Cartilage‐Specific Autophagy Deficiency Promotes ER Stress and Impairs Chondrogenesis in PERK‐ATF4‐CHOP–Dependent Manner

Autophagy is activated during nutritionally depleted or hypoxic conditions to facilitate cell survival. Because growth plate is an avascular and hypoxic tissue, autophagy may have a crucial role during chondrogenesis; however, the functional role and underlying mechanism of autophagy in regulation of growth plate remains elusive. In this study, we generated ^TamCartAtg7^–/– (Atg7cKO) mice to explore the role of autophagy during endochondral ossification. Atg7cKO mice exhibited growth retardation associated with reduced chondrocyte proliferation and differentiation, and increased chondrocyte apoptosis. Meanwhile, we observed that Atg7 ablation mainly induced the PERK‐ATF4‐CHOP axis of the endoplasmic reticulum (ER) stress response in growth plate chondrocytes. Although Atg7 ablation induced ER stress in growth plate chondrocytes, the addition of phenylbutyric acid (PBA), a chemical chaperone known to attenuate ER stress, partly neutralized such effects of Atg7 ablation on longitudinal bone growth, indicating the causative interaction between autophagy and ER stress in growth plate. Consistent with these findings in vivo, we also observed that Atg7 ablation in cultured chondrocytes resulted in defective autophagy, elevated ER stress, decreased chondrocytes proliferation, impaired expression of col10a1, MMP­13, and VEGFA for chondrocyte differentiation, and increased chondrocyte apoptosis, while such effects were partly nullified by reduction of ER stress with PBA. In addition, Atg7 ablation‐mediated impaired chondrocyte function (chondrocyte proliferation, differentiation, and apoptosis) was partly reversed in CHOP^–/– cells, indicating the causative role of the PERK‐ATF4‐CHOP axis of the ER stress response in the action of autophagy deficiency in chondrocytes. In conclusion, our findings indicate that autophagy deficiency may trigger ER stress in growth plate chondrocytes and contribute to growth retardation, thus implicating autophagy as an important regulator during chondrogenesis and providing new insights into the clinical potential of autophagy in cartilage homeostasis. © 2017 American Society for Bone and Mineral Research.     

通腑理肺汤结肠透析联合纤维支气管镜肺泡灌洗对肺炎合并脓毒症患者HMGB-1、IL-10水平影响

目的 探讨通腑理肺汤结肠透析联合纤维支气管镜肺泡灌洗对肺炎合并脓毒症患者高迁移率蛋白(HMGB-1)、白细胞介素(IL)-10水平的影响.方法 将90例患者分为治疗组A、治疗组B、对照组,每组30例.治疗组A在常规治疗基础上给予通腑理肺汤结肠透析联合纤维支气管镜肺泡灌洗治疗,治疗组B在常规治疗基础上给予温水结肠透析联合纤维支气管镜肺泡灌洗治疗,对照组在常规治疗基础上给予温水结肠透析治疗.于治疗前,治疗后1周末、2周末留取肺泡灌洗液检测HMGB-1、IL-10水平.结果 HMGB-1水平:3组患者治疗前差异无统计学意义(P＞0.05);治疗后1周末,治疗组A明显低于治疗组B及对照组;治疗后2周末,治疗组A、治疗组B水平均低于对照组,且治疗组A降低最为明显,差异有统计学意义(P＜0.05).IL-10水平:3组患者治疗前差异无统计学意义(P＞0.05);治疗后1周末、2周末3组患者均有不同程度升高,治疗组A、治疗组B均高于对照组,且治疗组A水平升高最为明显,差异有统计学意义(P＜0.05).结论 通腑理肺汤结肠透析联合纤维支气管镜肺泡灌洗能显著降低患者HMGB-1水平,提高IL-10水平,调节患者促炎/抗炎因子的平衡,减轻炎症反应和组织损伤,改善患者预后.     

胃肠激素的研究概况

胃肠激素是来源于生物体的多肽类激素 ,现已用于多种疾病机制的研究、诊断和治疗。对胃肠激素的研究进展及其应用进行了综述     

结缔组织生长因子的分泌表达及ELISA检测法的建立

目的　制备结缔组织生长因子 (CTGF)抗原 ,建立ELISA检测方法。方法　从血管内皮细胞中提取总RNA ,逆转录合成cDNA ,设计特异性引物 ,通过PCR方法扩增CTGFC区 2 4 2～ 349位氨基酸基因 ,插入噬菌体包膜蛋白基因Ⅲ的上游 ,制备CTGF融合蛋白。用纯化后的融合蛋白免疫家兔 ,获得抗体 ,抗体纯化后标记HRP ,建立ELISA。结果　成功克隆CTGFC区基因 ,插入表达载体经IPTG诱导后获得分子量为 2 5 0 0 0的融合蛋白 ,免疫学检测证实为CTGF。所得抗体用HRP标记。建立的ELISA法检测灵敏度为 2ng/ml,批内及批间平均变异系数为 5 .4 %和 7.5 % ,平均回收率为 10 4 .2 %。血红蛋白浓度在 0～ 5 0mmol/L ,总胆红素在 0～ 15 0 μmol/L ,三酰甘油在 0～ 2 .0mmol/L对测定结果无影响。 2例慢性乙型肝炎病人血标本 ,5例糖尿病肾病、3例肾功能衰竭、3例慢性肾炎尿标本为阳性。结论　CTGF可以作为判断纤维化发生、进展及预后的一个新指标。CTGFELISA检测方法的成功建立 ,为临床应用打下基础     

苦杏仁水煎剂对佐剂性关节炎大鼠抗炎作用研究

目的研究苦杏仁水煎剂对佐剂性关节炎(AA)大鼠的抗炎作用。方法建立AA大鼠模型,观察苦杏仁水煎剂对AA大鼠足肿胀、踝关节组织病理变化的影响。结果苦杏仁水煎剂能有效抑制AA大鼠关节肿胀及减缓组织炎症的发展。结论苦杏仁水煎剂对AA大鼠具有良好的抗类风湿关节炎作用,机制还需进一步探讨。     

Prominent roles of Ni(OH)2 deposited on ZnIn2S4 microspheres in efficient charge separation and photocatalytic H2 evolution

In this work, Ni(OH)₂-deposited ZnIn₂S₄ microspheres (Ni(OH)₂/ZnIn₂S₄) were fabricated using a hydrothermal process, followed by a facile in situ precipitation method. It was demonstrated that the deposition of Ni(OH)₂ on ZnIn₂S₄ effectively promotes the separation of charges photogenerated over ZnIn₂S₄, and significantly enhances photocatalytic H₂ evolution. The optimum rate of the photocatalytic H₂ evolution over the 6% Ni(OH)₂/ZnIn₂S₄ composite reaches 4.43 mmol g⁻¹ h⁻¹, which is 21.1 times higher than that of the pure ZnIn₂S₄. Based on various characterization results and Au photo-deposition on the composite, it was proposed that the capture of the photogenerated holes by the deposited Ni(OH)₂ would be responsible for the efficient charge separation, which allows more photogenerated electrons to be left on the ZnIn₂S₄ for the reduction of H⁺ to H₂ with a higher rate.

The capture of the photogenerated holes by the deposited Ni(OH)₂ contributes to the efficient charge separation, allowing more photogenerated electrons to be left on ZnIn₂S₄ to reduce H⁺ to H₂.     

隔姜灸疗法治疗脑卒中急性期吞咽障碍临床观察

目的 进一步探讨隔姜灸疗法在脑卒中急性期对吞咽障碍临床疗效.方法 选取在广东省第二中医院针灸康复科病房进行住院治疗且符合纳入、排除标准的150例吞咽障碍患者随机分为对照组和治疗组,每组75例患者.2组患者均统一给予规范的脑卒中常规治疗,除常规治疗外,对照组患者进行吞咽功能训练;治疗组在对照组基础上进行隔姜灸疗法治疗,2...     

阿仑膦酸钠局部给药调节骨代谢在口腔医学中的应用

阿仑膦酸钠(ALN)作为经典的含氮双膦酸盐药物,对治疗骨质流失引起的疾病非常有效,主要通过下调破骨细胞活性,抑制骨吸收,发挥成骨作用。成骨细胞促进骨生成与破骨细胞介导骨吸收在体内形成的平衡被破坏,可能是导致颌骨骨吸收性疾病的唯一原因。尽管ALN在颌骨骨吸收性疾病中应用时具有优势,但长期静脉或口服应用ALN会导致相关性颌骨骨坏死、肾功能衰竭、食道损害等副作用。能否通过改变给药途径减少ALN的不良反应,将其安全有效地应用于颌骨骨吸收疾病中,是目前亟待突破的难点。因此,本文将ALN对骨代谢的作用机制进行简单的阐述,并对其在颌骨骨吸收疾病中应用的优劣进行探讨,以期为ALN局部给药治疗颌骨骨吸收性疾病提供理论指导。     

婴幼儿急性胃肠炎伴良性惊厥临床分析及远期随访观察

目的：探讨急性胃肠炎伴婴幼儿良性惊厥的临床特点及远期预后。方法：选择2012年2月至2015年12月我院收治的98例急性胃肠炎伴良性惊厥患儿,总结、分析其临床及实验室检查资料,并进行远期随访观察。结果：98例急性胃肠炎伴良性惊厥患儿发病年龄集中在1~2岁,占全部患儿的78.6%;全年均有发病;惊厥在急性胃肠炎3 d内的发病率高,占86.7%;惊厥平均发作次数为1.8次,期间无癫痫持续状态,为全身强直-阵挛形式发作。血生化检测、血常规检查、脑脊液常规、生化及培养检查等均正常,大便轮状病毒检测阳性者12例。脑电图检测结果显示,4例背景活动慢化,3例额中央区或中央顶区尖-慢波发放或有尖波,其他患儿脑电图均正常。随访结果显示,4例患儿复发,其中1例为热性惊厥,1例为癫痫,其他无复发。结论：急性胃肠炎伴婴幼儿良性惊厥高发于1~2岁幼儿,惊厥发作早期易于控制,预后良好,不需进行长期抗惊厥治疗。     

肠必清栓对UC模型大鼠肠黏膜内IL-1β、TNF-α及SOD的影响

目的：通过检测肠必清栓治疗后UC模型大鼠肠组织中IL-1β、TNF-α、SOD表达的变化,研究肠必清栓治疗UC的作用机制。方法：用2,4-二硝基氯苯免疫加醋酸局部灌肠法建立的UC模型大鼠48只随机分为五组,模型对照组（A组,8只）,肠必清栓低、中、高剂量组（B、C、D组,各10只）,柳氮磺吡啶药物对照组（E组,10只）,另设正常对照组（F组,6只）。给药治疗14d后处死,留取结肠检测组织中细胞因子IL-1β、TNF-α、SOD的表达。结果：模型组大鼠肠组织中IL-1β、TNF-α表达显著增多（P〈0.01）,而SOD显著减少（P〈0.01）,给药治疗可下调IL-1β、TNF-α的表达,提高组织中SOD的表达。IL-1β、TNF-α的表达在肠必清栓低、中、高剂量组间呈剂量依赖关系,高剂量组与柳氮磺吡啶药物对照组间差异无统计学意义（P〉0.05）;SOD的表达在肠必清栓中、高剂量组、柳氮磺吡啶药物对照组和正常对照组间差异无统计学意义（P〉0.05）。结论：肠必清栓可下调结肠组织中促炎性细胞因子的表达,提高组织SOD活性,这可能为其治疗UC调节免疫抗感染、抗氧化的作用机制。