SOCS3结构和作用机制研究进展

SOCS3是酪氨酸蛋白激酶/信号传导子和转录激活子(JAK/STAT)途径的负反馈调节因子之一,由SOCS盒、SH2结构域和激酶抑制区三个部分组成.SOCS3参与了体内多种信号分子转导的调控.本文结合近年的研究成果对其结构和作用机制进行了综述,并对其中尚存在的问题进行展望.     

Transnasal Endoscopic and Transoral Approaches in the Biopsies of Ventral Atlas and Axis Vertebrae: A Comprehensive Retrospective Study for Preprocedural Scheme,Biopsy Procedure,Core Technique Analysis,Diagnostic Yield and Clinical Outcome

ObjectiveThis study aims to describe and analyze the transoral and transnasal approaches for pathologies of the ventral atlas and axis vertebrae, which are considered technically challenging regions for diagnostic biopsy.MethodsA series of transnasal endoscopic approach (TNA) and transoral approach (TOA) biopsies for the pathologies of the first and second cervical vertebrae were conducted and retrospectively analyzed from July 2014 to May 2021. The depth of the biopsy trajectory was measured on computed tomography images for all nine patients (eight males and one female with an average age of 58.11 ± 11.60 years), as were the coronal, sagittal, and vertical biopsy safe ranges. The characteristics of each lesion, including radiographic features, blood supply, and destruction of anterior or posterior vertebral body edges, were evaluated to guide the biopsy. Four biopsy core techniques (BCTs), including “lesion perforating”, “aspiration”, “cutting‐and‐scraping” and “biopsy forceps utilization” were elaborated in this study. The biopsy procedures and periprocedural precautions were demonstrated. Patient demographics, clinical data, lesion characteristics, diagnostic yield, and complications were recorded for each case.ResultsEight TOA biopsies for the axis vertebral body and one TNA biopsy for the atlas anterior arch were successfully performed and yielded adequate pathologies. All biopsies were organized based on the preprocedural radiographic measurements, which showed that the average length of biopsy trajectory and coronal, sagittal, and vertical safe biopsy ranges were 85.00 ± 5.88, 20.63 ± 4.75, 16.25 ± 1.49, and 24.63 ± 2.26 mm, respectively, and these corresponding data were 95, 36, 9, and 26 mm in the TNA patient. Six osteolytic lesions (66.7%), one osteoblastic lesion (11.1%), and two mixed lesions (22.2%) were observed, among which seven lesions had a rich blood supply. Biopsy forceps and core needles were utilized to obtain samples in six and three patients, respectively. All the TNA and TOA biopsies were performed with cooperative application of multiple BCTs under compound anatomic and stereotactic navigations. Intraprocedural or postprocedural complications occurred in no patients who underwent the biopsy in the follow‐up period (1–39 months). No significant differences were found between the preprocedural and postprocedural blood indexes and visual analogue scale scores.ConclusionWith a sophisticated preprocedural arrangement, cooperative application of BCTs, and careful periprocedural precautions, transnasal endoscopic and transoral biopsies are two feasible, efficient, and well‐tolerated procedures that achieve satisfactory diagnostic yield, complication rate, and clinical outcome.     

认知行为疗法、中医情志护理配合重复经颅磁刺激干预精神分裂症临床研究

目的:观察认知行为疗法、中医情志护理配合重复经颅磁刺激(rTMS)干预精神分裂症的临床疗效。方法:选取120例精神分裂症患者,按随机数字表法分为观察组和对照组各60例。观察组实施认知行为疗法、中医情志护理配合rTMS治疗,对照组实施认知行为疗法、情志护理及伪rTMS治疗,2组均干预4周。比较2组临床疗效及治疗前后阳性与阴性症状量表(PANSS)、临床总体印象量表(CGI)、精神分裂症认知功能简明成套测评量表(BACS)及个人与社会功能量表(PSP)评分。结果:观察组总有效率96.67%,对照组总有效率83.33%, 2组比较,差异有统计学意义(P<0.05)。治疗后,2组PANSS、CGI评分均较治疗前降低(P<0.05),观察组PANSS、CGI评分均低于对照组(P<0.05)。治疗后,2组BACS、PSP评分均较治疗前升高(P<0.05),观察组BACS、PSP评分均高于对照组(P<0.05)。结论:认知行为疗法、中医情志护理配合rTMS干预精神分裂症,可有效缓解患者的阳性、阴性症状,改善其认知功能和社会功能。     

颈椎人工椎间盘置换术的研究现状

颈椎人工椎间盘置换术（artificial cervical disc replacement,ACDR）,亦称颈椎间盘成形术（cervical disc arthroplasty,CDA）。随着人工髋、膝关节置换术取代了导致关节功能严重丧失的髋、膝关节融合术,且腰椎人工椎间盘广泛、成功运用于临床,为了解决颈椎前路减压植骨融合术由于融合节段运动功能丧失所造成的相邻节段的过度运动和应力集中而导致相邻节段退变加速,越来越多的科研人员及医务工作者投入到颈椎人工椎间盘置换术的研究之中。     

Development of a humanized HLA‐A30 transgenic mouse model

BackgroundThere are remarkable genetic differences between animal major histocompatibility complex (MHC) systems and the human leukocyte antigen (HLA) system. HLA transgenic humanized mouse model systems offer a much better method to study the HLA‐A‐related principal mechanisms for vaccine development and HLA‐A‐restricted responses against infection in human.MethodsA recombinant gene encoding the chimeric HLA‐A30 monochain was constructed. This HHD molecule contains the following: α1‐α2 domains of HLA‐A30, α3 and cytoplasmic domains of H‐2D^b, linked at its N‐terminus to the C‐terminus of human β2m by a 15‐amino‐acid peptide linker. The recombinant gene encoding the chimeric HLA‐A30 monochain cassette was introduced into bacterial artificial chromosome (BAC) CH502‐67J3 containing the HLA‐A01 gene locus by Red‐mediated homologous recombination. Modified BAC CH502‐67J3 was microinjected into the pronuclei of wild‐type mouse oocytes. This humanized mouse model was further used to assess the immune responses against influenza A virus (H1N1) pdm09 clinically isolated from human patients. Immune cell population, cytokine production, and histopathology in the lung were analyzed.ResultsWe describe a novel human β2m‐HLA‐A30 (α1α2)‐H‐2D^b (α3 transmembrane cytoplasmic) (HHD) monochain transgenic mouse strain, which contains the intact HLA‐A01 gene locus including 49 kb 5′‐UTR and 74 kb 3′‐UTR of HLA‐A01*01. Five transgenic lines integrated into the large genomic region of HLA‐A gene locus were obtained, and the robust expression of exogenous transgene was detected in various tissues from A30‐18# and A30‐19# lines encompassing the intact flanking sequences. Flow cytometry revealed that the introduction of a large genomic region in HLA‐A gene locus can influence the immune cell constitution in humanized mice. Pdm09 infection caused a similar immune response among HLA‐A30 Tg humanized mice and wild‐type mice, and induced the rapid increase of cytokines, including IFN‐γ, TNF‐α, and IL‐6, in both HLA‐A30 humanized Tg mice and wild‐type mice. The expression of HLA‐A30 transgene was dramatically promoted in tissues from A30‐9# line at 3 days post‐infection (dpi).ConclusionsWe established a promising preclinical research animal model of HLA‐A30 Tg humanized mouse, which could accelerate the identification of novel HLA‐A30‐restricted epitopes and vaccine development, and support the study of HLA‐A‐restricted responses against infection in humans.     

DDSM: Design-Oriented Dual-Scale Shape-Material Model for Lattice Material Components

This paper proposes a new CAD model for the design of lattice material components. The CAD model better captures the user’s design intent and provides a dual-scale framework to represent the geometry and material distribution. Conventional CAD model formats based on B-Rep generate millions of data files, which also makes design intent and material information missing. In the present work, a new shape-material model for lattice material components is proposed. At the macroscopic scale, a compact face-based non-manifold topological data structure is proposed to express the lattice shape-material information without ambiguity. At the microscopic scale, implicit function is adopted for the representation of lattice material components. Numerical experiments verify that the proposed CAD model provides a powerful support for design intent with minor space costs. Meanwhile, the representation method supports solid modeling queries of geometric and material information on each scale.     

A Study on the Preparation and Cavitation Erosion Mechanism of Polyether Polyurethane Coating

Polyurethane elastomers are anticipated to be applied in the field of cavitation erosion (CE) resistance, but their protection and damage mechanisms are not clear, which greatly restricts their further development. In this article, five polyether polyurethanes (PU_x) with different crosslinking densities were prepared. Their mechanical properties, thermal properties, water absorption, surface morphology and chemical structure before and after CE tests were compared with ESEM, OM, TG-DSC, FTIR and XPS in detail. The results showed that with an increase in crosslinking density, the tensile strength of PU_x increased first and then decreased, elongation at break and water absorption reduced gradually and thermal decomposition temperature and adhesion strength increased steadily. During the CE process, cavitation load aggravated the degree of microphase separation and made brittle hard segments concentrate on the coating surface; meanwhile, cavitation heat accelerated hydrolysis, pyrolysis, oxidation and the fracture of molecular chains. As a result, the mechano-thermal coupling intensified the formation and propagation of fatigue cracks, which should be the fundamental reason for the CE damage of polyurethane elastomer. PU_0.4 exhibited the best CE resistance among the five coatings thanks to its good comprehensive properties and may find potential applications on the surface of hydraulic components.     

Lysyl Oxidase-like Protein Recognizes Viral Envelope Proteins and Bacterial Polysaccharides against Pathogen Infection via Induction of Expression of Antimicrobial Peptides

Lysyl oxidases (LOXs) are copper-dependent monoamine oxidases, and they play critical roles in extracellular matrix (ECM) remodeling. The LOX and LOX-like (LOXL) proteins also have a variety of biological functions, such as development and growth regulation, tumor suppression, and cellular senescence. However, the functions of LOXLs containing repeated scavenger receptor cysteine-rich (SRCR) domains in immunity are rarely reported. In this study, we characterized the antiviral and antibacterial functions of a lysyl oxidase-like (LOXL) protein containing tandem SRCR domains in Marsupenaeus japonicus. The mRNA level of LoxL was significantly upregulated in the hemocytes and intestines of shrimp challenged using white spot syndrome virus (WSSV) or bacteria. After the knockdown of LoxL via RNA interference, WSSV replication and bacterial loads were apparently increased, and the survival rate of the shrimp decreased significantly, suggesting that LOXL functions against pathogen infection in shrimp. Mechanistically, LOXL interacted with the envelope proteins of WSSV or with lipopolysaccharide and peptidoglycan from bacteria in shrimp challenged using WSSV or bacteria, and it promoted the expression of a battery of antimicrobial peptides (AMPs) via the induction of Dorsal nuclear translocation against viral and bacterial infection. Moreover, LOXL expression was also positively regulated by Dorsal in the shrimp challenged by pathogens. These results indicate that, by acting as a pattern recognition receptor, LOXL plays vital roles in antiviral and antibacterial innate immunity by enhancing the expression of AMPs in shrimp.