TRIM59 通过结合 BCLAF1 调控人皮肤黑色素瘤 SK-MEL-2 细胞的恶 性生物学行为

目的：探究三结构域蛋白59（TRIM59）调控人皮肤黑色素瘤细胞SK-MEL-2增殖、细胞周期、凋亡及迁移侵袭的作用机制，及其与Bcl2相关转录因子1（BCLAF1)之间的关系。方法：qPCR和WB法检测人表皮黑色素细胞HEMn-LP、人皮肤黑色素瘤细胞SK-MEL-2、UACC903、A375及36例邢台市人民医院2019年2月至2021年7月收集的皮肤黑色素瘤组织中TRIM59的mRNA和蛋白表达，使用脂质体将si-con、si-TRIM59转染至SK-MEL-2细胞中，WB法检测干扰TRIM59表达对细胞中周期蛋白D1（CCND1）、细胞周期素依赖性激酶2（CDK2）、肿瘤抑制蛋白基因（TP53）和 BCLAF1 蛋白表达的影响，CCK-8法、流式细胞术、划痕愈合实验、Transwell实验检测对细胞的活性、凋亡、迁移和侵袭的影响，免疫共沉淀（Co-IP）实验检测对细胞中TRIM59蛋白与BCLAF1结合能力的影响。结果：与HEMn-LP细胞相比，SK-MEL-2、UACC903、A375细胞中TRIM59 mRNA和TRIM59、BCLAF1蛋白均呈高表达（均P<0.05），SK-MEL-2细胞中TRIM59表达水平最高。相较于si-con组和Normal组，沉默TRIM59后，SK-MEL-2细胞的活性显著降低，细胞周期阻滞于G2期，CCND1、CDK2的蛋白表达显著降低，TP53蛋白和细胞凋亡率均显著升高，划痕抑制率明显升高，迁移侵袭细胞数明显降低（均P<0.05）。免疫共沉淀实验结果显示，TRIM59与BCLAF1之间存在蛋白结合关系。TRIM59与 BCLAF1 在肿瘤组织中的表达呈显著的正相关（r=0.878，P<0.001）。结论：干扰TRIM59表达能够抑制人皮肤黑色素瘤SK-MEL-2细胞的增殖、迁移和侵袭而促进凋亡，抑制SK-MEL-2细胞的恶性生物学行为，其机制可能与TRIM59结合BCLAF1有关。     

Quantification of exhaled propofol is not feasible during single-lung ventilation using double-lumen tubes: A multicenter prospective observational trial

Background

Volatile propofol can be measured in exhaled air and correlates to plasma concentrations with a time delay. However, the effect of single-lung ventilation on exhaled propofol is unclear. Therefore, our goal was to evaluate exhaled propofol concentrations during single-lung compared to double-lung ventilation using double-lumen tubes.

Methods

In a first step, we quantified adhesion of volatile propofol to the inner surface of double-lumen tubes during double- and single-lumen ventilation in vitro. In a second step, we enrolled 30 patients scheduled for lung surgery in two study centers. Anesthesia was provided with propofol and remifentanil. We utilized left-sided double-lumen tubes to separately ventilate each lung. Exhaled propofol concentrations were measured at 1-min intervals and plasma for propofol analyses was sampled every 20 min. To eliminate the influence of dosing on volatile propofol concentration, exhalation rate was normalized to plasma concentration.

Results

In-vitro ventilation of double-lumen tubes resulted in increasing propofol concentrations at the distal end of the tube over time. In vitro clamping the bronchial lumen led to an even more pronounced increase (Δ AUC +62%) in propofol gas concentration over time. Normalized propofol exhalation during lung surgery was 31% higher during single-lung compared to double-lung ventilation.

Conclusion

During single-lung ventilation, propofol concentration in exhaled air, in contrast to our expectations, increased by approximately one third. However, this observation might not be affected by change in perfusion-ventilation during single-lung ventilation but rather arises from reduced propofol absorption on the inner surface area of the double-lumen tube. Thus, it is only possible to utilize exhaled propofol concentration to a limited extent during single-lung ventilation.

Registration of Clinical Trial

DRKS-ID DRKS00014788 ( www.drks.de ).     

Prosthetic choice in mitral valve replacement for severe chronic ischemic mitral regurgitation: Long-term follow-up

BackgroundProsthetic choice for mitral valve replacement is generally driven by patient age and patient and surgeon preference, and current guidelines do not discriminate between different etiologies of mitral valve disease. Our objective was to assess and compare short- and long-term outcomes after mitral valve replacement among patients with biological or mechanical prostheses in the setting of severe ischemic mitral regurgitation.MethodsBetween 2000 and 2016, 424 patients underwent mitral valve replacement for severe ischemic mitral regurgitation at our institution, using biological prosthesis in 188 (44%) and mechanical prosthesis in 236 (56%). A 1:1 propensity score match (n = 126 per group) and inverse probability of treatment weighting were used to compare groups. Short-term outcomes included in-hospital mortality and other cardiovascular adverse events. Long-term outcomes included survival and hospital readmission for cardiovascular causes, stroke, and major bleeding.ResultsIn-hospital mortality and early postoperative adverse events were similar between groups in the propensity score match and inverse probability of treatment weighting cohorts. Overall long-term survival was similar at 5 and 9 years, but mechanical prosthesis recipients were more frequently readmitted to hospital for cardiovascular causes, including stroke and non-neurological bleeding in propensity score matching and inverse probability of treatment weighting analyses (all P values < .004). Type of prosthesis did not independently influence all-cause mortality (hazard ratio, 1.01; 95% confidence interval, 0.71-1.43; P = .959), but placement of a mechanical prosthesis was associated with increased risk of readmission for cardiovascular events (hazard ratio, 1.65; 95% confidence interval, 1.17-2.32; P = .004) among matched patients.ConclusionsThe type of prosthesis has no influence on long-term survival among patients with severe ischemic mitral regurgitation undergoing mitral valve replacement. There may be an increased risk of neurologic events and serious bleeding associated with mechanical prostheses.     

肾周脂肪梅奥粘连概率评分系统在肾癌后腹腔镜肾部分切除术中的应用

目的探讨肾周脂肪梅奥粘连概率评分系统（MAP）在肾癌后腹腔镜肾部分切除术中的临床应用价值。 方法回顾性分析2015年1月至2020年6月徐州医科大学附属淮安医院泌尿外科收治的行后腹腔镜肾部分切除术的153例肾癌患者的临床病例资料。依据MAP评分系统将其分为低度复杂组、中度复杂组和高度复杂组三组。比较各组间的手术时间、术中出血量、术中及术后并发症、术中热缺血时间、术后住院时间及术后血肌酐变化情况。 结果在153例患者中，低度复杂组68例，中度复杂组58例和高度复杂组27例。三组患者在年龄、性别、术前血肌酐水平、肿瘤最大径、肿瘤位置、BMI、RENAL评分等方面差异无统计学意义（P>0.05）。随着复杂程度的提高，手术时间、术中出血量也在不断增加（P<0.05）；而术中热缺血时间、术后住院时间及术后血肌酐水平无明显变化（P>0.05）。在术中并发症方面，随着复杂程度的提高，术中并发症的发生率也在增加（P<0.05），且高度复杂组的术后并发症发生风险是低度复杂组的13.895倍（P=0.002)，MAP评分系统预测术中并发症发生的精度较高（AUC=0.757，P=0.002）。但是术后并发症各组比较差异无统计学意义（P>0.05）。 结论MAP评分系统在肾癌后腹腔镜肾部分切除术中，对预估手术难度及术中并发症发生风险有较好的临床应用价值。     

健脾消癌方通过PI3K/Akt信号通路抑制结肠癌血管生成的研究＊

目的 观察结肠癌HCT116细胞健脾消癌方的条件培养液对HUVEC细胞管腔形成的影响，从PI3K/Akt生物轴调控角度探讨其作用机制。方法 培养HCT116细胞，细胞设3组：对照组，健脾消癌方组（加入15%健脾消癌方含药血清）及人参皂苷Rg3组；制备HCT116细胞健脾消癌方条件培养液（分组及制备方法见实验方法），用条件培养液干预HUVEC（脐静脉内皮细胞，Human Umbilical Vein Endothelial Cells），Matrigel基质胶法检测HCT116细胞健脾消癌方条件培养液对HUVEC小管形成的影响。随后采用蛋白免疫印迹法（Western blot）检测各组HCT116细胞磷脂酰肌醇3-激酶（PI3K）、蛋白激酶B（Akt）、p-Akt、VEGF（血管内皮生长因子，Vascular endothelial growth factor）蛋白表达。最后在结肠癌HCT116荷瘤小鼠中验证健脾消癌方对肿瘤生长速度的影响，并经瘤组织VEGF蛋白表达、CD31免疫组化染色检测肿瘤内血管生成情况。结果 模型组HUVEC细胞管腔形成较空白血清组显著增加（P<0.05）；健脾消癌方组及人参皂苷Rg3组较模型组HUVEC细胞管腔形成显著减少（P<0.01）。p-Akt和VEGF蛋白表达水平模型组高于空白血清组（P<0.05），健脾消癌方组及人参皂苷Rg3组显著低于模型组（P<0.01）；PI3K、Akt蛋白表达量组间差异无统计学意义。与对照组比较，模型组荷瘤小鼠肿瘤体积显著性增大，瘤组织内VEGF表达、CD31阳性面积显著性增加，差异有统计学意义（P<0.05）；与模型组比较，健脾消癌方组及人参皂苷Rg3组荷瘤小鼠肿瘤体积显著减小，瘤组织内VEGF表达、CD31阳性面积降低，差异有统计学意义（P<0.05）。结论 健脾消癌方可抑制肿瘤的血管生成和生长，其作用机制可能与PI3K/Akt生物轴调控VEGF表达有关。     

泽泻化学成分及药理作用研究进展

泽泻为我国传统中药,广泛应用于中医临床复方及多种中成药中。目前从泽泻中分离到了220余个化合物,包括三萜、倍半萜、二萜、糖类、含氮化合物、苯丙素、黄酮、甾体等。药理学研究表明泽泻醇提物、水提物及一些单体类成分具有利尿、抗结石及肾脏保护、降血脂及保肝、降血糖、抗癌、抗氧化损伤、抗炎、抗补体等作用。该文对近五十年来泽泻的化学成分和药理作用进行了全面系统的整理,以期为泽泻的深入研究和开发利用提供理论依据。     

The impact of canister geometry on chemical biological radiological and nuclear filter performance: A computational fluid dynamics analysis

Steady-state axisymmetric simulations using the Reynolds-Averaged Navier-Stokes equations have been carried out in order to optimize the performance of a Chemical, Biological, Radiological, and Nuclear (CBRN) canister filter for its use in a powered air-purifying respirator (PAPR). Alterations have been made to the shape of the canister, the spacing of the rear wall of the canister with regard to the carbon filter, and the bracketing between (i) the particulate filter and the carbon bed and (ii) the carbon bed and the canister wall. The pressure drops across the canister and the residence time distribution at the rear of the carbon bed have been analyzed in detail based on an extensive parametric analysis involving the aforementioned variations. It has been demonstrated that the non-uniform porosity profile of the carbon bed resulted in alternating regions of high and low velocity close to the canister wall, providing a possible route for breakthrough. Designs, which included a bracket at the rear of the carbon bed, blocked this route and consequently had a longer minimum mean residence time than those, which did not. It has also been shown that the spacing between the carbon bed and the canister rear wall had a large impact on both residence time and pressure drop. In cases where the carbon backed directly onto the canister rear wall flow in the axial direction from the outside wall toward the canister axis resulted in far greater pressure drop and a reduction in minimum mean residence time within the carbon bed.     

以机油为分散剂高温热解人发合成新型碳点及其生物效应研究

目的以机油为分散剂高温热解人发后发现新型纳米碳点,通过动物实验评价了该碳点的生物效应。方法利用高温热解法对人发和机油进行炭化,对炭化产物进行萃取、过滤分离和透析得到一种具有水溶性的新型物质碳点,并命名为JYRF-CDs。利用透射电子显微镜(TEM)、高分辨透射电子显微镜(HR-TEM)、紫外-可见分光光谱、傅里叶变换红外光谱、荧光光谱、X射线光电子能谱分析(XPS)等多种方法对JYRF-CDs进行表征,利用小鼠单核巨噬细胞RAW264.7细胞进行CCK-8毒性实验来评价JYRF-CDs的安全性,并通过小鼠耳肿胀实验和小鼠醋酸扭体实验对JYRF-CDs的生物效应进行评价。结果 JYRF-CDs外形为类球形,粒径均匀分布在1.8～3.6 nm,晶格间距为0.219 7 nm。细胞毒性实验结果显示,JYRF-CDs具有低毒性,动物实验结果表明JYRF-CDs具有良好的抗炎和镇痛作用。结论首次以机油为分散剂高温热解人发后发现一种全新的碳点JYRF-CDs,以JYRF-CDs为突破口,更加明确阐释以机油为分散剂高温热解人发后炭化产物具有生物效应的物质基础,为纳米类成分的研究提供了一种新方法。     

针灸联合西药对中重度间歇性过敏性鼻炎患者T淋巴细胞亚群、IL-4、IL-10、VACM-1水平的影响

目的观察针灸联合西药对中重度间歇性过敏性鼻炎患者血清T淋巴细胞亚群、炎性因子及血管细胞黏附分子-1(VACM-1)的影响。方法将120例中重度间歇性过敏性鼻炎患者随机分为对照组和治疗组,每组60例。对照组予丙酸氟替卡松鼻喷雾剂、盐酸氮卓斯汀片治疗,治疗组在对照组治疗措施的基础上加用针灸疗法。两组疗程均为28天,观察临床疗效,比较中医证候积分、血清T淋巴细胞亚群、炎性因子[白介素-4(IL-4)、白介素-10(IL-10)]及VACM-1水平的变化情况。结果①治疗组、对照组总有效率分别为95.0%、81.7%,治疗组临床疗效优于对照组(P0.05)。②治疗前与疗程结束后7天组内比较,两组中医证候(鼻塞不通、鼻痒难耐、鼻流清涕、喷嚏频作)较治疗前改善(P0.05);组间疗程结束后7天比较,治疗组中医证候改善情况优于对照组(P0.05)。③治疗前与疗程结束后7天组内比较,两组血清CD3~+、CD4~+水平和CD4~+/CD8~+较治疗前升高(P0.05),血清CD8~+、IL-4、IL-10、VCAM-1水平较治疗前降低(P0.05);组间疗程结束后7天比较,上述指标差异有统计学意义(P0.05)。结论针灸联合西医治疗中重度间歇性过敏性鼻炎疗效满意,可有效缓解患者的临床症状,改善机体免疫状态,减轻炎症反应。