简介：摘要目的探讨自噬相关分子Beclin1和LC3在糖尿病足多重耐药金黄色葡萄球菌感染中的作用。方法选取2017年3月至12月间杭州市余杭区第一人民医院收治的金黄色葡萄球菌感染的糖尿病足患者62例为糖尿病足感染组，同期在本院就诊的足部烧伤患者38例为对照组。分离、鉴定金黄色葡萄球菌并进行药敏试验，根据耐药情况将糖尿病足感染组患者进一步分为多重耐药组、非多重耐药组。免疫组化法检测足部创面肉芽组织中Beclin1和LC3表达水平，免疫荧光双染色法检测巨噬细胞中LC3表达水平。结果糖尿病足感染组患者糖化血红蛋白、白细胞计数、红细胞沉降率明显高于对照组，差异有统计学意义(P<0.05)。糖尿病足感染组62例患者中检出多重耐药金黄色葡萄球菌30例(48.39%)；对照组38例患者中检出多重耐药金黄色葡萄球菌2例(5.26%)；糖尿病足感染组多重耐药金黄色葡萄球菌检出率明显高于对照组，差异有统计学意义(P<0.05)。多重耐药组患者白细胞计数、中性粒细胞比率、C反应蛋白水平明显高于非多重耐药组，差异有统计学意义(P<0.05)。免疫组化检测显示，糖尿病足感染组创面肉芽组织中Beclin1、LC3表达水平明显低于对照组，差异有统计学意义(P<0.01)；多重耐药组患者创面肉芽组织中Beclin1、LC3表达水平明显低于非多重耐药组患者，差异有统计学意义(P<0.05)。免疫荧光双染色检测显示，糖尿病足感染组患者创面肉芽组织中LC3、CD14共表达强度明显低于对照组。结论金黄色葡萄球菌感染的糖尿病足患者创面肉芽组织中Beclin1、LC3表达明显下降，且多重耐药金黄色葡萄球菌感染者下降更明显；糖尿病足患者金黄色葡萄球菌多重耐药性的发生与发展可能与自噬水平减弱有关。

简介：摘要目的探讨自噬相关分子Beclin1和LC3在糖尿病足多重耐药金黄色葡萄球菌感染中的作用。方法选取2017年3月至12月间杭州市余杭区第一人民医院收治的金黄色葡萄球菌感染的糖尿病足患者62例为糖尿病足感染组，同期在本院就诊的足部烧伤患者38例为对照组。分离、鉴定金黄色葡萄球菌并进行药敏试验，根据耐药情况将糖尿病足感染组患者进一步分为多重耐药组、非多重耐药组。免疫组化法检测足部创面肉芽组织中Beclin1和LC3表达水平，免疫荧光双染色法检测巨噬细胞中LC3表达水平。结果糖尿病足感染组患者糖化血红蛋白、白细胞计数、红细胞沉降率明显高于对照组，差异有统计学意义(P<0.05)。糖尿病足感染组62例患者中检出多重耐药金黄色葡萄球菌30例(48.39%)；对照组38例患者中检出多重耐药金黄色葡萄球菌2例(5.26%)；糖尿病足感染组多重耐药金黄色葡萄球菌检出率明显高于对照组，差异有统计学意义(P<0.05)。多重耐药组患者白细胞计数、中性粒细胞比率、C反应蛋白水平明显高于非多重耐药组，差异有统计学意义(P<0.05)。免疫组化检测显示，糖尿病足感染组创面肉芽组织中Beclin1、LC3表达水平明显低于对照组，差异有统计学意义(P<0.01)；多重耐药组患者创面肉芽组织中Beclin1、LC3表达水平明显低于非多重耐药组患者，差异有统计学意义(P<0.05)。免疫荧光双染色检测显示，糖尿病足感染组患者创面肉芽组织中LC3、CD14共表达强度明显低于对照组。结论金黄色葡萄球菌感染的糖尿病足患者创面肉芽组织中Beclin1、LC3表达明显下降，且多重耐药金黄色葡萄球菌感染者下降更明显；糖尿病足患者金黄色葡萄球菌多重耐药性的发生与发展可能与自噬水平减弱有关。

简介：摘要目的观察慢性氟中毒大鼠肝脏微管相关蛋白1轻链3（LC3）B、P62、Beclin1的蛋白和mRNA表达，探讨自噬在氟中毒肝损伤发病机制中的作用。方法采用成组设计，54只SD大鼠，按照体重（100 ~ 120 g）采用随机数字表法分为9组，每组6只，雌雄各半，分别为对照组（NC组）、低氟组（LF组）、高氟组（HF组）、NC +雷帕霉素（RAP）组、LF + RAP组、HF + RAP组、NC +氯喹（CQ）组、LF + CQ组、HF + CQ组。NC组饮用自来水（氟离子浓度< 0.5 mg/L），LF和HF组分别饮用氟离子浓度为5.0、50.0 mg/L含氟水；NC + RAP、LF + RAP、HF + RAP组分别以相应的饮水饲养3个月后经腹腔每天注射1.5 mg/kg RAP，共10 d；NC + CQ、LF + CQ、HF + CQ组分别以相应的饮水饲养3个月后经腹腔每天注射60 mg/kg CQ，共10 d。采集各组大鼠四肢骨、24 h尿液，检测骨氟、尿氟含量；苏木素-伊红染色法观察肝组织形态学变化；免疫组织化学法、实时荧光定量PCR法检测肝脏LC3B、P62、Beclin1蛋白和mRNA表达情况。结果染氟后，与NC组比较[（0.03 ± 0.00）mg/kg、（0.34 ± 0.08）mg/L]，HF组骨氟[（3.86 ± 0.08）mg/kg]、尿氟含量[（1.11 ± 0.16）mg/L]均较高（P均< 0.05）。光镜下，NC组大鼠肝组织小叶结构清晰，肝索排列整齐，细胞结构正常，LF、HF组出现不同程度的肝细胞水肿；给予RAP后，与相应染氟组比较，肝细胞形态未见明显变化；给予CQ后，与相应染氟组比较，可见肝细胞明显水肿，随染氟浓度增加水肿程度加重。与NC组比较，HF组LC3B、Beclin1蛋白表达量较高（P均< 0.05），P62蛋白表达量较低（P < 0.05）。腹腔注射RAP后，与LF组比较，LF + RAP组LC3B、P62蛋白表达量较低（P均< 0.05）；与HF组比较，HF + RAP组LC3B、Beclin1蛋白表达量较低（P均< 0.05）。腹腔注射CQ后，与LF组比较，LF + CQ组P62蛋白表达量较高（P < 0.05）；与HF组比较，HF + CQ组P62蛋白表达量较高（P < 0.05）。结论早期（3个月）氟摄入可促进大鼠肝细胞自噬，引起肝细胞水肿，RAP有类似作用；CQ可能通过抑制肝细胞自噬而诱导肝脏损伤。

简介：摘要目的探讨自噬相关基因Beclin-1、LC3和p62在食管鳞状细胞癌（ESCC）中的表达及意义。方法回顾性分析2015年1月至2016年12月解放军陆军第八十一集团军医院接受手术治疗的112例原发性ESCC患者的临床资料。免疫组织化学法检测112例ESCC组织及31例癌旁正常食管黏膜组织中Beclin-1、p62和LC3蛋白的表达情况，分析3种自噬相关标志物在ESCC中的表达及其与患者临床病理特征的关系。结果112例ESCC组织中Beclin-1、LC3和p62阳性表达率分别为32.14%（36/112）、37.50%（42/112）和63.39%（71/112），31例癌旁正常食管黏膜阳性表达率分别为61.29%（19/31）、64.52%（20/31）和32.26%（10/31），差异均有统计学意义（χ2值分别为8.715、7.216、9.584，均P<0.01）。Beclin-1、LC3在ESCC中的阳性表达率均低于癌旁正常食管黏膜，p62在ESCC中的阳性表达率则高于癌旁正常食管黏膜。Beclin-1表达与ESCC患者组织学分级、肿瘤浸润深度、TNM分期、是否存在淋巴结转移均有关（均P<0.05）；LC3表达与ESCC患者肿瘤浸润深度、TNM分期均有关（均P<0.01）；p62表达与ESCC患者是否存在淋巴结转移有关（P<0.01）。在ESCC中，LC3与Beclin-1的表达呈正相关（r＝0.731，P＝0.001），而与p62的表达呈负相关（r＝-0.215，P＝0.023）。结论自噬在ESCC的发生、发展中发挥一定作用，联合检测自噬相关基因Beclin-1、p62和LC3可辅助临床诊断并指导后续综合治疗。

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简介：AbstractBackground:Emerging evidence indicates that the sineoculis homeobox homolog 1-eyes absent homolog 1 (SIX1-EYA1) transcriptional complex significantly contributes to the pathogenesis of multiple cancers by mediating the expression of genes involved in different biological processes, such as cell-cycle progression and metastasis. However, the roles of the SIX1-EYA1 transcriptional complex and its targets in colorectal cancer (CRC) are still being investigated. This study aimed to investigate the roles of SIX1-EYA1 in the pathogenesis of CRC, to screen inhibitors disrupting the SIX1-EYA1 interaction and to evaluate the efficiency of small molecules in the inhibition of CRC cell growth.Methods:Real-time quantitative polymerase chain reaction and western blotting were performed to examine gene and protein levels in CRC cells and clinical tissues (collected from CRC patients who underwent surgery in the Department of Integrated Traditional and Western Medicine, West China Hospital of Sichuan University, between 2016 and 2018, n = 24). In vivo immunoprecipitation and in vitro pulldown assays were carried out to determine SIX1-EYA1 interaction. Cell proliferation, cell survival, and cell invasion were determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, clonogenic assay, and Boyden chamber assay, respectively. The Amplified Luminescent Proximity Homogeneous Assay Screen (AlphaScreen) method was used to obtain small molecules that specifically disrupted SIX1-EYA1 interaction. CRC cells harboring different levels of SIX1/EYA1 were injected into nude mice to establish tumor xenografts, and small molecules were also injected into mice to evaluate their efficiency to inhibit tumor growth.Results:Both SIX1 and EYA1 were overexpressed in CRC cancerous tissues (for SIX1, 7.47 ± 3.54 vs.1.88 ± 0.35, t = 4.92, P = 0.008; for EYA1, 7.61 ± 2.03 vs. 2.22 ± 0.45, t = 6.73, P = 0.005). The SIX1/EYA1 complex could mediate the expression of two important genes including cyclin A1 (CCNA1) and transforming growth factor beta 1 (TGFB1) by binding to the myocyte enhancer factor 3 consensus. Knockdown of both SIX1 and EYA1 could decrease cell proliferation, cell invasion, tumor growth, and in vivo tumor growth (all P < 0.01). Two small molecules, NSC0191 and NSC0933, were obtained using AlphaScreen and they could significantly inhibit the SIX1-EYA1 interaction with a half-maximal inhibitory concentration (IC50) of 12.60 ± 1.15 μmol/L and 83.43 ± 7.24 μmol/L, respectively. Administration of these two compounds could significantly repress the expression of CCNA1 and TGFB1 and inhibit the growth of CRC cells in vitro and in vivo.Conclusions:Overexpression of the SIX1/EYA1 complex transactivated the expression of CCNA1 and TGFB1, causing the pathogenesis of CRC. Pharmacological inhibition of the SIX1-EYA1 interaction with NSC0191 and NSC0933 significantly inhibited CRC cell growth by affecting cell-cycle progression and metastasis.

简介：摘要帕金森病(PD)是世界上第二常见的神经退行性疾病，它的发病机制与线粒体功能障碍、氧化应激反应以及钙稳态失衡有关。近年来，PD与Ca2+的关系成为研究热点，钙稳态失衡可通过不同的途径导致PD。细胞内Ca2+水平取决于钙库操纵性钙内流(SOCE)，而SOCE由钙释放激活钙通道调节分子1(Orai1)、基质相互作用分子1(STIM1)及瞬时受体电位通道1(TRPC1)相互作用组成的功能复合体调节。常见的PD神经毒素可通过降低Orai1-STIM1-TRPC1复合体功能，损伤SOCE及其下游的信号通路选择性损伤多巴胺能神经元，并且Orai1-STIM1-TRPC1复合体可能通过作用于小胶质细胞以及内质网调控神经炎症、自噬现象以影响PD的发生发展。因此恢复Orai1-STIM1-TRPC1复合体表达及功能，维持钙稳态可能成为PD的有效治疗靶点。

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简介：[摘要]目的探讨使用维生素K1患者过敏后的护理措施。方法对2021年01月19日收治的重度妊娠期肝内胆汁淤积症患者使用维生素K1过敏后的护理治疗经验进行总结分析。结论本文旨在探讨肌内注射维生素 K1过敏的治疗及护理方法，提醒医护人员在临床使用中加强对药物不良反应的观察，对此类案例的治疗及护理方法提供借鉴，确保患者用药安全[1]。

简介：AbstractBackground:Macrophages play an important role in renal ischemia reperfusion injury, but the functional changes of macrophages under hypoxia/reoxygenation and the related mechanism are unclear and need to be further clarified.Methods:The effects of hypoxia/reoxygenation on functional characteristics of RAW264.7 macrophages were analyzed through the protein expression detection of pro-inflammatory factors TNF-α and CD80, anti-inflammatory factors ARG-1 and CD206. The functional implications of C-X3-C motif chemokine receptor 1(CX3CR1) down-regulation in hypoxic macrophages were explored using small interfering RNA technology. Significance was assessed by the parametric t-test or nonparametric Mann-Whitney test for two group comparisons, and a one-way ANOVA or the Kruskal-Wallis test for multiple group comparisons.Results:Hypoxia/reoxygenation significantly increased the protein expression of M1-related pro-inflammatory factors TNF-α, CD80 and chemokine C-X3-C motif chemokine ligand 1 (CX3CL1)/CX3CR1 and inhibited the protein expression of M2-related anti-inflammatory factors ARG-1 and CD206 in a time-dependent manner in RAW264.7 cells. However, the silencing of CX3CR1 in RAW264.7 cells using specific CX3CR1-siRNA, significantly attenuated the increase in protein expression of TNF-α (P < 0.05) and CD80 (P < 0.01) and the inhibition of ARG-1 (P < 0.01) and CD206 (P < 0.01) induced by hypoxia/reoxygenation. In addition, we also found that hypoxia/reoxygenation could significantly enhance the migration (2.2-fold, P < 0.01) and adhesion capacity (1.5-fold, P < 0.01) of RAW264.7 macrophages compared with the control group, and CX3CR1-siRNA had an inhibitory role (40% and 20% reduction, respectively). For elucidating the mechanism, we showed that the phosphorylation levels of ERK (P < 0.01) and the p65 subunit of NF-κB (P < 0.01) of the RAW264.7 cells in the hypoxic/reoxygenation group were significantly increased, which could be attenuated by down-regulation of CX3CR1 expression (P < 0.01, both). ERK inhibitors also significantly blocked the effects of hypoxic/reoxygenation on the protein expression of M1-related pro-inflammatory factors TNF-α, CD80 and M2-related anti-inflammatory factors ARG-1 and CD206. Moreover, we found that conditioned medium from polarized M1 macrophages induced by hypoxia/reoxygenation, notably increased the degree of apoptosis of hypoxia/reoxygenation-induced TCMK-1 cells, and promoted the protein expression of pro-apoptotic proteins bax (P < 0.01) and cleaved-caspase 3 (P < 0.01) and inhibited the expression of anti-apoptotic protein bcl-2 (P < 0.01), but silencing CX3CR1 in macrophages had a protective role. Finally, we also found that the secretion of soluble CX3CL1 in RAW264.7 macrophages under hypoxia/reoxygenation was significantly increased.Conclusions:The findings suggest that hypoxia/reoxygenation could promote M1 polarization, cell migration, and adhesion of macrophages, and that polarized macrophages induce further apoptosis of hypoxic renal tubular epithelial cells by regulating of CX3CL1/CX3CR1 signaling pathway.

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简介：【摘要】原发于肾盂的黏液腺癌一种罕见的肿瘤，文献报道并不多。患者无特征性的临床症状，影像学也无特征性的表现，术前常误诊为肾结石、肾积水和肾脓肿，常是通过术后病理检查确诊。本文通过报道1例肾盂黏液腺癌，并结合相关文献，总结经验，增强对肾盂黏液腺癌的认识。

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简介：摘要目的探究“1+1+1”组合签约家庭医生服务模式下糖尿病患者的生命质量状况，分析影响因素。方法于2018年7—9月，采用整群分层随机抽样，纳入413例已接受“1+1+1”家庭医生签约服务者为研究对象，将糖尿病患者203例归入糖尿病组，健康人群210例归入对照组。使用自制一般情况问卷、生存质量评价量表（SF-36量表）进行调查，比较两组的生命质量；应用单因素分析和线性逐步回归模型分析糖尿病患者生命质量的影响因素。结果两组生命质量总分分别为（711.36±103.40）、（736.72±85.42）分。糖尿病组的生命质量总分、健康变化、生理功能、总体健康、生理内容综合测量得分低于对照组（t=-2.712、-2.326、-4.872、-5.509、-3.504，均P<0.05）；但在生理职能、躯体疼痛、情感职能、精神健康、生命活力、社会职能、心理内容综合测量方面两组差异无统计学意义（均P>0.05）。分析影响因素，单因素分析显示，年龄、文化程度、睡眠质量评分、应激事件、平时精神状况、家庭医生签约服务年限是糖尿病患者生命质量的影响因素（t/F=3.373、3.216、5.716、58.146、28.325、14.450，均P<0.05）。多重逐步线性回归分析显示，应激事件、平时精神状况、年龄、家庭医生签约服务年限是糖尿病患者生命质量的主要影响因素（t=7.157、4.741、-2.779、2.129，均P<0.05）。结论提示在“1+1+1”组合签约家庭医生服务模式下，糖尿病患者生命质量的心理内容评分接近健康人群。应激事件、平时精神状况、年龄、家庭医生签约服务年限可影响糖尿病患者的生命质量，家庭医生应针对性关注应激事件、患者平时精神状况变化以及对高龄患者的签约服务。

简介：摘要目的探究“1+1+1”组合签约家庭医生服务模式下糖尿病患者的生命质量状况，分析影响因素。方法于2018年7—9月，采用整群分层随机抽样，纳入413例已接受“1+1+1”家庭医生签约服务者为研究对象，将糖尿病患者203例归入糖尿病组，健康人群210例归入对照组。使用自制一般情况问卷、生存质量评价量表（SF-36量表）进行调查，比较两组的生命质量；应用单因素分析和线性逐步回归模型分析糖尿病患者生命质量的影响因素。结果两组生命质量总分分别为（711.36±103.40）、（736.72±85.42）分。糖尿病组的生命质量总分、健康变化、生理功能、总体健康、生理内容综合测量得分低于对照组（t=-2.712、-2.326、-4.872、-5.509、-3.504，均P<0.05）；但在生理职能、躯体疼痛、情感职能、精神健康、生命活力、社会职能、心理内容综合测量方面两组差异无统计学意义（均P>0.05）。分析影响因素，单因素分析显示，年龄、文化程度、睡眠质量评分、应激事件、平时精神状况、家庭医生签约服务年限是糖尿病患者生命质量的影响因素（t/F=3.373、3.216、5.716、58.146、28.325、14.450，均P<0.05）。多重逐步线性回归分析显示，应激事件、平时精神状况、年龄、家庭医生签约服务年限是糖尿病患者生命质量的主要影响因素（t=7.157、4.741、-2.779、2.129，均P<0.05）。结论提示在“1+1+1”组合签约家庭医生服务模式下，糖尿病患者生命质量的心理内容评分接近健康人群。应激事件、平时精神状况、年龄、家庭医生签约服务年限可影响糖尿病患者的生命质量，家庭医生应针对性关注应激事件、患者平时精神状况变化以及对高龄患者的签约服务。

简介：摘要目的观察基线HIV-1 RNA > 50万copies/mL的HIV-1感染者，在高效抗反转录病毒治疗（highly active antiretroviral therapy，HAART）前后外周血totalHIV-1 DNA的变化。方法从国家十二五科技重大专项课题中选取基线HIV-1 RNA > 50万copies/mL且HAART 96周HIV-1 RNA < 50 copies/mL的初治HIV-1感染者为试验组，年龄性别相当的基线HIV-1 RNA < 50万copies/mL的HIV-1感染者为对照组。检测两组患者基线和HAART 24、48、96周时total HIV-1 DNA水平。结果基线及HAART 96周，试验组total HIV-1 DNA均高于对照组3.48（3.21~3.80）lg copies/106 PBMCsvs 2.90（2.54~3.30）lg copies /106 PBMCs（p<0.001），2.82（2.38~2.96）lgcopies/106 PBMCs vs 2.37（1.99~2.65） lg copies /106 PBMCs（p=0.001）。HAART 24周、48周，试验组detal HIV-1 DNA较对照组高0.67（0.41~1.03）lg copies/106 PBMCs vs 0.39（0.09~0.73）lg copies/106 PBMCs（P<0.001）, 0.8（0.46~1.16）lg copies/106 PBMCs vs 0.43（0.04~0.63）lg copies/106 PBMCs（P<0.001）。且HAART前后total HIV-1 DNA水平均与基线病载正相关。结论基线极高病载患者HAART 96周内存在较高total HIV DNA水平，建议选择强效HAART方案来有效降低储存库。