Silencing of Nesprin‐2 inhibits the differentiation of myofibroblasts from fibroblasts induced by mechanical stretch

Mechanical force plays a pivotal role in the pathogenesis of hypertrophic scar (HTS). Dermal fibroblasts and myofibroblasts are the key cells involved in HTS. Myofibroblasts in HTS possess different biochemical and biophysical characteristics by which myofibroblasts are often distinguished from fibroblasts. The role of mechanotransducers outside the nucleus in the pathogenesis of HTS has been reported in many studies. However, the role of Nesprin‐2 in HTS is not clear. Hence, we aim to construct a cell model of HTS and explore the role of Nesprin‐2 in this process. Myofibroblasts and fibroblasts were isolated from HTS and healthy skin tissues of the same patient. Fibroblasts were exposed to cyclic stretch with 10% magnitude and a frequency of 0.1 Hz for 3 days, 5 days, and 7 days, respectively. After the cell model was confirmed, fibroblasts transfected with siRNA targeting human Nesprin‐2 were exposed to cyclic stretch. The mechanical behaviour and biochemical reaction of the dermal fibroblasts were analysed. The stretched fibroblasts at day 5 showed the same mechanotransductive and biochemical features as unstretched myofibroblasts. Mechanical strain could induce the myofibroblasts differentiation and a cell model of HTS was established successfully at day 5. The expressions of lamin A/C, alpha‐smooth muscle actin, transforming growth factor beta 1, and collagen type I in fibroblasts were reduced by the silencing of Nesprin‐2. Mechanical strain could induce the myofibroblasts differentiation and silencing of Nesprin‐2 could block the mechanical stimulation of terminal myofibroblasts differentiation. Nesprin‐2 might be a potential target to treat the HTS.     

热环境对机体功能影响的机制及防护研究进展

热环境增加高温作业人员发生热损伤的风险,充分认识热环境对高温作业人员机体的影响和危害,对提高高温作业人员防暑意识、减少作业时的职业性热损伤具有重要意义.笔者主要从热环境的定义、热环境对人体主要功能系统影响的机制、热应激的影响因素及防护研究进展进行综述,为高温作业人员对热致疾病的认识及防护提供参考.     

Fatigue Cracking Evolution and Model of Cold Recycled Asphalt Mixtures during Different Curing Times

This paper aims to investigate the fatigue cracking evolution of cold recycled asphalt mixtures with asphalt emulsion (CRME) under different curing times. The fatigue cracking model of CRME based on damage mechanics and fracture mechanics was analyzed according to the fatigue loading curve. Firstly, the fatigue cracking evolution of CRME was studied through an SCB strength test and SCB fatigue test. Then, the fatigue damage mechanics were used to establish a nonlinear fatigue cracking model, and the damage degree of CRME at the initial cracking point was determined. The Paris formula was used to characterize the law of fatigue crack propagation. Finally, the microstructure of CRME was observed by scanning electron microscopy (SEM) with the backscattering method. The results indicate that the initial cracking point appears at around 60% of the fatigue life according to the SCB fatigue test by means of image analysis. The damage variable was obtained through the cracking model, and the value of the damage variable was determined as 0.06–0.17 at the initial cracking point. In addition, the Paris formula showed that the crack growth of CRME can be reflected by the stress intensity factor and correlative parameters. Moreover, cement hydration products were mixed with the asphalt membrane to form a denser spatial structure during the curing process, which may provide higher fatigue performance of CRME. This research may provide a theoretical reference for studying the fatigue cracking behavior of CRME.     

抑郁障碍患者主观与客观认知功能的差异性研究

背景 抑郁障碍患者的主观认知功能与客观认知功能存在差异。目前,关于主客观认知功能差异影响因素的研究有限。目的 探索抑郁障碍患者主观和客观认知功能的差异及其影响因素,为进一步理解抑郁障碍患者认知功能受损情况提供参考。方法 纳入2022年1月13日—2023年12月11日在成都市第四人民医院门诊就诊或住院治疗的、符合《精神障碍诊断与统计手册（第5版）》（DSM-5）抑郁障碍诊断标准的77例患者为研究对象。采用蒙哥马利-艾森贝格抑郁量表（MADRS）评定患者抑郁症状严重程度,采用抑郁感知缺陷问卷（PDQ-D）和中国简版神经认知成套测验（C-BCT）分别评定患者的主观认知功能和客观认知功能,采用席汉残疾量表（SDS）评定患者的社会功能,以临床总体印象量表-疾病严重程度量表（CGI-SI）评定患者病情严重程度。采用Pearson相关分析考查年龄、受教育年限、MADRS总评分、SDS总评分、CGI-SI评分与主客观认知功能及其差异的相关性。采用多元线性回归探索主客观认知功能差异的影响因素。结果 是否用药的抑郁障碍患者PDQ-D总评分和主客观认知功能差异（D值）比较差异均有统计学意义（t=-4.2...     

计算机少儿智力测评软件的研究与开发

介绍一种用VB软件编写的数据库管理软件,用于《韦氏学龄儿童智力量表(WISC-R)和婴儿～初中学生社会生活能力量表(日本S-M社会生活能力检查修订版)》的计算机评价与统计.该软件操作简单,评价准确,携带方便,是一种专用的少儿智力测评软件.     

Evaluation of efficacy and safety of esmolol in treating patients with septic shock: A protocol for systematic review and meta-analysis

Background:In septic shock cases, tachycardia and a hyperdynamic hemodynamic profile are characteristics of the condition. It has been reported that using beta antagonist esmolol constitutes a form of treatment to reduce heart rate to improve diastolic filling time and elevate cardiac output, which reduces vasopressor support. Still, there are controversial results. Therefore, in this study, the primary objective is to perform a meta-analysis by systematically evaluating the efficiency and security of using esmolol to treat septic shocks.Methods:A systematic literature search for relevant randomized controlled trials that report evaluations on the efficiency and safety of using esmolol to treat septic shock patients from their inception to February 2022 will be conducted in three databases containing publications in Chinese language (WanFang, Chinese BioMedical Literature Database, and China National Knowledge Infrastructure) and four databases containing English language publications (Cochrane Library, PubMed, Web of Science, and EMBASE). The screening of the relevant studies will be performed by a pair of authors independently, and the screening involves examining the title, abstract and full-text stages, data extraction, and bias risk assessment. The results are summarized through the fixed-effects and random-effects models, the respective models will be utilized for data pooling according to the heterogeneity of studies that will be included. Moreover, publication bias is assessed if more than ten studies are considered.Results:The results are a high-quality synthesis of the most recent evidence for esmolol usage in septic shock treatment.Conclusion:Up-to-date evidence will be provided through the results of this systematic review related to assessing the efficacy and safeness of esmolol usage in treating septic shock.Ethics and dissemination:Ethical permissions are not required as prepublished data are used.OSF registration number:DOI 10.17605/OSF.IO/SKEZ7     

A comparative study of the efficacy and safety of high-flow nasal cannula and nasal continuous positive airway pressure in neonatal respiratory distress syndrome: A protocol for systematic review and meta-analysis

Background:When it comes to preterm newborns, respiratory distress syndrome (RDS) is the most frequent respiratory condition. Despite the fact that it is well acknowledged that preterm delivery plays a significant role, the causes of lung damage are still not completely understood. In newborns with extremely low birth weight and neonatal RDS, nasal continuous positive airway pressure has been suggested as the first respiratory assistance for spontaneous breathing. In the current research, we aim to carry out a meta-analysis to assess the effectiveness and safety of high-flow nasal cannula (HFNC) and non-invasive continuous positive airway pressure (nCPAP) in patients with neonatal respiratory distress syndrome (NRDS).Methods:We intend to search the following databases: PubMed, EMBASE, Cochrane Library, Wanfang database, China National Knowledge Infrastructure (CNKI), and Google Scholar, starting from their initial publication until February 2022, to identify randomized controlled trials comparing HFNC to nCPAP in patients with NRDS. The suitable papers will be chosen by 2 writers who will work independently of one another. Using the Cochrane updated technique for risk of bias, each included article will be subjected to an independent data extraction process by the 2 writers who will then independently evaluate the risk of bias. Consequently, a third author will be asked to address any discrepancies that may arise between the writers. It will be necessary to pool the data and do a meta-analysis with the help of the RevMan 5.3 software.Results:In this study, the effectiveness and safety of HFNC will be compared with those of nCPAP in patients with NRDS.Conclusion:If the results of this research are confirmed, they may serve as a summary of the most recent data for non-invasive respiratory assistance in NRDS.Ethics and dissemination:The study will require ethical approval.Registration number:DOI 10.17605/OSF.IO/BKSQ5     

大剂量甲氨蝶呤静脉给药时间对淋巴瘤患者脑脊液中药物浓度的影响

背景与目的:甲氨蝶呤(methotrexate,MTX)在脑脊液中高于最小有效治疗浓度是治疗中枢淋巴瘤的必要条件,目前尚不明确大剂量MTX(high doseMTX,HD-MTX)静脉给药时间对MTX穿透血脑屏障的影响.本研究探索HD-MTX静脉不同给药时间对脑脊液中MTX浓度的影响,以获得更好的中枢淋巴瘤防治效果并尽可能减少MTX外周毒性.方法:34例非霍奇金淋巴瘤患者分别接受MTX 1～3g/m2 6 h持续静脉给药或24 h持续静脉给药,其中17例交替使用两种给药方法;采用高效液相色谱法检测MTX停药0 h、24 h、48 h的MTX血清浓度,及停药0 h后脑脊液中MTX浓度;比较两组血中和脑脊液中MTX浓度以及毒性反应,并对影响MTX浓度的因素进行相关分析.结果:给药结束时6 h给药组的MTX血清浓度显著高于24 h给药组:自身对照结果6 h给药组的脑脊液中MTX浓度为0.70 Ixmol/L,明显高于24 h给药组的0.49 Ixmol/L(校正值,P=0.044).MTX的脑脊液浓度与血清浓度呈正相关,中枢侵犯患者脑脊液MTX浓度显著高于无中枢侵犯的患者.自身对照结果6 h组和24 h组Ⅱ～Ⅳ度粘膜炎的发生率分别15.4%和37.8%.Ⅲ～Ⅳ度骨髓抑制的发生率分别为46.2%和67.6%.结论:在提高MTX的中枢浓度和降低外周毒性方面,HD-MTX 6 h给药方案优于24 h给药方案.     

Synergistic integration of metal nanoclusters and biomolecules as hybrid systems for therapeutic applications

Therapeutic nanoparticles are designed to enhance efficacy, real-time monitoring, targeting accuracy, biocompatibility, biodegradability, safety, and the synergy of diagnosis and treatment of diseases by leveraging the unique physicochemical and biological properties of well-developed bio-nanomaterials. Recently, bio-inspired metal nanoclusters (NCs) consisting of several to roughly dozens of atoms (<2 nm) have attracted increasing research interest, owing to their ultrafine size, tunable fluorescent capability, good biocompatibility, variable metallic composition, and extensive surface bio-functionalization. Hybrid core–shell nanostructures that effectively incorporate unique fluorescent inorganic moieties with various biomolecules, such as proteins (enzymes, antigens, and antibodies), DNA, and specific cells, create fluorescently visualized molecular nanoparticle. The resultant nanoparticles possess combinatorial properties and synergistic efficacy, such as simplicity, active bio-responsiveness, improved applicability, and low cost, for combination therapy, such as accurate targeting, bioimaging, and enhanced therapeutic and biocatalytic effects. In contrast to larger nanoparticles, bio-inspired metal NCs allow rapid renal clearance and better pharmacokinetics in biological systems. Notably, advances in nanoscience, interfacial chemistry, and biotechnologies have further spurred researchers to explore bio-inspired metal NCs for therapeutic purposes. The current review presents a comprehensive and timely overview of various metal NCs for various therapeutic applications, with a special emphasis on the design rationale behind the use of biomolecules/cells as the main scaffolds. In the different hybrid platform, we summarize the current challenges and emerging perspectives, which are expected to offer in-depth insight into the rational design of bio-inspired metal NCs for personalized treatment and clinical translation.Key words: Metal nanoclusters, Biomolecule, Nanoparticles, Hybrid system, Synergistic properties, Fluorescence, Bioprobe, Therapy