牙源性干细胞用于治疗神经系统疾病的研究进展

神经系统疾病包括中枢神经系统疾病和外周神经系统疾病,如脊髓损伤、阿尔茨海默症、脑卒中、慢性脑缺血和坐骨神经损伤等,目前尚无有效治疗方法。间充质干细胞具有自我更新和多向分化潜能,成为治疗神经系统疾病的新策略。牙源性干细胞来源于胚胎神经嵴,与神经组织同源。与其他组织来源的干细胞相比,具有容易获得、取材损伤小和免疫排斥反应低等特点。本文就牙源性干细胞应用于神经系统疾病组织修复与再生的研究进展作一综述。     

Silencing of Nesprin‐2 inhibits the differentiation of myofibroblasts from fibroblasts induced by mechanical stretch

Mechanical force plays a pivotal role in the pathogenesis of hypertrophic scar (HTS). Dermal fibroblasts and myofibroblasts are the key cells involved in HTS. Myofibroblasts in HTS possess different biochemical and biophysical characteristics by which myofibroblasts are often distinguished from fibroblasts. The role of mechanotransducers outside the nucleus in the pathogenesis of HTS has been reported in many studies. However, the role of Nesprin‐2 in HTS is not clear. Hence, we aim to construct a cell model of HTS and explore the role of Nesprin‐2 in this process. Myofibroblasts and fibroblasts were isolated from HTS and healthy skin tissues of the same patient. Fibroblasts were exposed to cyclic stretch with 10% magnitude and a frequency of 0.1 Hz for 3 days, 5 days, and 7 days, respectively. After the cell model was confirmed, fibroblasts transfected with siRNA targeting human Nesprin‐2 were exposed to cyclic stretch. The mechanical behaviour and biochemical reaction of the dermal fibroblasts were analysed. The stretched fibroblasts at day 5 showed the same mechanotransductive and biochemical features as unstretched myofibroblasts. Mechanical strain could induce the myofibroblasts differentiation and a cell model of HTS was established successfully at day 5. The expressions of lamin A/C, alpha‐smooth muscle actin, transforming growth factor beta 1, and collagen type I in fibroblasts were reduced by the silencing of Nesprin‐2. Mechanical strain could induce the myofibroblasts differentiation and silencing of Nesprin‐2 could block the mechanical stimulation of terminal myofibroblasts differentiation. Nesprin‐2 might be a potential target to treat the HTS.     

3T高分辨MR对颈动脉粥样硬化斑块表面钙化与斑块稳定性的量化分析

目的:通过3T高分辨MR扫描,分析颈动脉斑块的表面钙化与斑块表面溃疡和斑块内出血的关系。方法:使用3T MR扫描仪对颈动脉斑块患者进行局部高分辨扫描,分析51例患者的钙化斑块。共纳入183个层面,记录每一层面的表面钙化类型(点状、弧形或大片状)、钙化部位(边缘型、中央型)、同一或相邻层面有无斑块内出血和表面溃疡,使用χ2检验分别分析钙化类型和部位与斑块内出血及表面溃疡的关系。结果:183层表面钙化斑块中,122层伴斑块内出血(66.7%),86层可见表面溃疡(47%)。按钙化类型和部位划分后,158层为点状、弧形的不规则钙化,25层为大片状钙化;142层为边缘钙化,41层为中央钙化。不规则钙化组伴斑块内出血的几率显著高于大片状钙化组(72.8% vs 28%,P<0.01);边缘钙化组较中央钙化组更易伴斑块内出血(71.1% vs 51.2%,P<0.05)。然而,不规则钙化、边缘型钙化与大片状钙化、中央型钙化比较,表面溃疡的发生率无统计学差异(P>0.05)。结论:表面钙化是斑块不稳定的重要因素之一,容易导致斑块内出血和溃疡形成;表面钙化的类型、部位对斑块的稳定性有重要影响。     

138例晚期食管癌的化疗疗效和预后因素分析

背景与目的:晚期食管癌患者预后差,目前仍无标准的治疗方案,影响其预后的独立因素也不明确。本研究旨在分析晚期食管癌的化疗疗效,并探讨影响其预后的因素。方法:回顾性分析中国医学科学院中国协和医科大学肿瘤医院1984年12月至2006年4月收治的、经病理和/或细胞学确诊的138例初治晚期食管鳞癌患者的临床资料。全组患者分为新药组(含紫杉醇、健择或草酸铂)和非新药组(不含紫杉醇、健择或草酸铂)。新药组有68例,其中化疗方案中含顺铂64例(94.1%);非新药组有70例,其中化疗方案中含顺铂48例(68.6%)。对可能影响生存因素的比较采用log-rank检验,死亡相对风险的比较采用Cox比例风险模型进行计算。结果:全组138例患者的化疗有效率47.8%,中位疾病进展时间4个月,中位生存时间10个月。采用含紫杉醇或健择化疗新药组患者有效率(58.8%)明显高于非新药组(37.1%)(P=0.011)。单因素分析表明,年龄、治疗前血红蛋白水平、化疗周期数、化疗近期疗效、疾病进展时间以及治疗手段与预后相关。多因素分析表明,疾病进展时间、治疗手段、疗前血红蛋白水平是影响生存的独立预后因素。结论:紫杉醇或健择联合顺铂方案用于晚期食管癌化疗有较高的有效性。疾病进展时间、治疗手段、疗前血红蛋白水平是影响生存的独立预后因素。     

大剂量甲氨蝶呤静脉给药时间对淋巴瘤患者脑脊液中药物浓度的影响

背景与目的:甲氨蝶呤(methotrexate,MTX)在脑脊液中高于最小有效治疗浓度是治疗中枢淋巴瘤的必要条件,目前尚不明确大剂量MTX(high doseMTX,HD-MTX)静脉给药时间对MTX穿透血脑屏障的影响.本研究探索HD-MTX静脉不同给药时间对脑脊液中MTX浓度的影响,以获得更好的中枢淋巴瘤防治效果并尽可能减少MTX外周毒性.方法:34例非霍奇金淋巴瘤患者分别接受MTX 1～3g/m2 6 h持续静脉给药或24 h持续静脉给药,其中17例交替使用两种给药方法;采用高效液相色谱法检测MTX停药0 h、24 h、48 h的MTX血清浓度,及停药0 h后脑脊液中MTX浓度;比较两组血中和脑脊液中MTX浓度以及毒性反应,并对影响MTX浓度的因素进行相关分析.结果:给药结束时6 h给药组的MTX血清浓度显著高于24 h给药组:自身对照结果6 h给药组的脑脊液中MTX浓度为0.70 Ixmol/L,明显高于24 h给药组的0.49 Ixmol/L(校正值,P=0.044).MTX的脑脊液浓度与血清浓度呈正相关,中枢侵犯患者脑脊液MTX浓度显著高于无中枢侵犯的患者.自身对照结果6 h组和24 h组Ⅱ～Ⅳ度粘膜炎的发生率分别15.4%和37.8%.Ⅲ～Ⅳ度骨髓抑制的发生率分别为46.2%和67.6%.结论:在提高MTX的中枢浓度和降低外周毒性方面,HD-MTX 6 h给药方案优于24 h给药方案.     

Synergistic integration of metal nanoclusters and biomolecules as hybrid systems for therapeutic applications

Therapeutic nanoparticles are designed to enhance efficacy, real-time monitoring, targeting accuracy, biocompatibility, biodegradability, safety, and the synergy of diagnosis and treatment of diseases by leveraging the unique physicochemical and biological properties of well-developed bio-nanomaterials. Recently, bio-inspired metal nanoclusters (NCs) consisting of several to roughly dozens of atoms (<2 nm) have attracted increasing research interest, owing to their ultrafine size, tunable fluorescent capability, good biocompatibility, variable metallic composition, and extensive surface bio-functionalization. Hybrid core–shell nanostructures that effectively incorporate unique fluorescent inorganic moieties with various biomolecules, such as proteins (enzymes, antigens, and antibodies), DNA, and specific cells, create fluorescently visualized molecular nanoparticle. The resultant nanoparticles possess combinatorial properties and synergistic efficacy, such as simplicity, active bio-responsiveness, improved applicability, and low cost, for combination therapy, such as accurate targeting, bioimaging, and enhanced therapeutic and biocatalytic effects. In contrast to larger nanoparticles, bio-inspired metal NCs allow rapid renal clearance and better pharmacokinetics in biological systems. Notably, advances in nanoscience, interfacial chemistry, and biotechnologies have further spurred researchers to explore bio-inspired metal NCs for therapeutic purposes. The current review presents a comprehensive and timely overview of various metal NCs for various therapeutic applications, with a special emphasis on the design rationale behind the use of biomolecules/cells as the main scaffolds. In the different hybrid platform, we summarize the current challenges and emerging perspectives, which are expected to offer in-depth insight into the rational design of bio-inspired metal NCs for personalized treatment and clinical translation.Key words: Metal nanoclusters, Biomolecule, Nanoparticles, Hybrid system, Synergistic properties, Fluorescence, Bioprobe, Therapy     

上海市居民期望寿命与健康期望寿命的差异分析

目的:分析不同年龄、性别的上海市居民期望寿命和健康期望寿命的差异。方法:分析比较上海市和全球长寿国家/地区期望寿命的变化趋势;利用全球疾病负担研究建立的疾病和健康结局的失能权重,应用Sullivan法测算上海市居民健康期望寿命,并分析不同年龄、性别人群的健康寿命损失。结果:近40年,上海市期望寿命增长了10.86岁,2...     

尿甲壳质酶蛋白-40对新生儿急性尿路感染的早期诊断价值及与其他指标相关性分析

目的 探讨尿甲壳质酶蛋白-40(YKL-40)对新生儿急性尿路感染(UTI)的早期诊断价值,并分析其与其他临床指标的相关性.方法 选择2015年1月至2018年6月在本院就诊的疑似急性UTI患儿88例作为研究对象,取清洁中段尿10 mL,放人带塞无菌试管中并在1 h内送检,经细菌培养后进行成分分析.根据细菌培养结果将患...     

负压治疗联合盆底肌训练对前列腺癌根治术后患者控尿功能及性功能的影响

目的探讨负压治疗联合盆底肌训练对前列腺癌根治术后患者控尿功能及主观幸福感的影响。方法将中山大学附属第三医院2016年10月至2019年4月泌尿外科确诊为前列腺癌并行腹腔镜下前列腺癌根治术治疗的70例患者,按随机数字表法分为干预组和对照组各35例,其中对照组35例采用常规护理(盆底肌功能锻炼),干预组35例在常规护理基础上,术后6周起再增加负压治疗。比较对照组和干预组术后6周、10周、18周控尿功能恢复情况,同时进行国际勃起功能评分表(IIEF-5)评分及主观幸福感调查,观察其治疗效果。结果干预组术后6周、10周、18周尿失禁评分中位值分别2分、1分与0分,低于对照组的2分、2分与2分,提示干预组术后平均控尿功能恢复时间较对照组短,差异有统计学意义(P<0.05);此外干预组相比对照组,IIEF-5评分及主观幸福感评分上升速度较快,提示干预组术后勃起功能和生活质量改善情况明显优于对照组。结论负压治疗联合盆底肌训练对前列腺癌根治术后患者的控尿功能和性功能有明显改善,且缩短其恢复时间。     

肝切除术后门静脉血栓形成16例诊治分析

目的总结16例肝切除术后门静脉血栓(PH-PVT)形成的诊治方法及预后情况。方法回顾性分析2015年2月至2021年2月北京清华长庚医院收治的16例PH-PVT患者的临床资料,总结其临床特征及诊疗经过。16例均经增强CT检查确诊。其中男7例,女9例,年龄34～74(58.44±11.29)岁。肝细胞癌(HCC) 4例,肝门部胆管癌(PHCC) 8例,胆管癌1例,胆囊癌(GBca)侵犯肝脏1例,肝内胆管乳头状瘤1例,肝内胆管结石1例。结果 16例中除2例患者于肝切除术后第144天和第351天确诊为慢性PH-PVT外,其余14例患者PH-PVT确诊时间为术后第1～24天,平均为第9天。4例患者PH-PVT形成后无任何临床症状,9例出现不明原因的发热,4例出现腹痛和恶心症状,3例出现腹胀、呕血、便血和黄疸症状,5例最终发展为肝性脑病和肝衰竭。经抗凝、溶栓和手术等治疗后,8例好转出院,8例死亡。结论 PH-PVT发生的危险因素众多,可经增强CT确诊,其治疗方法包括抗凝、溶栓和手术取栓等。目前没有明确的PH-PVT预测和预防方法,早发现、早治疗是改善患者预后的关键。