Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life ...Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.展开更多
胆囊癌是胆道系统恶性肿瘤,患者会出现黄疸、腹痛等症状,还会出现胆囊炎和胆囊穿孔等[1,2]。胆囊癌在早期会对邻近周围器官肝脏进行侵犯,不适合进行根治性手术,而且患者易产生化疗耐药性,导致预后不良[3,4]。因此在早期诊断胆囊癌尤为...胆囊癌是胆道系统恶性肿瘤,患者会出现黄疸、腹痛等症状,还会出现胆囊炎和胆囊穿孔等[1,2]。胆囊癌在早期会对邻近周围器官肝脏进行侵犯,不适合进行根治性手术,而且患者易产生化疗耐药性,导致预后不良[3,4]。因此在早期诊断胆囊癌尤为重要。多层螺旋CT(multi-slice spiral CT,MSCT)能提高早期诊断恶性肿瘤准确率,但也在影像学图像判断上存在局限[5]。壳多糖酶3样蛋白1(chitosan enzyme 3-like protein 1,CHI3L1)可参与机体炎症以及血管形成[6]。CHI3L1在多种癌症中呈现高表达[7]。血管生成素样蛋白2(angiopoietin-like protein 2,ANGPTL2)作为癌症治疗的靶点,可参与乳腺癌进展[8]。目前关于MSCT联合血清CHI3L1、ANGPTL2在胆囊癌中的研究鲜有报道,因此,本研究旨在探讨MSCT联合血清CHI3L1、ANGPTL2对胆囊癌的诊断价值。展开更多
目的:观察川黄方治疗3~4期慢性肾脏病(CKD)患者的临床疗效,及对急性肾损伤(AKI)标志物尿L-FABP、CHI3L1的影响。方法:将3~4期CKD患者92例,按照1∶1的比例随机分到治疗组或对照组,即每组46例。对照组给予内科基础治疗;治疗组在对照组基...目的:观察川黄方治疗3~4期慢性肾脏病(CKD)患者的临床疗效,及对急性肾损伤(AKI)标志物尿L-FABP、CHI3L1的影响。方法:将3~4期CKD患者92例,按照1∶1的比例随机分到治疗组或对照组,即每组46例。对照组给予内科基础治疗;治疗组在对照组基础上加服川黄方。疗程为12周。进行临床疗效评价,并观察中医证候积分变化。检测治疗前后肾功能(Scr、BUN、UA、eGFR),24 h U-pro,尿L-FABP、尿CHI3L1变化。结果:(1)治疗组总有效率为73.9%,对照组43.5%,治疗组高于对照组(P<0.05)。(2)用药后,两组患者肾Scr、BUN、UA均有一定程度的降低,eGFR均有一定程度的升高,肾功能得到了改善。治疗组更明显(P<0.01)。两组患者UA差异无统计学意义(P>0.05)。(3)治疗后两组患者24 h U-pro均有降低,治疗组更显著(P<0.01)。(4)两组患者尿L-FABP、CHI3L1治疗前后比较,差异均有统计学意义(P<0.01)。治疗组降低更明显。(5)治疗后,两组患者中医证候积分均显著降低(P<0.01),说明两种治疗方法均有利于改善患者临床症状。结论:川黄方联合内科基础治疗的临床疗效优于单纯内科基础治疗,能更好地促进3~4期CKD患者肾功能恢复、延缓CKD进展,并能显著降低患者尿L-FABP和尿CHI3L1。展开更多
目的:观察跑台运动对高脂饮食诱导的肥胖小鼠骨骼肌几丁质酶-3样蛋白-1(CHI3L1)表达的影响及机制探讨。方法:5周龄健康雄性C57BL/6小鼠随机分成对照组和高脂喂养组,分别进行普通饲料和高脂饲料喂养,8周后筛选肥胖小鼠16只,随机分为高脂...目的:观察跑台运动对高脂饮食诱导的肥胖小鼠骨骼肌几丁质酶-3样蛋白-1(CHI3L1)表达的影响及机制探讨。方法:5周龄健康雄性C57BL/6小鼠随机分成对照组和高脂喂养组,分别进行普通饲料和高脂饲料喂养,8周后筛选肥胖小鼠16只,随机分为高脂安静组和高脂运动组。跑台训练持续8周,每周5次,每次60分钟,跑速25米/分钟。测定小鼠体重,免疫组化法观察比目鱼肌和腓肠肌CHI3L1的蛋白表达水平,real-time PCR方法分别测定比目鱼肌和腓肠肌CHI3L1、TNF-α和IL-6的m RNA表达。结果:与对照组相比,高脂饮食喂养小鼠体重显著增加(P<0.01);比目鱼肌和腓肠肌CHI3L1的m RNA表达均显著上调(P<0.01和P<0.001),腓肠肌中CHI3L1的蛋白表达显著增加,比目鱼肌中CHI3L1的蛋白水平没有显著改变;腓肠肌TNF-α和IL-6 m RNA表达均显著上调(P<0.001和P<0.01),比目鱼肌中TNF-α和IL-6 m RNA表达有上调趋势,但无显著差异。与单纯高脂饮食组小鼠相比,8周跑台运动小鼠体重显著降低(P<0.01);比目鱼肌和腓肠肌CHI3L1 m RNA表达显著下降(P<0.001),CHI3L1蛋白表达均显著减少;腓肠肌TNF-α和IL-6 m RNA表达均显著下调(P<0.001和P<0.01),但比目鱼肌TNF-α和IL-6 m RNA表达无显著变化。结论:跑台运动能显著减少肥胖小鼠比目鱼肌和腓肠肌CHI3L1的表达,显著下调腓肠肌促炎因子TNF-α和IL-6的表达,提示运动通过减轻肥胖时骨骼肌炎症间接地调节骨骼肌CHI3L1表达。展开更多
目的探讨腹膜透析患者血清CHI3L1、FABP4、容量超负荷及蛋白质能量消耗的相关性。方法本研究纳入160例临床状况稳定、在北京大学第三医院腹膜透析中心规律随访的腹膜透析患者。通过ELISA方法测定血清CHI3L1及FABP4浓度。根据多频生物电...目的探讨腹膜透析患者血清CHI3L1、FABP4、容量超负荷及蛋白质能量消耗的相关性。方法本研究纳入160例临床状况稳定、在北京大学第三医院腹膜透析中心规律随访的腹膜透析患者。通过ELISA方法测定血清CHI3L1及FABP4浓度。根据多频生物电阻抗原理测定患者体成分,以水负荷(overdydration,OH)值来评估腹膜透析患者的容量负荷状态,OH值≥2L为容量超负荷,OH值<2L为容量正常。纳入分析的生化指标包括血清白蛋白、尿毒氮、血肌酐、三酰甘油、总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇等。根据蛋白质能量消耗(protein energy wasting,PEW)诊断标准,将入组腹膜透析患者分为蛋白质能量消耗组(PEW组)和非蛋白质能量消耗组(非PEW组)。结果腹膜透析患者血清CHI3L1和FABP4水平呈正相关(r=0.273,P=0.001)。血清CHI3L1水平与容量超负荷呈负相关(r=-0.191,P=0.020),与肌肉重量呈负相关(r=-0.443,P=0.000)。血清FABP4水平与容量超负荷呈负相关(r=-0.172,P=0.040),与肌肉重量呈负相关(r=-0.188,P=0.025)。与容量正常组相比,容量超负荷组的血清CHI3L1水平更低(289.6±117.9ng/ml比335.3±119.3ng/ml,t=2.349,P=0.020),FABP4水平也更低[152.0(131.6,194.6)ng/ml比170.0(132.0,374.9)ng/ml,z=-2.051,P=0.040]。容量超负荷患者的PEW发生率更高(61.7%比42.3%,χ~2=5.756,P=0.013),但是PEW组和非PEW组的CHI3L1、FABP4水平无显著性差异。Logistic回归分析提示PEW的独立危险因素是容量负荷(OR=2.744,95%CI 1.190~6.327,P=0.018)、血清白蛋白(OR=0.837,95%CI 0.734~0.955,P=0.008)和肌肉重量(OR=0.936,95%CI0.891~0.982,P=0.007)。结论腹膜透析患者的血清CHI3L1、FABP4水平显著升高,首次发现两者呈正相关且均与容量超负荷呈负相关,并与肌肉量负相关;PEW发生的独立危险因素是低白蛋白血症、低肌肉量及容量超负荷,而与CHI3L1、FABP4水平无关。展开更多
基金supported by the National Natural Science Foundation of China,Nos.81730033,82171193(to XG)the Key Talent Project for Strengthening Health during the 13^(th)Five-Year Plan Period,No.ZDRCA2016069(to XG)+1 种基金the National Key R&D Program of China,No.2018YFC2001901(to XG)Jiangsu Provincial Medical Key Discipline,No.ZDXK202232(to XG)。
文摘Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.
文摘胆囊癌是胆道系统恶性肿瘤,患者会出现黄疸、腹痛等症状,还会出现胆囊炎和胆囊穿孔等[1,2]。胆囊癌在早期会对邻近周围器官肝脏进行侵犯,不适合进行根治性手术,而且患者易产生化疗耐药性,导致预后不良[3,4]。因此在早期诊断胆囊癌尤为重要。多层螺旋CT(multi-slice spiral CT,MSCT)能提高早期诊断恶性肿瘤准确率,但也在影像学图像判断上存在局限[5]。壳多糖酶3样蛋白1(chitosan enzyme 3-like protein 1,CHI3L1)可参与机体炎症以及血管形成[6]。CHI3L1在多种癌症中呈现高表达[7]。血管生成素样蛋白2(angiopoietin-like protein 2,ANGPTL2)作为癌症治疗的靶点,可参与乳腺癌进展[8]。目前关于MSCT联合血清CHI3L1、ANGPTL2在胆囊癌中的研究鲜有报道,因此,本研究旨在探讨MSCT联合血清CHI3L1、ANGPTL2对胆囊癌的诊断价值。
文摘目的:观察川黄方治疗3~4期慢性肾脏病(CKD)患者的临床疗效,及对急性肾损伤(AKI)标志物尿L-FABP、CHI3L1的影响。方法:将3~4期CKD患者92例,按照1∶1的比例随机分到治疗组或对照组,即每组46例。对照组给予内科基础治疗;治疗组在对照组基础上加服川黄方。疗程为12周。进行临床疗效评价,并观察中医证候积分变化。检测治疗前后肾功能(Scr、BUN、UA、eGFR),24 h U-pro,尿L-FABP、尿CHI3L1变化。结果:(1)治疗组总有效率为73.9%,对照组43.5%,治疗组高于对照组(P<0.05)。(2)用药后,两组患者肾Scr、BUN、UA均有一定程度的降低,eGFR均有一定程度的升高,肾功能得到了改善。治疗组更明显(P<0.01)。两组患者UA差异无统计学意义(P>0.05)。(3)治疗后两组患者24 h U-pro均有降低,治疗组更显著(P<0.01)。(4)两组患者尿L-FABP、CHI3L1治疗前后比较,差异均有统计学意义(P<0.01)。治疗组降低更明显。(5)治疗后,两组患者中医证候积分均显著降低(P<0.01),说明两种治疗方法均有利于改善患者临床症状。结论:川黄方联合内科基础治疗的临床疗效优于单纯内科基础治疗,能更好地促进3~4期CKD患者肾功能恢复、延缓CKD进展,并能显著降低患者尿L-FABP和尿CHI3L1。
文摘目的:观察跑台运动对高脂饮食诱导的肥胖小鼠骨骼肌几丁质酶-3样蛋白-1(CHI3L1)表达的影响及机制探讨。方法:5周龄健康雄性C57BL/6小鼠随机分成对照组和高脂喂养组,分别进行普通饲料和高脂饲料喂养,8周后筛选肥胖小鼠16只,随机分为高脂安静组和高脂运动组。跑台训练持续8周,每周5次,每次60分钟,跑速25米/分钟。测定小鼠体重,免疫组化法观察比目鱼肌和腓肠肌CHI3L1的蛋白表达水平,real-time PCR方法分别测定比目鱼肌和腓肠肌CHI3L1、TNF-α和IL-6的m RNA表达。结果:与对照组相比,高脂饮食喂养小鼠体重显著增加(P<0.01);比目鱼肌和腓肠肌CHI3L1的m RNA表达均显著上调(P<0.01和P<0.001),腓肠肌中CHI3L1的蛋白表达显著增加,比目鱼肌中CHI3L1的蛋白水平没有显著改变;腓肠肌TNF-α和IL-6 m RNA表达均显著上调(P<0.001和P<0.01),比目鱼肌中TNF-α和IL-6 m RNA表达有上调趋势,但无显著差异。与单纯高脂饮食组小鼠相比,8周跑台运动小鼠体重显著降低(P<0.01);比目鱼肌和腓肠肌CHI3L1 m RNA表达显著下降(P<0.001),CHI3L1蛋白表达均显著减少;腓肠肌TNF-α和IL-6 m RNA表达均显著下调(P<0.001和P<0.01),但比目鱼肌TNF-α和IL-6 m RNA表达无显著变化。结论:跑台运动能显著减少肥胖小鼠比目鱼肌和腓肠肌CHI3L1的表达,显著下调腓肠肌促炎因子TNF-α和IL-6的表达,提示运动通过减轻肥胖时骨骼肌炎症间接地调节骨骼肌CHI3L1表达。
文摘目的探讨腹膜透析患者血清CHI3L1、FABP4、容量超负荷及蛋白质能量消耗的相关性。方法本研究纳入160例临床状况稳定、在北京大学第三医院腹膜透析中心规律随访的腹膜透析患者。通过ELISA方法测定血清CHI3L1及FABP4浓度。根据多频生物电阻抗原理测定患者体成分,以水负荷(overdydration,OH)值来评估腹膜透析患者的容量负荷状态,OH值≥2L为容量超负荷,OH值<2L为容量正常。纳入分析的生化指标包括血清白蛋白、尿毒氮、血肌酐、三酰甘油、总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇等。根据蛋白质能量消耗(protein energy wasting,PEW)诊断标准,将入组腹膜透析患者分为蛋白质能量消耗组(PEW组)和非蛋白质能量消耗组(非PEW组)。结果腹膜透析患者血清CHI3L1和FABP4水平呈正相关(r=0.273,P=0.001)。血清CHI3L1水平与容量超负荷呈负相关(r=-0.191,P=0.020),与肌肉重量呈负相关(r=-0.443,P=0.000)。血清FABP4水平与容量超负荷呈负相关(r=-0.172,P=0.040),与肌肉重量呈负相关(r=-0.188,P=0.025)。与容量正常组相比,容量超负荷组的血清CHI3L1水平更低(289.6±117.9ng/ml比335.3±119.3ng/ml,t=2.349,P=0.020),FABP4水平也更低[152.0(131.6,194.6)ng/ml比170.0(132.0,374.9)ng/ml,z=-2.051,P=0.040]。容量超负荷患者的PEW发生率更高(61.7%比42.3%,χ~2=5.756,P=0.013),但是PEW组和非PEW组的CHI3L1、FABP4水平无显著性差异。Logistic回归分析提示PEW的独立危险因素是容量负荷(OR=2.744,95%CI 1.190~6.327,P=0.018)、血清白蛋白(OR=0.837,95%CI 0.734~0.955,P=0.008)和肌肉重量(OR=0.936,95%CI0.891~0.982,P=0.007)。结论腹膜透析患者的血清CHI3L1、FABP4水平显著升高,首次发现两者呈正相关且均与容量超负荷呈负相关,并与肌肉量负相关;PEW发生的独立危险因素是低白蛋白血症、低肌肉量及容量超负荷,而与CHI3L1、FABP4水平无关。
