碘乙酸钠诱导的大鼠膝骨关节炎模型肠道菌群变化及其潜在影响

目的:研究碘乙酸钠诱导的大鼠膝骨关节炎(KOA)模型肠道菌群变化情况,探究肠道菌群与KOA的潜在联系。方法:将SPF级大鼠分为空白对照组和KOA组,通过膝关节局部注射碘乙酸钠制造大鼠KOA模型。通过16SrDNA检测大鼠粪便中的肠道菌群变化情况,蛋白印记法检测结肠组织中NF-κB和TNF-α蛋白表达,RT-qPCR检测结肠组织中Caspase-1和IL-1β基因表达情况,苏木精-伊红染色观察结肠黏膜通透性变化,苏木精-伊红染色观察关节滑膜和软骨组织的病理变化情况。ELISA检测血液上清中LBP,IL-1β,TNF-α及IL-10炎症因子水平。结果:与空白对照组相比,从KOA组中筛选出明显变化的肠道菌群,以Akkermansia和疣微菌门变化最为显著,结肠黏膜通透性增加,结肠组织中NF-κB p65及TNF-α蛋白表达升高,结肠组织中Caspase-1和IL-1β基因表达升高,血液中促炎因子LBP,IL-1β及TNF-α蛋白含量升高,抗炎因子IL-10蛋白含量降低。结论:KOA病理状态下肠道菌群发生变化,结肠炎症反应增强,结肠炎症反应或许在提高全身炎症反应水平、促进与肠道菌群相关的KOA的病理进程中起到重要的桥梁作用。     

基于p38 MAPK信号通路探讨苍膝通痹胶囊对KOA大鼠关节软骨的保护作用

目的:观察苍膝通痹胶囊治疗膝骨关节炎(KOA)模型大鼠的疗效及相关作用机制。方法:将60只4周龄SPF级健康雄性SD大鼠,随机分为空白组,模型组,二甲基亚砜(DMSO)组,苍膝通痹胶囊组,SB203580组以及苍膝通痹胶囊联合SB203580组,每组10只。除正常组外,其余各组采用改良Hulth法建立KOA模型,造模成功后,苍膝通痹胶囊组每日给予0.25 g·kg~(-1)苍膝通痹胶囊溶液灌胃,SB203580组每日给予0.015 g·kg~(-1)的SB203580溶液灌胃,苍膝通痹胶囊联合SB203580组组每日给予含0.015 g·kg~(-1)SB203580及0.25 g·kg~(-1)苍膝通痹胶囊的混合溶液灌胃,DMSO组给予1%DMSO溶液灌胃,模型组和空白组给予生理盐水灌胃,用药干预4周后处死、取材。苏木素-伊红(HE)染色观察软骨组织形态学改变,酶联免疫吸附测定(ELISA)检测外周血上清液中白细胞介素-1β(IL-1β),肿瘤坏死因子-α(TNF-α)表达水平,实时荧光定量PCR(Real-tine PCR)及蛋白免疫印迹法(Western blot)检测软骨组织中p38 MAPK信号通路中相关因子p38,p-p38,基质金属蛋白酶-13(MMP-13),Ⅱ型胶原蛋白(CollagenⅡ)mRNA及蛋白的表达水平,免疫组化法检测p-p38的定位表达。结果:与正常组比较,模型组关节软骨中p38,p-p38,MMP-13表达水平显著上调(P0.01),CollagenⅡ表达水平显著下调(P0.01),血清IL-1β,TNF-α表达水平显著上调(P0.01);与模型组比较,苍膝通痹胶囊组,SB203580组以及苍膝通痹胶囊联合SB203580组关节软骨中p38,p-p38,MMP-13表达水平显著下调(P0.01),CollagenⅡ表达水平显著上调(P0.01),血清IL-1β,TNF-α表达水平显著下调(P0.01)。结论:苍膝通痹胶囊可有效保护KOA大鼠软骨组织,其机制可能与靶向阻断p38 MAPK信号通路有关。     

Impact of preoperative chemotherapy on the histological response of patients with peritoneal metastases from colorectal cancer according to peritoneal regression grading score (PRGS) and TRG

BackgroundThis study evaluated the histologic response after preoperative systemic therapy (pST) using the Peritoneal Regression Grading Score (PRGS) and tumor regression grade (TRG) classifications for patients with peritoneal metastases (PM) from colorectal cancer (CRC).MethodsTwenty-three patients were selected from a prospective database of 196 patients who underwent CRS followed by HIPEC for synchronous PM from CRC. In all study patients, biopsies of the PM obtained before pST (during the first laparoscopy) and after pST (during cytoreductive surgery) were compared.ResultsComplete (PRGS 1), Major (PRGS 2), Minor (PRGS 3) and no histological responses (PRGS 4) were obtained in 17,5%, 52% and 13% and 17,5% of patients, respectively. Major (TRG 1–2), partial (TRG3), and no (TRG4-5) histological tumor regression were observed in 61%, 9% and 30% of patients, respectively. Regardless of the classification applied, median OS was significantly higher in patients with a “complete or major” response than in those with a “minor/partial or no” response (54 vs. 26 months, p < 0.05).ConclusionsThe PRGS and TRG can be used in clinical practice to evaluate the histological response after pST. This study demonstrated that a complete histologic response of PM from CRC can be obtained after pST.     

Biochemical responses revealed in an amphibian species after exposure to a forgotten contaminant: An integrated biomarker assessment

Vanadium is a metal whose toxicity towards terrestrial and aquatic species has been under-reported to date.. The biochemical responses of vanadium in amphibian species have not been determined. To establish the effects of vanadium (V) on exposed adult Xenopus laevis, acute and chronic exposures were conducted, and biomarker analyses were performed on liver and muscle tissues from exposed frogs. Biomarkers of exposure, such as acetylcholinesterase (AChE) and metallothioneins (MT), were analysed. Biomarkers of effect were also analysed to determine possible increases in reactive oxygen species (ROS), and the effect of the exposure on the energy balance in the organisms. These included superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), protein carbonyls (PC), malondialdehyde (MDA), and cellular energy allocation (CEA) (energy available, energy consumption, lipids, proteins and glucose). In acute exposures, the energy balances in organisms were distinctly affected, possibly due to insulin mimetic properties of V. In chronic exposures, MT, AChE, SOD, CAT and GSH responses were more pronounced. Although AChE is generally inhibited by pollutant exposure, in this study, it was stimulated. There were significant inhibitions of SOD and CAT, previously observed in frog species. PC levels increased in the highest acute exposure concentration, indicating protein damage. The IBR.v2 revealed the biochemical responses of V more effectively than traditional statistical analysis.     

Pressurized IntraPeritoneal Aerosol Chemotherapy with one minute of electrostatic precipitation (ePIPAC) is feasible,but the histological tumor response in peritoneal metastasis is insufficient

IntroductionElectrostatic precipitation Pressurized IntraPeritoneal Aerosol Chemotherapy (ePIPAC) has shown superior penetration depth and tissue uptake compared to standard PIPAC. We investigated the feasibility and objective tumor response to ePIPAC with 1 min of precipitation in patients with peritoneal metastasis (PM).Materials and methodsPatients with PM from various abdominal cancers were included in an amendment to the ongoing prospective PIPAC-OPC2 trial. Colorectal and appendiceal PM were treated with oxaliplatin, patients with PM from other primaries were treated with a combination of cisplatin and doxorubicin. Three ePIPAC procedures were planned in each patient including repeated peritoneal biopsies for response evaluation. After emission to the peritoneal cavity, the aerosolized chemotherapeutics were precipitated for 1 min followed by immediate exsufflation and abdominal closure. Histological regression from the first to the third ePIPAC was evaluated according to the Peritoneal Regression Grading Score (PRGS) and compared to data from the PIPAC-OPC1 trial. Complications and toxicities were recorded according to Dindo-Clavien and CTCAE.ResultsSixty-five ePIPAC procedures were performed in 33 patients (median 2, range 1–6). Ten patients were eligible for response evaluation based on biopsies from the first and third ePIPAC procedure. Four patients had disease progression, four patients had regressive disease, and two patients had stable disease according to PRGS. No life threatening adverse reactions and no mortality was observed following ePIPAC.ConclusionOne minute ePIPAC was feasible and safe, but the histological tumor response was insufficient compared to standard PIPAC directed therapy with 30 min passive diffusion time.     

Does perturbation in the mitochondrial protein folding pave the way for neurodegeneration diseases?

Mitochondria, which are cell compartments that are widely present in eukaryotic cells, have been shown to be involved in a variety of synthetic, metabolic, and signaling processes, thereby playing a vital role in cells. The mitochondrial unfolded protein response (mtUPR) is a response in which mitochondria reverse the signal to the nucleus and maintain mitochondrial protein homeostasis when unfolded and misfolded proteins continue to accumulate. Multiple neurodegeneration diseases, including Alzheimer's disease (AD), Parkinson’s disease (PD), and familial amyotrophic lateral sclerosis (fALS), are public health challenges. Every year, countless efforts are expended trying to clarify the pathogenesis and treatment of neurological disorders, which are associated with mitochondrial dysfunction to some extent. Numerous studies have shown that mtUPR is involved in and plays an important role in the pathogenesis of neurological disorders, but the exact mechanism of the disorders is still unclear. Further study of the process of mtUPR in neurological disorders can help us more accurately understand their pathogenesis in order to provide new therapeutic targets. In this paper, we briefly review mtUPR signaling in Caenorhabditis elegans (C. elegans) and mammals and summarize the role of mtUPR in neurodegeneration diseases, including AD, PD and fALS.     

镫骨骨质缺损对听力传导影响的有限元分析

目的建立完善的鼓膜-听骨链模型,利用有限元初步探讨镫骨前、后脚骨质缺损对听力传导的影响。方法实验数据源于对一名无中耳病史的成年男性左侧颞骨进行Micro-CT扫描,在医学影像处理软件Mimics上进行三维重建,利用Geomagic形成需要的曲面,最后在SolidWorks上将成型的鼓膜-听骨链模型进行切割组装,建立正常听骨链模型以及镫骨前、后脚骨质缺损模型,利用模型分析骨质缺损对听力传导的影响。结果建立的鼓膜-听骨链模型镫骨足板频振曲线符合相关文献报道,在镫骨前、后脚骨质缺损病理模型下,曲线与正常中耳模型曲线接近。结论利用多软件综合处理,可建立可信度较高的中耳听骨链模型;有限元模拟分析结果显示,镫骨前、后脚缺损部分骨质,未对听力传导产生明显影响。     

Spectral CT Imaging–Based Quantification of Iodized Oil Retention following Chemoembolization: Phantom and Animal Studies

PurposeTo evaluate accuracy of iodine quantification using spectral CT and the potential of quantitative iodized oil analysis as an imaging biomarker of chemoembolization.Materials and MethodsA phantom of an artificial liver with 6 artificial tumors containing different amounts of iodized oil (0–8 vol%) was scanned by spectral CT, and iodized oil density (mg/mL) and Hounsfield unit (HU) values were measured. In addition, VX2 hepatoma was induced in 23 rabbits. After chemoembolization using iodized oil chemoemulsion, the rabbits were scanned by spectral CT. The accumulation of iodized oil in the tumor was quantified in terms of iodized oil density and HUs, and the performances in predicting a pathologic complete response (CR) were evaluated by receiver operating characteristic curve analyses.ResultsThe mean difference between true iodine densities and spectral image–based measurements was 0.5 mg/mL. Mean HU values were highly correlated with mean iodine density (r² = 1.000, P < .001). In the animal study, a pathologic CR was observed in 17 of 23 rabbits (73.9%). The range of area under the curve values of iodine and HU measurements was 0.863–0.882. A tumoral iodine density of 3.57 mg/mL, which corresponds to 0.7 vol% iodized oil in the tumor, predicted a pathologic CR with a sensitivity of 70.6% and a specificity of 100.0%.ConclusionsSpectral CT imaging has a potential to predict tumor responses after chemoembolization by quantitatively assessing iodized oil in targets.     

移动医生查房系统临床实施应用研究

结合陆军军医大学第一附属医院移动医护信息化建设实践，介绍移动查房系统软件架构、网络架构、具体功能及应用优势，指出该系统可实现患者临床信息实时更新和共享，有助于提高医护人员临床决策响应能力和工作效率。