ANP在大鼠高血压进展为心力衰竭中的作用

目的：探讨心房钠尿钛ANP 在高血压心力衰竭发展过程中的变化和氨氯地平保护心肌细胞的作用。方法：对大鼠行腹主动 脉结扎术，术后随机选择40 只大鼠分为氨氯地平（中、高、低剂量）组以及模型组，另外选取10 只健康雄性SD 大鼠作为假手术 组。采用ELISA 方法检测各组血清ANP 浓度变化。结果：随着心功能不全加重，ANP 水平逐渐上升。氨氯地平用药组大鼠的心功 能改善明显优于模型组，ANP 明显降低，且随着氨氯地平用药量上升，心功能不断改善，ANP显著下降，P<0.05。结论：对血清 ANP浓度进行测定能够反映出高血压大鼠模型心室功能不全及充血性心力衰竭严重程度。而氨氯地平能够影响机体的ANP 分 泌对心肌细胞起到保护作用，从而有效抑制心室重构，延缓高血压心力衰竭疾病进展。     

Development of PEGylated serum albumin with multiple reduced thiols as a long-circulating scavenger of reactive oxygen species for the treatment of fulminant hepatic failure in mice

Reactive oxygen species (ROS) are involved in the pathophysiology of fulminant hepatic failure. Therefore, we developed polyethylene glycol-conjugated bovine serum albumin with multiple reduced thiols (PEG-BSA-SH) for the treatment of fulminant hepatic failure. As a long-circulating ROS scavenger, PEG-BSA-SH effectively scavenged highly reactive oxygen species and hydrogen peroxide in buffer solution. PEG-BSA-SH showed a long circulation time in the plasma after intravenous injection into mice. Fulminant hepatic failure was induced by intraperitoneal injection of lipopolysaccharide and d-galactosamine (LPS/d-GalN) into mice. The LPS/d-GalN-induced elevation of plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels was significantly inhibited by a bolus intravenous injection of PEG-BSA-SH. Furthermore, the changes in hepatic lipid peroxide and hepatic blood flow were effectively suppressed by PEG-BSA-SH. In contrast, l-cysteine, glutathione, and dithiothreitol, three traditional reduced thiols, had no statistically significant effects on the serum levels of ALT or AST. These findings indicate that PEG-BSA-SH is a promising ROS scavenger and useful in the treatment of fulminant hepatic failure.     

血浆置换与血浆灌流联合治疗肝衰竭的疗效及对炎症因子及肝功能的影响

目的:探讨血浆置换(PE)与血浆灌流(PP)联合治疗肝衰竭的疗效和安全性,以及其对炎症因子和肝功能的影响。方法:选择2014年2月至2016年2月我院收治的98例肝衰竭患者为研究对象,按随机数字表法分为实验组和对照组,每组各49例。实验组行PE联合PP治疗,对照组行单纯PE治疗。采用全自动生化分析仪检测治疗前后患者肝功能指标;采用酶联免疫吸附法(ELISA)检测血清中炎症因子C-反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)水平。对比两组患者临床总有效率、不良反应发生率以及治疗前后肝功能指标和炎症因子水平。结果:实验组临床总有效率为91.84%,显著高于对照组的73.47%,差异有统计学意义(P0.05)。实验组不良反应发生率为10.20%,明显低于对照组的38.78%,差异有统计学意义(P0.05)。治疗后两组患者血清谷丙转氨酶(ALT)、总胆红素(TBIL)和血氨(NH3)水平明显下降(均P0.05),白蛋白(ALB)和凝血酶活动度(PTA)明显上升(均P0.05),治疗后实验组血清ALT、TBIL和NH3水平均低于对照组,ALB和PTA水平均高于对照组,差异具有统计学意义(均P0.05)。治疗后血清中炎症因子CRP、TNF-α、IL-6水平均低于治疗前,实验组血清CRP、TNF-α、IL-6水平均低于对照组(均P0.05)。结论:PE与PP联合治疗肝衰竭具有较好的疗效,且不良反应发生率较低,可有效清除炎症因子,改善肝功能,提高患者生存质量。     

Functional lung imaging with synchrotron radiation: Methods and preclinical applications

Many lung disease processes are characterized by structural and functional heterogeneity that is not directly appreciable with traditional physiological measurements. Experimental methods and lung function modeling to study regional lung function are crucial for better understanding of disease mechanisms and for targeting treatment. Synchrotron radiation offers useful properties to this end: coherence, utilized in phase-contrast imaging, and high flux and a wide energy spectrum which allow the selection of very narrow energy bands of radiation, thus allowing imaging at very specific energies. K-edge subtraction imaging (KES) has thus been developed at synchrotrons for both human and small animal imaging. The unique properties of synchrotron radiation extend X-ray computed tomography (CT) capabilities to quantitatively assess lung morphology, and also to map regional lung ventilation, perfusion, inflammation and biomechanical properties, with microscopic spatial resolution. Four-dimensional imaging, allows the investigation of the dynamics of regional lung functional parameters simultaneously with structural deformation of the lung as a function of time. This review summarizes synchrotron radiation imaging methods and overviews examples of its application in the study of disease mechanisms in preclinical animal models, as well as the potential for clinical translation both through the knowledge gained using these techniques and transfer of imaging technology to laboratory X-ray sources.     

骨化三醇联合补气口服液对慢性肾功能衰竭患者血清瘦素及睾酮水平的影响

目的:探究骨化三醇联合补气口服液对慢性肾功能衰竭患者血清瘦素及睾酮水平的影响。方法:选取我院诊治慢性肾功能衰竭患者116例为研究对象,根据随机数字对照表分为对照组(58例)与试验组(58例)。两组患者均常规给予血管紧张素酶抑制剂或β受体阻滞剂,对照组给予口服骨化三醇胶丸,试验组在对照组的基础上联合给予补气口服液。治疗结束后,比较两组患者肾功能指标、血清瘦素及睾酮水平、营养生化指标。结果:治疗结束后,两组患者血清肌酐(Cr)、血尿素氮(BUN)及瘦素水平均较治疗前显著降低(P0.05),睾酮、血钙水平较治疗前升高(P0.05),血磷水平降低(P0.05)。与对照组相比,试验组血Cr、BUN及瘦素水平较低(P0.05),而血清睾酮、血钙水平较高,血磷水平较低(P0.05)。结论:骨化三醇联合补气口服液能够更有效改善慢性肾功能衰竭患者的肾功能,纠正患者体内电解质紊乱,改善患者食欲不振营养不良症状,推测其与降低血清瘦素水平及升高睾酮水平有关。     

Epigenetic silencing of TIMP4 in heart failure

Tissue inhibitor of matrix metalloprotease 4 (TIMP4) is endogenously one of the key modulators of matrix metalloprotease 9 (MMP9) and we have reported earlier that cardiac specific TIMP4 instigates contractility and helps in differentiation of cardiac progenitor cells. Although studies show that the expression of TIMP4 goes down in heart failure but the mechanism is unknown. This study aims to determine the mechanism of silencing of TIMP4 in heart failure progression created by aorta‐vena cava (AV) fistula. We hypothesize that there is epigenetic silencing of TIMP4 in heart failure. To validate this hypothesis, we created heart failure model by creating AV fistula in C57BL/6 mice and looked into the promoter methylation (methylation specific PCR, high resolution melting, methylation sensitive restriction enzyme and Na bisulphite treatment followed by sequencing), histone modification (ChIP assay) and microRNAs that regulate TIMP4 (mir122a) and MMP9 (mir29b and mir455‐5p). The physiological parameters in terms of cardiac function after AV fistula were assessed by echocardiography. We observed that there are 7 CpG islands in the TIMP4 promoter which get methylated during the progression of heart failure which leads to its epigenetic silencing. In addition, the up‐regulated levels of mir122a in part, contribute to regulation of TIMP4. Consequently, MMP9 gets up‐regulated and leads to cardiac remodeling. This is a novel report to explain the epigenetic silencing of TIMP4 in heart failure.     

Identification of potentially critical genes in the development of heart failure after ST-segment elevation myocardial infarction (STEMI)

Heart failure (HF) remains a common complication after acute ST-segment elevation myocardial infarction (STEMI). Here, we aim to identify critical genes related to the developed HF in patients with STEMI using bioinformatics analysis. The microarray data of GSE59867, including peripheral blood samples from nine patients with post-infarct HF and eight patients without post-infarct HF, were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between HF and non-HF groups were screened by LIMMA package. Functional enrichment analyses of DEGs were conducted, followed by construction of a protein-protein interaction (PPI) network. The dynamic messenger RNA (mRNA) level of the hub genes during the follow-up was analyzed to further elucidate their role in HF development. A total of 58 upregulated and 75 downregulated DEGs were screen out. They were mainly enriched in biological processes about inflammatory response, extracellular matrix organization, response to cAMP, immune response, and positive regulation of cytosolic calcium ion concentration. Pathway analysis revealed that the DEGs were also involved in hematopoietic cell lineage, pathways in cancer, and extracellular matrix-receptor interaction. In the PPI network consisting of 58 nodes and 72 interactions, CXCL8 (degree = 15), THBS1 (degree = 8), FOS (degree = 7), and ITGA2B (degree = 6) were identified as the hub genes. In the comparison of patients with and without post-infarct HF, the mRNA level of these hub genes were all higher within 30 days but reached similar at 6 months after STEMI. In conclusion, CXCL8, THBS1, FOS, and ITGA2B may play important roles in the development of HF after acute STEMI.     

替加环素对重症呼吸机相关性肺炎患者呼吸力学与血清炎症因子的影响

目的:研究替加环素治疗重症呼吸机相关性肺炎的疗效及对患者呼吸力学及血清炎症因子水平的影响。方法:选取2014年9月至2016年8月本院收治的88例重症呼吸机相关性肺炎患者,根据投硬币法分为观察组和对照组,44例每组。对照组采用常规治疗方案,观察组在常规治疗基础上采用替加环素治疗。观察并比较两组患者治疗前后呼吸力学、血清炎症因子指标及临床疗效。结果:治疗后,观察组临床总有效率高于对照组(P0.05)。观察组肺部感染控制时间、治愈时间均短于对照组(P0.05)。观察组呼吸做功、气道峰压、气道阻力均低于对照组,动态顺应性高于对照组(P0.05)。观察组IL-6、IL-8、TNF-α水平低于对照组(P0.05)。结论:重症呼吸机相关性肺炎患者经替加环素治疗后,能有效改善患者呼吸力学与血清炎症因子水平,临床疗效良好。     

Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection

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Bone remodelling around the tibia due to total ankle replacement: effects of implant material and implant–bone interfacial conditions

Abstract

One of the major causes of implant loosening is due to excessive bone resorption surrounding the implant due to bone remodelling. The objective of the study is to investigate the effects of implant material and implant–bone interface conditions on bone remodelling around tibia bone due to total ankle replacement. Finite element models of intact and implanted ankles were developed using CT scan data sets. Bone remodelling algorithm was used in combination with FE analysis to predict the bone density changes around the ankle joint. Dorsiflexion, neutral, and plantar flexion positions were considered, along with muscle force and ligaments. Implant–bone interfacial conditions were assumed as debonded and bonded to represent non-osseointegration and fully osseointegration at the porous coated surface of the implant. To investigate the effect of implant material, three finite element models having different material combinations of the implant were developed. For model 1, tibial and talar components were made of Co–Cr–Mo, and meniscal bearing was made of UHMWPE. For model 2, tibial and talar components were made of ceramic and meniscal bearing was made of UHMWPE. For model 3, tibial and talar components were made of ceramic and meniscal bearing was made of CFR-PEEK. Changes in implant material showed no significant changes in bone density due to bone remodelling. Therefore, ceramic appears to be a viable alternative to metal and CFR-PEEK can be used in place of UHMWPE. This study also indicates that proper bonding between implant and bone is essential for long-term survival of the prosthetic components.