合并高同型半胱氨酸血症颈动脉狭窄患者的临床特征及预后分析

目的 探讨合并高同型半胱氨酸血症的颈动脉狭窄患者的临床特征及预后情况。方法 收集2017年1月至2021年12月北京大学人民医院收治的106例颈动脉狭窄患者的临床资料,根据血清同型半胱氨酸水平不同将其分为试验组（n=48,血清同型半胱氨酸水平﹥15μmol/L）和对照组（n=58,血清同型半胱氨酸水平为5～15μmol/L）。分析两组患者发生颈动脉狭窄的影响因素,比较两组患者入院时的超声、超声造影、颈动脉计算机断层扫描血管成像（CTA）检查情况,观察两组患者的干预措施,分析两组患者的预后情况。结果 单因素分析结果显示,两组患者年龄、吸烟史、冠心病、脑梗死病史、慢性肾脏疾病、椎动脉狭窄比较,差异均有统计学意义（P﹤0.05）。两组患者颈动脉狭窄的累及范围及临床表现比较,差异均无统计学意义（P﹥0.05）。试验组患者重度狭窄发生率最高为73.6%,对照组患者重度狭窄发生率最高为55.3%,两组患者狭窄程度比较,差异均有统计学意义（P﹤0.05）。两组患者颈总动脉内中膜厚度、颈内动脉内中膜厚度、斑块厚度比较,差异均有统计学意义（P﹤0.05）。两组患者颈动脉斑块超声表现、CT表现、斑块性质比...     

血清淀粉样蛋白A与2型糖尿病肾病患者颈动脉内膜中层厚度的相关性研究

目的 探讨血清淀粉样蛋白A （SAA）在2型糖尿病肾病（DN）的改变及与颈动脉内膜中层厚度（CIMT）的相关性.方法 根据24h尿微量白蛋白排泄率（UAER）将75例2型糖尿病患者分为2组：单纯糖尿病组（SDM组,39例）和早期糖尿病肾病组（EDA组,36例）,同时以35例健康人作为正常对照组（NC组）.用ELISA法检测各组空腹血清SAA浓度,同时测定各组的肌酐（Cr）、尿素氮（BUN）、血糖血脂、胰岛素抵抗指数（HOMA-IR）、超敏C反应蛋白（Hs-CRP）、CIMT等指标,并分析血清SAA与CIMT及其他指标的相关性.结果 EDA组和SDM组SAA水平明显高于NC组[分别为（7.98±0.63 vs.6.09 ±0.72vs.2.75 ±0.30 mg/L）,P＜0.05或P＜0.01];EDA组、SDM组和NC组CIMT值组间比较均有统计学差异[分别为（1.07±0.13vs.0.86 ±0.22 vs.0.72±0.13mm）,P＜0.05或P＜0.01].SAA水平与Hs-CRP、IL-6、FBG、HOMA-IR、CIMT、颈动脉斑块数量和UAER成明显正相关,与HDL-C成明显负相关（P＜0.05或P ＜0.01）.EDN组双侧斑块数量≥2个的患者SAA水平显著高于斑块只有1个或无斑块的患者（P＜0.01）,与斑块厚度呈正相关（r=0.409,P ＜0.05）.UAER、HOMA-IR、CIMT和Hs-CRP是影响DN患者SAA水平的独立影响因素.结论 联合检测SAA和CIMT可推断SAA对动脉粥样硬化的影响,全面的评价早期糖尿病肾损害,提示临床应早期干预血浆SAA水平防治DN及其他微血管和大血管病变.     

急性脑梗死患者CRP、UA与颈动脉斑块的相关性分析

目的探讨脑梗死患者CRP、UA与颈动脉斑块的相关性。方法选择84例2013年1月-2014年1月期间住院的急性脑梗死患者。所有患者均行颈动脉彩超检查及血清CRP、UA检查。结果有斑块组CRP、UA水平高于无斑块组,两组比较有统计学差异（P〈0.05）。不稳定斑块组CRP、UA水平高于稳定斑块组,两者有统计学差异（P〈0.05）。结论血清CRP、UA是脑梗死颈动脉粥样硬化斑块发生发展的危险因素。     

糖尿病肾病患者血清瘦素浓度与血管钙化的关系

目的：观察糖尿病肾病（DN）患者血清瘦素浓度水平与血管钙化的关系。方法：收集我院40例DN患者的临床资料,检测血清瘦素浓度水平及对患者进行颈总动脉B超检查。40例糖尿病患者为对照组。结果：DN患者血清瘦素浓度水平较对照组明显升高（P〈0.01）,有血管钙化的DN患者瘦素水平明显高于无钙化者（P〈0.01）。相关性分析显示血清瘦素浓度水平与C-反应蛋白（r=0.405,P〈0.01）,血清磷（r=0.372,P〈0.05）及血肌酐水平（r=0.328,P〈0.01）呈正相关,而与血浆白蛋白（r=-0.386,P〈0.05）呈负相关。结论：有颈总动脉钙化的DN患者血清瘦素浓度水平明显升高,高瘦素水平可能参与DN患者血管钙化的发生发展。     

维持性血液透析患者血清胱抑素C与细胞因子及颈动脉病变的关系

目的 研究维持性血液透析（MHD）患者的血清胱抑素C（半胱氨酸蛋白酶抑制剂,CysC）水平的变化及其与细胞因子及颈动脉病变的关系。 方法 选择透析龄超过6个月的MHD患者110例（MHD组）和健康对照组60例为对象。用免疫透射比浊法检测CysC;超声检查颈动脉病变的程度;检测高敏C反应蛋白（hsCRP）、总同型半胱氨酸（tHcy）、血清白介素1β（IL-1β）、IL-6、肿瘤坏死因子α（TNF-α）水平。分析CysC水平与细胞因子及颈动脉病变的关系。 结果 MHD组血清CysC水平为（6.19±0.95） mg/L,显著高于健康对照组的（0.76±0.21） mg/L（P < 0.01）。MHD组hsCRP、tHcy、IL-1β、IL-6、TNF-α水平均显著高于健康对照组（P < 0.05或<0.01）。MHD组患者颈动脉内膜中层厚度（IMT）及斑块形成、颈动脉硬化的患病率均显著高于健康对照组（P < 0.05或P < 0.01）。直线相关分析显示,MHD组血CysC水平与hsCRP、tHcy、IL-1β、IL-6、TNF-α、IMT及斑块形成、颈动脉硬化的患病率呈正相关;与透析龄、收缩压、iPTH亦呈正相关（P < 0.05或P < 0.01）。多因素逐步回归分析显示,CysC、hsCRP、tHcy和年龄是MHD患者颈动脉病变的危险因素。 结论 血液透析不能有效清除CysC等大分子物质,随着透析龄的增加,MHD患者血清CysC水平逐渐升高。CysC与hsCRP等微炎性反应指标及tHcy、颈动脉病变呈正相关,血清CysC水平升高可能是MHD患者并发动脉粥样硬化的危险因素之一。     

非创伤性股骨头坏死血清视黄醇结合蛋白-4的意义

[目的]探讨视黄醇结合蛋白-4 (retinol binding protein-4, RBP4)在非创伤性股骨头坏死（nontraumatic necrosis of femoral head, NONFH）中的诊断价值。[方法]选取2021年8月—2021年12月在临沂市人民医院就诊的NONFH患者70例作为坏死组,选取同期年龄、性别与坏死组相匹配的62例健康体检者作为正常人组,采用酶联免疫吸附法检测两组受试者血清RBP4浓度水平。比较两组间一般资料,坏死组按不同因素（病因、ARCO分期等）比较血清RBP4浓度水平,并绘制检测ROC曲线,分析血清RBP4对NONFH的诊断价值。[结果]坏死组血清RBP4水平显著低于正常人组（P<0.05）。坏死组中,股骨头塌陷患者血清RBP4水平显著低于未塌陷患者（P<0.05）,双侧坏死患者的RBP4水平显著低于单侧坏死（P<0.05）;不同ARCO分期的患者血清RBP4水平比较,差异有统计学意义（P<0.05）,随着分期的加重,血清RBP4水平显著降低（P<0.05）。相关分析方面,血清RBP4水平与VAS评分、A...     

高寒地区高血压患者血清25羟维生素D3水平与颈动脉狭窄程度相关性研究

目的探讨高寒地区高血压患者颈动脉狭窄程度与血清25羟维生素D_3相关性。方法对230例长期生活在呼伦贝尔地区的原发性高血压患者行颈动脉彩色多普勒超声检查,分为正常组63例、斑块组136例和狭窄组31例,应用半定量积分判断颈动脉狭窄程度。测定血清25羟维生素D_3水平,按照25羟维生素D_3四分位数分为:Q1组(7.47 ng/m L)58例,Q2(7.47~13.78)ng/m L 57例,Q3组(13.79~21.04)ng/m L 57例,Q4组(21.04 ng/m L)58例。结果正常组与斑块组、狭窄组25羟维生素D_3比较,差异具有统计学意义[(23.77±12.23)vs(13.77±8.92),P=0.000**]、[(23.77±12.23)vs(9.18±9.79),P=0.000**],斑块组与狭窄组比较,差异同样具有统计学意义[(13.77±8.92)vs(9.18±9.79),P=0.012*];Q1组、Q2组、Q3组与Q4组颈动脉斑块积分比较,差异有统计学意义(P0.05,P0.01)。血清25羟维生素D_3与颈动脉斑块积分呈负相关(r=-0.396,P=0.000)。多元logistic回归分析显示,血清25羟维生素D_3是高寒地区高血压患者颈动脉斑块、狭窄独立保护因素(P0.05,P0.01)。结论低水平25羟维生素D_3与高寒地区高血压患者颈动脉狭窄程度相关。     

糖尿病对慢性肾脏病患者血清RBP4水平的影响和临床意义

目的：探讨糖尿病对CKD患者血清RBP4水平的影响和临床意义。方法：选取212例CKD1～5期患者及健康体检者24例,采用ELISA方法检测血清RBP4及甲状腺转运蛋白（TTR）的水平。结果：糖尿病对CKD患者血清RBP4水平影响的研究结果显示：CKD合并糖尿病组以及CKD不伴糖尿病组间eGFR、RBP4、RBP4/TTR水平差异无统计学意义;根据eGFR对患者进行分层研究,发现各组内糖尿病组与非糖尿病组的RBP4水平差异无统计学意义（CKD1～4,P＆gt;0.05）。而随着eGFR的下降,无论在糖尿病或非糖尿病患者中RBP4水平均明显升高。结论：随着eGFR的下降血清RBP4逐步升高,而RBP4水平与糖尿病之间差异无统计学意义相关。     

非酒精性脂肪肝患者血清视黄醇结合蛋白4的变化及意义

目的研究非酒精性脂肪肝患者血清视黄醇结合蛋白4（RBP4）的变化及其与胰岛素抵抗（IR）的关系。方法采用ELISA法测定26例健康对照者及34例非酒精性脂肪肝患者血清RBP4水平。结果非酒精性脂肪肝患者血清RBP4水平[（25．6±11．2）mg／L]较健康对照者[（18．5±9．7）mg／L]明显升高,差异有统计学意义（P〈0．01）。相关分析显示RBP4与腰围、腰臀比、体重指数、总胆固醇、三酰甘油、空腹血糖、空腹血清胰岛素、稳态模型评估法胰岛素抵抗指数（HOMA-IR）有显著相关性（r=0．457、0．361、0．387、0．259、0．366、0．342、0．338、0．379,P〈0．01）。结论非酒精性脂肪肝患者血清RBP4水平升高,且与HOMA—IR呈正相关,提示RBP4在IR的发展中可能起一定的作用。     

尿毒症患者血清脂联素与慢性炎症状态的临床意义研究

目的：通过检测尿毒症患者血清脂联素与体内炎症指标的水平,分析血清脂联素与体内炎症反应的关系,探讨血清脂联素对心血管疾病影响的机制。方法：在本实验中,采用ELISA方法测定60例尿毒症患者的血清脂联素（adiponectin,ADPN）水平,炎症指标血C-反应蛋白（C-reactive protein,CRP）,肿瘤坏死因子（tumor necrosis factor,TNF-α）,纤维蛋白原（fibrinogen,Fbg）,并分析血清脂联素与炎症指标、颈动脉斑块的关系。结果：在所有研究对象中有46.7%的患者CRP水平超过正常参考值5 mg/L。在实验组中血ADPN、TNF-α、Fbg均高于健康对照组（P值均〈0.05）并且单因素相关分析结果表明血ADPN与CRP、TNF-α、Fbg均呈明显负相关,相关系数分别为-0.49、-0.51、-0.43（P值均〈0.01）。有颈动脉粥样斑块患者血清显著降低（11.23±4.92）μg/ml与无颈动脉粥样斑块患者血清ADPN（15.71±4.68）μg/ml相比差异有统计学意义（P〈0.01）。结论：在尿毒症患者中,血清脂联素水平与体内炎症反应密切相关,脂联素可能是一种负性炎症因子并具有心血管系统的保护作用。     

Peripancreatic vascular involvement in patients with type 1 autoimmune pancreatitis

BackgroundType 1 autoimmune pancreatitis (AIP) is the pancreatic manifestation of IgG4-related disease. However, this benign disease can result in the peripancreatic vascular involvement (PVI) on occasion, which increases the difficulty of diagnosis and treatment of this clinical entity as well as for differentiating it from pancreatic malignancies.MethodsWe retrospectively reviewed the information on demographics, clinical presentation, laboratory, imaging and endoscopic findings of 101 hospitalized patients with type 1 AIP treated in our department. All the patients were divided into non-PVI and PVI groups according to the first hospitalized medical data. Univariate and multivariate analyses were performed to analyse the potential predictive parameter(s) of PVI in AIP patients.ResultsAmong the 101 type 1 AIP patients, 52 (51.5%) exhibited PVI, with a male/female ratio 5.5:1. Their average age was 58.37±8.68 years old. Univariate analysis revealed that the location of pancreatitis lesions, including the pancreatic tail (P=0.010), the presence of splenomegaly (P=0.001) and the white blood cell (WBC) number in peripheral blood (P=0.020), were significantly associated with PVI. The location of pancreatitis lesions, including the pancreatic tail (P=0.023), and the presence of splenomegaly (P=0.010) were found to be independent predictors of the development of PVI by a multivariable regression analysis. A total of 18 out of 25 patients in PVI group who underwent corticosteroid treatment and no less than 6 months radiological follow-up showed improvement in vascular lesions, and no case exhibited exacerbation of PVI lesions during follow-up. Of 36 patients in non-PVI group who were followed up for no less than 6 months, only one case exhibited PVI.ConclusionsThis retrospective study demonstrated that type 1 AIP was associated with a high proportion of PVI. Pancreatic tail involvement and splenomegaly may predict the PVI in type 1 AIP. PVI lesions are reversible in a subset of patients.     

Further study of anti-ICOS immunotherapy for rat cardiac allograft rejection

PURPOSE: To study the effect of B7-CD28 costimulatory signal blockade by adenovirus-mediated cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin (AdCTLA-4Ig) on cardiac allograft survival in DA (RT1(a)) to LEW (Lewis RT1(l)) rat combinations. METHODS: We evaluated the effect of combined AdCTLA-4Ig and anti-inducible costimulator (ICOS) antibody immunotherapy on rat cardiac allograft acceptance. RESULTS: Unlike AdCTLA-4Ig alone, anti-ICOS immunotherapy combined with AdCTLA-4Ig induced stable tolerance without causing chronic rejection. The combined immunotherapy also prevented the accelerated cardiac rejection caused by donor-type test skin grafting. Immunohistochemical analyses revealed remarkable inflammatory mononuclear cell infiltration with typical vasculopathy, especially ICOS-positive cells in the grafts, in recipients treated with AdCTLA-4Ig alone. In contrast, anti-ICOS therapy combined with AdCTLA-4Ig reduced the ICOS-positive inflammatory cell infiltration of the graft significantly. The most important finding is that possible cardiac arrest caused by secondary donor-type skin graft was prevented by combined immunotherapy of AdCTLA-4Ig and anti-ICOS antibody, despite skin graft rejection. CONCLUSIONS: Our results identified a major role played by the ICOS-ICOSL pathway in chronic and accelerated cardiac allograft rejection, providing a novel approach to preventing the chronic rejection of vascularized organ allografts.     

Tracking chondrocytes and assessing their proliferation with PKH26: effects on secretion of proteoglycan 4 (PRG4).

Distinguishing between implanted and host-derived cells, as well as between distinct cell phenotypes, would be useful in assessing the mechanisms of cell-based repair of cartilage. The fluorescent tracker dye, PKH26, was previously applied to several cell types to assess proliferation in vitro and to track cells in vivo. The objectives of this study were to assess the utility of PKH26 for tracking chondrocytes from superficial and middle zones and their proliferation, and determine the effects of PKH26 on chondrocyte functions, in particular, proliferation and secretion of Proteoglycan 4 (PRG4). PKH26-labeled and unlabeled superficial and middle zone chondrocytes were plated in either low- or high-density monolayer culture and analyzed for retention of PKH26 by flow cytometry and fluorescence microscopy at days 0 and 7. Cell suspensions and conditioned media were analyzed for DNA and secretion of PRG4, respectively. Flow cytometric histograms were deconvolved so that the number of cells in each doubling generation contributing to the final cell population could be estimated. Chondrocytes were consistently and intensely labeled with PKH26 through 7 cycles of division. At day 7 of culture, >97% of superficial zone cells seeded at low or high density could be distinguished as fluorescent, as could middle zone cells seeded at high density. Retention of cell fluorescence after PKH26 labeling and lack of adverse effects on cell proliferation and synthesis of PRG4 suggest that PKH26 can be useful in determining the fate and function of implanted chondrocytes in vivo, as well as monitoring proliferation in vitro.     

KPNA4在胰腺癌中高表达并且与不良预后相关

目的 分析KPNA4在胰腺癌中的临床意义和潜在作用机制。方法 联合TCGA、GTEx和GEO数据库评估KPNA4在肿瘤和正常组织中的表达水平,收集临床样本通过免疫组化进一步验证。通过Cox分析和生存分析评估KPNA4对胰腺癌患者预后的影响,生物信息学分析用于预测KPNA4的相关功能和潜在机制。结果 生物信息学分析和免疫组化结果显示KPNA4的mRNA和蛋白表达水平在胰腺癌组织中均上调(P<0.05),相关性分析显示其mRNA表达水平与肿瘤大小(r=0.261,P<0.001)和淋巴结转移(r=0.193,P<0.05)正相关。生存分析显示KPNA4的mRNA高表达组患者的生存时间短于低表达组(P<0.001)。Cox多因素分析显示KPNA4是胰腺癌患者预后的独立危险因素(95%CI 1.132～2.808,P<0.05)。富集分析显示KPNA4参与了TGF-β信号通路、细胞外基质受体相互作用等多种肿瘤相关的生物学过程。结论 KPNA4在胰腺癌中异常上调,与患者的肿瘤大小和淋巴结转移呈正相关,并且预示着不良预后。KPNA4可能是胰腺癌诊断和治疗的潜在生物标记...     

重组人骨形态发生蛋白4基因腺相关病毒载体对兔骨髓基质干细胞生物学行为的影响

目的应用重组人骨形态发生蛋白4基因腺相关病毒载体(AAV-hBMP4)转染兔骨髓基质干细胞(BMSCs),观察其对BMSCs生物学行为的影响,从而为骨组织工程寻找理想的病毒载体及种子细胞。方法全骨髓法培养兔BMSCs,按感染复数(MOI)值不同设定为四组,分别转染兔BMSCs,观察病毒量对细胞形态的影响。选取影响最小的MOI值,进行后续实验。转染兔BMSCs,MTT法描记细胞生长曲线,观察AAV对细胞增殖活性的影响。以重组增强型绿色荧光蛋白基因的腺相关病毒载体(AAV-EGFP)为参照,行流式细胞仪检测,计算转染效率。AAV-hBMP4与对照病毒AAV-EGFP分别转染细胞,观察细胞形态,行碱性磷酸酶(ALP)染色、Von Kossa染色及ALP含量测定,观察成骨活性。兔肌袋实验观察异位成骨情况。结果MOI值为5×10~4 vg/cell时,AAV对细胞形态影响最小,以此值进行后续实验。AAV转染后,细胞增殖活性良好,转染效率为55％～65％。AAV-hBMP4转染后,细胞形态呈现典型的成骨改变,ALP染色及Von Kossa染色均出现成骨的特征性改变,而AAV-EGFP组无上述改变。细胞上清ALP含量测定显示,实验组ALP含量显著增高,与对照组比较差异有统计学意义(t=218．65,P＜0．01)。兔肌袋实验术后4周组织学检测可见大量钙盐沉积,矿化结节形成。结论AAV-hBMP4转染效率高,对BMSCs的增殖活性影响小,AAV-hBMP4转染的BMSCs可望成为组织工程化骨的理想种子细胞。     

The Role of Oxidative Stress in Aseptic Loosening of Total Hip Arthroplasties

This study investigated the hypothesis that wear particle-induced oxidative stress initiates osteolysis after total hip arthroplasty (THA). Patient radiographs were scored for osteolysis and periprosthetic tissues were immunostained and imaged to quantify polyethylene wear, inflammation, and five osteoinflammatory and oxidative stress-responsive factors. These included high mobility group protein-B1 (HMGB1), cyclooxygenase-2 (COX2), inducible nitric oxide synthase (iNOS), 4-hydroxynonenal (4-HNE), and nitrotyrosine (NT). The results show wear debris correlated with inflammation, 4-HNE, NT and HMGB1, whereas inflammation only correlated with NT and HMGB1. Similar to wear debris and inflammation, osteolysis correlated with HMGB1. Additionally, osteolysis correlated with COX2 and 4-HNE, but not iNOS or NT. Understanding the involvement of oxidative stress in wear-induced osteolysis will help identify diagnostic biomarkers and therapeutic targets to prevent osteolysis after THA.     

New insights into necrotizing enterocolitis: From laboratory observation to personalized prevention and treatment

Background/purpose

Necrotizing enterocolitis (NEC) is a devastating disease of prematurity that develops after feeding, often without warning, and results in diffuse intestinal necrosis leading to sepsis and death in many cases. The lack of improvement in overall survival is influenced by nonspecific diagnostic modalities as well as inexact and nonpersonalized treatment strategies.