体外震波碎石术治疗中病人所受的体表剂量

在体外震波碎石术(ESWL)治疗中,需要用X线透视来判断结石的位置、大小及其粉碎情况,因此使患者受到X射线的照射。本文对在上海某医院接受ESWL治疗的134例肾脏结石患者所 受的体表剂量进行了调查测量。结果表明,患者受到的皮肤剂量当量平均为162mSv;所受剂量的大小与结石的大小与位置等因素有关。     

Prenatal Exposure to Lipopolysaccharide Results in Myocardial Fibrosis in Rat Offspring

The epigenetic plasticity hypothesis indicates that exposure during pregnancy may cause adult-onset disorders, including hypertension, myocardial infarction and heart failure. Moreover, myocardial fibrosis coincides with hypertension, myocardial infarction and heart failure. This study was designed to investigate the effects of prenatal exposure to lipopolysaccharide (LPS) on myocardial fibrosis. The result showed that at six and 16 weeks of age, the LPS-treated offspring exhibited increased collagen synthesis, an elevated cardiac index (CI), higher mRNA levels of TIMP-2 and TGFβ and a reduced mRNA level of MMP2. The protein levels corresponded to the mRNA levels. The offspring that were prenatally treated with pyrrolidine dithiocarbamic acid (PDTC), an inhibitor of NF-κB, displayed improvements in the CI and in collagen synthesis. Moreover, PDTC ameliorated the expression of cytokines and proteins associated with myocardial fibrosis. The results showed that maternal inflammation can induce myocardial fibrosis in offspring during aging accompanied by an imbalance of TIMP-2/MMP2 and TGFβ expression.     

Anti-Fibrotic Effects of Class I HDAC Inhibitor,Mocetinostat Is Associated with IL-6/Stat3 Signaling in Ischemic Heart Failure

Background: Recent studies have linked histone deacetylases (HDAC) to remodeling of the heart and cardiac fibrosis in heart failure. However, the molecular mechanisms linking chromatin remodeling events with observed anti-fibrotic effects are unknown. Here, we investigated the molecular players involved in anti-fibrotic effects of HDAC inhibition in congestive heart failure (CHF) myocardium and cardiac fibroblasts in vivo. Methods and Results: MI was created by coronary artery occlusion. Class I HDACs were inhibited in three-week post MI rats by intraperitoneal injection of Mocetinostat (20 mg/kg/day) for duration of three weeks. Cardiac function and heart tissue were analyzed at six week post-MI. CD90⁺ cardiac fibroblasts were isolated from ventricles through enzymatic digestion of heart. In vivo treatment of CHF animals with Mocetinostat reduced CHF-dependent up-regulation of HDAC1 and HDAC2 in CHF myocardium, improved cardiac function and decreased scar size and total collagen amount. Moreover, expression of pro-fibrotic markers, collagen-1, fibronectin and Connective Tissue Growth Factor (CTGF) were reduced in the left ventricle (LV) of Mocetinostat-treated CHF hearts. Cardiac fibroblasts isolated from Mocetinostat-treated CHF ventricles showed a decrease in expression of collagen I and III, fibronectin and Timp1. In addition, Mocetinostat attenuated CHF-induced elevation of IL-6 levels in CHF myocardium and cardiac fibroblasts. In parallel, levels of pSTAT3 were reduced via Mocetinostat in CHF myocardium. Conclusions: Anti-fibrotic effects of Mocetinostat in CHF are associated with the IL-6/STAT3 signaling pathway. In addition, our study demonstrates in vivo regulation of cardiac fibroblasts via HDAC inhibition.     

Ghrelin Attenuates Liver Fibrosis through Regulation of TGF-β1 Expression and Autophagy

Ghrelin is a stomach-derived growth hormone secretagogue that promotes various physiological effects, including energy metabolism and amelioration of inflammation. The purpose of this study was to investigate the protective mechanism of ghrelin against liver fibrosis. Liver fibrosis was induced in C57BL/6 mice by intraperitoneal injection of CCl₄ (2.0 mL/kg of 10% CCl₄ v/v solution in peanut oil) two times per week for eight weeks. Ghrelin (10 μg/kg) was intraperitoneally injected two times per week for eight weeks. A second murine liver fibrosis model was induced by bile duct ligation (BDL) and concurrent ghrelin administration for four weeks. Hematoxylin eosin (H&E), and Masson’s trichrome were used to detect pathological changes to liver tissue. Western blotting was used to detect protein levels of transforming growth factor (TGF)-β1, phosphorylated Smad3 (p-Smad3), I-collage, α-smooth muscle actin (α-SMA), matrix metalloproteinases (MMPs) 2, tissue inhibitor of matrix metalloproteinases (TIMPs) 1, phosphorylated NF-κB (p-NF-κB), and microtubule-associated protein light chain 3 (LC3). In addition, qRT-PCR was used to detect mRNA levels of TGF-β1, I-collage, α-SMA, MMP2, TIMP1 and LC3, while levels of TGF-β1, p-Smad3, I-collage, α-SMA, and LC3 were detected immunohistochemically. Levels of aspartate aminotransferase and alanine aminotransferase were significantly decreased by ghrelin treatment. Ghrelin administration also significantly reduced the extent of pathological changes in both murine liver fibrosis models. Expression levels of I-collage and α-SMA in both models were clearly reduced by ghrelin administration. Furthermore, ghrelin treatment decreased protein expression of TGF-β1 and p-Smad3. The protein levels of NF-κB and LC3 were increased in the CCl₄- and BDL-treatment groups but were significantly reduced following ghrelin treatment. In addition, ghrelin inhibited extracellular matrix formation by decreasing NF-κB expression and maintaining the balance between MMP2 and TIMP1. Our results demonstrated that ghrelin attenuates liver fibrosis via inhibition of the TGF-β1/Smad3 and NF-κB signaling pathways, as well as autophagy suppression.     

Peptide-Based Nanoarchitectonics for the Treatment of Liver Fibrosis

Liver fibrosis is a process of excessive accumulation of extracellular matrix caused by liver injury. Liver fibrosis can progress to cirrhosis or even liver cancer without proper intervention. Until now, no effective therapeutic drugs have been clinically approved for treating liver fibrosis. Hence, the development of safe and effective antifibrotic drugs is particularly important. As a representative biomaterial, peptides have been investigated as key components for constructing antifibrotic nanomaterials given their advantages of biological origination, synthetic availability, and good biocompatibility. Peptides serve as multifunctional motifs in antifibrotic nanomaterials, such as liver-targeting molecules, antifibrotic molecules, and self-assembling building blocks for the formation of the nanomaterials. In this review, we focus on peptide-based nanoarchitectonics for treating liver fibrosis, including nanomaterials modified with liver-targeting peptides, nanomaterials for the efficient delivery of antifibrotic peptides, and self-assembled peptide nanomaterials for the delivery of antifibrotic drugs. The design rules of these peptide-based nanomaterials are described. The antifibrotic mechanisms and effects of these peptide-based nanomaterials in treating liver fibrosis and related diseases are highlighted. The challenges and future perspectives of using peptide-based nanoarchitectonics for the treatment of liver fibrosis are discussed. These results are expected to accelerate the rational design and clinical translation of antifibrotic nanomaterials.     

miR-181b promotes the oncogenesis of renal cell carcinoma by targeting TIMP3

Renal cell carcinoma (RCC) has a poor prognosis due to limited diagnosis and treatment. Thus, it is necessary to find novel prognostic biomarkers and therapeutic targets. The aberrant expression of microRNAs plays an important role in RCC oncogenesis. Tissue inhibitors of metalloproteinase 3 (TIMP3) acts as a downstream target of miR-181b. The aim of this study was to understand the role and molecular mechanism of miR-181b in RCC oncogenesis. The results showed that miR-181b expression was significantly higher in RCC tumour tissues, especially in those with significant invasion or metastasis. miR-181b overexpression promoted proliferation and migration of the RCC cell line 786-O, while miR-181b knockdown had the opposite effect. In addition, miR-181b was inversely correlated with TIMP3 expression in RCC tumour tissues. miR-181b overexpression reduced TIMP3 expression in RCC cell line 786-O or OS-RC-2, while miR-181b knockdown had the inverse effect. Mechanistically, a luciferase reporter assay confirmed the binding sites of miR-181b on the 3’-UTR of TIMP3, confirming the targeting effect of miR-181b on TIMP3. Overall, miR-181b promotes the development and progression of RCC by targeting TIMP3 expression, indicating the potential use of miR-181b in the diagnosis and treatment of RCC.     

Preventive approach against drug-induced pulmonary fibrosis through the suppression of epithelial-mesenchymal transition

A number of drugs induce pulmonary injury and subsequently lead to serious lung diseases such as pulmonaryfibrosis as the adverse drug reactions. However, an effective preventive approach against drug-induced pulmonary fibrosishas not been established due to poor understanding of common preventive targets in a variety of drugs showing pulmonarytoxicity. Epithelial-mesenchymal transition (EMT), a cellular phenotypic change of the epithelial to mesenchymal state,contributes to the development of pulmonary fibrosis through the conversion of damaged alveolar epithelium intomyofibroblasts. As several drugs with pulmonary toxicity have been reported to induce EMT, EMT serves as a bridgebetween the drugs and pulmonary fibrosis. Accumulated evidence supports the potential of EMT as a preventive targetagainst drug-induced pulmonary fibrosis. Additionally, since there are mechanistic differences between the mainpharmacological effect and EMT induced by the drug, prevention based on EMT suppression would be possible andwould contribute to continuous clinical treatment with the drug to avoid EMT-mediated serious pulmonary fibrosis.Furthermore, targeting EMT seems to be adequate for exerting a preventive effect since EMT in damaged alveolarepithelial cells occurs prior to the development of the pathophysiological state of the whole lung in a bleomycin-inducedlung injury rat model. This viewpoint deals with the benefits and perspectives of preventive approaches against druginduced pulmonary fibrosis through the suppression of EMT, which has rarely been addressed.     

负压吸引技术应用于大面积烧伤患者围术期的效果探究

目的:探究环磷酸腺苷联合负压吸引技术应用于大面积烧伤患者围术期的效果及肾保护作用探究。方法:选择2018年12月到2020年12月于医院治疗的120例大面积烧伤患者为研究对象,以随机数字表法对患者分组,60例患者为研究组,60例患者为对照组,对照组给予负压吸引技术治疗,研究组在此基础上给予环磷酸腺苷治疗,治疗前、后测定两组患者干扰素-γ(IFN-γ)、白细胞介素-2(IL-2)、白细胞介素-10(IL-0)、白细胞介素-6(IL-6)、可溶性血管细胞粘附分子-1(sVCAM-1)、一氧化氮(NO)、内皮素(ET-1)、血管内皮生长因子(VEGF)、胱抑素C(Cys-C)、肌酐(Scr)、血尿素氮(BUN)、肾损伤分子-1(KIM-1)水平,记录两组患者手术时间、麻醉苏醒时间、住院时间。结果:研究组IFN-γ、IL-6水平低于对照组(P<0.05),研究组患者IL-2、IL-10水平高于对照组(P<0.05),研究组NO、VEGF水平高于对照组(P<0.05),研究组患者sVCAM-1、ET-1水平低于对照组(P<0.05),研究组患者Cys-C、Scr、BUN、KIM-1水平低于对照组(P<0.05),研究组手术时间低于对照组(P>0.05),研究组麻醉苏醒时间、住院时间低于对照组(P<0.05)。结论:环磷酸腺苷联合负压吸引技术应用于大面积烧伤围术期患者,可降低患者IFN-γ、IL-6水平,提升患者IL-2、IL-10水平,抑制患者炎症,改善患者血管内皮功能,降低患者Cys-C、Scr、BUN、KIM-1水平,减少患者肾功能损伤,减少患者麻醉苏醒时间及住院时间。