中国人群33104例单基因病携带者筛查的多中心研究

目的 通过大规模多中心的多种遗传病携带者筛查,调查中国人群单基因病的流行病学特征以及突变谱,为制定适合中国人群的遗传病预防策略提供依据。方法 本研究在中国的12个临床中心共招募33 104例受检者(16 610例女性),基于高通量测序和多种PCR对223个基因的携带者状态进行检测。结果 197个常染色体基因的合并携带者频率为55.58%,26个X连锁基因的合并携带者频率为1.84%。在16 669例家系中,共检出874对(5.24%)高危夫妇。其中常染色体基因高危夫妇584对(3.50%),X连锁基因高危夫妇306对(1.84%),16对夫妇同时为常染色体基因和X连锁基因高危夫妇。最常检出的常染色体高危基因包括GJB2(常染色体隐性耳聋1A,393对),HBA1/HBA2(α-地中海贫血,36对)和PAH(苯丙酮尿症,14对),SMN1(脊髓性肌萎缩症,14对)。最常检出的X连锁高危基因包括G6PD(G6PD缺乏症,236对),DMD(进行性假肥大性肌营养不良,23对)和FMR1(脆性X综合征,17对)。除外G6PD后的高危夫妇率为3.91%(651/16 669),进一步除外GJB2 c.109G>A位点后,高危夫妇率为1.72%(287/16 669)。理论上严重的单基因病出生缺陷的发病率约为4.35‰(72.5/16 669)。对导致高危夫妇最多的22个基因进行筛查可检出95%以上的高危夫妇,对导致高危夫妇最多的54个基因进行筛查可检出99%以上的高危夫妇。结论 本研究揭示了我国人群中223种单基因病的携带者频率,为中国人群的携带者筛查策略制定和panel设计提供依据。在携带者筛查实践中,针对某些特殊基因或变异位点的遗传咨询可能会面临困难。这些特殊基因或变异需要在检测前告知受检夫妇,并在可能的情况下提供不筛查这些基因或变异的选择。

Mitochondria-engine with self-regulation to restore degenerated intervertebral disc cells via bioenergetic robust hydrogel design

Previous studies have confirmed that intervertebral disc degeneration(IDD)is closely associated with inflammation-induced reactive oxygen species(ROS)and resultant cell mitochondrial membrane potential(MMP)decline.Clearance of ROS in an inflammatory environment is essential for breaking the vicious cycle of MMP decline.Additionally,re-energizing the mitochondria damaged in the inflammatory milieu to restore their function,is equally important.Herein,we proposed an interesting concept of mitochondrion-engine equipped with coolant,which enables first to“cool-down”the inflammatory environment,next to restore the MMP,finally to allow cells to regain normal energy metabolism through materials design.As such,we developed a multifunctional composite composed of a reactive oxygen species(ROS)-responsive sodium alginate/gelatin hydrogel infused into a rigid 3D-printed thermoplastic polyurethane(TPU)scaffold.The TPU scaffold was coated with conductive polypyrrole(PPy)to electrophoretically deposit L-arginine,which could upregulate the Mammalian target of rapamycin(mTOR)pathway,thus increasing MMP and energy metabolism to stimulate extracellular matrix synthesis for IVD repair.While the ROS-responsive hydrogel acting as the“mito-engine coolant”could scavenge the excessive ROS to create a favorable environment for IVD cells recovery.Demonstrated by in vitro and in vivo evaluations,the mito-engine system markedly promoted the proliferation and collagen synthesis of nucleus pulposus cells while enhancing the mitochondrial respiration and MMP under oxidative stress.Radiological and histological assessments in vivo revealed the efficacy of this system in IVD repair.This unique bioinspired design integrated biomaterial science with mitochondrial biology,presents a promising paradigm for IDD treatment.

Corrigendum to“Mitochondria-engine with self-regulation to restore degenerated intervertebral disc cells via bioenergetic robust hydrogel design”[Bioact.Mater.40C(2024)1–18]

The authors regret that in Fig.2Aa of the article,the images for TPUPPy and TPU-aa in the first column were mistakenly duplicated due to a formatting error.The correct version of Fig.2 is provided below,along with the original data for reference.The authors confirm that the rest of the article remains unaffected.

水声FBMC-OQAM通信的时变信道估计与符号检测

Filter bank multicarrier(FBMC)systems with offset quadrature amplitude modulation(OQAM)need long data blocks to achieve high spectral efficiency.However,the transmission of long data blocks in underwater acoustic(UWA)communication systems often encounters the challenge of time-varying channels.This paper proposes a time-varying channel tracking method for short-range high-rate UWA FBMC-OQAM communication applications.First,a known preamble is used to initialize the channel estimation at the initial time of the signal block.Next,the estimated channel is applied to detect data symbols at several symbol periods.The detected data symbols are then reused as new pilots to estimate the next time channel.In the above steps,the unified transmission matrix model is extended to describe the time-varying channel input-output model in this paper and is used for symbol detection.Simulation results show that the channel tracking error can be reduced to less than−20 dB when the channel temporal coherence coefficient exceeds 0.75 within one block period of FBMC-OQAM signals.Compared with conventional known-pilot-based methods,the proposed method needs lower system overhead while exhibiting similar time-varying channel tracking performance.The sea trial results further proved the practicability of the proposed method.

A New Processing Method for the Nonlinear Signals Produced by Electromagnetic Flowmeters in Conditions of Pipe Partial Filling

When a pipe is partially filled with a given working liquid,the relationship between the electromotive force(EMF)measured by the sensor(flowmeter)and the average velocity is nonlinear and non-monotonic.This relationship varies with the inclination of the pipe,the fluid density,the pipe wall friction coefficient,and other factors.Therefore,existing measurement methods cannot meet the accuracy requirements of many industrial applications.In this study,a new processing method is proposed by which the flow rate can be measured with an ordinary electromagnetic flowmeter even if the pipe is only partially filled.First,a B-spline curve fitting method is applied to a limited set of measurements.Second,matrix inversion required in the B-spline curve method is optimized in order to reduce the number of needed computations.Dedicated experimental tests prove that the proposed method can effectively measure the average flow velocity of the fluid.When the fluid level of the pipeline is between 50%and 100%,the relative error is less than 3.5%.

Design of The Desirable Interface to Improve the High Energy Density in Fine-Scale Composites - Combined with the Modified Hybrid Processing

Due to the miniaturization of modern devices re-quire components with light weight,high integra-tion and the ability to store energy in as small vol-ume as possible.As a result,energy storage densitybecomes an important figure of merit for energy stor-age devices.In this paper,firstly,we discussedthe energy density in fine-grained lead zirconate tita-nate glass-ceramics composite with the help of

3D-printed auxetic-structured intervertebral disc implant for potential treatment of lumbar herniated disc

In this study,a novel artificial intervertebral disc implant with modified“Bucklicrystal”structure was designed and 3D printed using thermoplastic polyurethane.The new implant has a unique auxetic structure with building blocks joined“face-to-face”.The accompanied negative Poisson’s ratio enables its excellent energy absorption and stability under compression.The deformation and load distribution behavior of the implant under various loading conditions(bending,torsion,extension and flexion)has been thoroughly evaluated through finite element method.Results show that,compared to natural intervertebral disc and conventional 3D implant,our new implant exhibits more effective stress transfer and attenuation under practical loading conditions.The implant’s ability to contract laterally under compression can be potentially used to alleviate the symptoms of lumbar disc herniation.Finally,the biocompatibility of the implant was assessed in vitro and its ability to restore the physiological function of the disc segment was validated in vivo using an animal model.

Ex utero intrapartum therapy in infants with congenital diaphragmatic hernia:a propensity score matching analysis

Objective Previous studies have shown that ex utero intrapartum therapy(EXIT)is safe and feasible for newborns with congenital diaphragmatic hernia(CDH).This study reports our experience with EXIT in fetuses with CDH in an attempt to explore the efficacy of EXIT on the survival rate of this population.Methods A retrospective analysis of the clinical data of 116 children with CDH was conducted.The children were assigned to EXIT and non-EXIT groups.Propensity score matching(PSM)toward clinical data was performed,and the clinical characteristics and outcomes were compared.Taking survival at discharge as the main outcome,logistic regression analysis was carried out to explore the efficacy of EXIT on survival.Results During the study period,30 of 116 children received EXIT.After PSM,the survival rates of the EXIT group and the non-EXIT group were 82.76%(24/29)and 48.28%(14/29),respectively(p=0.006).EXIT(OR=0.083,95%CI=0.013to 0.525,p=0.008),liver herniation(OR=16.955,95%CI=2.342 to 122.767,p=0.005),and gestational age at diagnosis(OR=0.662,95%CI=0.497 to 0.881,p=0.005)were independent mortality-related risk factors of all children with CDH.Ninety-nine of 116 children underwent surgery.After PSM,the postoperative survival rates of the EXIT group and non-EXIT group were 84.6%(22/26)and 76.9%(20/26),respectively(p=0.754).Liver herniation(OR=10.451,95%CI=1.641 to 66.544,p=0.013)and gestational age at diagnosis(OR=0.736,95%CI=0.577 to 0.938,p=0.013)were independent mortality-related risk factors of children after surgery.Conclusion EXIT can be performed safely for selected prenatally diagnosed CDH neonates with potentially better survival and does not cause more maternal complications compared with traditional cesarean section.