关节灌洗术联合透明质酸钠注射治疗颞下颌关节骨关节炎的疗效观察

目的:评价关节腔灌洗联合透明质酸钠注射治疗颞下颌关节骨关节炎(TMJOA)的疗效及安全性。方法:选取我院2014年5月-2015年5月收治颞下颌关节骨关节炎患者68例作为研究对象,根据入院时间先后顺序按照随机数字表法随机分为实验组和对照组各34例。所有患者在颞颌关节区域局麻下建立关节上腔的双通道灌洗系统,实验组用生理盐水反复冲洗关节腔后注射透明质酸钠,对照组只进行关节腔灌洗术,术后随访对比两组治疗前、治疗后4周、6个月时患者非辅助最大开口度、侧向运动幅度、咀嚼时疼痛感;同时采用酶联免疫吸附法(ELISA)测定两组治疗前、治疗后4周血清中白细胞介素6(IL-6)和肿瘤坏死因子α(TNF-α)水平并进行比较。结果:实验组患者治疗后4周、治疗后6个月时颞下颌关节最大张口度和侧向活动距离明显增大,而咀嚼时疼痛感明显减轻,且优于同期对照组,差异具有统计学意义(P0.05);实验组患者治疗后4周时血清IL-6、TNF-α水平较术前及同时期对照组均明显降低,差异具有统计学意义(P0.05)。结论:关节灌洗术联合透明质酸钠注射是治疗颞下颌关节骨关节炎的简单、安全有效治疗方法,治疗效果明显优于单纯关节腔灌洗,值得临床推广应用。     

关节腔注射强力霉素对兔膝骨关节炎模型的影响

目的:研究关节腔内注射强力霉素对兔制动性骨关节炎模型的影响.方法:30只新西兰大白兔随机分成正常组6只及实验组24只,试验组左膝关节伸直位石膏固定4周随机选取6只处死左膝关节取材证实造模成功后剩余18只为左膝骨关节炎模型,随机分为治疗组、阴性对照组和模型对照组,治疗组每日给予1.33%的强力霉素0.3毫升左膝关节腔内注射,阴性对照组每日给予生理盐水0.3毫升左膝关节腔注射,模型对照组不做处理,于8周处死取材.观察指标包括关节软骨大体形态,软骨Mankin's评分,软骨细胞基质金属蛋白酶-3(MMP-3)表达及滑膜细胞白介素-1(IL-1)表达.结果:强力霉素治疗组软骨面退变明显轻于模型组及生理盐水对照组,软骨大体评分,Mankin评分,MMP-3表达及滑膜IL-1表达亦显著降低.结论:强力霉素关节腔内注射对兔制动性骨关节炎模型软骨退变有明显的缓解作用.     

TGF-beta1、HIF-1alpha、VEGF在胃癌组织及癌旁组织中的表达及临床意义

目的：研究TGF-beta1（转化生长因子-beta1）、HIF-1alpha（低氧诱导因子-1alpha）、VEGF（血管内皮生长因子）在胃癌组织及癌旁组织中 的表达及临床意义。方法：选取于我院就诊的160 例胃癌手术患者切除的组织,采用免疫组化技术检测手术切除的胃癌组织中的 TGF-beta 1、HIF-1alpha及VEGF的表达,分析其与患者临床病理参数的关系。结果：免疫组化结果显示：TGF-beta1、HIF-1alpha及VEGF 在胃 癌组织中的表达均高于癌旁组织,差异均有统计学意义（P<0.05）;TGF-beta1、HIF-1alpha及VEGF 的表达均与肿瘤分期、淋巴结转移及 浸润深度有关（P<0.05）;VEGF的表达分别与TGF-beta1、HIF-1alpgha的表达呈相关关系（P<0.05）。结论：TGF-beta1、HIF-1alpha及VEGF在胃 癌组织中的表达与胃癌的病理学特征有关,检测TGF-beta1、HIF-1alpha及VEGF的表达将有助于临床诊治胃癌患者。     

玻璃酸钠联合臭氧关节腔内注射对创伤性踝关节炎患者血清hs-CRP、IL-1β、IL-6和TNF-α水平的影响

目的:探讨玻璃酸钠联合臭氧关节腔内注射对创伤性踝关节炎患者血清超敏C反应蛋白(hs-CRP)、白介素(IL)-1β、IL-6和肿瘤坏死因子(TNF)-α水平的影响。方法:选择2013年1月至2016年8月我院接诊的92例创伤性踝关节炎患者作为本次研究对象,通过随机数表法分为观察组(n=46)和对照组(n=46)。对照组在关节腔给注射玻璃酸钠治疗,观察组联合臭氧治疗,均1次/周,连续治疗5次。比较两组治疗前后视觉模拟评分法(VAS)、Mc Guire踝关节评分以及血清hs-CRP、IL-1β、IL-6和TNF-α的变化及治疗后临床疗效优良率。结果:治疗前,两组VAS评分、Mc Guire踝关节评分、血清hs-CRP、IL-1β、IL-6和TNF-α水平比较差异均无统计学意义(P0.05)。治疗后,两组VAS评分、Mc Guire踝关节评分均较治疗前显著改善(P0.05),且观察组VAS评分明显低于对照组,Mc Guire踝关节评分明显高于对照组(P0.05);两组血清hs-CRP、IL-1β、IL-6和TNF-α水平较治疗前均显著降低(P0.05),且观察组血清hs-CRP、IL-1β、IL-6和TNF-α比较均明显低于对照组(P0.05);观察组临床疗效优良率明显高于对照组(P0.05)。结论:关节腔内注射玻璃酸钠联合臭氧治疗创伤性踝关节炎患者的临床效果优于单用关节腔注射玻璃酸钠,可有效缓解疼痛,改善关节功能,可能与其有效降低血清hs-CRP、IL-1β、IL-6和TNF-α水平有关。     

软骨寡聚基质蛋白过表达对BMP-2诱导骨髓间充质干细胞分化的影响

目的：研究软骨寡聚基质蛋白（cartilage oligomeric matrix protein,COMP）过表达对BMP-2诱导骨髓间充质干细胞成骨及成软骨分化的影响。方法：BMP-2诱导骨髓间充质干细胞分化,通过脂质体转染含人COMP基因的质粒使骨髓间充质干细胞过表达COMP,采用实时定量PCR和Western blotting分析COMP基因过表达、成骨相关基因Ⅰ型胶原、RUNX2、骨钙蛋白以及成软骨相关基因Ⅱ型胶原、SOX9、蛋白聚糖、X型胶原的表达变化;通过茜素红染色观察成骨终末阶段矿化结节的生成情况,阿利新蓝染色观察细胞基质蛋白多糖的合成情况。结果：质粒转染后骨髓间充质干细胞COMP基因蛋白和mRNA表达水平显著提高（P<0.05）。COMP基因过表达后,成骨标记基因RUNX2、Ⅰ型胶原（Col1a1）mRNA水平均显著低于对照组（P<0.05）,RUNX2、骨钙蛋白（Osteocalcin）蛋白表达水平明显低于对照组（P<0.05）,而成软骨标记基因SOX9、蛋白聚糖（Aggrecan）mRNA水平均显著高于对照组（P<0.05）,SOX9、Ⅱ型胶原（Col2a1）蛋白表达均明显多于对照组（P<0.05）。细胞成骨茜素红染色弱于对照组,而阿利新蓝染色强于对照组。过表达组细胞X型胶原（Col10a1）基因表达显著低于对照组（P<0.05）,结论：骨髓间充质干细胞COMP基因过表达可抑制BMP-2诱导其成骨分化,促进骨髓间充质干细胞成软骨分化,并抑制软骨细胞的成熟肥大,为软骨组织工程研究提供新的方向。     

一种新方法获取颞下颌关节骨关节病患者滑膜间充质干细胞及细胞培养鉴定

该研究探讨从颞下颌关节骨关节病患者的关节冲洗液中获取滑膜间充质干细胞(synovial mesenchymal stem cells,SMSCs)并进行体外培养,研究其间充质干细胞特性。采用离心、贴壁培养法从颞下颌关节骨关节病患者的关节冲洗液中提取并分离细胞,进行细胞形态学观察、细胞生长及周期的分析,细胞表面物标志物流式细胞术检测,间充质干细胞标志物免疫荧光检测,成骨、成脂、成软骨多向分化能力检测,促血管分泌因子检测。结果显示,通过离心、贴壁培养法可稳定地从患者颞下颌关节冲洗液中获取滑膜间充质干细胞,体外培养呈对数生长。SMSCs表达间质源性细胞的特异性标记物CD73、CD90、CD105、波形蛋白(Vimentin)以及α平滑肌肌动蛋白的特异性标记物α-SMA。经诱导培养基诱导,SMSCs可分化为骨、软骨和脂肪细胞,细胞分泌液中可检测到如成纤维细胞生长因子(fibroblast growth factor,FGF)、angiopoietin、转化生长因子-β(transforming growth factor-β,TGF-β)等10余种促血管生长因子。以上结果表明,该研究成功建立了以微创的方式获取颞下颌关节骨关节病患者的滑膜间充质干细胞,有望为组织工程应用于骨软骨修复提供良好种子细胞的来源。     

Jagged1蛋白在膝关节骨性关节炎软骨组织中的表达

目的:研究Jagged1蛋白在膝关节骨性关节炎关节软骨中表达的特点,探讨Jagged1蛋白的表达对关节软骨病理改变的影响。方法:选取宁夏医科大学总医院骨科2018年11月1日至2019年10月31日34例因膝关节骨性关节炎行全膝关节置换的患者,取术中去除的股骨髁软骨组织,磨损较重的一侧为负重区(实验组),磨损较轻的一侧为非负重区(对照组)。通过番红、HE染色观察软骨组织形态学变化,通过免疫组织化学检测Jagged1蛋白在不同软骨组织中的表达强度,对比分析Jagged1蛋白表达的差异对关节软骨病变的影响。结果:外观照可见实验组软骨面色泽暗淡,表面粗糙,有大量软骨缺失,对照组软骨面较平整,呈白色,未见软骨明显缺失;HE染色可见实验组软骨面不整,软骨细胞排列紊乱,呈簇状分布,对照组软骨面平整,软骨细胞数量多,胞质丰富;番红染色见实验组软骨组织残留较少,软骨层结构模糊不清,软骨细胞较少,对照组软骨层次结构清晰,软骨细胞及软骨下骨细胞排列整齐;免疫组化可见Jagged1蛋白实验组软骨中有较多阳性表达,在对照组中表达较少,差异有统计学意义(P0.05)。结论:Jagged1蛋白在软骨中的表达强度与关节软骨的磨损程度呈正相关,在膝关节骨性关节炎的病理变化过程中有着重要的作用。     

白介素1受体拮抗剂及转化生长因子β1对兔膝关节骨性关节炎（OA）的治疗研究

目的：通过关节腔内注射白介素l受体拮抗剂（IL-1Ra）及转化生长因子β1（TGF]B1）,观察其对骨性关节炎的治疗作用。方法：16只3-4个月龄新西兰大白兔（雌雄不限）随机分为四组,每组四只,分为正常组,对照组,IL1-Ra组,TGF-β组,正常组仅打开左膝关节关节腔,剩余三组均给予左膝关节前交叉韧带离断术（anterior cruciate ligament transaction ACLT）。四周后IL-1Ra组给予关节腔内注射IL-1Ra5g／ml,TGF-β1组给予关节腔内注射TGF-β150mg／ml,每周两次,连续四周,正常组及对照组未采取任何措施。术后八周时采用空气栓塞法处死全部实验动物,取股骨远端长约1cm,固定后切片行细胞形态学观察。结果：大体肉眼观察：对照组股骨远端软骨面色颜色变暗并稍显粗糙,可见少量软骨脱落,其余两组关节软骨大体形态均接近正常。镜下观察：TGF-β1组软骨细胞增生明显,软骨细胞排列较正常软骨细胞排列轻度紊乱。IL—1Ra组软骨细胞增生数量未及TGF-β1组明显,软骨细胞排列也不及TGF-β1组规则。IL-1Ra组及TGF-β1组软骨细胞形态接近正常软骨细胞,基质染色接近正常。两组软骨膜表面光滑,无纤维细胞形成,软骨膜下未见纤维化。对照纽软骨细胞数量明显减少且排列紊乱,软骨细胞形态发生改变,可见软骨细胞凋亡,镜下可见软骨细胞核浓缩、裂解,并可见新生软骨形成,突出于正常软骨膜表面,软骨膜表面下方可见血管翳及纤维母细胞形成,出现轻度纤维化。基质染色不均匀且染色较淡。结论：IL-1Ra及TGF-β1关节腔内注射均能有效抑制骨性关节炎关节软骨的退变并增加软骨细胞再生,促进软骨基质合成,延缓骨性关节炎的发病进程.     

碱性成纤维细胞生长因子对下颌阻生牙手术患者血清IL-6水平及牙槽骨密度的影响

目的:探讨碱性成纤维细胞生长因子对对下颌阻生牙手术患者血清IL-6水平及牙槽骨密度的影响。方法:收集我院就诊的104例行下颌阻生牙手术患者,随机分为实验组和对照组,每组52例。所有患者均行下颌阻生牙手术。对照组患者术后注射生理盐水,实验组患者术后注射碱性成纤维细胞生长因子。观察并比较两组患者血清白介素6(IL-6)、牙槽骨密度水平、临床治疗有效率以及不良反应发生情况。结果:与治疗前相比,两组患者治疗后的骨密度水平均升高,IL-6水平均下降,差异具有统计学意义(P0.05);与对照组相比,实验组患者的牙槽骨密度水平及临床治疗有效率均较高,IL-6水平较低,差异具有统计学意义(P0.05)。实验组患者未出现不良明显反应。结论:碱性成纤维细胞生长因子可显著提高下颌阻生牙术后患者的创口恢复,且有效预防感染的发生。     

MMP-1、MMP-3 和MMP-13在慢性睡眠剥夺所致颞下颌关节损伤中的变化

目的：观察MMP-1、MMP-3 和MMP-13 在慢性睡眠剥夺所致颞下颌关节损伤中表达的变化,探讨慢性睡眠剥夺所致颞下颌 关节损伤的可能机制。方法：采用改良多平台(MMPM)建立大鼠慢性睡眠剥夺模型,将90 只成年雄性Wastar 大鼠随机分为小平 台组、网格组和对照组。小平台组和网格组大鼠接受每天18 h的睡眠剥夺和6 h间歇期(10:00-16:00),间歇期大鼠正常笼养。实验 第7、14 和21 d时分别观察动物的行为学观察、检测动物血浆皮质醇(CORT)和促肾上腺皮质激素(ACTH)水平检测,通过免疫印 迹法和实时定量聚合酶链反应(PRC)检测颞下颌关节软骨中MMP-1、MMP-3 和MMP-13 的蛋白和mRNA表达,并通过HE 染色 法观察颞下颌关节结构的变化。结果：与对照组和网格组大鼠相比,小平台组大鼠第14 d和21 d 时髁突软骨中间部位表面纤维 在出现明显的炎症、松解及脱落现象;第21天时的血浆ACTH 和CORT 水平均显著高于网格组和对照组,差异有统计学意义 (P<0.05);第7、14、21 d时关节软骨MMP-1 和MMP-13 蛋白和mRNA 的表达水平均显著上调(P<0.05)。结论：慢性睡眠剥夺所致 的颞下颌关节损伤可能与关节软骨中MMP-1、MMP-3 和MMP-13 的表达上调有关。     

Recent advances in the study of Kaposi's sarcoma-associated herpesvirus replication and pathogenesis

It has now been over twenty years since a novel herpesviral genome was identified in Kaposi's sarcoma biopsies. Since then, the cumulative research effort by molecular biologists, virologists, clinicians, and epidemiologists alike has led to the extensive characterization of this tumor virus, Kaposi's sarcoma-associated herpesvirus(KSHV; also known as human herpesvirus 8(HHV-8)), and its associated diseases. Here we review the current knowledge of KSHV biology and pathogenesis, with a particular emphasis on new and exciting advances in the field of epigenetics. We also discuss the development and practicality of various cell culture and animal model systems to study KSHV replication and pathogenesis.     

A Unique Protease Cleavage Site Predicted in the Spike Protein of the Novel Pneumonia Coronavirus (2019-nCoV) Potentially Related to Viral Transmissibility

正Dear Editor,In December 2019, a novel human coronavirus caused an epidemic of severe pneumonia(Coronavirus Disease 2019,COVID-19) in Wuhan, Hubei, China(Wu et al. 2020; Zhu et al. 2020). So far, this virus has spread to all areas of China and even to other countries. The epidemic has caused 67,102 confirmed infections with 1526 fatal cases     

Curcuminoids as inhibitors of thioredoxin reductase: A receptor based pharmacophore study with distance mapping of the active site

Curcumin is the yellow pigment of turmeric that interacts irreversibly forming an adduct with thioredoxin reductase (TrxR), an enzyme responsible for redox control of cell and defence against oxidative stress. Docking at both the active sites of TrxR was performed to compare the potency of three naturally occurring curcuminoids, namely curcumin, demethoxy curcumin and bis-demethoxy curcumin. Results show that active sites of TrxR occur at the junction of E and F chains. Volume and area of both cavities is predicted. It has been concluded by distance mapping of the most active conformations that Se atom of catalytic residue SeCYS498, is at a distance of 3.56 from C13 of demethoxy curcumin at the E chain active site, whereas C13 carbon atom forms adduct with Se atom of SeCys 498. We report that at least one methoxy group in curcuminoids is necessary for interation with catalytic residues of thioredoxin. Pharmacophore of both active sites of the TrxR receptor for curcumin and demethoxy curcumin molecules has been drawn and proposed for design and synthesis of most probable potent antiproliferative synthetic drugs.     

Comparative morphology of the carpel in the Liliaceae: Hewardieae, Petrosavieae, and Tricyrteae

The young pistils in the melanthioid tribes, Hewardieae, Petrosavieae and Tricyrteae, are uniformly tricarpellate and syncarpous. They lack raphide idioblasts. All are multiovulate, with bitegmic ovules. The Petrosavieae are marked by the presence of septal glands and incomplete syncarpy. Tepals and stamens adhere to the ovary in the Hewardieae and the Petrosavieae but not in the Tricyrteae. Two vascular bundles occur in the stamens of the Hewartlieae and Tricyrtis latifolia. Ventral bundles in the upper part of the ovary of the Hewardieae are continuous with compound septal bundles and placental bundles in the lower part. Putative ventral bundles occur in the alternate position in the Tricyrteae and putative placental bundles in the opposite. position in the Petrosavieae. The dichtomously branched stigma in each carpel of the Tricyrteae is supplied by a bifurcated dorsal bundle.     

Synthesis and antimicrobial studies of hydrazone derivatives of 4-[3-(2,4-difluorophenyl)-4-formyl-1H-pyrazol-1-yl]benzoic acid and 4-[3-(3,4-difluorophenyl)-4-formyl-1H-pyrazol-1-yl]benzoic acid

Microbial resistance to antibiotics is an unresolved global concern, which needs urgent and coordinated action. One of the guidelines of the Centers for Disease Control and Preventions (CDC) to combat antibiotic resistance is the development of new antibiotics to treat drug-resistant bacteria. In our effort to find new antibiotics, we report the synthesis and antimicrobial studies of 30 new pyrazole derivatives. These novel molecules have been synthesized by using readily available starting materials and benign reaction conditions. Some of these molecules have shown activity with MIC values as low as 0.78?µg/mL against four bacterial strains; Staphylococcus aureus, methicillin-resistant S. aureus, Bacillus subtilis, and Acinetobacter baumannii. Furthermore, active molecules are non-toxic to mammalian cell line.

     

Novel compounds with potent CDK9 inhibitory activity for the treatment of myeloma

Cyclin-dependent kinases (CDKs) and Polo-like kinases (PLKs) play key role in the regulation of the cell cycle. The aim of our study was originally the further development of our recently discovered polo-like kinase 1 (PLK1) inhibitors. A series of new 2,4-disubstituted pyrimidine derivatives were synthesized around the original hit, but their PLK1 inhibitory activity was very poor. However the novel compounds showed nanomolar CDK9 inhibitory activity and very good antiproliferative effect on multiple myeloma cell lines (RPMI-8226).