; however, the average tumor growth rates in groups B and C were substantially lower than that in group A, exhibiting a statistically significant difference. The difference in the tumor growth rate between group B and group C was not statistically significant. The serum concentrations of IL-6 and TNF-α increased in the three groups at each time point, with larger increases occurring in groups B and C; however, the greater increases did not reach statistical significance. Although the diameters of the necrotic areas were larger in both groups B and C than that in group A, significant differences in necrotic area diameters were only found when comparing groups A and C on days 4 and 12 following treatment. Conclusion Direct injection of different concentrations of ozonated saline into VX2 tumors significantly increased intratumoral necrosis and reduced the tumor growth rate. The associated mechanism may be partially mediated by IL-6 and TNF-α, as the serum concentrations of these molecules increased after the treatment.

Compressive strength and frost heave resistance of different types of semi-rigid base materials after freeze-thaw cycles

Freeze-thaw damage is the most common disease of semi-rigid bases in cold regions, which may greatly affect the dura- bility of roadways. In this study, the compressive strength and frost resistance of four different types of semi-rigid bases （lime-fly ash-stabilized sand, cement-stabilized sand, lime-fly ash-stabilized gravel, and cement-stabilized gravel） are assessed by varying the materials content. Based on freeze-thaw and compressive strength tests, this paper presents the performance of the different materials, each having different physical properties, and the optimal amounts of materials contents are proposed.

Terahertz metasurface zone plates with arbitrary polarizations to a fixed polarization conversion

Metasurfaces that can realize the polarization manipulation of electromagnetic waves on the sub-wavelength scale have become an emerging research field.Here,a novel strategy of combining the metasurface and Fresnel zone plate to form a metasurface zone plate is proposed to realize the conversion from nearly arbitrary polarizations to a fixed polarization.Specifically,when one polarized wave is incident on adjacent ring zones constructed by different types of meta-atoms,the transmitted waves generated by odd-numbered and even-numbered ring zones converge at the same focus and superimpose to generate a fixed polarized wave.As function demonstrations,we have designed two types of metasurface zone plates:one is a focused linear polarizer,and the other can convert nearly arbitrary polarized waves into focused circularly polarized waves.The simulated and measured results are consistent with theoretical expectations,suggesting that the proposed concept is flexible and feasible.Our work provides an alternative platform for polarization manipulation and may vigorously promote the development of polarization photonic devices.

Numerical simulation of roadbed slope under seismic action in permafrost regions

The deformation and strength characteristics of roadbed slope under seismic loading in permafrost regions are simulated numerically. The seismic response of roadbed at different positions and inclinations of a slope section was analyzed. Results show that, roadbed slope damage is mainly led by lateral displacement, and the deformation gradually decreases with increasing depth; roadbed and foundation displacement and plastic strain increases with the magnitude of slope angle, hence the roadbed safety factor will be reduced.

Dynamic regulation of anti-oxidation following donation repairing after circulatory determined death renal transplantation with prolonged non-heart-beating time

Donation after circulatory-determined death(DCD)is an important part of renal transplantation.Therefore,DCD renal transplantation animal model should be established to study the mechanism of organ injury.Here,we established a stable DCD rat renal transplantation model and investigated the dynamic regulation of graft self-repairing and antioxidant capacities with different non-heart-beating times(NHBTs).Male Sprague-Dawley rats were randomly divided into four groups with the NHBT of the donors from 0 to 15,30,and 45 minutes.Recipients in long NHBT groups had a significantly lower survival rate and poorer graft function than those in short NHBT groups.Grafts from the 15-minute and 30-minute NHBT groups showed light and severe injury respectively at an early stage after transplantation and recovered within 7 days after transplantation,whereas the self-repairing of the grafts in the 45-minute NHBT group was delayed.The expressions of proliferating cell nuclear antigen(PCNA)and von Willebrand factor(vWF)were dependent on NHBT.The expression of antioxidant proteins paralleled graft recovery.In conclusion,the recipients can up-regulate antioxidant capacity to enhance graft self-repairing in DCD renal transplantation.Prolonged NHBT can delay the self-repairing and antioxidation of grafts.

Experimental study of the effects of non-uniformly distributed fine soil on mechanical properties of Shenyang–Dandong Railway coarse-grained soil

The stress produced by repeated train loads decreases with increasing railway subgrade bed depth, and slightly weathered coarse particles of subgrade bed fillings can be broken at different levels under continuous load. Thus, the mass of fine soil, with a diameter of not more than 0.075 mm, is different at different depths. Fine soil is also sensitive to frost heave and thaw settlement. In order to study the effects of non-uniformly distributed fine soil on the mechanical properties of coarse-grained soil of the Shenyang-Dandong Railway, triaxial tests were conducted with three types of specimens, un- dergoing six freeze-thaw cycle numbers （0, 1, 3, 7, 9, 12） and three confining pressures （100, 200, 300 kPa）. The freezing temperature is -5 ~C and the thawing temperature is ＋15 ~C. The stress-strain behavior, static strength, resilient modulus, cohesive force and the angle of internal friction were measured for different tested specimens. As a result, the law of static strength and resilient modulus of different specimens following the increase of freeze-thaw cycles under three confining pressures is obtained. The changing law of cohesive force and friction angle of three specimens following the increase of freeze-thaw cycles is also calculated, and the different results of different specimens are also compared.

Full-Stokes metasurface polarimetry requiring only a single measurement

Polarization is crucial in various fields such as imaging,sensing,and substance detection.A compact,fast,and accurate polarization detection device is vital for these applications.Herein,we demonstrate a multifocus metalens for terahertz polarization detection that requires only a single measurement to obtain complete polarization parameters and reconstruct the polarization state of the incident field.The individual subarrays of this metalens convert each of the six polarized components into the same polarization,which in turn links the Stokes parameters to these six foci.The incident linear polarizations and elliptical polarizations are characterized by Stokes parameters and polarization ellipses.Simulations and experimental results show that the scheme can accurately detect the incident polarization with a single measurement.The proposed metasurface polarimetry may find applications in the fields of real-time terahertz detection and integrated optics.

系列遗传学检测法评估真性胎儿染色体嵌合体的价值

目的探讨染色体核型分析、染色体微阵列分析(chromosomal microarray analysis,CMA)及荧光原位杂交(fluorescence in situ hybridization,FISH)技术在真性胎儿染色体嵌合体产前诊断中的应用价值。方法2018年4月至2021年8月,有明确产前诊断指征并在中山大学附属第一医院行羊膜腔穿刺术或/和脐静脉穿刺术产前诊断的单胎妊娠孕妇共4071例,其中产前诊断为胎儿真性染色体嵌合体的40例孕妇纳入回顾性分析。分析其染色体核型分析、CMA及FISH结果及嵌合染色体分布、嵌合比例及妊娠结局。采用χ2检验进行统计学分析。结果(1)真性胎儿染色体嵌合体的检出率为0.98%(40/4071)。(2)性染色体嵌合体占42.5%(17/40),其他染色体嵌合体包括21、22、18、16、7、12、15、17和20号染色体及染色体平衡易位嵌合。(3)真性胎儿染色体嵌合体在羊水染色体核型分析中的检出率为77.4%(24/31);在羊水CMA中的检出率为76.7%(23/30);在脐血染色体核型分析中的检出率为10/19;在脐血CMA中的检出率为7/11。(4)40例孕妇中的20例行FISH验证(14例同时行羊水及脐血FISH验证,5例行羊水FISH验证,1例行脐血FISH验证),均证实嵌合体诊断。对于嵌合比例<30%的低比例嵌合体检出率,羊水FISH的检出率(14/19)高于羊水CMA的检出率[43.5%(10/23)],差异有统计学意义(χ2=3.88,P=0.049)。(5)40例孕妇中5例失访,18例选择终止妊娠,17例分娩。17例新生儿娩出后及生后6~24个月电话随访未见智力及生长发育异常。14例FISH验证嵌合比例<30%的孕妇,8例选择继续妊娠至分娩,生后随访未见智力及生长发育异常。结论对于产前诊断真性胎儿染色体嵌合体,性染色体嵌合体发生率最高。产前发现胎儿染色体嵌合体,FISH验证可提高诊断率,且可较精确确定嵌合比例。FISH、CMA与染色体核型分析的联合应用可显著提高染色体嵌合体的检出率,并较精确评估嵌合比例,对预后咨询有指导价值。

A critical review of on-site inorganic arsenic screening methods

Approximately 94 to 220 million people worldwide are at risk of drinking well water containing arsenic > 10 μg/L, the WHO guideline value. To identify non-compliant domestic wells, assess health risks and reduce exposure, accurate and rapid on-site inorganic arsenic screening methods are desirable because all domestic wells worldwide need to be tested.Here, the principles, advantages and limitations of commonly used colorimetry, electrochemistry, and biosensing methods are critically reviewed, with the performance compared with laboratory-based benchmark methods. Most commercial kits are based on the classic Gutzeit reaction. Despite being semi-quantitative, the more recent and more expensive products display improved and acceptable accuracy and shorter testing time (~10 min). Carried out by trained professionals, electrochemical methods are also feasible for on-site analysis, although miniaturization is desirable yet challenging. Biosensing using whole bacterial cells or bio-engineered materials such as aptamers is promising, if incorporated with function specific nanomaterials and biomaterials. Since arsenic is frequently found as arsenite in reducing groundwater and subject to oxidation during sampling, transportation and storage, on-site separation and sample preservation are feasible but the specific methods should be chosen based on sample matrix and tested before use. To eliminate arsenic exposure among hundreds of millions of mostly rural residents worldwide, we call for concerted efforts in research community and regulatory authority to develop accurate, rapid, and affordable tests for on-site screening and monitoring of arsenic in drinking water. Access to affordable testing will benefit people who are socioeconomically disadvantaged.

射频消融减胎术治疗选择性胎儿生长受限的效果及影响预后的因素:75例分析

目的探讨射频消融(radiofrequency ablation,RFA)减胎术治疗选择性胎儿生长受限(selective intrauterine growth restriction,sIUGR)保留胎妊娠结局及其影响因素,初步评价活产儿神经发育情况。方法回顾性纳入2017年1月1日至2022年3月31日在中山大学附属第一医院接受RFA减胎术并已分娩的75例sIUGR。根据减胎孕周分为孕16~19周+6组(16例)、孕20~23周+6组(44例)和≥孕24周组(15例);根据是否合并双胎输血综合征(twin-twin transfusion syndrome,TTTS)分为sIUGR合并TTTS组(36例)和单纯型sIUGR组(39例),单纯型sIUGR进一步分为Ⅰ型(3例)、Ⅱ型(27例)及Ⅲ型(9例);按保留胎是否发生不良妊娠结局分为不良妊娠结局组(49例)和非不良妊娠结局组(26例)。采用两独立样本t检验、方差分析及LSD检验、非参数检验及Nemenyi检验、χ^(2)检验和Fisher精确概率法比较组间临床特征及妊娠结局的差异;采用Kaplan-Meier法和Log-rank检验进行生存分析;采用单因素logistic回归分析保留胎不良妊娠结局的影响因素。结果(1)75例sIUGR病例RFA减胎孕周为(21.9±2.3)周(16.6~26.0周)。孕16~19周+6减胎组术前双胎估重差及RFA时长均小于孕20~23周+6组和≥孕24周组[分别为(27.8±8.4)%与(36.2±12.0)%和(39.8±15.5)%;7 min(5~14 min)与10 min(5~16 min)和12 min(8~18 min),LSD检验或Nemenyi检验,P值均<0.017];孕16~19周+6减胎组合并TTTS的比例高于孕20~23周+6组和≥孕24周组[12/16与43%(19/44)和5/15,Bonferroni校正χ^(2)检验,P值均<0.017]。不同减胎孕周组间胎膜早破、流产、胎死宫内、早产发生率及分娩孕周差异均无统计学意义(P值均>0.05)。(2)sIUGR合并TTTS组与单纯型sIUGR组比较,术前双胎估重差更小[(29.6±11.4)%与(40.1±11.8)%,t=3.88,P<0.001],胎膜早破发生率更高[47%(17/36)与21%(8/39),χ^(2)=6.01,P=0.014],活产率更低[69%(25/36)与95%(37/39),χ^(2)=8.45,P=0.004],分娩孕周更早[34.1周(26.7~40.7周)与38.0周(29.3~40.0周),Z=311.50,P=0.018]。(3)单纯型sIUGRⅠ、Ⅱ及Ⅲ型组术后胎膜早破发生率、活产率及生后30 d存活率差异均无统计学意义(P值均>0.05)。(4)sIUGR合并TTTS是保留胎不良妊娠结局的危险因素(OR=3.94,95%CI:1.40~11.10,P=0.010)。(5)13例保留胎术前超声提示心脏结构或功能异常,其中9例为sIUGR合并TTTS;8例活产儿随访至1月龄~4.5岁,心脏功能尚未发现明显异常。(6)活产儿共62例,其中2例新生儿期死亡,4例失访,余56例活产儿随访至1月龄~5岁,2例出现大运动发育落后(均为早产儿)。结论RFA减胎孕周对保留胎围产结局无明显影响,sIUGR合并TTTS可能是RFA减胎术后保留胎不良妊娠结局的危险因素。经RFA减胎术治疗后sIUGR保留胎存活率较高,且短期随访未发现严重神经系统发育异常。

波前可控的全硅太赫兹超构起偏器

直接从非偏振波中产生偏振波并同时操纵波前的超材料器件可用于先进的光学系统.然而,传统的波前可控偏振转换超表面(PCMs)依赖于具有特定偏振状态的入射波,而不是非偏振波.少数经特殊设计的超构起偏器虽然已经从非偏振波中获得了偏振波,但没有同步地实现波前操控.本文报道了基于全硅材料的波前可控的太赫兹超构起偏器,它比传统的超构起偏器和波前可控PCMs具有更高的集成特性.这种太赫兹超构起偏器将特定相位分布融入超构原子的波束干涉中,直接从非偏振太赫兹波产生偏振太赫兹波,并同步实现波前操控,有望为太赫兹波操控领域带来新的影响.

金腰箭依赖于种子二型性的跨世代效应促进胁迫耐受力分异

植物的跨世代效应对物种适应可预测和不可预测环境具有相反的作用。种子二型性植物能产生具有不同适应性策略的二型性子代,但是亲本是否会对种子二型性子代的胁迫适应性进行差异性跨世代调控尚不清楚。本研究旨在探索来自二型性种子的母株是否传递给二型性种子子代不同的跨世代效应,以及是如何传递的。研究物种金腰箭(Synedrella nodiflora)能够适应较广水分梯度,同时产生两种不同类型的种子(较轻的中心花种子和较重的边花种子)。通过两个世代的同质园种植实验,我们检验了亲代干旱胁迫对子代生长表现和死亡率的跨世代效应是否依赖于亲代和子代植株初始的种子形态,并测定了母株对种子的物质资助、化学调控物质传递和其他相关繁殖过程的指标,以探索其潜在的调控机制。研究结果显示,跨世代效应同时依赖于亲代和子代植株初始的种子形态。干旱胁迫下,由边花种子长成的母株提高其边花种子相对于中心花种子的比例,并向萌发自边花种子的子代传递更强的跨世代效应,而由中心花种子长成的母株表现出完全相反的规律。子代表现的跨世代效应与种子内脱落酸和可溶性糖含量变化密切相关,但与亲代对种子的物质资助不相关。依赖于种子二型性的跨世代效应能使子代的干旱胁迫耐受力出现较大分化,这可能是解释种子二型性物种平衡种群维持和种群扩张的新机制。

Structure-Property Relationship of Conjugated Polymers Utilizing Isomerized Fused Benzothiadiazole-Based Building Blocks

Only a few fused benzothiadizole(BTz)based conjugated polymers have been applied in organic field-effect transistors(OFETs),and their performances were low,mainly due to the lack of available building blocks and in-depth study of the relationship between structure and performance.Herein,we report two isomeric fused BTz-based building blocks(M1 and M2)and their copolymers PBTzVBTz-T and PBTzVBTz-TT,PTVT-T and PTVT-TT.DFT study showed all polymers had nearly planar backbone geometries,and PBTzVBTz-TT exhibited the most linear backbone.PTVT-T and PTVT-TT exhibited red-shift absorption spectra and deeper LUMO level than those of PBTzVBTz-T and PBTzVBTz-TT.Thin film microstructure study demonstrated PBTzVBTz-TT and PTVT-TT had edge-on molecular orientation,while the others had the mixed molecular orientation of edge-on and face-on.Furthermore,PBTzVBTz-TT had the longest coherence length in thin film.All these features of PBTzVBTz-TT resulted in its highest carrier mobility of 0.1 cm^(2)·V^(–1)·s^(–1) among these polymers.

Binary encoding-inspired generation of vector vortex beams

Vortex and vector terahertz(THz)beams with inhomogeneous polarization states have become a considerable hot topic in the last decade due to their important roles in multiplexed wireless data transmission.However,the technical instruments to form and evaluate such beams are rather limited,as they are mainly collected in the visible range.The emergence of coded metasurfaces has reinvigorated the design of functional devices with multiple degrees of freedom.Here,we demonstrate a versatile design inspired by a binary encoding approach for generating off-axis vectorial THz beams on all-silicon metasurfaces.Experimentally,simultaneous manipulation of the encoding method within the orthogonal circularly polarized(CP)channel provides strong support for developing versatility in vector THz beams,including the generation of arbitrary polarization profiles and the directional emission of multiplexed vector vortex beams(VVBs)with specified polarization states.The introduction of the latitudinal polarization control factor guarantees that continuously rotating or independently designed vector polarization profiles can be obtained on a pre-defined focal plane.Subsequently,a universal parametric theoretical model is developed to analyze the evolutionary trend of off-axis VVB in detail.Notably,the proposed monolayer vector metasurface bypasses the requirement of multiple cascaded optical elements,further inducing the advancement of ultra-thin vector THz sources,and also facilitating the generation of vector fields with tailored polarization distributions in 3D space.

Terahertz metasurface polarization detection employing vortex pattern recognition

The manipulation and detection of polarization states play a crucial role in the application of 6G terahertz communication.Nonetheless,the development of compact and versatile polarization detection devices capable of detecting arbitrary polarizations continues to be a challenging endeavor.Here,we demonstrate a terahertz polarization detection scheme by performing mode purity analysis and multidimensional analysis of the transmitted vortex field.The power of the proposed polarization recognition is verified by using three polarization trajectories,including linear polarizations,circular polarizations,and elliptical polarizations.Using the reconstructed complete polarization parameters,the detected polarization states are characterized using polarization ellipses,Poincarésphere,and full-Stokes parameters.The experimental results validate the power of this scheme in polarization detection.This scheme holds promise for applications in polarization imaging and terahertz communication.

Transplantation of UC-MSCs on collagen scaffold activates follicles in dormant ovaries of POF patients with long history of infertility

Premature ovarian failure(POF) is a refractory disease for clinical treatment with the goal of restoring fertility. In this study,umbilical cord mesenchymal stem cells on a collagen scaffold(collagen/UC-MSCs) can activate primordial follicles in vitro via phosphorylation of FOXO3 a and FOXO1. Transplantation of collagen/UC-MSCs to the ovaries of POF patients rescued overall ovarian function, evidenced by elevated estradiol concentrations, improved follicular development, and increased number of antral follicles. Successful clinical pregnancy was achieved in women with POF after transplantation of collagen/UC-MSCs or UC-MSCs. In summary, collagen/UC-MSC transplantation may provide an effective treatment for POF.

Collagen-binding basic fibroblast growth factor improves functional remodeling of scarred endometrium in uterine infertile women: a pilot study

Intrauterine adhesion(IUA) is a common cause of uterine infertility and one of the most severe clinical features is endometrial fibrosis namely endometrial scarring for which there are few cures currently. Blocked angiogenesis is the main pathological change in the scarred endometrium. The fibroblast growth factor 2(b FGF), a member of FGF family, is usually applied to promote healing of refractory ulcer and contributes to angiogenesis of tissues. In this study, the sustained-release system of b FGF100 μg was administrated around scarred endometrium guiding by ultrasound every 4 weeks in 18 patients(2–4 times). Results showed that after treatment, the menstrual blood volume, endometrial thickness and the scarred endometrial area were improved.Histological study showed blood vessel density increased obviously. Three patients(3/18) achieved pregnancy over 20 gestational weeks. Therefore, administrating the b FGF surrounding scarred endometrium may provide a new therapeutic approach for the patients with endometrial fibrosis.