结直肠癌表观沉默蛋白Bmi1与Notch信号通路调控的关系

目的 探讨人结直肠癌中表观沉默蛋白Bmi1和Notch1的蛋白表达与结直肠癌病理特征的关系,观察Notch通路对结直肠癌细胞增殖凋亡及Bmi1表达的影响。方法 应用免疫组织化学技术(SP法)检测85例结直肠癌组织及其邻近正常肠黏膜中Notch1及Bmi1的蛋白表达;将Notch1通路中γ-分泌酶抑制剂DAPT,作用于结肠癌SW480细胞株,运用噻唑蓝(MTT)比色法检测细胞增殖状态;流式细胞仪观察其对细胞凋亡的影响,Western blot检测ICN及Bmi1蛋白的表达。结果 结直肠癌组织中Notch1和Bmi1蛋白表达的阳性率明显高于正常肠黏膜(P＜0.05),分别为61.2％ (52/85)对15.3％ (13/85)和56.5％ (48/85)对17.6％ (15/85);Bmi1表达率与Notch1表达率呈正相关(r =0.625,P＜0.01),并与肿瘤分化程度、分期及淋巴结转移有关(P＜0.05);阻断Notch1通路(DAPT)可抑制SW480细胞的增殖,诱导其凋亡,作用12、24、36 h后其增殖抑制率分别为13.1％、17.5及22.6％,而凋亡率为32.7％、45.6％及67.2％;同时Notch1胞内活性段ICN随作用时间延长而下降,而Bmi1表达水平也逐渐降低。结论 结直肠癌中Bmi1与Notch1表达密切相关,阻断Notch通路可抑制Bmi1表达,同时可抑制结肠癌细胞的增殖,促进其凋亡。     

微小RNA-195靶向调控Delta样配体4抗结直肠癌分子机制研究

目的观察微小RNA(microRNA,miR)-195调控结直肠癌中Notch通路配体Delta样配体4(Dll4)表达,探讨其作用靶点,明确miR-195通过Notch通路抗结直肠癌的分子机制。方法收集北京大学人民医院胃肠外科2010年11月至2011年2月56例行结直肠癌根治术切除的标本,3、应用芯片技术筛选6例结直肠肿瘤组织和正常肠黏膜组织中micro-RNA的表达差异,用实时荧光定量聚合酶链反应(PCR)检测miR-195在组织中相对表达量,应用固定化蛋白质印迹法(Western blot)检测56例结直肠癌组织及其邻近正常肠黏膜中Notch通路中Dll4蛋白表达;采用双荧光素酶报告基因实验检测miR-195与Dll43’端非编码区(3’UTR)区的相互作用及活性,采用基因过表达miR-195(40 pmol/L)处理结肠癌细胞系SW480,运用流式细胞仪观察其对细胞凋亡的影响,Western blot检测通路相关蛋白Dll4、锯齿状蛋白1(Jagged1)、Notch受体胞内段(NICD)、细胞周期蛋白(Cyclin)D1、转录因子发状分裂相关增强子1(HES1)、B细胞淋巴瘤/白血病-2(bcl-2)、核因子-κB(NF-κB)的表达。组间比较采用方差分析(ANOVA),独立样本t检验比较蛋白表达量差异,统计学方法分别采用独立样本t检验、配对样本t检验及单因素方差分析。结果结直肠癌组织中miR-195表达水平明显低于正常肠黏膜,而Dll4蛋白表达水平高于正常肠黏膜,分别为正常肠黏膜的0.34倍(0.341±0.008)及1.92倍(1.922±0.003)(t=3.116、2.374,P<0.05),差异均有统计学意义,体外转入miR-195后,Dll4荧光素酶活性低于对照组(0.442±0.010、1.010±0.002,t=4.305,P<0.01),差异有统计学意义,miR-195和γ-分泌酶抑制剂(DAPT)都可阻断Notch1通路,抑制SW480细胞的增殖(3.1%比17.3%,t=4.232,P<0.01),差异有统计学意义,诱导其凋亡(13.7%比48.3%,t=8.355,P<0.01),两者具有协同作用(t=7.474,P<0.01),差异有统计学意义。同时Notch通路相关蛋白NICD、Hes-1随作用时间延长而表达下降。结论结直肠癌中miR-195及Dll4呈拮抗性表达,与其病理学特征密切相关,Dll4为miR-195调控的下游靶基因,miR-195通过负性调控Dll4/Notch信号通路抗结直肠癌。     

表观沉默蛋白Bmil在结直肠癌组织中的表达及其对结直肠癌细胞增殖和凋亡的影响

目的研究人结直肠癌中表观沉默蛋白Bmil表达与结直肠癌病理特征的关系,探讨Bmil蛋白对结直肠癌细胞增殖凋亡的影响。方法应用免疫组织化学技术检测85例结直肠癌组织及其邻近正常肠黏膜中Bmil蛋白表达：用BmilsiRNA转染结肠癌细胞系SW480．运用MTY法检测细胞增殖状态：流式细胞仪观察其对细胞凋亡的影响．Westemblot检测Bmil及Bcl-2蛋白的表达。结果结直肠癌组织中Bmil蛋白表达的阳性率为56．5％（48／85）．明显高于正常肠黏膜[17．6％（15／85）]（P〈0．05）;其阳性表达与肿瘤分化程度、分期及淋巴结转移有关（P〈0．05）。SW480转染BmilsiRNA后,细胞增殖受到抑制,凋亡明显;转染24、48和72h后,其抑制率分别为13．1％、16．5％和18．3％．细胞凋亡率分别为15．7％、45．6％和40．2％：同时,Bmil表达水平在转染48h后下降,Bcl-2表达水平也降低（P〈0．01）。结论结直肠癌中Bmil表达与肿瘤病理学特征关系密切,阻断Bmil表达可抑制结肠癌细胞的增殖．促进其凋亡。     

自噬抑制剂3-甲基腺嘌呤对结直肠腺癌细胞生长与Notch1蛋白表的影响

目的：探讨自噬抑制剂3-甲基腺嘌呤（3-MA）对人大肠癌SW480细胞生长与Notch1蛋白表达的影响。方法：将3-MA（5 mmol/L）作用于SW480细胞24 h后（以培养相同时间无处理的SW480细胞为对照）,分别免疫组化和Western blot法检测细胞Notch1蛋白的表达,用CCK-8法和Annexin/PI双染法检测细胞增殖与凋亡。结果：免疫组化与Western blot结果均显示,3-MA作用后,SW480细胞Notch1蛋白的表达明显下调（均P<0.05）;增殖与凋亡检测结果显示,3-MA作用后,SW480细胞增殖率明显降低,而凋亡率明显增加（均P<0.05）。结论： 3-MA能抑制结直肠癌细胞的增殖并促进其凋亡,该作用可能与3-MA抑制Notch1蛋白表达从而改变细胞自噬水平有关。

     

结直肠癌中MEK2/ERK信号传导通路的研究

目的　研究丝裂原激活化蛋白激酶 (MAPK )中MEK2 /ERK信号传导通路在结直肠癌发生发展中的作用。方法　 ( 1)采用Westernblot检测 5 2例结直肠癌组织及其邻近肠黏膜中MEK 2蛋白的表达。 ( 2 )用丝裂原细胞外激酶 (MEK )抑制剂作用于结肠癌细胞系SW 480 ,然后以MTT法检测细胞增殖状态 ;用Westernblot检测MEK2 ,p ERK及其靶基因产物C myc的表达。结果　结直肠癌组织中MEK2蛋白表达水平明显高于邻近的肠黏膜 (P <0 .0 5 ) ,且与肿瘤的分化、Dukes分期及淋巴结转移有关 (P <0 .0 5 )。应用MEK的抑制剂后SW 480细胞中MEK2 ,p ERK ,C myc表达水平随作用时间延长而下降。结论　MEK2活性增高与结直肠癌细胞侵袭力有关 ,阻断MEK2 /ERK信号传导通路可以抑制结肠癌细胞的增殖 ,促进其凋亡。     

细胞分化决定蛋白Numb/Notch1拮抗性表达与结直肠癌病理特征及预后的关系

目的 观察细胞分化决定蛋白Numb与Notch1在结直肠癌组织中的表达模式,探讨两者与结直肠癌临床病理指标及患者预后的关系.方法 采用固定化蛋白质印迹法( Western blot)及免疫组织化学回顾性检测Numb与Notch1在60例切除结直肠癌组织中的表达,分析两者表达模式与结直肠癌临床病理学指标的关系;同时研究其表达与患者生存的关系.结果 结直肠癌组织中Notch1蛋白表达水平明显高于正常肠黏膜,平均为正常肠黏膜中的2.60倍(43/60比17/60,P＜0.01).而Numb蛋白表达水平明显低于正常肠黏膜,平均为正常肠黏膜的0.52倍(39/60比21/60,P＜0.01).Notch1表达水平与Numb表达呈显著负相关(r=-0.782,P＜0.05).同时两者表达与结直肠癌的分化程度、淋巴结转移、TNM分期密切相关.Notch1高表达的患者(43例)预后明显差于Notch1低表达表达的患者(17例,P＜0.05),而与之相反的是Numb低表达(39例)预后差于Numb高表达患者(21例),差异有统计学意义(P＜0.05).结论 Numb与Notch拮抗性表达可能与结直肠癌发生发展密切相关,可作为结直肠癌某些生物学行为及判定预后的新的参考指标.     

肿瘤浸润淋巴细胞对结肠癌细胞的杀伤作用及机制

目的探讨肿瘤浸润淋巴细胞在结肠癌细胞杀伤中的作用及机制。方法从6例结肠癌患者转移淋巴结中分离TIL细胞,采用^51Cr释放法测定其杀伤结肠癌SW480细胞的作用;采用流式细胞术测定结肠癌细胞的凋亡;采用固定化蛋白印迹法（Western blot）测定TIL细胞和结肠癌细胞Fas、FasL蛋白的表达。结果TIL细胞能有效杀伤结肠癌SW480细胞,其杀伤作用明显强于淋巴因子活化的杀伤细胞（100：1,P=0.004;50：1,P=0.002;10：1,P=0.006）和细胞因子诱导的杀伤细胞（100：1,P=0.001;50：1,P=0.002;10：1,P=0.008）,差异具有统计学意义（P〈0.01）;TIL细胞能促进结肠癌细胞的早期凋亡;TTL细胞高表达FasL分子,而SW480细胞高表达Fas分子,不表达FasL分子。结论TIL细胞能有效杀伤不表达FasL分子的结肠癌细胞,其机制可能通过Fas/FasL通路诱导结肠癌细胞的凋亡。     

肝癌细胞迁移过程中Notch信号通路的作用效果

目的:探讨Notch信号通路在肝癌细胞迁移过程中的作用及相关机制。方法:体外培养正常非肿瘤肝细胞系HL-7702,肝癌细胞系HepG2、Huh-7。利用Transwell小室检测细胞的迁移能力,Western blot检测Notch、Snail、E-cadherin蛋白的表达。分别采用1μmol/L DAPT、5μmol/L DAPT阻断Notch信号通路,比较不同浓度下对细胞迁移能力的影响以及对肝癌细胞中Snail和E-cadherin蛋白表达的影响。结果:肝癌细胞系的侵袭迁移能力明显高于正常非肿瘤肝细胞(P0.05),肝癌细胞HepG2的侵袭迁移能力稍高于Huh-7,但差异未见统计学意义(P0.05)。采用Western blot蛋白印记方法检测细胞Notch、Snail、E-cadherin的蛋白表达量,肝癌细胞中Notch、Snail的表达高于正常细胞,E-cadherin的表达显著低于正常细胞。采用1μmol/L DAPT和5μmol/L DAPT阻断Notch信号通路,与对照组比较,1μmol/L DAPT和5μmol/L DAPT均能明显下调Snail的表达,上调E-cadherin的表达,且随着浓度的增加作用加强(P0.05)。结论:Notch信号通路在肝癌细胞侵袭迁移过程中发挥着重要作用,初步认为与Snail、E-cadherin的表达有关。     

CXCR3在结直肠癌组织中的表达及临床意义

目的 探讨CXCR3在结直肠癌组织中的表达及其临床意义.方法 应用SP免疫组织化学方法检测52例结直肠癌组织CXCR3的表达,Western印迹和体外迁移实验检测趋化因子受体CXCR3在大肠癌细胞株SW480、SW620、HT29细胞的表达及迁移能力.结果 CXCR3的阳性表达率为88%(46/52),CXCR3的高表达与结直肠癌患者的年龄、性别、结直肠癌组织类型、分化程度无关,而与临床转移(肝脏、淋巴结转移)有关(x2=12.1、21.5,P＜0.01).SW480、SW620及HT29的CXCR3表达均呈阳性,其中大肠癌细胞HT29和SW620 CXCR3高表达,大肠癌细胞SW480 CXCR3低表达.在体外迁移实验中,大肠癌细胞HT29和SW620发生体外迁移细胞明显增多(75±6比147±8、63±5比9l±6,P＜0.01),而大肠癌细胞SW480体外迁移无明显变化(47±4比45±3,P>0.05).结论 CXCR3上调表达与结直肠癌转移有关.     

RNA干扰靶向抑制磷脂酰肌醇3-激酶P85α蛋白表达对结直肠癌细胞周期和细胞凋亡的影响

目的探讨RNA干扰靶向抑制磷脂酰肌醇3-激酶（P13K）P85α蛋白表达对结直肠癌细胞周期与细胞凋亡的影响。方法设计4条shRNA干扰载体及1条阴性对照载体．分别稳定转染结直肠癌SW480细胞。采用Western blot筛选出对P13K P85α蛋白抑制效率最高的shRNA干扰片段．然后通过PI标记法和Annexin V—FITC标记法分别检测干扰后SW480细胞周期和细胞凋亡情况。结果转染shRNA／324后．SW480细胞P13K P85α蛋白降低最为显著．抑制率为90％。选择该干扰片段进行后续实验。干扰组与对照组SW480细胞的G1期细胞数量分别占（62．4±2．7）％和（51．2±3．5）％;S期细胞数量占（23．9±1．7）％和（34．1±3．4）％;氟尿嘧啶所诱导的细胞凋亡率为（11．1±3．7）％和（1．4±0．6）％;上述差异均有统计学意义（P〈0．05）。结论P13K P85α蛋白表达下降可引起结直肠癌SW480细胞周期阻滞,细胞凋亡增加：PI3K P85α可能成为结直肠癌基因治疗的新靶点。     

维生素D受体在糖尿病肾病足细胞损伤及蛋白尿缓解中的作用

目的探讨维生素D受体(VDR)在糖尿病肾病(DKD)足细胞中的表达水平及在足细胞损伤及蛋白尿缓解中的作用。方法(1)本研究纳入了65例诊断患有2型糖尿病(伴或不伴蛋白尿)的患者,并纳入了25例年龄和性别相匹配的健康体检者为对照组。根据白蛋白/肌酐(ACR)的尿排泄比例对2型糖尿病患者进行分组,分别为无蛋白尿(ACR<30 mg/g,n=24)、微量白蛋白尿(ACR 30~300 mg/g,n=18)和临床蛋白尿(ACR>300 mg/g,n=23)。另选择25例经肾活检确诊的DKD患者作为DKD组。正常肾脏组织标本均取自泌尿外科同一时期肾脏肿瘤切除患者10例。将各组检测指标进行对比,同时采用实时定量PCR、ELISA法和免疫组化法检测VDR在各组患者的血液、尿液样本和肾脏组织中的表达情况,以及使用Pearson相关分析分析VDR与尿蛋白的相关性。(2)在2型糖尿病肾病小鼠模型中对上述结果进行验证,将遗传背景均为C57BLKs/J的雄性db/db小鼠及同窝出生的db/m小鼠,随机分为正常对照组(A组)、DKD对照组(B组)、DKD二甲基亚砜处理组(C组)、DKD帕立骨化醇(VDR激动剂)处理组(D组),C、D组连续腹腔注射处理8周,对照组不做任何处理。小鼠10周龄时开始连续干预8周,在小鼠22周龄(开始干预后12周)检测各组小鼠体重、血、尿生化指标对比;Western印迹法检测β⁃catenin、VDR的变化;免疫荧光观察足细胞标志蛋白podocin及足细胞损伤蛋白α⁃SMA的表达变化。结果(1)与正常健康对照组相比,无蛋白尿组、微量白蛋白尿组和临床蛋白尿组的糖尿病患者血浆中VDR的mRNA和蛋白水平均较低(均P<0.05);与无蛋白尿组的糖尿病患者相比,微量白蛋白尿组和临床蛋白尿组的糖尿病患者血浆中VDR的mRNA和蛋白水平均较低(均P<0.05)。(2)与正常健康对照组相比,无蛋白尿糖尿病组和DKD组患者血浆中VDR的mRNA和蛋白水平均较低(均P<0.05);与无蛋白尿糖尿病组患者相比,DKD组患者血浆中VDR的mRNA和蛋白水平亦较低(均P<0.05)。(3)免疫组化结果显示,DKD组肾组织中VDR的表达明显少于正常对照组。(4)DKD患者血浆中VDR mRNA相对水平与ACR呈负相关(r=-0.342,P<0.05)。(5)各组尿液上清液中VDR的水平与血浆中的水平呈相反趋势。(6)Western印迹结果显示,B组、C组肾小球足细胞β⁃catenin蛋白表达高于D组(均P<0.05),VDR蛋白的表达低于D组(均P<0.05);免疫荧光结果显示,B组、C组肾小球足细胞podocin的表达低于D组(均P<0.05),α⁃SMA的表达高于D组(均P<0.05)。结论VDR高表达缓解DKD足细胞损伤及蛋白尿。     

Anterior Interosseous Nerve Palsy After Shoulder Arthroscopy Treated With Surgical Decompression: A Case Series and Systematic Review of the Literature

Background: Anterior interosseous nerve (AIN) palsy is a very uncommon cause of upper extremity pain and weakness that comprises less than 1% of all upper extremity nerve palsies. Rarely reported but also mentioned in the literature is AIN palsy after shoulder arthroscopy. Methods: A systematic review of the literature to date using PubMed was conducted to identify patients who suffered AIN palsy after shoulder arthroscopy procedures. Articles included met the following criteria: (1) published in English; (2) primary presentation of the data; (3) patients had undergone shoulder arthroscopy before developing symptoms of AIN palsy; and (4) diagnosis was confirmed with clinical symptoms of AIN palsy. Measured outcomes included patient demographics, specific shoulder procedure, anesthesia procedure, intra-operative patient positioning, intra-operative compressive dressing, intra-operative traction, surgical versus conservative treatment, abnormal findings during decompression procedure, proposed mechanism of injury, and follow-up. Results: The search yielded 6 articles, of which 4 (13 cases) met inclusion criteria. An additional 2 cases were included in this report totaling 15 cases. The average patient age was 49 years (range: 31-64) with 73% males. At average follow-up of 24 months, 67% of patients experienced complete resolution of symptoms—more than half of which underwent surgical decompression. Patients who failed to progress experienced weakness of the flexor digitorum profundus and flexor pollicis longus muscles. Conclusions: Proposed injury mechanisms for AIN palsy after shoulder arthroscopy range from mechanical trauma, compressive hematoma, and direct anesthetic neurotoxicity. Management should be directed by clinical symptoms, imaging, and patient factors with majority of patients expected to have excellent clinical outcomes.     

不同尿钙水平的Gitelman综合征患者临床特点比较

目的观察不同尿钙水平Gitelman综合征(GS)患者的临床特点,探讨尿钙在GS疾病临床分型中的价值。方法收集2016—2018年来自中国国家罕见病注册系统(NRSC)、在北京协和医院行SLC12A3基因检测诊断为GS患者的临床资料,分析其尿钙特点,比较不同尿钙水平患者的临床和实验室检查指标。氢氯噻嗪试验按照标准操作流程进行,测定患者基线和用药后3 h内氯离子排泄分数改变量的最大值(ΔFECl)。结果共有83例GS患者被纳入研究,其中低尿钙患者53例(63.86%)。低尿钙组尿钙/肌酐比明显低于非低尿钙组[(0.085±0.058)mmol/mmol比(0.471±0.284)mmol/mmol,t=7.349,P<0.001]。两组患者在年龄、性别、估算肾小球滤过率、血压、血尿电解质水平、代谢性碱中毒方面差异均无统计学意义。低尿钙组患者乏力(χ2=4.595,P=0.032)及多尿(χ2=5.778,P=0.016)发生比例低于非低尿钙组,两组患者在其他临床症状方面差异无统计学意义。低尿钙和非低尿钙组各有16例患者行氢氯噻嗪试验,中位ΔFECl结果分别为0.539%(0.430%,1.283%)和0.829%(0.119%,1.298%),均提示对氢氯噻嗪无反应,组间差异无统计学意义(U=130.000,P=0.956)。结论GS患者中低尿钙比例为63.86%,尿钙水平与疾病临床表型、NCC功能损伤严重程度之间均无明确相关性。     

Role of Conventional and Diffusion-Weighted Magnetic Resonance Imaging of Spinal Treatment Protocol for Hydatid Disease

Objective:

To demonstrate the role of magnetic resonance imaging (MRI) in determining the treatment protocol for hydatid disease of the spine.

Design:

Case report; literature review.

Findings:

Diffusion-weighted MRI can help differentiate complicated infected hydatidosis from abscesses, epidermoid cysts from arachnoid cysts, and benign from malignant vertebral compression fractures. It is also helpful in differentiating between abscesses and necrotic tumors.

Conclusion:

Diffusion-weighted MRI can help differentiate between infections requiring immediate surgery and those that can be treated medically with antihelmintic treatment.     

Fibrinogen-thrombin collagen patch reinforcement of highrisk colonic anastomoses in rats

AIM To evaluate the effectiveness of human fibrinogenthrombin collagen patch(TachoSil~?) in the reinforcement of high-risk colon anastomoses.METHODS A quasi-experimental study was conducted in Wistar rats(n = 56) that all underwent high-risk anastomoses(anastomosis with only two sutures) after colectomies. The rats were divided into two randomized groups: Control group(24 rats) and treatment group(24 rats). In the treatment group, high-risk anastomosis was reinforced with TachoSil~? (a piece of Tacho Sil? was applied over this high-risk anastomosis, covering the gap). Leak incidence, overall survival, intra-abdominal adhesions, and histologic healing of anastomoses were analyzed. Survivors were divided into two subgroups and euthanized at 15 and 30 d after intervention in order to analyze the adhesions and histologic changes. RESULTS Overall survival was 71.4% and 57.14% in the TachoSil~? group and control group, respectively(P = 0.29); four rats died from other causes and six rats in the treatment group and 10 in the control group experienced colonic leakage(P 0.05). The intra-abdominal adhesion score was similar in both groups, with no differences between subgroups. We found non-significant differences in the healing process according to the histologic score used in both groups(P = 0.066).CONCLUSION In our study, the use of TachoSil~? was associated with a non-statistically significant reduction in the rate of leakage in high-risk anastomoses. TachoSil~? has been shown to be a safe product because it does not affect the histologic healing process or increase intra-abdominal adhesions.     

罗伊适应模式对腹股沟疝无张力疝修补术后恢复情况的影响

目的探讨罗伊适应模式对患者腹股沟疝无张力疝修补术后恢复情况的影响。 方法将2016年1月至2019年5月在秦皇岛市第二医院择期进行无张力修补术治疗的120例腹股沟疝患者，按照随机数字法分为对照组和观察组，每组各60例。对照组采用常规护理治疗，观察组在对照组的基础上采用罗伊适应模式。比较2组患者的术后临床指标、心理状态、围手术期并发症发生情况及满意度。 结果术后观察组患者的首次排气时间、恢复正常饮食时间、离床活动时间和术后住院时间均低于对照组（P<0.05）；术后观察组患者的抑郁自评量表（SDS）和焦虑自评量表（SAS）评分显著低于对照组（P<0.05）；术后2组患者均无切口感染发生，2组患者尿潴留、急性疼痛、认知功能障碍、发热、血肿等发生率相比无统计学差异（P>0.05）；术后观察组患者护理满意度为96.67%，显著高于对照组的83.33%（P<0.05）。 结论在常规护理的基础上，罗伊适应模式用于患者腹股沟疝无张力修补围手术期，能有效改善术后患者的焦虑/抑郁情绪，不增加围手术期并发症，促进术后患者的恢复及提高治疗满意度。     

Safety and tolerability of single intravenous doses of sugammadex administered simultaneously with rocuronium or vecuronium in healthy volunteers

BACKGROUND: Sugammadex rapidly reverses rocuronium- and vecuronium-induced neuromuscular block. To investigate the effect of combination of sugammadex and rocuronium or vecuronium on QT interval, it would be preferable to avoid the interference of anaesthesia. Therefore, this pilot study was performed to investigate the safety, tolerability, and plasma pharmacokinetics of single i.v. doses of sugammadex administered simultaneously with rocuronium or vecuronium to anaesthetized and non-anaesthetized healthy volunteers. METHODS: In this phase I study, 12 subjects were anaesthetized with propofol/remifentanil and received sugammadex 16, 20, or 32 mg kg(-1) combined with rocuronium 1.2 mg kg(-1) or vecuronium 0.1 mg kg(-1); four subjects were not anaesthetized and received sugammadex 32 mg kg(-1) with rocuronium 1.2 mg kg(-1) or vecuronium 0.1 mg kg(-1) (n=2 per treatment). Neuromuscular function was assessed by TOF-Watch SX monitoring in anaesthetized subjects and by clinical tests in non-anaesthetized volunteers. Sugammadex, rocuronium, and vecuronium plasma concentrations were measured at several time points. RESULTS: No serious adverse events (AEs) were reported. Fourteen subjects reported 23 AEs after study drug administration. Episodes of mild headache, tiredness, cold feeling (application site), dry mouth, oral discomfort, nausea, increased aspartate aminotransferase and gamma-glutamyltransferase levels, and moderate injection site irritation were considered as possibly related to the study drug. The ECG and vital signs showed no clinically relevant changes. Rocuronium/vecuronium plasma concentrations declined faster than those of sugammadex. CONCLUSIONS: Single-dose administration of sugammadex 16, 20, or 32 mg kg(-1) in combination with rocuronium 1.2 mg kg(-1) or vecuronium 0.1 mg kg(-1) was well tolerated with no clinical evidence of residual neuromuscular block, confirming that these combinations can safely be administered simultaneously to non-anaesthetized subjects. Rocuronium and vecuronium plasma concentrations decreased faster than those of sugammadex, reducing the theoretical risk of neuromuscular block developing over time.     

血浆凝血因子VIII水平与IgA肾病患者临床病理改变及预后的关系

目的探讨血浆凝血因子VIII(factor VIII,FVIII)水平与IgA肾病(IgAN)患者临床参数及预后的关系。方法收集2016年1月至2016年12月中南大学湘雅二医院确诊的IgAN患者的临床资料。按照时间依赖的受试者工作特征曲线(ROC)得出的血浆FVIII预测IgAN预后的临界值,将患者分为高FVIII组(FVIII>140.50%)和低FVIII组(FVIII≤140.50%),比较两组患者肾活检时基线临床参数的差异。以估算肾小球滤过率(eGFR)下降≥30%或进入终末期肾脏病(ESRD)为终点事件,采用Kaplan-Meier生存曲线及Cox回归方程法分析血浆FVIII水平对IgAN患者预后的影响。结果共93例IgAN患者纳入本研究,中位随访时间为35.15(33.77,36.76)个月,12例(12.90%)患者发生终点事件。高FVIII组患者年龄、血肌酐、尿素氮、血三酰甘油、血总胆固醇、血浆纤维蛋白原、D-二聚体、24 h尿蛋白量、蛋白C、蛋白S和eGFR下降速率高于低FVIII组(均P<0.05);eGFR、血白蛋白、中位随访时间低于低FVIII组(均P<0.05)。Kaplan-Meier生存分析结果显示,与低FVIII组比较,高FVIII组患者肾脏累积生存率降低(χ2=5.635,P=0.018)。在校正收缩压、eGFR、尿蛋白、肾小管萎缩/间质纤维化程度等因素后,多因素Cox回归分析结果显示,高血浆FVIII水平是IgAN患者肾脏预后不良的独立危险因素(HR=4.147,95%CI 1.055~16.308,P=0.042)。结论血浆FVIII水平与IgAN患者临床指标及预后相关,高血浆FVIII水平是IgAN患者肾脏预后不良的独立危险因素。     

Factors Associated With Reoperation After Silicone Proximal Interphalangeal Joint Arthroplasty

Background: Silicone proximal interphalangeal (PIP) joint arthroplasty has a high revision rate. It has been suggested that persistent ulnar deviation and joint instability influence the durability of PIP silicone arthroplasties. The goal of this study was to evaluate what factors are associated with reoperation after silicone PIP arthroplasty. Methods: We retrospectively evaluated all adult patients who underwent PIP silicone arthroplasty between 2002 and 2016 at one institutional system for inflammatory-, posttraumatic-, and primary degenerative arthritis. After manual chart review, we included 91 patients who underwent 114 arthroplasties. Fingers operated included 14 index, 41 middle, 38 ring, and 21 small fingers. Results: The overall reoperation rate was 14% (n = 16). Non-Caucasian race (P = .040), smoking (P = .022) and PIP silicone arthroplasty for post-traumatic osteoarthritis (P = .021) were associated with reoperation. The 1-, 5- and 10-year implant survival rates were 87%, 85%, and 85%, respectively. Conclusion: Caution should be exercised when considering PIP silicone arthroplasty of the index finger or in patients with post-traumatic osteoarthritis. It may be worthwhile addressing smoking behavior before pursuing silicone PIP arthroplasty.     

Effect of the implementation of NICE guidelines for ultrasound guidance on the complication rates associated with central venous catheter placement in patients presenting for routine surgery in a tertiary referral centre

BACKGROUND: The National Institute for Clinical Excellence (NICE) guidelines of 2002 recommended the use of ultrasound (US) for central venous catheterization in order to minimize complications associated with central line placement. An ongoing audit of line placement by anaesthetists in the theatre complex of a tertiary referral centre looked at the associated complication rates. The objective of the study was to compare complication rates pre- and post-implementation of NICE guidelines. METHODS: This prospective, single centre audit looked at all patients in whom a central venous catheter was placed for surgery. Complication rates were assessed for procedures that were performed pre- and post-implementation of NICE guidelines. In total, 438 patients were identified for the study, and the procedures were performed either by trainee or by consultant anaesthetists. RESULTS: The pre- and post-implementation complication rates were 10.5% (16/152) and 4.6% (13/284), respectively, representing an absolute risk reduction of 5.9% (95% CI 0.5-11.3%). Comparison of those procedures in which US was used when compared with the landmark technique after implementation found a reduction of 6.9% in complications (95% CI 1.4-12.4%). The reduction in complication rates was larger for specialist registrars than for consultants (11.2% vs 1.6%). CONCLUSIONS: The implementation of NICE guidelines has been associated with a significant reduction in complication rates in our tertiary referral centre. In the light of the cross-speciality evidence of US superiority and our results, it is imperative that routine use of US guidance becomes more widespread.