异种脱蛋白骨修复长骨大段骨缺损实验研究

目的研究改良法制备的异种脱蛋白骨（deproteinated bone,DPB）作为组织工程支架材料修复大动物长骨大段缺损24周后新生骨的生物力学变化。方法山羊18只,采用完全随机设计法分为正常骨对照组、自体骨组和实验组,每组6只,在自体骨组和实验组每只山羊右侧胫骨中下段造成胫骨总长度20％骨膜和骨缺损,正常骨对照组不截骨,其余2组分别在缺损处植入自体骨、DPB＋自体MSCs＋rhBMP2,采用半环槽外固定,术后24周取手术侧胫骨进行生物力学检测。结果术后24周,正常骨对照组、自体骨组和实验组新骨生物力学相比无统计学差异（P〉0．05）。结论改良法制备的异种DPB复合物作为组织工程支架材料修复大动物长骨大段缺损形成的新骨,其生物力学与正常骨对照组、自体骨组相当,可作为骨移植材料试应用于临床。     

吡咯烷二硫代氨基甲酸盐对大鼠缺血性心肌损伤后心室扩张及心衰的干预效应

目的研究核因子-κB（nuclearfactor—κB,NF—κB）抑制剂——吡咯烷二硫代氨基甲酸盐（pyrrolidine dithiocarbamate,PDTC）对异丙肾上腺素（isoprenaline,ISO）所致大鼠缺血性心肌损伤后心室扩张、心衰的防治作用及其作用机制。方法应用大剂量ISO建立大鼠缺血性心肌损伤模型。70只雄性Wistar大鼠利用随机数字表法分为3组：对照组20只,实验组（ISO组）30只,治疗组（ISO＋PDTC组）20只。检查心肌病理形态学、心肌NF—κB激活情况、心肌单核细胞趋化蛋白-1（MCP-1）mRNA表达情况及血清MCP-1水平,并在实验第14天进行超声心动图检查,观察心室扩张及心功能变化情况。结果ISO所致大鼠缺血性心肌损伤后心肌NF—κB被激活,心肌MCP-1mRNA表达增加（P〈0．01）,血清MCP-1增高（P〈0．01）;PDTC能够抑制NF—κB的激活,下调心肌MCP-1mRNA的表达及血清MCP-1水平（P〈0．01）,减轻心肌炎症反应,减小心肌细胞损伤范围,但同时可导致肉芽组织替代受损心肌延迟;实验第14天,治疗组左心室收缩末期内径（LVESD）较实验组减小（P〈0．05）,射血分数（EF）优于实验组（P〈0．05）。结论应用PDTC能够对心肌缺血性损伤后的心室扩张、心功能损害起到-定的防治作用,该作用可能主要得益于在心肌损伤急性期对心肌细胞的保护作用,其机制可能与抑制NF—κB的激活进而下调MCP-1的表达、减轻心肌炎症损伤有关。     

Evolution of ischemic stroke drug clinical trials in mainland China from 2005 to 2021

BackgroundTo assess the temporal changes in the characteristics of ischemic stroke drug clinical trials conducted in mainland China in 2005–2021.MethodsA statistical analysis of registered clinical trials on ischemic stroke was performed using the platform of the Center for Drug Evaluation of China National Medical Products Administration, the Chinese Clinical Trial Registry, and ClinicalTrials.gov websites.ResultsFrom January 1, 2005 to August 1, 2021, a total of 384 registered drug clinical trials on ischemic stroke were identified in mainland China. Over time, the number of trials gradually increased each year, with a significant growth in 2014, from 16 in 2013 to 42 in 2014. Phase IV trials (31.8%) accounted for the majority, followed by phase II (16.4%), phase I (10.9%), and phase III (8.6%). In terms of sponsorship, the proportion of investigator‐initiated trials (IITs) (60.7%) was higher than industry‐sponsored trials (ISTs) (39.3%). Additionally, trials involving traditional Chinese medicines (TCMs) (36.2%) accounted for the largest proportion, followed by trials involving antithrombotic therapy (19.5%) and cerebral protection agents (16.7%). Furthermore, over the past 17 years, the number of leading drug clinical trial units for ischemic stroke in mainland China has continuously increased. The leading principal units from Beijing, Shanghai, Guangdong, Jiangsu, and Liaoning accounted for the majority of the trials (67.4%).ConclusionIn the past 17 years, great progress has been made in the research and development (R&D) of drugs and clinical trials for ischemic stroke in mainland China. The most extensive progress was observed in TCMs, antithrombotic therapy, and cerebral protection agents. More clinical trials are needed to confirm whether the newly developed drugs can improve the clinical efficacy of ischemic stroke. Simultaneously, more pharmaceutical R&D efforts of innovative drugs are warranted.     

Lignin-based composites for high-performance supercapacitor electrode materials

With the rapid development of the global economy, the depletion of fossil fuels and the intensification of environmental pollution, there is an increasingly urgent need for new and green electrochemical energy storage technologies in society. In this thesis, ligninsulfonate/polyaniline nanocomposites were synthesized by in situ chemical oxidation using aniline as the monomer, lignin as the template and dopant, and ammonium persulfate as the oxidant. The results showed that the average diameter of the ligninsulfonate/polyaniline nanocomposite was 85 nm, and the composite electrode exhibited good electron conduction ability and excellent capacitive performance by ligninsulfonate doping. The electrode material showed the best electrochemical performance when the ligninsulfonate addition was 0.1 g. The specific capacitance can reach 553.7 F g⁻¹ under the current density of charge/discharge 1 A g⁻¹, which is higher than that of the pure PANI electrode. The composite electrode material has good multiplicative performance and cycling stability, and the capacitance retention rate can be maintained at 68.01% after 5000 cycles at a charge/discharge current density of 10 A g⁻¹ (three-electrode system), and the capacitance retention rate can be maintained at 54.84% after 5000 cycles at a charge/discharge current density of 5 A g⁻¹ (two-electrode system).

The lignosulfonate/polyaniline nanocomposite electrode material was made by polymerization of aniline with lignosulfonate as dispersant and structure-directing agent. Redox can convert the catechol/quinone groups on lignin, promoted by electron transfer of polyaniline.     

急性乙型肝炎患者外周血单个核细胞颗粒溶素mRNA定量测定及临床意义

目的应用实时荧光定量逆转录聚合酶链反应（RT-PCR）检测乙型肝炎（简称乙肝）患者外周血单个核细胞（PBMC）中颗粒溶素（GNLY）mRNA的表达,探讨GNLY基因表达水平与急性乙肝的关系。方法实时荧光定量RT-PCR分别检测40例急性乙肝患者及100名正常对照的PBMC的GNLY基因表达水平,同时检测血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）水平。结果急性乙肝患者发病期mRNA表达显著高于正常对照组（P〈0.01）,恢复期GNLY基因表达与正常对照组差异无统计学意义（P〉0.05）。乙肝患者GNLYmRNA与血清ALT、AST呈正相关。结论实时荧光定量RT-PCR检测GNLY mRNA的表达准确可靠。患者外周血GNLY基因表达水平与急性乙肝的发生发展存在一定的相关性。     

颐脑解郁方改善抑郁症肾虚肝郁型患者中医证候的临床观察

目的观察颐脑解郁方对抑郁症肾虚肝郁型患者中医证候的影响。方法将60例抑郁症肾虚肝郁型患者随机分为颐脑解郁组30例和氟西汀组30例。颐脑解郁组给予颐脑解郁方治疗,氟西汀组给予氟西汀治疗,用药疗程均为6周。在治疗2周、4周、6周时,观察两组患者主要中医证候的改善情况。结果颐脑解郁方对性欲减退、时有太息的疗效在2周、4周、6周时均优于氟西汀(P<0.05或0.01);对腰酸背痛的疗效在2周、4周时优于氟西汀(P<0.01),在6周时组间比较无明显差异(P>0.05);对胁肋胀痛的疗效在2周时优于氟西汀(P<0.01),在4周、6周时组间比较无明显差异(P>0.05);对神思不聚的疗效在2周、4周时组间比较无明显差异(P>0.05),在6周时优于氟西汀(P<0.01);对忧愁善感、兴趣索然、精神委靡的疗效与氟西汀相当(P>0.05)。结论颐脑解郁方能有效改善抑郁症肾虚肝郁型患者的主要中医证候。     

愈疡胶囊对细菌感染皮炎模型大鼠的抗炎作用及对TLR/NF-κB通路的影响

目的:研究愈疡胶囊对细菌感染皮炎模型大鼠的抗炎作用及对Toll样受体/核因子κB(TLR/NF-κB)通路的影响.方法:采用肉汤稀释法测定愈疡胶囊对金黄色葡萄球菌的最低抑菌浓度(MIC)和最低杀菌浓度(MBC).将50只大鼠随机分为模型组、阳性对照组(阿莫西林克拉维酸钾,以阿莫西林计120 mg/kg)和愈疡胶囊高、中...     

GAD67-GFP转基因小鼠三叉神经脊束核吻侧亚核和极间亚核内GABA和甘氨酸共存神经元的观察

本文以GAD67-GFP基因敲入小鼠为研究工具,利用免疫荧光组织化学双重染色技术观察了小鼠三叉神经脊束核(spi-nal trigeminalnucleus,V)的吻侧亚核(Vo)和极间亚核(Vi)神经元内谷氨酸脱羧酶67[GAD67,γ-氨基丁酸(GABA)能神经元的标识物质]和甘氨酸(glycine,Gly)的定位分布和共存情况。结果显示,在Vo和Vi内均有比较密集分布的GAD67和Gly阳性神经元。此外,在Vo和Vi内也可见一些GAD67阳性神经元同时呈Gly阳性反应,即存在GAD67/Gly双标神经元。结果表明,Vo和Vi内有GABA和Gly共存神经元,它们可能在初级传入信息的传递和调制中发挥重要作用。     

骨髓间充质干细胞不同移植方法治疗脊髓损伤的实验研究

为探讨骨髓基质干细胞(MSCs)不同的移植方法对脊髓损伤修复的影响,我们采用静脉移植、蛛网膜下腔移植或腹腔移植荧光标记MSCs的方法检测MSCs在损伤处的分布迁移情况及运动功能恢复情况。结果显示:各种移植方法在损伤脊髓节段上、下均可检测到荧光标记的MSCs,不同移植方法在损伤脊髓内荧光标记的MSCs数量有所不同。损伤脊髓节段和非损伤脊髓节段内的细胞数量和密度也有明显差异(P<0.05)。BBB评分显示:术后第2d各组平均未超过1分者,移植后的1周内无明显差异(P>0.05);3周后,各组间差异也不大(P>0.05),但各移植组同对照组相比有明显差异(P<0.05)。以上结果提示:通过各种移植方法MSCs均可迁移到损伤脊髓节段,并在该部位存活、聚集和向损伤部位迁移,说明MSCs不同的移植方法对于治疗脊髓损伤均有一定的作用。     

经冠脉自体骨髓单个核细胞移植治疗扩张型心肌病的随机对照研究

目的采用随机、对照、前瞻性的临床试验,旨在评价经冠脉自体骨髓单个核细胞(BMMNCs)移植治疗扩张型心肌病的有效性和安全性。方法连续入选26例扩张型心肌病患者,细胞移植组(14例)行经冠脉自体BMMNCs移植联合标准药物治疗;对照组(12例)接受标准药物治疗。结果3个月后,细胞移植组的左室射血分数(LVEF)由(29.21±4.41)%提高至(31.08±4.54)%(P=0.004),与对照组比较,无统计学差异(P=0.216);PET/CT示心肌13N-NH3灌注和18F-FDG代谢显像显著改善;氮末端脑钠素前体(NT-proBNP)、6min步行试验和明尼苏达生活质量评分的改变均具有统计学意义。结论经冠脉自体BMMNCs移植治疗扩张型心肌病安全而有效,可能是通过BMMNCs转分化为心肌细胞和血管内皮细胞而改善心功能。