解毒通络方通过TGF-β1/Smad和ROCK通路对大鼠心肌纤维化的改善作用

目的:探讨解毒通络方在大鼠心肌纤维化进程中的作用,并阐明其作用机制.方法:30只SPF级Wistar大鼠随机分为正常对照组、模型组、卡托普利组、低剂量解毒通络方组和高剂量解毒通络方组(n=6),以5 mg·kg-1盐酸异丙肾上腺素皮下注射法复制大鼠心肌纤维化模型,卡托普利组、低剂量解毒通络方组和高剂量解毒通络方组大鼠分...     

Human Milk Metabolomics Are Related to Maternal Adiposity,Infant Growth Rate and Allergies: The Chinese Human Milk Project

The metabolomic profiles of Chinese human milk have been poorly documented. The objective of the study was to explore associations between human milk metabotypes, maternal adiposity, infant growth patterns, and risk of allergies. Two hundred mother–infant dyads from seven cities were randomly selected from the Chinese Human Milk Project (CHMP). Untargeted human milk metabolomic profiles were determined using HPLC-MS/MS. Two human milk metabotypes were identified using principal component analysis. Principal component (PC) 1 was characterized by high linoleic acid metabolites with low purine nucleosides and metabolites of glutamate and glutathione metabolism. PC 2 was characterized by high glycerophospholipids and sphingomyelins content. Higher PC1 scores were associated with slower infant growth rate and higher ambient temperature (p < 0.05). Higher PC 2 scores were related to higher maternal BMI and increased risk of infant allergies (p < 0.05). Future work is needed to understand the biologic mechanisms of these human milk metabotypes.     

Fraxinol attenuates LPS-induced acute lung injury by equilibrating ACE-Ang II-AT1R and ACE2-Ang (1-7)-Mas and inhibiting NLRP3

ContextAcute lung injury (ALI) is a serious heterogenous pulmonary disorder. Fraxinol was selected for this study since it is a simple coumarin compound, not previously investigated in ALI.ObjectivesThis study investigates the ALI therapeutic effect and mechanisms of fraxinol.Materials and methodsMale BALB/c mice were treated with fraxinol (20, 40, and 80 mg/kg) following intranasal injection of lipopolysaccharide (LPS; 10 μg in 50 μL). The mice in control group were intratracheally injected with 50 μL phosphate buffered saline (PBS). Raw264.7 cells were treated with fraxinol by 100 ng/mL LPS for 6 h, then treated by different concentrations of fraxinol (5, 10, and 25 μM) for 48 h. Cells in control group were treated with PBS.ResultsFraxinol with doses of 20, 40, and 80 mg/kg significantly attenuated LPS-induced lung injury in mice (lung injury score, 10.4, 31.2, 50.3%). Fraxinol attenuated the apoptosis and nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing-3 (NLRP3) activation induced by LPS (apoptosis, 18.3, 30.2, 55.6%; NLRP3, 30.0, 47.7, 63.6%). The anti-apoptosis and anti-inflammation effects of fraxinol were also confirmed in Raw264.7 cells (apoptosis, 38.8, 55.3, 68.9%; NLRP3, 20.6, 55.7, 73.9%).Discussion and conclusionThe anti-ALI effects of fraxinol maybe by equilibrating ACE-Ang II-AT1R and ACE2-Ang (1-7)-Mas axis and inhibiting NLRP3 inflammasome. Our research provides a candidate drug in the treatment of ALI.     

Vertical split fracture of the vertebral body following oblique lumbar interbody fusion: A case report

Rationale:Oblique lumbar interbody fusion (OLIF) is an effective and safe surgical technique widely used for treating spondylolisthesis; however, its use is controversial because of several associated complications, including endplate injury. We report a rare vertebral body fracture following OLIF in a patient with poor bone quality.Patient concerns:A 72-year-old male patient visited our clinic for 2 years with lower back pain, leg radiating pain, and intermittent neurogenic claudication.Diagnoses:Lumbar magnetic resonance imaging revealed L4-5 stenosis.Intervention:We performed OLIF with percutaneous pedicle screw fixation and L4 subtotal decompressive laminectomy. We resected the anterior longitudinal ligament partially for anterior column release and inserted a huge cage to maximize segmental lordosis. No complications during and after the operation were observed. Further, the radiating pain and back pain improved, and the patient was discharged. Two weeks after the operation, the patient visited the outpatient department complaining of sudden recurred pain, which occurred while going to the bathroom. Radiography and computed tomography revealed a split fracture of the L5 body and an anterior cage displacement. In revision of OLIF, we removed the dislocated cage and filled the bone cement between the anterior longitudinal ligament and empty disc space. Further, we performed posterior lumbar interbody fusion L4-5, and the screw was extended to S1.Outcomes:After the second surgery, back pain and radiating pain in the left leg improved, and he was discharged without complications.Lesson:In this case, owing to insufficient intervertebral space during L4-5 OLIF, a huge cage was used to achieve sufficient segmental lordosis after anterior column release, but a vertebral body coronal fracture occurred. In patients with poor bone quality and less flexibility, a huge cage and over-distraction could cause a vertebral fracture; hence, selecting an appropriate cage or considering a posterior approach is recommended.     

基因重组毕赤酵母表达瑞替普酶过程中的酶活性分析

目的 研究毕赤酵母诱导表达瑞替普酶过程中的关键酶活性.方法 以摇瓶培养为研究对象,在用甲醇诱导后,连续取样,破碎菌体制成无细胞悬液,检测乙醇氧化酶、甲醛脱氢酶、PDC、G-6-PD、ID、α-KGD和SD的活性.结果 乙醇氧化酶比活在0～6 h逐渐增加,在第6h达到最大44.5 U/mg蛋白.随后迅速下降.在第24～48 h有所回升,然后又逐渐降低.FAD比活在第0～48h逐渐增加.在第48h达到最大值6.72U/mg蛋白,随后逐渐降低.直至放瓶.G-6-PD比活在第2h～6h逐渐增加,在第6～24h逐渐降低,在第24～48h逐渐升高,48h后又逐渐降低直至放瓶.PDC比活在第0～6h逐渐降低,随后略有升高的趋势.ID、α-KGD、SD的活性变化有相似趋势.在前6 h酶活均迅速下降,在第6～24 h缓慢下降,随后ID活性继续缓慢下降,而α-KGD和SD活性在第2～48 h逐渐升高,在第48 h均达到最高值,然后又逐渐降低,直至放瓶.结论 根据酶活变化规律,可将整个诱导期分为4个阶段:第1阶段为诱导0～6 h,是甲醇适应期;第Ⅱ阶段为诱导6～24h,是快速生长期;第Ⅲ阶段为诱导24～48h,是产物积累期;第Ⅳ阶段为诱导48～72h,是代谢缓慢期.在甲醇适应期,甲醇完全氧化代谢流占主导地位.在快速生长期和产物积累期,代谢流逐渐向糖酵解途径和TCA循环途径迁移.     

脑梗塞对大鼠膀胱功能的影响

目的探讨脑梗塞对大鼠膀胱功能的影响。方法雄性SD大鼠,用线栓法制作大脑中动脉栓塞模型。脑梗塞24小时后,测定膀胱容量、排尿潜时、膀胱内压、尿流率、尿道抵抗值。结果大鼠脑梗塞后膀胱功能发生明显变化,排尿量减少、排尿潜时缩短、尿流率降低、尿道抵抗增强。结论脑梗塞可致大鼠膀胱过度活动症。*     

Cell-penetrating peptide-doxorubicin conjugate loaded NGR-modified nanobubbles for ultrasound triggered drug delivery

A new drug-targeting system for CD13⁺ tumors has been developed, based on ultrasound-sensitive nanobubbles (NBs) and cell-permeable peptides (CPPs). Here, the CPP-doxorubicin conjugate (CPP-DOX) was entrapped in the asparagine–glycine–arginine (NGR) peptide modified NB (CPP-DOX/NGR-NB) and the penetration of CPP-DOX was temporally masked; local ultrasound stimulation could trigger the CPP-DOX release from NB and activate its penetration. The CPP-DOX/NGR-NBs had particle sizes of about 200?nm and drug entrapment efficiency larger than 90%. In vitro release results showed that over 85% of the encapsulated DOX or CPP-DOX would release from NBs in the presence of ultrasound, while less than 1.5% of that (30?min) without ultrasound. Cell experiments showed the higher cellular CPP-DOX uptake of CPP-DOX/NGR-NB among the various NB formulations in Human fibrosarcoma cells (HT-1080, CD13⁺). The CPP-DOX/NGR-NB with ultrasound treatment exhibited an increased cytotoxic activity than the one without ultrasound. In nude mice xenograft of HT-1080 cells, CPP-DOX/NGR-NB with ultrasound showed a higher tumor inhibition effect (3.1% of T/C%, day 24), longer median survival time (50 days) and excellent body safety compared with the normal DOX injection group. These results indicate that the constructed vesicle would be a promising drug delivery system for specific cancer treatment.     

P253R突变型FGFR2Ⅲc胞外段的表达、复性及活性研究(英文)

成纤维细胞生长因子(Fibroblast growth factor,FGF)具有促进细胞增殖,诱导新生血管形成等重要生理作用,与肿瘤的发生及发展也有十分密切的关系。P253R是Apert综合症中发现的一种突变,可使FGFR2IIIc与FGF2亲和力大大增加,从而导致过度自分泌和旁分泌活性,引起骨骼发育异常。从人胎盘组织提取总RNA,通过RT-PCR扩增得到野生型FGFR2IIIc胞外段基因片段(wsFGFR2);再利用重叠延伸法以wsFGFR2基因片段为模板扩增得到P253R突变型FGFR2IIIc胞外段基因片段(msFGFR2,P253R是Apert综合征中发现的一种突变,可使FGFR2与FGF2亲和力大大增加)。msFGFR2基因克隆到pET3c载体,并在大肠杆菌BL21(DE3)中以包涵体的形式表达。经凝胶层析复性和肝素亲和层析纯化得到复性成功的活性蛋白,复性率为12%,纯度大于95%。MTT结果表明,msFGFR2能显著抑制FGF2促NIH3T3细胞增殖能力,并抑制前列腺癌DU145细胞的增殖,提示msFGFR2能有效阻断FGFs的细胞内信号通路,具有很好的产业化和临床应用前景。     

白内障超声乳化术后应用非甾体抗炎药滴眼剂的疗效分析

目的 观察0.1%吲哚美辛滴眼剂、0.03%欧可芬滴眼剂和0.025%地塞米松滴眼剂对白内障超声乳化联合人工晶状体植入术后炎症的疗效。方法 随机将72例老年性白内障患者分为3组，分别于术前术后滴用0．1％吲哚美辛滴眼剂、0.03%欧可芬滴眼剂和0.025%地塞米松滴眼剂，三组均合并使用抗生素滴眼剂，术后询问症状，进行视力、裂隙灯、眼底镜、眼压检查。结果 术后第1、3、7、14天天三组症状、体征评分差异无显著性。不同时间三组眼压值差异无显著性。结论 非甾体抗炎药滴眼剂与糖皮质激素滴眼剂在控制白内障亏声乳化联合人工晶状体植入术后炎症反应具有相同疗效。