糖皮质激素干预后大鼠骨量、骨转换指标、雌激素水平变化及其相互关系

目的探讨糖皮质激素(glucocorticoid,GC)干预后不同时间点大鼠骨量、骨转换指标、雌激素水平的变化及其相互关系。方法取3月龄雌性SD大鼠34只,体质量(208.73±23.94)g,随机分为基线组(n=6)、对照组(n=14)、地塞米松(dexamethasone,DXM)组(n=14)。DXM组皮下注射DXM 0.75 mg/kg,每周2次,连续12周;对照组注射等量生理盐水;基线组大鼠不做处理。基线组于实验前,对照组及DXM组于4、8、12周取大鼠,测量体质量及子宫、肾上腺重量;ELISA法测量血清中Ⅰ型前胶原氨基末端前肽(N-terminal propeptide of type I procollagen,PINP)、Ⅰ型胶原羧基端肽(C-terminal cross-linking telopeptide of type I collagen,β-CTX)及雌激素水平;采用双能X线骨密度仪扫描L1~3椎体及左侧股骨,测量股骨头颈、股骨粗隆、股骨干、股骨全段和L1、L2、L3、L1~3区域的骨密度(bone mineral density,BMD)、骨矿物含量(bone mineral content,BMC)、骨面积(bone area,BA)。对大鼠的体质量、腰椎BMD、股骨BMD、PINP、β-CTX、雌激素水平进行相关性分析。结果各时间点DXM组大鼠体质量及子宫、肾上腺重量均显著低于对照组及基线组(P0.05)。DXM组激素干预后大鼠血清PINP、β-CTX升高,但4、8周时与基线组及对照组比较差异无统计学意义(P0.05),12周时差异有统计学意义(P0.05);大鼠血清雌激素水平下降,各时间点均较基线组及对照组明显降低(P0.05)。各时间点DXM组BMD、BMC、BA均显著低于对照组(P0.05),其中以L2及股骨粗隆部骨量丢失最严重。4周时,L1 BMC、BA及股骨干BA较基线组显著降低(P0.05),而其余部位BMD、BMC、BA在各时间点与基线组比较,差异均无统计学意义(P0.05)。相关分析显示,腰椎及股骨BMD与PINP、β-CTX成负相关(P0.05),与雌激素水平成正相关(P0.05)。结论 GC干预后大鼠腰椎及股骨骨量呈先快速降低、再维持低水平趋势,骨转换指标在激素干预后呈持续上升趋势,血清雌激素水平呈整体下降趋势,体质量、骨转换指标及雌激素水平与骨量密切相关。     

间歇皮下注射人甲状旁腺激素不同片段(hFTH1-34及 hFTH1-84)对去卵巢大鼠股骨及腰椎骨量的影响

目的 比较间歇皮下注射人甲状旁腺激素不同片段（hPTH1-34)及（hPTH1-84)对完整雌性（Non-OVX)大鼠和去卵巢（OVX）大鼠股骨及腰椎1－4骨矿物含量（BMC）和骨密度（BMD）的影响。方法 Wistar雌性大鼠176只，分为hPTH1-34和hPTH1-84两大组（各80只及96只），每大组及各自分4组（每组各20只或24只），分别为：两组安慰剂组（未切卵巢及切卵巢）用安慰剂（PBS）进行皮下注射，每周3次，共2周；两组治疗组（未切卵巢及切卵巢）用hPTH1-34或hPTH1-84，皮下注射，每周3次，共2周。结果 1．卵巢切除术后3个月大鼠股骨及腰椎1－4BMC和BMD明显下降；2．两种片段的甲状旁腺激素（hPTH1-34及pPTH1-84)间歇注射均能使Non-OVX大鼠和OVX大鼠股骨及腰椎1－4BMC和BMD较相应对照组明显升高；且腰椎1－4较股骨的BMC和BMD升高更明显；3．OVX大鼠治疗后股骨与腰椎1－4BMC和BMD的升高率较Non-OVX大鼠更明显；OVX大鼠在治疗后股骨及腰椎骨量能恢复到去卵巢前水平；4．hPTH1-34较hPTH1-84更明显的使完整大鼠和OVX大鼠股骨BMC和BMD升高。结论 间歇皮下注射人甲状旁腺激素对大鼠股骨及腰椎骨量均有增高作用，尤其对腰椎的骨量以及对去卵巢大鼠骨量升高作用更明显；hPTH1-34片段对大鼠股骨骨量的增高作用强于hPTH1-84片段。     

ACEI对去卵巢骨质疏松大鼠激肽释放酶-激肽系统及骨丢失的影响

目的探究血管紧张素转换酶抑制剂(angiotensin-converting enzyme inhibitor,ACEI)卡托普利对去卵巢(OVX)骨质疏松大鼠骨丢失及激肽释放酶-激肽(kallikrein-kinin system,KKS)系统的影响。方法去卵巢法制备绝经骨质疏松大鼠模型,分为OVX组、ACEI组[6 mg/(kg·d)卡托普利]、阳性对照雌激素组[0.05 mg/(kg·d)己烯雌酚],另不去卵巢为Sham组。给药8周后,全自动生化分析仪检测血清钙(Ca)、Ⅰ型前胶原N-端肽(PINP)、碱性磷酸酶(ALP)、骨钙素(OCN)、抗酒石酸酸性磷酸酶(TRAP)及Ⅰ型胶原交联C端肽β序列(β-CTX)水平,微型计算机断层摄影术(micro CT)法检测骨密度及微结构,TRAP法观察骨组织破骨细胞数量,Western blot法检测骨组织中骨形态发生蛋白2(BMP2)、Runt相关转录因子2(Runx2)、组织激肽释放酶(KLK)、缓激肽受体1(B1R)及缓激肽(BK)蛋白表达。结果相较于Sham组,OVX组大鼠骨密度、骨小梁数量及厚度、骨体积分数、SMI、PINP、ALP、OCN水平、BMP2、Runx2蛋白表达均降低(P均0.05),骨小梁分离度、TRAP、β-CTX水平、破骨细胞数量、KLK、B1R及BK蛋白水平均增加(P均0.05)。相较于OVX组,ACEI组、阳性组大鼠骨密度、骨小梁数量及厚度、骨体积分数、SMI、PINP、ALP、OCN水平、BMP2、Runx2蛋白表达均增加,骨小梁分离度、TRAP、β-CTX水平、破骨细胞数量、KLK、B1R及BK蛋白水平降低(P0.05)。结论 ACEI可抑制KKS系统,降低破骨细胞活性减少骨吸收,增强成骨细胞活性增加骨形成,提高骨密度,改善骨微结构,进而改善OVX大鼠骨质疏松症状。     

白茅苷对去卵巢大鼠骨髓间充质干细胞功能和骨量的影响

目的观察白茅苷治疗去卵巢大鼠骨髓间充质干细胞功能和骨量的影响并初步探索可能机制。方法通过双侧去卵巢建立骨质疏松大鼠模型;随后随机分为假手术组(Sham)、去卵巢组(OVX)以及白茅苷组(BMG),每组10只;其中BMG组去卵巢大鼠每天给予白茅苷(20 mg/kg)灌胃治疗;待12周治疗结束后分离培养各组大鼠骨髓间充质干细胞(BMSCs),使用碱性磷酸酶(ALP)和茜素红(ARS)染色并使用蛋白质印迹检测BMP-2、Runx2、OPN、OCN、ALP和Col1蛋白表达;进一步使用Micro-CT和骨生物力学检测观察治疗效果。结果 OVX组大鼠BMSCs向成骨细胞分化后ALP和ARS染色阳性面积以及BMP-2、Runx2、OPN、OCN、ALP和Col1表达较Sham组明显降低(P0.05);而经过BMG治疗,BMG组大鼠BMSCs向成骨细胞分化后ALP和ARS染色阳性面积以及BMP-2、Runx2、OPN、OCN、ALP和Col1表达较OVX组明显增加(P0.05)。OVX组股骨最大载荷和弹性模量、BMD、BV/TV、Tb.N和Tb.Th较Sham组明显降低,而Tb.Sp则明显升高(P0.05)。BMG组左侧股骨最大载荷和弹性模量、BMD、BV/TV、Tb.N和Tb.Th均明显高于OVX组(P0.05),而Tb.Sp明显低于OVX组(P0.05)。结论白茅苷通过促进BMSCs诱导成骨分化来减少去卵巢大鼠骨骨密度、骨量和骨强度下降。     

高脂饮食通过抑制Wnt/β-catenin信号介导对骨质疏松大鼠骨密度和骨修复的负面影响

目的 评估高脂饮食（HFD）对骨质疏松大鼠骨密度（bone mineral density, BMD)及骨修复的影响并探讨可能的机制。方法 将雌性SD大鼠随机分为三组：假手术卵巢切除组（Sham）、手术卵巢切除模型组（OVX）、手术卵巢切除模型+HFD（OVX+HFD）;随后所有大鼠在双侧去卵巢手术或假手术后12周基础上制作双侧股骨干建立骨缺损模型,OVX+HFD组大鼠在股骨上接受HFD干预4周。随后使用影像学、血清学、骨生物力学以及基因水平检测来评估骨修复效果。结果 与Sham组相比,OVX和OVX+HFD组的血清E2、ALP水平均显著降低( P<0.05),而TRAP水平均显著升高(P<0.05);OVX和OVX+HFD组之间有显著差异(P<0.05)。Micro-CT检测显示OVX+HFD组骨修复效果较OVX和Sham组明显降低;定量检测结果显示OVX+HFD组的BMD、Tb.N和Tb.Th显著小于OVX组(P<0.01),而Tb.Sp(P<0.05)在OVX+HFD组中明显大于在OVX组。生物力学显示HFD干预后明显降低了去卵巢大鼠骨缺损部位的机械强度,包括大鼠股骨的极限载荷、刚度、能量吸收和弹性模量(P均<0.05);基因检测表明与OVX组相比,OVX + HFD组Smad2、Smad3和GSK-3βmRNA表达显著增加(P<0.01),而Wnt1和β-cateninmRNA表达均显著降低(P<0.01)。结论 HFD对骨质疏松状态下骨缺损愈合有负面影响,而这种影响可能是通过对Wnt/β-catenin信号传导抑制来实现的。     

大黄酸-雌酮对去卵巢大鼠子宫及骨组织 ERα和 ERβmRNA 表达的影响

目的：研究骨靶向雌激素大黄酸-雌酮（ LC）对去卵巢大鼠骨组织中的ERα和ERβmRNA表达的影响。方法72只6月龄雌性未孕Wistar大鼠，分为6组：假手术组（ Sham）、去卵巢模型组（ OVX）、雌酚酮组（ E，OVX＋雌酚酮1.0 mg/kg· d）、大黄酸-雌酮高（ H-LC， OVX＋LC 1.0 mg/kg· d）、中（ M-LC，OVX＋LC 0.5 mg/kg· d）、低（ L-LC，OVX＋LC 0.25 mg/kg· d）剂量组，除假手术组外其余各组均行双侧卵巢切除。给药24周后，采用放射免疫方法测定血中雌二醇水平，采用RT-PCR法测定子宫及骨组织ERα和ERβmRNA水平。结果与Sham组比较，OVX组雌二醇水平明显降低，与OVX组比较，E组和H-LC、M-LC组大鼠血清雌二醇明显升高，L-LC组与OVX组无明显差别。 Sham组胫骨近端ERαmRNA和ERβmRNA均有表达，OVX组ERβmRNA表达水平与Sham组相比降低，未检出ERαmRNA。 E组ERαmRNA和ERβmRNA水平均与Sham组无差异，大黄酸-雌酮各组均未检出ERαmRNA，ERβmRNA相对表达量高于OVX组，大黄酸-雌酮各剂量组之间ERβmRNA无明显差异。Sham组大鼠子宫组织有ERαmRNA和ERβmRNA表达，OVX组ERαmRNA表达量明显降低，未检出ERβmRNA。 E组大鼠子宫组织ERαmRNA和ERβmRNA均较OVX组上调。大黄酸-雌酮各剂量组之间ERαmRNA无明显差异，但均低于E和Sham组。结论大黄酸-雌酮在骨及子宫均能选择性上调ERβmRNA表达，而对ERαmRNA无影响，雌酚酮对两种亚型无选择性，这可能是大黄酸-雌酮对骨具有保护作用而对子宫并无雌激素样刺激作用的原因之一。     

大黄素治疗对去卵巢大鼠骨量流失的保护作用机制研究

目的探讨大黄素(emodin,DHS)对去卵巢大鼠骨量流失的影响,并探索可能的机制。方法通过双侧去卵巢建立骨质疏松大鼠模型;随后随机分为假手术组(Sham)、去卵巢组(OVX)以及大黄素组(DHS),每组10只;其中DHS组大鼠接受大黄素[90 mg/(kg·d)]治疗12周;待治疗结束后使用Micro-CT、HE染色切片、骨代谢指标、以及蛋白质印迹观察治疗效果以及可能的机制。结果治疗12周后,与OVX组相比,Micro-CT和HE染色切片结果显示DHS组的大鼠骨小梁数量和骨密度得到明显改善。DHS组大鼠BMD、TV/BV、Tb.N、Tb.Th和Tb.Sp较OVX组明显改善(P<0.05)。与OVX组相比,DHS组的BALP水平明显升高(P<0.05);而TRACP-5b和β-CTX水平显著降低(P<0.05)。和OVX组比较,DHS组OPG表达水平上调(P<0.05),而RANKL和β2AR表达水平下调(P<0.05)。结论大黄素可以通过降低β2AR表达和激活OPG/RANKL信号通路介导对去卵巢大鼠骨量流失的保护作用。     

二甲双胍对去卵巢大鼠骨质疏松症的影响及机制研究

目的 以雌二醇为对照,观察二甲双胍(metformin, MF)对去卵巢大鼠骨密度及骨矿含量的影响,并从细胞、分子水平探究MF可能的骨保护机制。方法 将60只雌性SD大鼠随机均分4组：假手术（SHAM）组、去卵巢（OVX）组、去卵巢+二甲双胍（OVX+MF）组和去卵巢+雌二醇(OVX+E2 )组。分组灌胃给药60 d后测量大鼠右侧胫骨骨密度和骨矿含量;分离培养各组大鼠骨髓间充质干细胞（BMSCs）并诱导其向成骨细胞分化,用MTT法测定细胞活性及增殖能力;测定各组碱性磷酸酶（ALP）活性、矿化结节数目、钙含量以及I型胶原（collagen type I）、骨钙素（OC）、骨保护素 (OPG)、NFκB受体的配体 (RANKL)、白细胞介素-6（IL-6）基因表达水平。结果 与OVX组相比,OVX+MF组和OVX+E2组成骨细胞的增殖能力与ALP活性明显增强,骨密度、骨矿含量以及钙沉积量显著增加(P均<0.05),且两组collagen type I、OC、OPG mRNA的表达水平显著升高,而RANKL、IL-6mRNA表达明显受到抑制;但OVX+MF组去卵巢大鼠成骨细胞的增殖能力、ALP活性、钙沉积量、collagen type I、OC、OPG mRNA表达水平低于OVX+E2组,RANKL、IL-6mRNA表达高于OVX+E2组（P均<0.05）;与SHAM组比较,OVX+MF组的collagen type I、OC、OPG mRNA的表达水平更高（P<0.05）。结论 二甲双胍可能通过OPG/RANKL/RANK信号通路促进BMSCs向成骨细胞分化,有效逆转去卵巢大鼠骨质疏松的状态,这种潜在的骨保护作用可能会改善糖尿病引起的骨质疏松。     

选择性雌激素受体调节剂-雷诺昔酚对去势后大鼠骨组织中TNF-α表达的影响

目的 了解选择性雌激素受体调节剂（SERM）对去卵巢大鼠骨组织形态计量学指标、骨密度及松质骨中TNF-α表达的影响.方法 将8月龄未经产雌性二级SD大鼠30只,随机分为假手术（SHAM）组、去势（OVX）组、去势＋雷诺昔酚（OVX＋RAL）组.OVX＋RAL组大鼠术后第2天开始给予雷诺昔酚灌胃.术后20 wk处死各组大鼠,对各组大鼠不同部位骨组织形态计量学指标、骨密度（BMD）进行检测,并利用免疫组织化学染色及图像分析方法对各组大鼠松质骨切片TNF-α表达图像进行分析,观察RAL对OVX大鼠腰椎松质骨中TNF-α表达的影响.结果 （1）与SHAM组相比,OVX组大鼠骨小梁体积、骨小梁平均厚度、皮质骨厚度等骨形态计量学指标明显下降（P＜0.01）,OVX＋RAL组大鼠骨形态计量学指标明显大于OVX组（P＜0.01）,接近SHAM组水平（P＞0.05）;（2）与SHAM组相比,OVX组股骨近端、股骨干、腰椎BMD明显降低（P＜0.01）;RAL治疗组各部位BMD高于OVX组（P＜0.01或P＜0.05）,接近SHAM组水平（P＞0.05）;（3）去势组与SHAM组相比较,TNF-α表达的灰度值明显降低（P＜0.01）;RAL组较OVX组灰度值明显升高（P＜0.01）,经RAL治疗后的去卵巢大鼠骨小梁周围及髓腔内TNF-α阳性表达明显减弱（P＜0.01）,接近SHAM组水平（P＞0.05）;结论 RAL可通过抑制破骨性因子TNF-α表达来抑制因雌激素缺乏引起的骨密度降低及骨形态结构退变.     

促胰液素对去卵巢骨质疏松大鼠血清骨转换指标和骨密度的影响

目的 观察促胰液素(secretin,SCT)对去卵巢骨质疏松大鼠骨转换指标和骨密度的影响。方法 采用双侧卵巢去除法制备绝经后骨质疏松大鼠模型,将60只SD大鼠随机分为假手术组、模型对照组、雌激素治疗组和促胰液素治疗组,每组各15只。干预3个月后,测定腰椎骨密度(bone mineral density,BMD),采取ELISA法测定血清I型胶原N前端肽(procollagen I N-Terminal propeptide,PINP)和I型胶原C末端肽(collagen type I C-terminal cross-linked telopeptide,CTX),另使用STRING10.0蛋白相互作用网络分析工具分析骨质疏松相关差异蛋白。结果 与假手术组比较,模型对照组、雌激素治疗组、促胰液素治疗组的PINP含量升高（P＜0.05）,模型对照组的CTX含量升高（P＜0.05）,模型对照组的BMD下降（P＜0.05）,雌激素治疗组和促胰液素治疗组的CTX、BMD含量无显著差异（P＞0.05）;与模型对照组比较,雌激素治疗组、促胰液素治疗组PINP、CTX含量有所下降,而BMD含量升高（P＜0.05）;雌激素组与促胰液素组之间PINP、CTX、BMD含量无显著差异（P＞0.05）。结论 促胰液素能改善去卵巢骨质疏松大鼠的PINP和CTX含量,增加骨密度,抑制骨质丢失,具有较好的抗骨质疏松效果。     

Presenteeism and Absenteeism Before and After Total Hip and Knee Arthroplasty

BackgroundAbsenteeism is costly, yet evidence suggests that presenteeism—illness-related reduced productivity at work—is costlier. We quantified employed patients’ presenteeism and absenteeism before and after total joint arthroplasty (TJA).MethodsWe measured presenteeism (0-100 scale, 100 full performance) and absenteeism using the World Health Organization’s Health and Work Performance Questionnaire before and after TJA among a convenience sample of employed patients. We captured detailed information about employment and job characteristics and evaluated how and among whom presenteeism and absenteeism improved.ResultsIn total, 636 primary, unilateral TJA patients responded to an enrollment email, confirmed employment, and completed a preoperative survey (mean age: 62.1 years, 55.3% women). Full at-work performance was reported by 19.7%. Among 520 (81.8%) who responded to a 1-year follow-up, 473 (91.0%) were still employed, and 461 (88.7%) had resumed working. Among patients reporting at baseline and 1 year, average at-work performance improved from 80.7 to 89.4. A Wilcoxon signed-rank test indicated that postoperative performance was significantly higher than preoperative performance (P < .0001). The percentage of patients who reported full at-work performance increased from 20.9% to 36.8% (delta = 15.9%, 95% confidence interval = [10.0%, 21.9%], P < .0001). Presenteeism gains were concentrated among patients who reported declining work performance leading up to surgery. Average changes in absences were relatively small. Combined, the average monthly value lost by employers to presenteeism declined from 15.3% to 8.3% and to absenteeism from 16.9% to 15.5% (ie, mitigated loss of 8.4% of monthly value).ConclusionAmong employed patients before TJA, presenteeism and absenteeism were similarly costly. After, employed patients reported increased performance, concentrated among those with declining performance leading up to surgery.     

The German emergency and disaster medicine and management systemdhistory and present

As well for optimized emergency management in individual cases as for optimized mass medicine in disaster management, the principle of the medical doctors approaching the patient directly and timely, even close to the site of the incident, is a long-standing marker for quality of care and patient survival in Germany. Professional rescue and emergency forces, including medical services, are the “Golden Standard” of emergency management systems. Regulative laws, proper organization of resources, equipment, training and adequate delivery of medical measures are key factors in systematic approaches to manage emergencies and disasters alike and thus save lives. During disasters command, communication, coordination and cooperation are essential to cope with extreme situations, even more so in a globalized world. In this article, we describe the major historical milestones, the current state of the German system in emergency and disaster management and its integration into the broader European approach.     

Differences in Osteocyte Density and Bone Histomorphometry Between Men and Women and Between Healthy and Osteoporotic Subjects

Bone defects related to osteoporosis develop with increasing age and differ between males and females. It is currently thought that the bone remodeling process is supervised by osteocytes in a strain-dependent manner. We have shown an altered response of osteocytes from osteoporotic patients to mechanical loading, and osteocyte density is reduced in osteoporotic patients, which might relate to imperfect bone remodeling, leading to lack of bone mass and strength. Hence, information on osteocyte density will contribute to a better understanding of bone biology in males and females and to the assessment of osteoporosis. Osteocyte density as well as conventional histomorphometric parameters of trabecular bone were determined in cancellous iliac crest bone of healthy postmenopausal women and men and of osteoporotic women and men. Osteocyte density was higher in healthy females than in healthy males and lower in osteoporotic females than in healthy females. Bone mass was reduced in osteoporotic patients, both male and female. In females, trabecular number was reduced, whereas in males, trabecular thickness was reduced and eroded surface was increased. There were no correlations between the parameter groups bone architecture, bone formation, bone resorption, and osteocyte density. These results are consistent with impaired osteoblast function in osteoporotic patients and with a different mechanism of bone loss between men and women, in which osteocyte density might play a role. The reduced osteocyte numbers in female osteoporotic patients might relate to imperfect bone remodeling leading to lack of bone mass and strength. M. G. Mullender and S. D. Tan contributed equally to this work.     

肝内胆管囊腺瘤和囊腺癌的CT、MRI及病理表现

目的探讨肝内胆管囊腺瘤和囊腺癌的CT、MRI和病理特点。方法回顾性分析经手术病理证实的6例肝内胆管囊腺瘤和2例肝内胆管囊腺癌的影像及临床病理资料，将病变的影像表现与其病理大体形态及组织学表现作对照分析。结果6例肝内胆管囊腺瘤，女4例、男2例；2例肝内胆管囊腺癌均为女性病人；8例病人平均年龄55岁。所有病灶均表现为多房囊性肿块，肿瘤囊腔各分房内常为多种液体成分，在CT上可表现为不同密度、在MRI上可表现为不同信号强度。囊内出现多发大小不等的壁结节在胆管囊腺癌内更常见，囊内有分隔但无壁结节只见于胆管囊腺瘤。在7例CT扫描中，4例胆管囊腺瘤和1例胆管囊腺癌可见囊壁或分隔上钙化，囊壁、囊内分隔及囊内结节均为轻、中度延迟增强。肿瘤中出现卵巢样间质见于3例胆管囊腺瘤和1例胆管囊腺癌，且均为女性病人。结论肝内胆管囊腺瘤和囊腺癌是肝脏不常见的囊性肿瘤，影像上多房、囊内有分隔且各分房囊内密度或信号不一致，高度提示肝内胆管囊腺瘤或囊腺癌的诊断，如囊内伴有多发大小不等的结节，则进一步提示囊腺癌的可能。但影像学表现不能区分肿瘤中有无卵巢样间质。