Thirteen Chinese patients with sporadic Paget’s disease of bone: clinical features, SQSTM1 mutation identification, and functional analysis

To increase awareness of the rarity of Paget's disease of bone (PDB) in the Chinese population, we characterized the clinical manifestations and features of 13 Chinese sporadic PDB patients. The clinical features of our Chinese PDB patients show similarities with cases reported in Western countries. The most common lesion sites were the pelvis, femur, and tibia; the next most common lesion sites were the spine and skull. Most patients had a higher serum alkaline phosphatase (ALP) level. Treatment with bisphosphonates was effective. In addition, we screened for PDB-causing mutations and performed a functional analysis in an attempt to elucidate the molecular pathogenesis of PDB. A total of 216 persons, including 13 sporadic PDB patients, three unaffected relatives of 1 patient, and 200 healthy donors, were recruited. All eight exons and exon-intron boundaries of the SQSTM1 gene were amplified by polymerase chain reaction (PCR) and directly sequenced. We identified a 53-year-old man who harbored a heterozygous T-to-C transversion at position 1250 in exon 8 (1250T?>?C), which resulted in a methionine-to-threonine (ATG?>?ACG) substitution at codon 404 (M404T). The M404T mutant SQSTM1 protein exhibited increased NF-κB activation and drove a significantly increased number of osteoclast-like cells (OLCs) that formed in response to RANKL and an increased number of OLC nuclei. This is the first report of an SQSTM1 genetic mutation that contributes to the pathogenesis of PDB in Chinese patients. These results may partially explain the mechanism by which this SQSTM1 mutation contributes to the pathogenesis of sporadic PDB in Chinese patients.     

Toll-like receptor 4 promotes tubular inflammation in diabetic nephropathy

Inflammation contributes to the tubulointerstitial lesions of diabetic nephropathy. Toll-like receptors (TLRs) modulate immune responses and inflammatory diseases, but their role in diabetic nephropathy is not well understood. In this study, we found increased expression of TLR4 but not of TLR2 in the renal tubules of human kidneys with diabetic nephropathy compared with expression of TLR4 and TLR2 in normal kidney and in kidney disease from other causes. The intensity of tubular TLR4 expression correlated directly with interstitial macrophage infiltration and hemoglobin A1c level and inversely with estimated glomerular filtration rate. The tubules also upregulated the endogenous TLR4 ligand high-mobility group box 1 in diabetic nephropathy. In vitro, high glucose induced TLR4 expression via protein kinase C activation in a time- and dose-dependent manner, resulting in upregulation of IL-6 and chemokine (C-C motif) ligand 2 (CCL-2) expression via IκB/NF-κB activation in human proximal tubular epithelial cells. Silencing of TLR4 with small interfering RNA attenuated high glucose-induced IκB/NF-κB activation, inhibited the downstream synthesis of IL-6 and CCL-2, and impaired the ability of conditioned media from high glucose-treated proximal tubule cells to induce transmigration of mononuclear cells. We observed similar effects using a TLR4-neutralizing antibody. Finally, streptozotocin-induced diabetic and uninephrectomized TLR4-deficient mice had significantly less albuminuria, renal dysfunction, renal cortical NF-κB activation, tubular CCL-2 expression, and interstitial macrophage infiltration than wild-type animals. Taken together, these data suggest that a TLR4-mediated pathway may promote tubulointerstitial inflammation in diabetic nephropathy.     

Application of humanistic care to the reengineering of nursing process at maternity hospital

目的 从流程管理入手,探讨保证护理服务与人文关怀有机融合的有效途径.方法 依据卓越护理流程设计的原则、华生人文关怀理论、患者需求、患者权利,对所有直接服务于患者的护理项目中的人文关怀措施进行个性化设计,对设计后的流程试运行3个月,并在实施过程中不断征求患者的意见,定稿后进行培训和执行.结果 流程再造实施后患者对护理服务11项指标评价及舒适达标、护理质量、安全评价显著优于实施前(均P＜0.01).结论 将人文关怀融入各项护理流程再造中,有利于提高护理服务质量和患者满意度.     

一次性除菌吸氧管的应用效果

目的 观察一次性除菌吸氧管的临床应用效果.方法 将210例吸氧患者随机分为两组,分别使用一次性普通吸氧管和一次性除菌吸氧管给氧,流量2～5 L/min,连续使用24 h.结果 两组患者主诉和细菌培养阳性率比较,差异有统计学意义(均P＜0.01).结论 一次性除菌吸氧管给氧可明显减少患者不适感和细菌感染率,增加用氧安全.     

微孔引流在皮瓣法腋臭切除术预防瘢痕中的作用

目的:探讨微孔引流在皮瓣法腋臭切除术中预防瘢痕发生的作用。方法:76例腋臭患者采用皮瓣法腋臭切除术,去除大汗腺及毛囊后在皮瓣上用尖刀片沿皮纹戳数个长约3mm的微孔进行引流,缝合切口后用弹力绷带包扎压迫手术区敷料。术后第3天及第7天换药,10天拆线并观察皮瓣成活情况,术后3～6月进行随访。结果:76例患者术后均无血肿及感染发生,切口甲级愈合。随访全部患者腋部辛辣汗臭均消失、出汗减少,社交正常。除5例腋窝瘢痕宽约1～3mm外,其余患者瘢痕不明显,皮肤颜色及皮肤质地均正常,腋毛基本消失。结论:微孔引流在保证腋臭手术疗效的同时能显著降低腋部瘢痕的发生。     

彩色多普勒超声检查联合超声弹性成像对初次全髋关节置换术后下肢深静脉血栓形成的分期诊断价值

目的探讨彩色多普勒超声联合超声弹性成像对初次全髋关节置换术后下肢深静脉血栓形成的分期诊断价值。方法筛选32例初次全髋关节置换术后下肢深静脉血栓患者并根据患者症状开始时问将其分为急性期、亚急性期和慢性期血栓组。观察各组血栓的彩色多普勒超声和超声弹性图像特点,通过血栓超声弹性图像评分及血栓应变比值半定量评估不同分期血栓的弹性特征。结果急性期血栓彩色多普勒超声表现为低回声或等回声声影,超声弹性成像以红色为主;亚急性期血栓彩色多普勒超声表现为等回声或稍增强回声声影,超声弹性成像以绿色为主;慢性期血栓彩色多普勒超声表现为强回声声影,超声弹性成像以蓝色为主。慢性血栓组及亚急性血栓组超声弹性图像评分及血栓应变比值高于急性血栓组（P〈0．05）,慢性血栓组超声弹性图像评分及血栓应变比值高于亚急性血栓组（P〈0．05）。结论彩色多普勒超声联合超声弹性成像对初次全髋关节置换术后下肢深静脉血栓形成的分期诊断具有一定的临床意义。     

视网膜母细胞瘤患儿手术后局部化疗的护理配合

目的 探讨15例小儿视网膜母细胞瘤玻璃体手术后行局部化疗的护理配合方法.方法 行眼部玻璃体手术后,给予系统的检查及局部化疗术的护理配合.结果 患儿顺利渡过手术期,复查8例眼内肿瘤缩小,7例眼底出现新生瘤体,行眼球摘除术.结论 熟悉手术及局部化疗术步骤,术前做好充分的准备,术中密切配合,术后细心护理能有效提高治疗效果.     

“一带一路”背景下医学留学生计算机基础教育探讨

以中山大学中山医学院的医学留学生计算机基础教育课程为例,分析医学留学生教育基本情况和信息素养,构建“一带一路”背景下面向国际的数字化医生课程体系,阐述课程总体目标和主要内容以及多元化教学模式在课程中的应用,以期更好地适应国际社会对医学人才的需要。     

新型IKKβ激酶抑制剂的体外抗胃癌活性

目的：探究新型EF24类IKKβ激酶抑制剂H18的体外抗胃癌活性。方法：利用分子对接模拟H18与IKKβ的结合模式;利用MTT实验检测H18对胃癌细胞BGC-823抑制生长的作用;集落克隆实验检测H18对BGC-823增殖的影响;利用DAPI染色检测细胞凋亡情况;利用Western blot实验分析H18对胃癌细胞BGC-823的NF-κB信号通路的影响。结果：H18可与IKKβ的变构位点结合;H18对BGC-823细胞72 h IC50为（1.7±0.3）μmol/L;与IKK抑制剂BMS-345541相比,H18明显抑制细胞的增殖,而对凋亡无明显影响;H18可对胃癌细胞NF-κB信号通路产生明显抑制作用。结论：H18具有良好的体外抗胃癌活性,是一种具有研发前景的IKKβ抑制剂。     

2型糖尿病患者血浆同型半胱氨酸与血糖波动的相关性研究

目的探讨2型糖尿病患者血浆同型半胱氨酸（Hcy）与血糖波动之间的相关性。方法选取120例2型糖尿病患者,按本院实验室标准,Hcy水平≥10mmol/L的62例患者纳入高同型半胱氨酸组（HHcy）,Hcy水平＜10mmol/L的58例患者纳入正常同型半胱氨酸组（NHcy）,测定两组患者的血生化指标、胰岛功能,并进行动态血糖监测,比较两组的生化指标、胰岛素指数及血糖波动值。结果HHcy组患者日间血糖平均绝对差、胰岛素抵抗指数、血肌酐、尿微量白蛋白和24h尿蛋白定量均高于NHcy组,差异均有统计学意义（均P＜0.05）;但两组患者平均血糖值、糖化血红蛋白、日间平均血糖波动幅度（MAGE）、胰岛素分泌指数、胰岛素敏感指数、尿素氮和肾小球滤过率（GFR）比较差异均无统计学意义（均P＞0.05）。Pearson相关分析显示Hcy水平与MAGE呈正相关（r=0.548,P＜0.01）,与GFR值呈负相关（r=-0.577,P＜0.01）。结论Hcy水平在一定程度上能反映2型糖尿病患者的肾功能进展以及对胰岛素的敏感性和抵抗程度,并与血糖波动存在一定的相关性,可作为临床上反映血糖波动的一个简便的筛选指标。