Learning a functional grammar of protein domains using natural language word embedding techniques

In this paper, using Word2vec, a widely-used natural language processing method, we demonstrate that protein domains may have a learnable implicit semantic “meaning” in the context of their functional contributions to the multi-domain proteins in which they are found. Word2vec is a group of models which can be used to produce semantically meaningful embeddings of words or tokens in a fixed-dimension vector space. In this work, we treat multi-domain proteins as “sentences” where domain identifiers are tokens which may be considered as “words.” Using all InterPro (Finn et al. 2017) pfam domain assignments we observe that the embedding could be used to suggest putative GO assignments for Pfam (Finn et al. 2016) domains of unknown function.     

微创经皮钢板联合锁定加压钢板固定术治疗胫骨干骺端骨折的临床疗效

目的:探讨微创经皮钢板固定技术(MIPPO)与锁定加压钢板(LCP)治疗胫骨干骺端骨折的临床疗效。方法:选择2013年6月-2015年6月在我院接受手术治疗的胫骨干骺端骨折患者103例作为研究对象,根据手术方法不同将所选患者分为三组。其中,联合手术组(35例)患者采用MIPPO联合LCP内固定术治疗,外固定组(33例)患者采用超关节外固定支架术治疗,内固定术组(35例)患者采用切开复位钢板内固定术治疗。观察并比较三种手术方法的临床效果及对患者骨关节功能的影响。结果:与外固定术组及内固定术组比较,联合手术组患者的手术时间短,术中出血量少,骨折愈合时间早,差异具有统计学意义(P0.05);联合手术组患者的手术优良率高于外固定组和内固定组,差异有统计学意义(P0.05);内固定组手术优良率高于外固定组,差异具有统计学意义(P0.05);联合手术组患者术后并发症的发生率低于外固定组及内固定组,差异具有统计学意义(P0.05);外固定组与内固定组术后并发症的发生率比较,差异无统计学意义(P0.05)。结论:MIPPO联合LCP内固定治疗胫骨干骺端骨折具有手术切口小、术中出血量少、术后并发症发生率低、骨折愈合快、关节功能恢复较好等优点,是治疗胫骨干骺端骨折的理想方法,值得临床推广应用。     

抗感染活性骨治疗感染性胫骨骨不连的临床研究

目的:观察抗感染活性骨(ARBX)治疗感染性胫骨骨不连的临床效果。方法:回顾性分析我院自2008年1月-2015年1月收治并系统随访应用抗感染骨治疗的36例创伤后感染性骨不连病例,给予原内固定取出或外架拆除,病灶清除,去除硬化骨及死骨,髓腔再通,抗感染活性骨植骨,外架或钢板重新固定,统计患者病程时间,伤口愈合时间,患者院前手术次数,滴注引流时间及抗生素应用疗程,骨性愈合时间,内、外固定物拆除时间以及功能恢复情况,并总结治疗疗效。结果:平均随访2.4年(1年2月-4年10月),骨不连彻底治愈30例,4例患者感染控制,半皮质愈合,2例感染复发,骨不连未愈合。结论:1抗感染活性骨是治疗感染性骨不连的一种有效的植骨材料,具有控制感染,促进骨折愈合的作用;2彻底清除坏死,失活组织是控制感染,促进感染性骨不连愈合的关键;3清理断端,断端骨髓腔再通可促进成骨,促进骨折愈合。     

Virtual structural analysis of tibial fracture healing from low-dose clinical CT scans

Quantitative assessment of bone fracture healing remains a significant challenge in orthopaedic trauma research. Accordingly, we developed a new technique for assessing bone healing using virtual mechano-structural analysis of computed tomography (CT) scans. CT scans from 19 fractured human tibiae at 12 weeks after surgery were segmented and prepared for finite element analysis (FEA). Boundary conditions were applied to the models to simulate a torsion test that is commonly used to access the structural integrity of long bones in animal models of fracture healing. The output of each model was the virtual torsional rigidity (VTR) of the healing zone, normalized to the torsional rigidity of each patient’s virtually reconstructed tibia. This provided a structural measure to track the percentage of healing each patient had undergone. Callus morphometric measurements were also collected from the CT scans. Results showed that at 12 weeks post-op, more than 75% of patients achieved a normalized VTR (torsional rigidity relative to uninjured bone) of 85% or above. The predicted intact torsional rigidities compared well with published cadaveric data. Across all patients, callus volume and density were weakly and non-significantly correlated with normalized VTR and time to clinical union. Conversely, normalized VTR was significantly correlated with time to union (R² = 0.383, p = 0.005). This suggests that fracture scoring methods based on the visual appearance of callus may not accurately predict mechanical integrity. The image-based structural analysis presented here may be a useful technique for assessment of bone healing in orthopaedic trauma research.     

DNA-fluorescence of mammalian intra-nucleolar chromatin detected by confocal laser scanning microscopy (CLSM)

The complex spatial DNA distribution in the mammalian interphase nucleus was investigated in Feulgen stained thick sections through mouse trophoblast giant nuclei after Lowicryl embedding. DNA-fluorescence was visualized using confocal laser scanning microscopy. Our results show that the spatial arrangement of major interphase chromatin areas can be precisely documented, including the distribution of small intra-nucleolar chromatin zones.     

Exploring the nonlinear geometry of protein homology

The explosion of biological data resulting from genomic and proteomic research has created a pressing need for data analysis techniques that work effectively on a large scale. An area of particular interest is the organization and visualization of large families of protein sequences. An increasingly popular approach is to embed the sequences into a low-dimensional Euclidean space in a way that preserves some predefined measure of sequence similarity. This method has been shown to produce maps that exhibit global order and continuity and reveal important evolutionary, structural, and functional relationships between the embedded proteins. However, protein sequences are related by evolutionary pathways that exhibit highly nonlinear geometry, which is invisible to classical embedding procedures such as multidimensional scaling (MDS) and nonlinear mapping (NLM). Here, we describe the use of stochastic proximity embedding (SPE) for producing Euclidean maps that preserve the intrinsic dimensionality and metric structure of the data. SPE extends previous approaches in two important ways: (1) It preserves only local relationships between closely related sequences, thus allowing the map to unfold and reveal its intrinsic dimension, and (2) it scales linearly with the number of sequences and therefore can be applied to very large protein families. The merits of the algorithm are illustrated using examples from the protein kinase and nuclear hormone receptor superfamilies.     

兔后交叉韧带断裂后外侧胫骨平台退变的组织学研究

目的:探讨兔后交叉韧带(Posterior cruciate ligament,PCL)断裂对外侧胫骨平台组织学的影响。方法:48只家兔膝关节随机配对为实验侧和对照侧造模,造模后第4、8、16、24周各随机处死12只,行外侧胫骨平台大体观察、HE染色、免疫组化检测基质金属蛋白酶13(matrix metalloproteinase-13,MMP-13)、基质金属蛋白酶抑制剂1(Tisse inhibitor-1 of matrix metalloproteinase1,TIMP-1)表达。结果:①大体观察,随时间延长,实验组外侧胫骨平台软骨出现磨损,呈灰黄色,弹性差,骨赘形成。②组织学观察,随时间延长,胫骨平台软骨纤维化,细胞排列紊乱,簇聚细胞出现频率增加。③实验组MMP-13、TIMP-1表达均高于对照组,有显著性差异,P<0.05。④实验组MMP-13、TIMP-1表达阳性率第4、8、16周逐渐升高,24周下降,各组比较有显著性差异,P<0.05。结论:①兔膝关节PCL断裂会引起外侧胫骨平台软骨退行性变,且该退变随着时间的推移逐渐加重。②MMP-13与TIMP-1在PCL断裂膝关节外侧胫骨平台中的表达呈现先高后低的变化规律,造成MMP-13与TIMP-1的失衡,加速软骨退变。③MMP-13与TIMP-1表达增高提示MMP-13与TIMP-1可能参与了PCL断裂后外侧胫骨平台软骨的退变过程。     

个性化后侧入路治疗胫骨平台后髁冠状面骨折

目的:探讨个性化后侧入路治疗单纯性胫骨平台后髁冠状面骨折手术方法。方法:12例单纯性胫骨平台后髁冠状面骨折的患者,采用后内侧或后外侧以及后内后外联合入路切开复位内固定治疗。结果:12例均获随访,随访时间8-24个月,平均13个月。患者膝关节功能评定按Hohl评分标准:优10例,良2例。复查X线片:骨折复位良好,关节面未见明显塌陷。结论:个性化后侧入路治疗单纯性胫骨平台后髁骨折冠状面可直视下暴露胫骨平台后髁,提供了更广阔的操作空间,有利于骨折的解剖复位内固定。