富血小板血浆联合负压引流治疗慢性难愈性创面的Meta分析

文题释义：富血小板血浆：是一种调节炎症反应、刺激和加速组织愈合的新型生物技术,其富含各种生长因子,包括血小板源生长因子、转化生长因子β、成纤维细胞生长因子、血管内皮生长因子等,通过多种机制(包括调节炎症、血管生成及新组织的合成和重塑)在内部帮助创建最有利于组织稳态恢复的生物环境。慢性难愈性创面：目前对于慢性难愈性创面的定义尚未达成明确的共识,一般是指由于各种因素引起的经过常规治疗干预,不能在可预期的时间内按生物学规律完全愈合的创面,其潜在病因可能与全身性疾病或局部疾病有关。   背景：富血小板血浆与负压引流疗法已被广泛应用于各种慢性创面的治疗,并取得了良好的临床效果,但两者联合应用于慢性难愈性创面的效果尚缺乏来自随机对照研究的证据。 目的：评价富血小板血浆联合负压引流疗法治疗慢性难愈性创面的效果。方法：使用计算机对国内外数据库(CNKI、维普网、万方数据库、SinoMed、Web of Science、PubMed、EMbase等)进行检索,检索范围从建库至2019年6月,所有关于富血小板血浆联合负压引流疗法治疗慢性难愈性创面效果的随机对照试验,对纳入研究的文献采用Cochrane系统评价方法进行评价,采用Review manager 5.3软件进行Meta分析,分析的结局指标包括创面愈合率、创面愈合时间、住院时间、疼痛评分、细菌阳性率。结果与结论：①共纳入11篇随机对照试验,包括743例慢性创面患者,观察组均采用富血小板血浆联合负压引流疗法进行干预,对照组采用常规换药或者单纯负压引流疗法进行干预;②Meta分析显示与对照组比较,观察组创面愈合率升高[RR=2.19,95%CI(1.82,2.62),P < 0.000 01]、创面愈合时间缩短[SMD=-0.81,95%CI(-1.00,-0.62),P < 0.000 01]、住院时间缩短[MD=-7.11,95%CI(-8.12,-6.11),P < 0.000 01]、细菌阳性率降低[RR=0.35,95%CI(0.22,0.54),P < 0.000 01];两组疼痛评分比较差异无显著意义[SMD=-5.97,95%CI(-14.33,2.40),P=0.16];③结果表明,富血小板血浆联合负压引流疗法能促进慢性难愈性创面的愈合,降低感染发生率。 ORCID: 0000-0003-2057-9542(顾蓥璇) 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

重组人甲状旁腺激素(1-34)促成骨作用及在口腔领域的应用

文题释义： 特立帕肽(teriparatide)：即重组人甲状旁腺激素(1-34)(rhPTH 1-34),2002年经美国食品药品监督管理局(FDA)批准应用于骨质疏松症的治疗,是第一代骨合成代谢药。它可以直接刺激新骨的成骨细胞形成,实现有效的合成代谢,在口腔领域的研究也表现出良好的促进种植体-骨结合及牙周再生等效果。 甲状旁腺激素：由甲状旁腺主细胞合成与分泌,是含84个氨基酸残基的单链多肽,位于人类甲状旁腺激素分子氨基端(N-端)的1-34位氨基酸序列是其生物活性部位。甲状旁腺激素是调节人体钙磷内环境稳态及骨代谢的重要激素,间歇低剂量给予甲状旁腺激素对骨骼发挥合成代谢作用。 背景：重组人甲状旁腺激素(1-34)(recombinant human parathyroid hormone 1-34,rhPTH 1-34),即特立帕肽,为甲状旁腺激素氨基端片段,作为骨合成代谢药,因可以直接刺激新骨形成、增加骨量而成为研究热点,也因其强大的成骨效应引起口腔领域的关注与应用。 目的：对特立帕肽的成骨机制、有效性和安全性及其在口腔领域的研究进展进行综述。 方法：第一作者检索近20年PubMed数据库、万方数据库收录的相关文章。英文检索词为“rhPTH(1-34),teriparatide,osteoporosis,stomatology,Jaw,implant-osseointegration,periodontal”,中文检索词为“重组人甲状旁腺激素(1-34),特立帕肽,骨质疏松,口腔医学,颌骨,种植体-骨结合,牙周”。共选取56篇文献进行综述。 结果与结论：特立帕肽可以直接刺激新骨的成骨细胞形成,实现有效的合成代谢,其在口腔领域的研究表现出良好的促进种植体-骨结合、牙周再生、骨缺损愈合及提高正畸稳定性的效果,在口腔领域有良好的应用前景,但仍需要更多更高质量的动物实验及临床研究证实。未来甲状旁腺激素类药物及其类似物可与骨组织工程技术有机结合,更好地促进骨修复,同时也更好地服务于口腔颌面部的修复治疗。 ORCID: 0000-0002-2333-4260(董西玲) 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

Enhanced enrichment of prostate cancer stem-like cells with miniaturized 3D culture in liquid core-hydrogel shell microcapsules

Cancer stem-like cells (CSCs) are rare subpopulations of cancer cells that are reported to be responsible for cancer resistance and metastasis associated with conventional cancer therapies. Therefore, effective enrichment/culture of CSCs is of importance to both the understanding and treatment of cancer. However, it usually takes approximately 10 days for the widely used conventional approach to enrich CSCs through the formation of CSC-containing aggregates. Here we report the time can be shortened to 2 days while obtaining prostate CSC-containing aggregates with better quality based on the expression of surface receptor markers, dye exclusion, gene and protein expression, and in vivo tumorigenicity. This is achieved by encapsulating and culturing human prostate cancer cells in the miniaturized 3D liquid core of microcapsules with an alginate hydrogel shell. The miniaturized 3D culture in core–shell microcapsules is an effective strategy for enriching/culturing CSCs in vitro to facilitate cancer research and therapy development.     

Actively targeted delivery of anticancer drug to tumor cells by redox-responsive star-shaped micelles

In cancer therapy nanocargos based on star-shaped polymer exhibit unique features such as better stability, smaller size distribution and higher drug capacity in comparison to linear polymeric micelles. In this study, we developed a multifunctional star-shaped micellar system by combination of active targeting ability and redox-responsive behavior. The star-shaped micelles with good stability were self-assembled from four-arm poly(ε-caprolactone)-poly(ethylene glycol) copolymer. The redox-responsive behaviors of these micelles triggered by glutathione were evaluated from the changes of micellar size, morphology and molecular weight. In vitro drug release profiles exhibited that in a stimulated normal physiological environment, the redox-responsive star-shaped micelles could maintain good stability, whereas in a reducing and acid environment similar with that of tumor cells, the encapsulated agent was promptly released. In vitro cellular uptake and subcellular localization of these micelles were further studied with confocal laser scanning microscopy and flow cytometry against the human cervical cancer cell line HeLa. In vivo and ex vivo DOX fluorescence imaging displayed that these FA-functionalized star-shaped micelles possessed much better specificity to target solid tumor. Both the qualitative and quantitative results of the antitumor effect in 4T1 tumor-bearing BALB/c mice demonstrated that these redox-responsive star-shaped micelles have a high therapeutic efficiency to artificial solid tumor. Therefore, the multifunctional star-shaped micelles are a potential platform for targeted anticancer drug delivery.     

Redox-responsive polyanhydride micelles for cancer therapy

Biodegradable polyanhydrides possess unique features like those that they can predominantly undergo surface erosion, and the payloads can be released by a steady speed. However, there is little work that has been published to describe the polyanhydride micelles with redox-responsiveness as a nanocarrier for drug delivery. In this study, we develop one type of new amphiphilic polyanhydride copolymer containing disulfide bonds between the hydrophilic and hydrophobic segments. The copolymer can self-assemble into stable micelles with well-defined core–shell structure and a uniform size distribution with an average diameter of 69 nm. The disassembly behaviors of the micelles triggered by glutathione are evaluated from the changes of the micellar size, morphology and molecular weight. An approximate zero-order in vitro drug release mode with a fast speed can be achieved in a reducing and acid environment similar with that of tumor cells. In vitro cytotoxicity analysis demonstrate that the Cur-loaded micelles are of great efficiency in inhibiting the growth of cancer cells due to the rapidly intracellular delivery of therapeutic agent. Both the qualitative and quantitative results of the antitumor activity in 4T1 tumor-bearing BALB/c mice reveal that the redox-responsive micelles have a more significant therapeutic effect to artificial solid tumor compared to the redox-insensitive micelles. This study provides a new insight into the biomedical application of polyanhydrides in drug delivery.     

SiRNA-phospholipid conjugates for gene and drug delivery in cancer treatment

Due to low charge density and stiff backbone structure, small interfering RNA (siRNA) has inherently poor binding ability to cationic polymers and lipid carriers, which results in low siRNA loading efficiency and limits siRNA success in clinical application. Here, siRNA-phospholipids conjugates are developed, which integrate the characteristics of the two phospholipids to self-assemble via hydrophilic siRNA and hydrophobic phospholipid tails to overcome the siRNA's stiff backbone structures and enhance the siRNA loading efficiency. In this study, the thiol-modified sense and antisense siRNA are chemically conjugated with phospholipids to form sense and antisense siRNA-phospholipid, and then these sense or antisense siRNA-phospholipids with equal amounts are annealed to generate siRNA-phospholipids. The siRNA-phospholipids can serve dual functions as agents that can silence gene expression and as a component of nanoparticles to embed hydrophobic anticancer drugs to cure tumor. siRNA-phospholipids together with cationic lipids and DSPE-PEG2000 fuse around PLGA to form siRNA-phospholipids enveloped nanoparticles (siRNA-PCNPs), which can deliver siRNAs and hydrophobic anticancer drugs into tumor. In animal models, intravenously injected siRNA-PCNPs embedded DOX (siPlk1-PCNPs/DOX) is highly effective in inhibiting tumor growth. The results indicate that the siRNA-PCNPs can be potentially applied as a safe and efficient gene and anticancer drug delivery carrier.     

A recombinant adenovirus expressing CFP10, ESAT6, Ag85A and Ag85B of Mycobacterium tuberculosis elicits strong antigen-specific immune responses in mice

Tuberculosis (TB) is caused by an infection of Mycobacterium tuberculosis (Mtb) and remains an enormous and increasing health burden worldwide. To date, Mycobacterium bovis Bacillus Calmette Guerin (BCG) is the only licensed anti-TB vaccine worldwide, which provides an important but limited protection from the Mtb infection. The development of alternative anti-TB vaccines is therefore urgently needed. Here we report, the generation of Ad5-CEAB, a recombinant adenovirus expressing Mtb antigens of CFP10, ESAT6, Ag85A and Ag85B proteins in a form of mixture. In order to evaluate the immunogenicity of Ad5-CEAB, mice were immunized with Ad5-CEAB by intranasal instillation three times with 2-week intervals. The results demonstrated that Ad5-CEAB elicited a strong antigen-specific immune response, particularly of the Th1 immune responses that were characterized by an increased ratio of IgG2a/IgG1 and secretions of Th1 type cytokines, IFN-γ, TNF-α, IL-2 and IL-12. In addition, the Ad5-CEAB also showed an ability to enhance humoral responses with a dramatically augmented antigen-specific serum IgG. Furthermore, an elevated sIgA were also found in the bronchoalveolar lavage fluid of the immunized mice, suggesting the elicitation of mucosal immune responses. These data indicate that Ad5-CEAB can induce a broad range of antigen-specific immune responses in vivo, which provides a promising and novel route for developing anti-TB vaccines and warrants further investigation.     

Biological and genomic analysis of a PBSX-like defective phage induced from Bacillus pumilus AB94180

Defective prophages, which are found in the genomes of many bacteria, are unable to complete a viral replication cycle and propagate in their hosts as healthy prophages. They package random DNA fragments derived from various sites of the host chromosome instead of their own genomes. In this study, we characterized a defective phage, PBP180, which was induced from Bacillus pumilus AB94180 by treatment with mitomycin C. Electron microscopy showed that the PBP180 particle has a head with a hexagonal outline of ~40 nm in diameter and a long tail. The DNA packaged in the PBP180 head consists of 8-kb DNA fragments from random portions of the host chromosome. The head and tail proteins of the PBP180 particle consist of four major proteins of approximately 49, 33, 16 and 14 kDa. The protein profile of PBP180 is different from that of PBSX, a well-known defective phage induced from Bacillus subtilis 168. A killing activity test against two susceptible strains each of B. subtilis and B. pumilus showed that the defective particles of PBP180 killed three strains other than its own host, B. pumilus AB94180, differing from the host-killing ranges of the defective phages PBSX, PBSZ (induced from B. subtilis W23), and PBSX4 (induced from B. pumilus AB94044). The genome of the PBP180 prophage, which is integrated in the B. pumilus AB94180 chromosome, is 28,205 bp in length, with 40 predicted open reading frames (ORFs). Further genomic comparison of prophages PBP180, PBSX, PBSZ and other PBSX-like prophage elements in B. pumilus strains revealed that their overall architectures are similar, but significant low homology exists in ORF29-ORF38, which presumably encode tail fiber proteins involved in recognition and killing of susceptible strains.     

青少年颈椎钩突-横突孔间距的增龄变化及临床意义

目的通过对6~20岁青少年颈椎钩突的影像学扫描和三维重建,探讨钩突-横突孔间距的发育规律和增龄特征,为青少年颈椎病的诊治和预防提供影像解剖学依据。方法选取无外伤、神经症状和体征的青少年66例,行多排螺旋CT薄层扫描(0.625~1.25 mm),范围C1~T1,将原始数据以DICOM格式导入三维重建软件进行相关指标测量,并按性别、年龄分组进行统计分析。结果颈椎钩突-横突孔间距在性别与侧别间均无显著性差异,发育总体随着年龄和椎序的增长呈递增趋势,且存在显著统计学差异。结论颈椎钩突-横突孔间距与椎动脉型、神经根型等颈椎病的发病率有着密切相关。