甘氨鹅去氧胆酸对大鼠肝窦内皮细胞凋亡的影响

背景：肝窦内皮细胞（SEC）凋亡是肝脏疾病发生、发展的重要因素之一。在胆汁淤积症中，疏水性胆汁酸甘氨鹅去氧胆酸（GCDC）直接诱发肝细胞凋亡，而亲水性胆汁酸熊去氧胆酸（UDCA）能防止诱发肝细胞凋亡。目的：研究GCDC引起原代培养大鼠SEC损害和凋亡、UDCA对GCDC诱导凋亡的抑制作用以及涉及caspase-8的作用机制。方法：采用胶原酶A原位灌注和Pevcoll分离液（25％和50％）梯度离心法分离Wistar大鼠SEC，SEC于添加了EGM-2因子的EBM-2培养基中培养（5％CO2，37℃）3d，然后在含有GCDC和（或）UDCA的新鲜培养液中继续培养4h。以原位末端标记（TUNEL）技术检测SEC凋亡情况。以FLICE／caspase-8比色蛋向酶检测试剂盒测定caspase-8的表达情况。结果：相差显微镜下，培养3d时的SEC星纺锤状并基本融合。而在与GCDC孵育的过程中SEC趋于皱缩，孵育4h时最终从培养皿脱落。SEC与不同浓度的GCDC（50—250μmol／L）孵育1h后，TUNEL染色阳性的细胞数量开始增加，4h后儿乎所有细胞呈TUNEL染色阳性（P〈0．05）；对照组SEC仅少数呈TUNEL染色阳性。在原代培养SEC与终浓度100μmol／L GCDC培养液中加入UDCA（50～200μmol／L）可明显减少TUNEL染色阳性的SEC，且抑制作用呈剂量依赖性（P〈0．05）；200μmol／LUDCA存在时．GCDC引起SEC凋亡的水平是GCDC单独孵育4h时的20％。SEC与250μmol／LGCDC孵育2h，SEC中caspase-8表达明显增加．而加入200μmol／LUDCA则几乎可完全阻止caspase-8表达增加。结论：UDCA能阻止GCDC诱发的原代培养SEC凋亡，此作用至少部分是通过抑制GCDC上调SEC中caspase-8的表达而实现的。     

Patient-derived non-small cell lung cancer xenograft mirrors complex tumor heterogeneity

Objective:Patient-derived xenograft(PDX)models have shown great promise in preclinical and translational applications,but their consistency with primary tumors in phenotypic,genetic,and pharmacodynamic heterogeneity has not been well-studied.This study aimed to establish a PDX repository for non-small cell lung cancer(NSCLC)and to further elucidate whether it could preserve the heterogeneity within and between tumors in patients.Methods:A total of 75 surgically resected NSCLC specimens were implanted into immunodeficient NOD/SCID mice.Based on the successful establishment of the NSCLC PDX model,we compared the expressions of vimentin,Ki67,EGFR,and PD-L1 proteins between cancer tissues and PDX models using hematoxylin and eosin staining and immunohistochemical staining.In addition,we detected whole gene expression profiling between primary tumors and PDX generations.We also performed whole exome sequencing(WES)analysis in 17 first generation xenografts to further assess whether PDXs retained the patient heterogeneities.Finally,paclitaxel,cisplatin,doxorubicin,atezolizumab,afatininb,and AZD4547 were used to evaluate the responses of PDX models to the standard-of-care agents.Results:A large collection of serially transplantable PDX models for NSCLC were successfully developed.The histology and pathological immunohistochemistry of PDX xenografts were consistent with the patients’tumor samples.WES and RNA-seq further confirmed that PDX accurately replicated the molecular heterogeneities of primary tumors.Similar to clinical patients,PDX models responded differentially to the standard-of-care treatment,including chemo-,targeted-and immuno-therapeutics.Conclusions:Our established PDX models of NSCLC faithfully reproduced the molecular,histopathological,and therapeutic characteristics,as well as the corresponding tumor heterogeneities,which provides a clinically relevant platform for drug screening,biomarker discovery,and translational research.     

大于6月龄室间隔完整型肺动脉闭锁患者的外科治疗策略和中远期随访分析

目的 本研究总结及分析近十年接受首次外科干预时年龄已超过6个月龄室间隔完整型肺动脉闭锁(PA/IVS)患者的外科治疗策略.方法 回顾2007年1月至2018年12月,上海儿童医学中心共收治63例年龄超过6个月的PA/IVS患者,其首次干预时的年龄为6.2～79.6(20.1)个月,体重为4.6～17.5(9.5)kg,...     

ICU产超广谱β-内酰胺酶细菌医院感染危险因素与护理措施

目的总结ICU产超广谱β-内酰胺酶细菌医院感染的危险因素,为预防与控制产超广谱β-内酰胺酶细菌流行提供护理依据.方法将ICU的28例产超广谱β-内酰胺酶细菌感染病例作为观察组,随机抽取同一时期、同病房、同基础疾病28例产超广谱β-内酰胺酶菌阴性病例作为对照组,分析产超广谱β-内酰胺酶细菌感染的相关危险因素.结果产超广谱β-内酰胺酶细菌医院感染与患者入住ICU时间长、多次住院、长期使用三代头孢、侵入性操作等因素有关.结论切断病原菌传播途径、缩短患者在ICU的天数、严格控制广谱抗生素应用,是预防产超广谱β-内酰胺酶细菌感染的重要措施.     

基于虚实辨证的补泻平衡手法治疗膝骨关节炎临床研究

目的观察补泻平衡手法治疗膝骨关节炎的疗效及对患者临床症状、体征的影响。方法采用随机数字表法将220例单膝骨关节炎患者分为治疗组和对照组各110例。治疗组予补泻平衡手法,对照组予常规推拿手法,均每次20 min,每日2次,1周为1个疗程,连续治疗2个疗程。观察2组治疗前后及治疗后3、6个月全身临床症状、体征及中医证候评分,比较2组临床疗效及不良反应。结果与本组治疗前比较,2组治疗后全身临床症状、体征评分明显降低(P<0.05),治疗组中医证候评分明显降低(P<0.05);2组治疗后比较,治疗组全身临床症状、体征改善程度优于对照组(P<0.05);与本组治疗后比较,2组治疗后3、6个月全身临床症状、体征评分升高。治疗组治疗后3、6个月中医证候评分升高,仍低于治疗前(P<0.05)。治疗组总有效率为91.8%(101/110),对照组为78.2%(86/110),2组比较差异有统计学意义(P<0.05)。2组均未见不良反应。结论补泻平衡手法与常规推拿手法治疗膝骨关节炎均有效,前者疗效优于后者,且中远期疗效更佳。     

GeXP多重RT-PCR诊断小儿肺炎支原体感染性脑炎的价值分析

目的 探讨GeXP多重RT-聚合酶链反应(polymerase chain reaction,PCR)诊断小儿肺炎支原体(mycoplasma pneumoniae,MP)感染性脑炎的价值.方法 采用回顾性研究,选取2017-05—2020-05郑州儿童医院收治的85例初诊为感染性脑炎患儿为研究对象,采集患儿脑脊液标本...     

Hydroxylation of benzene to phenol over heteropoly acid H5PMo10V2O40 supported on amine-functionalized MCM-41

Supported catalysts with Keggin type heteropoly acids (H₅PMo₁₀V₂O₄₀) loaded onto amine-functionalized MCM-41 for the catalytic hydroxylation of benzene to phenol with H₂O₂ were prepared by a wet impregnation method. The effects of the preparation conditions on the properties and activity of the supported catalysts were fully investigated. The results showed that the catalyst retained the mesoporous structure of MCM-41 and H₅PMo₁₀V₂O₄₀ was dispersed uniformly on the surface of the amine-functionalized MCM-41. Meanwhile, the reusability and catalytic performance of the catalyst were affected by two key factors, i.e., the interaction between the heteropoly acid and the surface of MCM-41, and the hydrophobicity of the catalyst since they decide the leaching of H₅PMo₁₀V₂O₄₀ and the adsorption of benzene. The catalyst with H₅PMo₁₀V₂O₄₀ loaded onto amine-functionalized MCM-41, which was prepared using ethanol as the solvent, exhibited the highest phenol yield (20.4%), a turnover frequency value of 20.3 h⁻¹ and good reusability. We believe this work offers an effective and facile strategy for the preparation of a new catalyst for hydroxylation of benzene to phenol.

Supported catalysts with heteropoly acid loaded onto amine-functionalized MCM-41 for hydroxylation of benzene to phenol are prepared.     

Synthesis of nano-zirconium-iron oxide supported by activated carbon composite for the removal of Sb(v) in aqueous solution

In this study, nano zirconium iron oxide based on activated carbon (ZIC) was successfully prepared by using the coprecipitation method. Compared with unmodified activated carbon, ZIC increases the number of active sites by adding metal oxides and hydroxyl groups and greatly improves the adsorption capacity of Sb(v). The synthesized nanocomposites were characterized and analysed by XRD, SEM, FT-IR, VSM and other techniques. The results showed that the zirconium iron oxide particles were successfully loaded and uniformly distributed on the surface of the activated carbon, and the agglomeration phenomenon was reduced. The saturation magnetization of ZIC was 1.89 emu g⁻¹, which easily achieved solid–liquid separation under the action of an external magnetic field. In batch experiments, when the initial concentration was 1 mg L⁻¹, the dosage of ZIC was 600 mg L⁻¹, the pH value was 5.0, the contact time was 180 min, and the removal rate of Sb(v) reached 97.82%. The maximum adsorption capacity of ZIC for Sb(v) was 11.80 mg g⁻¹. Under the interference of various inorganic ions and dissolved organics, the excellent adsorption capacity was still due to ZIC. The adsorption form was multimolecular-layer adsorption, the adsorption process was an endothermic reaction, and chemical adsorption was dominant as the adsorption mechanism. ZIC has good removal efficiency and is reusable, which indicates that ZIC has prospects for practical wastewater treatment.

The adsorbent was highly effective in the removal of Sb(v). The adsorbent easily achieved solid–liquid separation under the action of an external magnetic field.