Two-photon live imaging of direct glia-to-neuron conversion in the mouse cortex

Over the past decade,a growing number of studies have reported transcription factor-based in situ reprogramming that can directly conve rt endogenous glial cells into functional neurons as an alternative approach for n euro regeneration in the adult mammalian central ne rvous system.Howeve r,many questions remain regarding how a terminally differentiated glial cell can transform into a delicate neuron that forms part of the intricate brain circuitry.In addition,concerns have recently been raised around the absence of astrocyte-to-neuron conversion in astrocytic lineage-tra cing mice.In this study,we employed repetitive two-photon imaging to continuously capture the in situ astrocyte-to-neuron conversion process following ecto pic expression of the neural transcription factor NeuroD1 in both prolife rating reactive astrocytes and lineage-tra ced astrocytes in the mouse cortex.Time-lapse imaging over several wee ks revealed the ste p-by-step transition from a typical astrocyte with numero us short,tapered branches to a typical neuro n with a few long neurites and dynamic growth cones that actively explored the local environment.In addition,these lineage-converting cells were able to migrate ra dially or to ngentially to relocate to suitable positions.Furthermore,two-photon Ca2+imaging and patch-clamp recordings confirmed that the newly generated neuro ns exhibited synchronous calcium signals,repetitive action potentials,and spontaneous synaptic responses,suggesting that they had made functional synaptic connections within local neural circuits.In conclusion,we directly visualized the step-by-step lineage conversion process from astrocytes to functional neurons in vivo and unambiguously demonstrated that adult mammalian brains are highly plastic with respect to their potential for neuro regeneration and neural circuit reconstruction.

垂体后叶素致腹泻、重度低血钠1例

1例52岁女性患者,因"反复咳嗽、咳痰50余年,加重伴痰中带血2 d"入院。入院诊断为"慢性阻塞性肺疾病并感染,支气管扩张伴咯血"。入院后生化检查示血钠141 mmol·L^(-1),因患者日咯血量达20 mL,给予垂体后叶素12 U,泵内注射,qd,止血治疗。住院第9日晨起,患者突然出现恶心、呕吐的症状,呕吐物为胃内容物。经询问得知患者自使用垂体后叶素第2天起即出现腹泻症状,为水样稀便,每日5~6次,并不伴腹痛。急查血生化示血钠111.1 mol·L^(-1),处于严重低血钠水平。因治疗需要无法停用垂体后叶素,经减量使用垂体后叶素、缓慢补钠以及止泻、止呕等对症处理4 d后,复测血生化示血钠138.9 mmol·L^(-1),血钠水平恢复正常。后续治疗中患者未再出现呕吐、腹泻、咯血症状,经治疗14 d,患者病情平稳,予以出院。

基于繁简平衡理念的低运维景观设计研究——以玉溪大河景观设计为例

云南省玉溪市因大河“形似玉带,溪水清澈如碧玉”而得名。大河既是城市防御洪水的水利工程,同时也是中心城区的生态基石。2021年,玉溪大河项目因建设调整以“减”“简”为方针,以不破坏原规划理念为前提,适当缩减景观造价。优化过程中,平衡景观中“繁”与“简”的关系。将原设计中部分即时成景的景观优化为十年成景的低运维景观,在平衡、缩减造价的同时,做到景观效果不打折,景观理念再提升,对未来建设生态、可持续景观有借鉴意义。

DL-3-n-butylphthalide improved physical and learning and memory performance of rodents exposed to acute and chronic hypobaric hypoxia

Background:Studies have revealed the protective effect of DL-3-n-butylphthalide(NBP)against diseases associated with ischemic hypoxia.However,the role of NBP in animals with hypobaric hypoxia has not been elucidated.This study investigated the effects of NBP on rodents with acute and chronic hypobaric hypoxia.Methods:Sprague-Dwaley rats and Kunming mice administered with NBP(0,60,120,and 240 mg/kg for rats and 0,90,180,and 360 mg/kg for mice)were placed in a hypobaric hypoxia chamber at 10,000 m and the survival percentages at 30 min were determined.Then,the time and distance to exhaustion of drug-treated rodents were evaluated during treadmill running and motor-driven wheel-track treadmill experiments,conducted at 5800 m for 3 days or 20 days,to evaluate changes in physical functions.The frequency of active escapes and duration of active escapes were also determined for rats in a shuttle-box experiment,conducted at 5800 m for 6 days or 27 days,to evaluate changes in learning and memory function.ATP levels were measured in the gastrocnemius muscle and malonaldehyde(MDA),superoxide dismutase(SOD),hydrogen peroxide(H_(2)O_(2)),glutathione peroxidase(GSH-Px),and lactate were detected in sera of rats,and routine blood tests were also performed.Results:Survival analysis at 10,000 m indicated NBP could improve hypoxia tolerance ability.The time and distance to exhaustion for mice(NBP,90 mg/kg)and time to exhaustion for rats(NBP,120 and 240 mg/kg)significantly increased under conditions of acute hypoxia compared with control group.NBP treatment also significantly increased the time to exhaustion for rats when exposed to chronic hypoxia.Moreover,240 mg/kg NBP significantly increased the frequency of active escapes under conditions of acute hypoxia.Furthermore,the levels of MDA and H_(2)O_(2) decreased but those of SOD and GSH-Px in the sera of rats increased under conditions of acute and chronic hypoxia.Additionally,ATP levels in the gastrocnemius muscle significantly increased,while lactate levels in sera significantly decreased.Conclusion:NBP improved physical and learning and memory functions in rodents exposed to acute or chronic hypobaric hypoxia by increasing their anti-oxidative capacity and energy supply.

全膝关节置换术198例患者镇痛方案分析

目的对医院接受人工全膝关节置换患者术后镇痛方案进行评价。方法选取行人工全膝关节置换患者203例作为研究对象,采用回顾分析法对患者术后镇痛方案进行分析,评估人工全膝关节置换镇痛方案。结果 203例患者采用多模式镇痛方案的患者占80%,主要是单纯患者自控镇痛(PCA,19.7%)、PCA-浸润麻醉两模式(49.75%)和PCA-浸润麻醉-神经阻滞三模式(28.08%)。与PCA单模式镇痛相比,PCA-神经阻滞两模式、PCA-神经阻滞-浸润麻醉三模式镇痛时的人均等效吗啡需求量显著少于PCA单模式镇痛(P<0.01)。联合镇痛组术后下床活动时间早于单纯PCA组:单纯PCA组人均为5±1.19 d,PCA-神经阻滞两模式组为3.98±1.04 d,PCA-神经阻滞-浸润麻醉三模式组为3.82±1.29 d(P<0.01);不同镇痛方案在开始康复训练时间方面未表现出明显差异。不同镇痛方案术后疼痛的主诉、住院时间和安全性事件的发生率无明显差异。结论多模式镇痛方案较单纯PCA可明显节省阿片类药物用量,患者下床活动时间更早,在疼痛主诉及安全性方面无明显差异。

药品货位编码在武汉某新型冠状病毒肺炎定点收治医院的管理与应用

目的:分析新型冠状病毒肺炎疫情期间新组建的医院药剂科采用药品货位编码进行药学保障服务的经验与不足,为突发公共卫生事件等紧急情况下新组建的医院开展药学服务提供借鉴。方法:武汉某新型冠状病毒肺炎定点收治医院采用四维立体编码法编制货位号编码,结合医院信息管理系统,用于药品的入库、出库和盘库。通过记忆字段假设法,比较药师在货位管理前后需记忆的字段数量;选择6名药师作为试验者,随机分为2组,在不同任务阶段(初期上岗第7天、中期第27天、后期第47天),观察与统计对照组(附无货位编码的出库单)和试验组(附有货位编码的拣货单)完成目标调配任务所需时间和调配差错率;比较该管理手段使用前后,20名药师完成药品盘库所需时间和盘库差错率。结果与结论:药品货位编码管理可提高药师的调配和盘库效率,降低调配差错风险。采用药品货位编码后,药师所需记忆字段由624个降至60个,盘库时间由3.17 h缩短至1.33 h,盘库差错率由7.98%降至1.83%。在不同任务阶段,试验组的调配时间均显著低于对照组(初期95.20 min vs.31.33 min,中期71.67 min vs.22.67 min,后期69.67 min vs.22.67 min),在任务初期经过货位编码管理的调配差错率显著降低(5.80%vs.1.45%)。同时,反思药品货位编码中的管理漏洞,如编制原则中"药品总数"设计不合理、高危、精麻、易混淆及近效期等特殊药品的编制原则缺失、机动码和应急预案的缺失,提出相应的解决策略,以期为突发公共卫生事件下药品的信息化管理提供借鉴。

疏林草地空间常用造景手法分析及实践

疏林草地是植物造景的重要组成部分,通过对北京、上海、杭州、沈阳8处成熟的草坪空间案例进行分析,并结合工程实践,从植物选择和配置、空间营造等方面入手,总结出疏林草地营建的8种常用手法和技巧,形成了便于操作和针对性较强的方法论。为园林从业人员的设计以及施工提供理论依据和实践参考。

基于FAERS数据库的氨吡啶缓释片不良反应信号挖掘分析

目的挖掘氨吡啶缓释片相关药品不良反应/不良事件(ADR/ADE)信号,为临床安全用药提供参考。方法基于美国食品药品监督管理局不良事件报告系统(FAERS),采用报告比值比法(ROR)和信息成分法(IC)对系统中2013年1月1日至2021年6月30日上报的氨吡啶缓释片ADR/ADE进行数据挖掘,按国际医学用语词典(MedDRA)的首选术语(PT)和系统-器官分类(SOC)进行统计分析。结果以氨吡啶缓释片为首要怀疑药品的ADR/ADE报告141768份,涉及患者47486例,其中女性占大多数(72.39%);41~70岁年龄段的患者占比最大(82.83%);美国是主要报告国家(90.98%);严重ADR/ADE共7873例(16.58%),主要为导致住院或住院时间延长(12.24%)。经筛选后共检测到ADR信号174个,其中说明书未记载的信号126个。报告例数前50位PT中可疑信号36个,说明书未记载的信号30个。信号强度前50位的PT涉及SOC主要为各类检查(19个)、各类神经系统疾病(11个)、全身性疾病及给药部位各种反应(5个)等。ADR信号共涉及13个系统-器官,主要为全身性疾病及给药部位各种反应(28.53%)、各类神经系统疾病(26.03%)和精神病类(8.79%)等。结论对氨吡啶缓释片ADR/ADE进行真实世界数据分析,提示临床应严格遵循说明书用药尤其要关注癫痫病史及肾功能,另外还检出新的较强信号如T淋巴细胞、CD4淋巴细胞、B淋巴细胞等免疫细胞异常,临床应关注密切监测患者各类检查,以及神经系统疾病等说明书未提及的风险。

园林景观建设中的现场设计——以四川省南部县禹迹岛公园为例

随着人们对园林艺术与品质的追求不断提高,园林建设对施工的追求也与日俱增。在四川省南部县禹迹岛公园施工建设中,项目以景观艺术效果为出发点,在保证规划风貌的前提下,以植物造景为主的景观建设强调了现场的二次深化设计。施工阶段不断优化景观方案,在充分跟踪施工的前提下,取得了良好的景观效果。

The influence of water-based drilling fluid on mechanical property of shale and the wellbore stability

Because of high cost and pollution of oil-based drilling fluid,the water-based drilling fluid is increasingly used now.However,bedding planes and micro-cracks are rich in shale formation.When water-based drilling fluid contacts formation rock,it causes the propagation of crack and invasion of drilling fluid,which decrease shale strength and cause wellbore instability.In this paper,we analyzed influence of water-based drilling fluid on shale strength and failure mode by mechanics experiment.Based on those experimental results,considering the effect of bedding plane and drilling time,we established modeling of wellbore stability for shale formation.The result from this model indicates that in certain azimuth of horizontal well,collapsing pressure increases dramatically due to shale failure along with bedding plane.In drilling operation,those azimuths are supposed to be avoided.This model is applicable for predication of collapsing pressure in shale formation and offers reference for choosing suitable mud weight.

Event-by-event efficiency fluctuations and efficiency correction for cumulants of superposed multiplicity distributions in relativistic heavy-ion collision experiments

We performed systematic studies on the effects of event-by-event efficiency fluctuations on efficiency correction for cumulant analysis in relativistic heavy-ion collision experiments. Experimentally, particle eficiencies of events measured under different experimental conditions should be different. For fluctuation measurements, the final event-by-event multiplicity distributions should be the superposed distributions of various type of events measured under different conditions. We demonstrate efficiency fluctuation effects using numerical simulation, in which we construct an event ensemble consisting of events with two different efficiencies. By using the mean particle efficiencies, we find that the efficiency corrected cumulants show large deviations from the original inputs when the discrepancy between the two efficiencies is large. We further studied the effects of efficiency fluctuations for the cumulants of net-proton distributions by implementing the UrQMD events of Au＋Au collisions at √SNN=7.7 GeV in a realistic STAR detector acceptance. We consider the unequal efficiency in two sides of the Time Projection Chamber （TPC）, multiplicity dependent efficiency, and the event-by-event variations of the collision vertex position along the longitudinal direction （Vz）. When the efficiencies fluctuate dramatically within the studied event sample, the effects of efficiency fluctuations have significant impacts on the efficiency corrections of cumulants with the mean efficiencies. We find that this effect can be effectively suppressed by binning the entire event ensemble into various sub-event samples, in which the efficiency variations are relatively small. The final efficiency corrected cumulants can be calculated from the weighted average of the corrected factorial moments of the sub-event samples with the mean efficiencies.

Effects of centrality fluctuation and deuteron formation on the proton number cumulant in Au+Au collisions at√SNN=3 GeV from the JAM model

We studied the effects of centrality fluctuation and deuteron formation on the cumulant(C_(n))and correlation functions(K_(n))of protons up to the sixth order in the most central(b<3 fm)Au+Au collisions at√SNN=3 GeV in a microscopic transport model(JAM).The results are presented as a function of rapidity acceptance within the transverse momentum 0.4<p T<2 GeV/c.We compared the results obtained by the centrality bin width correction(CBWC)using charged reference particle multiplicities with the CBWC using impact parameter bins.It was found that,at low energies,the centrality resolution for determining the collision centrality using charged particle multiplicities is not sufficient to reduce the initial volume fluctuation effect for higher-order cumulant analysis.New methods need to be developed to classify events with high centrality resolution for heavy-ion collisions at low energies.Finally,we observed that the formation of deuterons suppresses the higher-order cumulants and correlation functions of protons and found it to be similar to the efficiency effect.This work can serve as a noncritical baseline for the QCD critical point search in the high baryon density region.

In situ preparation of visible-light-driven carbon quantum dots/NaBiO3 hybrid materials for the photoreduction of Cr(Ⅵ)

In this study,different carbon quantum dots(CQDs)/NaBiO3 hybrid materials were synthesized as photocatalysts to effectively utilize visible light for the photocatalytic degradation of contaminants effectively.These hybrid materials exhibit an enhanced photocatalytic reduction of hexavalent chromium(Cr(Ⅵ))in the aqueous medium.Zero-dimensional nanoparticles of CQDs were embedded within the two-dimensional NaBiO3 nanosheets by the hydrothermal process.Compared with that of the pure NaBiO3 nanosheets,the photocatalytic performance of the hybrid catalysts was significantly high and 6 wt.%CQDs/NaBiO3 catalyst exhibited better photocatalytic performance.We performed the first-principles density functional theory calculations to study the interfacial properties of pure NaBiO3 nanosheets and hybrid photocatalysts,and confirmed the CQDs played an important role in the CQDs/NaBiO3 composites.The experimental results indicated that the enhanced reduction of Cr(Ⅵ)was probably due to the high loading of CQDs(electron acceptor)on NaBiO3,which made NaBiO3 nanomaterials to respond in visible light and significantly improved their electron-hole separation efficiency.

重症抗菌药物应用及对肺炎克雷伯菌耐药性分析研究

分析重症病房抗菌药物使用强度对肺炎克雷伯菌耐药率的影响。调查某医院重症病房近5年肺炎克雷伯菌的检出比率;使用曲线估算的方法分析肺炎克雷伯菌对常用抗生素耐药率的变迁;使用曲线估算的方法分析重症病房各种抗生素的使用强度;对重症病房抗生素使用强度与肺炎克雷伯菌耐药率变迁进行Person相关性分析。(1)重症病房共检出革兰阴性细菌424株,其中肺炎克雷伯菌64株。各年间肺炎克雷伯菌检出率无差异(X^(2)=6.114,P=0.191)。(2)重症肺炎克雷菌对哌拉西林他唑巴坦(R^(2)=0.848,P=0.026)、亚胺培南(R^(2)=0.832,P=0.031)、氨曲南(R^(2)=0.922,P=0.009)、头孢曲松(R^(2)=0.870,P=0.021)的耐药率各年度差异具有统计学意义,且呈逐年上升趋势。(3)环丙沙星的抗生素使用强度各年差异具有统计学意义(R^(2)=0.840,P=0.029)。(4)美罗培南使用强度与肺炎克雷伯菌的阿莫西林克拉维酸耐药率呈正相关(r=0.928,P=0.023)。环丙沙星使用强度与肺炎克雷伯菌的庆大霉素(r=-0.954,P=0.012)、氨曲南(r=-0.974,P=0.005)、头孢曲松(r=-0.987,P=0.002)、头孢呋辛(r=-0.947,P=0.02)、头孢噻肟(r=-0.974,P=0.005)耐药率呈负相关。美罗培南使用强度与肺炎克雷伯菌的耐药率呈正相关,美罗培南使用增多可能会诱导肺炎克雷伯菌对酶抑制剂复合物的耐药性。环丙沙星使用强度下降,可能会引发其它抗生素使用强度上升,从而间接影响肺炎克雷伯菌对抗生素的敏感性,其中机制值得进一步探讨。

Material transport in dip-pen nanolithography

Dip-pen na.nolithography （DPN） is a useful method for directly printing materials on surfaces with sub-50nm resolution. Because it, involves the physical transport of materials from a scanning probe tip to a surface and the subsequent chemical interaction of that material with the surface, there are many factors to consider when attempting to understand DPN. In this review, we overview the physical and chemical processes that are known to play a role in DPN, Through a detailed review of the literature, we classify inks into three general categories based on their transport properties, and highlight the myriad ways that. DPN can be used to perform chemistry at the tip of a scanning probe.