慢性肝病肝剪切波速与血清肝纤维化标志物在肝纤维化诊断中的对比研究

目的 探讨慢性肝病肝剪切波速及血清肝纤维化标志物在肝纤维化分级诊断中的临床应用价值.方法 选择235例慢性肝病患者(肝纤维化组),其中男性179例,女性56例;年龄17～64岁,平均年龄36.3岁.40例健康对照者,其中男性25例,女性15例;年龄25～62岁,平均年龄43.2岁.先进行肝剪切波速和抽血实验室检查,然后在超声引导下穿刺活组织检查,以病理结果为标准,分析剪切波速及血清肝纤维化标志物在评价肝纤维化分级之间的关系.并将检查结果与健康对照者进行比较.结果 235例慢性肝病患者有215例进行肝穿刺活组织检查,除F0级肝病患者与健康对照组F0级之间剪切波速比较差异无统计学意义(P＞0.05)外,其余肝病各分组剪切波速随肝纤维化程度的增高而波速增快;且血清肝纤维化标志物含量亦随肝纤维化病理分期的增高而增高.结论 肝剪切波速及血清肝纤维化标志物对肝纤维化患者的病理分期有良好相关性,对肝纤维化的诊断及疗效观察有重要的临床应用价值.     

基于动态孔径控制的剪切波传播速度检测方法

目的超声剪切波弹性成像临床应用前景广阔,其中剪切波传播速度检测是其技术的核心步骤。针对在小焦距下传统基于静态孔径聚焦超声发射方式的剪切波传播速度检测准确度低的问题,本文提出一种基于动态孔径控制的剪切波传播速度检测方法。方法对不同的焦距以控制活跃阵元数目的方式动态控制孔径大小;采用峰值时间法结合最小二乘法计算剪切波传播速度;利用超声仿真平台FieldⅡ,采用控制变量法对多个小焦距下的声辐射力场、标记点"位移-时间"曲线及剪切波传播速度进行了仿真研究。结果本方法可有效抑制栅瓣的出现,能获取呈现出明显主峰的走势良好的标记点"位移-时间"曲线。剪切波传播速度检测结果与理论值的相对误差更低,例如在焦距为7 mm时,与理论值相对误差降低了16.585%;在焦距为9 mm时,降低了15.205%。结论基于动态孔径控制的剪切波传播速度检测方法能合理控制小焦距下的声辐射力,提升剪切波传播速度检测准确度,为超声剪切波弹性成像技术的进一步发展提供理论依据。     

利用剪切波弹性成像技术评价大鼠非酒精性脂肪性肝病严重程度

目的:探讨剪切波弹性成像（SWE）技术评估非酒精性脂肪性肝病（NAFLD）严重程度的可行性及其影响因素。方法:SD大鼠随机分为对照组（40只）和实验组（48只）,实验组通过不同饮食建立严重程度不同的NAFLD大鼠模型,分别于第1、2、3、8、12周末检测肝脏杨氏模量平均值（Emean）并切除大鼠肝脏行组织病理学和mRNA表达分析。结果:Emean与NAFLD严重程度呈显著正相关（r=0.838, P<0.001）。NAFLD不同病理分组间的Emean差异有统计学意义（F=113.58, P<0.001）。非酒精性脂肪性肝炎（NASH）组和肝硬化组Emean显着高于正常组、单纯性脂肪变性和临界组（P<0.001）;肝硬化组的Emean显着高于NASH组（P<0.001）;正常组、单纯性脂肪变性组和临界组之间,Emean没有显着差异（P>0.05）。Emean与MCP-1、TNF-α、Ⅰ型胶原和α-SMA表达水平均呈显著正相关（r=0.340~0.678, P均<0.01）,而MCP-1（B=0.560, P<0.001）、I型胶原（B=0.429, P<0.001）是与肝脏Emean呈独立相关的因素。。SWE诊断NASH及肝硬化的截值分别为6.0 kPa、9.7 kPa,曲线下面积分别为0.95、0.98,敏感性分别为88.9%、86.5%,特异性分别为100%、92.7%。结论:SWE技术可用于评估NAFLD严重程度;MCP-1、I型胶原是影响肝脏硬度的主要生物分子。     

Which factors influence liver stiffness measured by real-time two dimensional shear wave elastography in patients on maintenance hemodialysis?

AimTo evaluate liver stiffness (LS) by real-time two-dimensional shear wave elastography (RT 2D-SWE) and to assess its correlation with the mean arterial pressure (MAP) in patients on maintenance hemodialysis (MHD). The secondary aim was to identify biological and biochemical parameters associated with elevated LS.MethodsThis study enrolled patients treated with MHD in the Split University Hospital from December 2017 through February 2018. LS was measured after a HD session using RT 2D-SWE. Mean arterial pressure was measured before RT-2D-SWE was performed.ResultsThe study enrolled 47 patients with the mean ± standard deviation age of 68.48 ± 14.33 years. Arterial hypertension was diagnosed in 70.2% of patients. Liver stiffness >7 kPa, suggesting clinically relevant fibrosis, was found in 59.5% of patients. Arterial pressure was significantly correlated with LS (ρ = 0.38, P = 0.008). C-reactive protein (ρ = 0.548, P = 0.023), parathyroid hormone (ρ = 0.507, P = 0.038), and total bilirubin (ρ = 0.423, P = 0.020) were correlated with elevated LS.ConclusionMean arterial pressure is correlated with increased LS in patients on MHD. Our results emphasize the importance of proper regulation of arterial blood pressure and indicate that LS should always be interpreted in combination with laboratory parameters. Further prospective studies with larger series are needed.

Chronic kidney disease (CKD) is an important public health problem. The number of CKD patients in the world has increased from approximately 10 000 patients in 1973 to 703 243 in 2015 (1,2). All CKD stages and end stage renal disease (ESRD) are associated with high morbidity, increased health care utilization, and mortality (3). Patients on long-term maintenance hemodialysis (MHD) have an increased risk for hepatitis B and C viral infection and chronic liver inflammation. Acute or chronic liver inflammation is frequently followed by a development of liver fibrosis (LF) (4-6). The clinical presentation of LF differs from that of cirrhosis. Mild LF, as well as early stage liver cirrhosis, are asymptomatic in most patients, which points to the importance of an early diagnosis. Appropriate staging of LF is important for prognosis and for therapeutic decision-making.Percutaneous liver biopsy is still the gold standard for the evaluation and staging of LF (7). It is an invasive procedure with substantial limitations and very serious potential side effects, primarily, post procedural bleeding. The risk is even higher in dialysis patients who have a bleeding tendency due to platelet dysfunction caused by uremic state. Not less important, liver biopsy carries the risk of pneumothorax and hematothorax (8,9). Another limitation is the possibility of a significant sampling error, since the biopsy specimen represents only 1/50 000 the size of the liver parenchyma (10,11). Due to these limitations, many non-invasive tools for the assessment of LF have been recently investigated, showing promising results (11,12). The most frequently applied novel methods, using ultrasound waves for tissue elasticity measurement, are transient elastography and two-dimensional real-time shear wave elastography (RT-2D-SWE) (13,14). RT 2D-SWE is a fast, quantitative method for assessing LF by measuring liver stiffness (LS) in real time. Acoustic push pulses induce shear waves, and their speed is observed as color image in the region of interest (ROI). Velocity (m/s) is determined by measuring the waves passing through the examined tissue. These values are converted into tissue elasticity expressed in kilopascals (Young’s module) (15). 2D-SWE has demonstrated high resolution and excellent reproducibility for assessing LF (16-19).LS can be affected by different parameters. LS values are elevated in healthy people with BMI>30 kg/m², and in patients with viral hepatitis, primary biliary cholangitis, alcoholic liver disease, and cholestatic liver diseases independent of the degree of fibrosis (20-23). LS correlates significantly with portal pressure and arterial pressure (24-27), and is affected by volume overload: either due to heart failure or liver failure with ascites (11,28). To avoid volume overload, LS measurement should be performed following a hemodialysis (HD) session (29-31). It remains unexplored to what extend blood pressure contributes to LS (25). Little is known about biological and biochemical factors associated with LS changes in ESRD patients on MHD. To the best of our knowledge, most such studies have been conducted on patients with underlying liver disease (32,33). Only a few have focused on factors that influence LS (measured by transient elastography) and fibrosis in HD population (28). In dialysis patients, active chronic inflammation possibly affects the liver and changes LS (34). Another pathophysiological mechanism could be chronic hepatic congestion with subsequent idiopathic noncirrhotic portal hypertension (35). This study aims to investigate the correlation between the mean arterial pressure (MAP) and LS in patients on MHD. The secondary aim was to identify biological and biochemical parameters correlated with elevated LS. Finally, we hypothesized that MAP influenced LS and that C-reactive protein (CRP), parathyroid hormone (PTH), and total bilirubin correlate with the LS value.     

The impact of slow wave sleep proximity on evoked K-complex generation

During human stage 2 non-rapid eye movement (NREM) sleep, spontaneous K-complexes are more likely to occur prior to transitions to stage 3 or stage 4 sleep (referred to as slow wave sleep or SWS) compared to transitions to REM sleep, suggesting that the K-complex may be the 'forerunner' of SWS. The present study investigated the impact of SWS or REM sleep proximity on the probability of evoking a K-complex (pKC) during stage 2 and on components of the NREM sleep averaged evoked potential. Ten subjects spent three nights in the laboratory. On either the second or third night tones were presented continuously during sleep. Evoked K-complexes and sleep-evoked potentials were assessed for the 10 min of stage 2 prior to SWS (SWS-10) or REM (REM-10) sleep episodes as well as for all of SWS. pKC did not differ between SWS-10 (0.88) and SWS (0.91) but was significantly larger in SWS-10 than REM-10 (0.63). Amplitude effects were seen for the P2, N350, P900 NREM sleep-evoked potential components but not for the K-complex related N550. In each case where amplitude effects were found, SWS-10 was larger than REM-10. No latency differences were seen between conditions for the earlier components (P2, N350) however, both N550 and P900 were significantly shorter during SWS-10 compared to REM-10. These results are consistent with previous spontaneous K-complex studies and are supportive of a relationship between the K-complex and delta activity. They also indicate that stage 2 may consist of a continuum of microstates between SWS and REM sleep that are indicative of different brain stem, diecephalic and cortical patterns of activation.     

The impact of COVID-19 on liver injury in various age

The coronavirus disease 2019 (COVID-19) disease was first detected in December 2019 in Wuhan, China. This disease is currently one of the most important global health problems. The novel coronavirus COVID-19 is a respiratory illness, that has caused a deadly pandemic that is spreading rapidly around the world. It is not only a respiratory system virus that causes severe lung disease, but also a systemic disease agent that can affect all systems. People with COVID-19 disease usually have respiratory signs, however, the liver disorder is not an uncommon presentation. In addition, many studies around the world have revealed that the liver is injured to various degrees in patients with severe acute respiratory syndrome coronavirus 2 disease. This review mainly focuses on the impact of COVID-19 on Liver Injury at various ages.     

Kinetics and mechanisms of hepatic acute phase response to subtotal partial hepatectomy and cultural impact on environmental hepatic end-stage liver injury in the homeless

Intoxication and liver damage induced by carbon tetrachloride (CCl(4)), aflatoxin B1, diabetes, and subtotal partial hepatectomy (PH(90)) in rats in which approximately 90% of the total hepatic tissue mass is surgically removed produces an acute-phase response (APR) whose initial stage prior to regression closely mimics the APRs associated with the life-threatening hepatic failure seen in the homeless.Rats treated by PH(90)were either healthy, CCl(4)-intoxicated, diabetic, or alflatoxin B1 (AFB1) intoxicated to the point of 75% liver insufficiency. It is well documented that high rates of mortality following PH(90)in aseptic rats could be minimized by supplementing drinking water with 20% glucose, organic components of L-15 medium and housing animals in cages maintained at 33-35;C. Aseptic rats showed a mild 20-30% decrease in APR proteins during the first 4-5 days following PH(90), while a maximal APR was noted 9-12 days post PH(90)and lasted for ~30 days when it returned to values close to those of healthy controls. This delay in hepatic APR of the remnant caudate lobe favoured replacement of lost basophilic clumps and ribosomes. The newly synthesized ribosomes of the nascent hepatocytes quantitatively maintained the APR signals of the injured caudate hepatocytes, and biosynthesized and released a typical spectrum of APR proteins. We suggest that massively injured liver has decoded an already stored and irreversible DNA-biochemical sequence of events in which priority is given to recovery of lost tissues by delaying an APR response to injury. In PH(90)of diabetic and CCl(4)-intoxicated rats, the hepatic dual functions of regeneration and APR processes associated with intoxication-initiated catabolic signals, created a heavy metabolic burden on the remnant caudate lobe leading to higher rates of mortality. APR of healthy rats to AFB1 parallels that of alpha-amanitin-induced intoxication. Similarly, within shorter time scale proportional to the severity of surgery, livers undergoing 75% partially hepatectomy (PH(75)) delayed both the onset and regression of APR.We are therefore led to believe that approaches other than liver transplantation should be considered as viable alternatives in the treatment of various acute and chronic liver diseases to avoid rejection and retransplantation. Scarcity of cadaveric liver has forced the medical community to investigate xenotransplantation with its unknown risks. Concomitantly, it is suggested that in view of the incalculable risks of indifference, the homeless must receive much improved medical care as we have found that two-dimensional immunoelectrophoretic assay of their serum is indicative of acute and chronic liver injury. The scientific and moral interrelationships of related matters are illuminated.     

Effects of light conditions on mating speed inDrosophila mercatorum

Mating speed of flies which have been aged either in the light, in the dark, or in a light-and-dark cycle was measured using two strains, Rochester (R) and Salvador (S), ofDrosophila mercatorum. A significant difference in mating tendency depending on the condition of pretreatment was found between R and S strains, while both strains showed a similar pattern of the diurnal rhythm in the light-and-dark cycle. Compared under the same conditions, S flies usually showed a higher mating speed than R flies. Mating speed seems to be affected by at least two different genetic systems. One of them is the genetic system determining absolute speed of mating. Another is the genetic system determining sensitivity to the environmental conditions. There may be considerable differentiation in both systems between R and S strains.This work was supported by a research grant from the Ministry of Education (No. 964125).     

The impact of the 2003 heat wave on mortality and hospital admissions in England

This article quantifies the impact of the heat wave, 4 to 13 August 2003, on mortality and emergency hospital admissions in England by region and age group. The August 2003 heat wave was associated with a large short-term increase in mortality, particularly in London. Overall in England there were 2,091 (17 per cent) excess deaths. Worst affected were those over the age of 75. The greatest increase of any region in England was in London in the over 75 age group with 522 excess deaths (59 per cent). Excess hospital admissions of 16 per cent were recorded in London for the over 75s. Temperatures in England were unusually hot. Ozone and particulate matter concentrations were also elevated during the heat wave. Estimated excess mortality was greater than for other recent heat waves in the UK.     

The impact of altered climatic conditions and altitude on circadian physiology

Knowing the output of the "body clock" is fundamental to the science of chronobiology. As the clock resides within the suprachiasmatic nuclei, direct measurement is not feasible and therefore, characteristics of the clock are often inferred from the measurement of marker rhythms, one of which is core temperature. Core temperature is often the marker rhythm of choice due to ease of measurement, particularly in field conditions. However, if the output of the "body clock" is to be inferred from measurement of this variable, it is important to establish whether environmental conditions change or moderate the circadian rhythm of core temperature. Although the majority of circadian patterns do demonstrate independence from such exogenous influences, there does appear to be seasonal variation to their period. Given that humans can easily travel to environments of altered temperature and altitude, there is a need to ascertain the exact effect of such change on the rhythm of core temperature. This review will therefore outline the evidence that the circadian rhythm of core temperature is affected by ambient temperature and by hypoxia. Furthermore, the review will discuss whether these environmental factors act as zeitgebers (affecting the endogenous rhythm) or as masking influences of the inherent rhythm.     

The effect of preconditioning on liver regeneration after hepatic resection in cirrhotic rats

Background/Aims

Ischemic preconditioning (IP) decreases severity of liver necrosis and has anti-apoptotic effects in previous studies using liver regeneration in normal rats. This study assessed the effect of IP on liver regeneration after hepatic resection in cirrhotic rats.

Methods

To induce liver cirrhosis, thioacetamide (300 mg/kg) was injected intraperitoneally into Sprague-Dawley rats twice per week for 16 weeks. Animals were divided into four groups: non-clamping (NC), total clamping (TC), IP, and intermittent clamping (IC). Ischemic injury was induced by clamping the left portal pedicle including the portal vein and hepatic artery. Liver enzymes alanine transaminase (ALT) and aspartate aminotransferase (AST) were measured to assess liver damage. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining for apoptosis and proliferating cell nuclear antigen (PCNA) staining for cell replication were also performed.

Results

Day-1 ALT and AST were highest in IP, however, levels in NC and IC were comparably low on days 1-7. There was no significant correlation of AST or ALT with experimental groups (P=0.615 and P=0.186). On TUNEL, numbers of apoptotic cells at 100× magnification (cells/field) were 31.8±24.2 in NC, 69.0±72.3 in TC, 80.2±63.1 in IP, and 21.2±20.8 in IC (P<0.05). When regeneration capacity was assessed by PCNA staining, PCNA-positive cells (cells/field) at 400× were 3.4±6.0 in NC, 16.9±69 in TC, 17.0±7.8 in IP and 7.4±7.6 in IC (P<0.05).

Conclusions

Although regeneration capacity in IP is higher than IC, the liver is vulnerable to ischemic damage in cirrhotic rats. Careful consideration is needed in applying IP in the clinical setting.     

The impact of pathologist experience on liver transplant biopsy interpretation.

We studied the impact of pathologist experience on liver transplant biopsy interpretation for cases designated 'nonspecific' by pathologists at a nontransplant center. Among 102 consecutive liver transplant biopsies from 92 patients performed at the Foothills Medical Center, 30 liver biopsies from 23 patients were designated 'nonspecific' by the local pathologist. These biopsy slides were independently reviewed by an expert in liver transplant pathology at a major US transplant center. The expert pathologist was given only the information on the original requisition. In seven biopsies from five patients, there was full agreement between the external expert and the local pathologist. In 10 biopsies from six patients, the expert concurred with the initial assessment but emphasized critical negatives such as 'no evidence of rejection or recurrent hepatitis'. A discrepant diagnosis was found in 13 biopsies from 12 patients. In five biopsies from four patients, the revised diagnoses were inaccurate due to insufficient or misleading clinical information on the requisition. In eight biopsies from eight patients, the revised diagnoses were proven to be correct by clinicopathologic correlation. Our study shows that pathology expertise helped to clarify the diagnosis in about 27% of cases, which justifies the cost of obtaining a second opinion in difficult biopsies. Misinterpretation by the expert pathologist in up to 17% of biopsies highlights the importance of direct communication between hepatologist and pathologist in order to achieve a correct diagnosis. Familiarity with those cases with relatively uncommon histology, a diligent search for subtle morphologic changes, and use of standard terminology could improve the quality of liver transplant biopsy interpretation in a nontransplant center.     

Micro RNA与肝病及肝纤维化相关研究

Micro RNA(miRNA)是转录后水平的细胞调控因子.在细胞核内,miRNA基因经由RNA聚合酶Ⅱ介导转录出含多聚腺苷酸尾(AAAAA)和帽子结构特征性标志的primiRNA,后者在核酸酶Drosha的作用下被切割成70个具有茎环结构的miRNA前体(pre-miRNA),随后由转运蛋白exportin-5转运出核,再由胞质中Dicer蛋白切割为成熟的miRNA.miRNA在RNA沉默复合物(RNA-induced silencing complex,RISC)的作用下可与多个互补mRNA结合,从而降解该mRNA或抑制其翻译.目前已在人细胞中发现1048种miRNA,参与调控全基因组中20%～30%基因的表达(MiRBase http://www.mirbase.org/).     

高脂血症患者血流剪切率的变化及对血管功能的影响

目的：观察高脂血症患者血流剪切率的变化特点及探讨非诺贝特提高血管舒张功能的机制。方法:以20例正常人、62例高甘油三酯血症病人(其中30例予以饮食治疗、32例予非诺贝特治疗)为观察对象，以肱动脉B超测量血流、血管弹性和舒张功能等指标，检测血浆一氧化氮(NO)、氧化型低密度脂蛋白(Ox-LDL)、血脂的变化。结果:高甘油三酯血症病人超声显示平均血流剪切率（MSR）、血流介导的扩张效应(FMD)和血管弹性指标Da、Dr显著小于正常对照组，而平均血管壁紧张度(MCWT)显著大于正常对照组；血Ox-LDL浓度高于、NO水平低于正常对照组，且NO与MSR、 FMD水平呈正相关，与甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)和Ox-LDL浓度呈负相关。8周的低脂饮食治疗可使TC、TG水平下降，但NO、Ox-LDL和血管超声指标未见显著改变；非诺贝特治疗组血管超声MSR 、FMD显著高于对照组，血TG、TC、LDL-C和Ox-LDL浓度低于、NO水平高于对照组。结论:高甘油三酯血症时MSR的下降和氧化因子Ox-LDL的升高共同参与内皮的损伤机制，导致NO水平下降，表现为血管舒张功能的下降和弹性下降，MSR的上升和Ox-LDL的下降有利于内皮功能的修复。     

实时剪切波弹性成像技术定量评价正常成人睾丸、附睾

目的测量正常成人睾丸、附睾的影像弹性模量值,为临床研究提供理论依据。方法利用具有实时剪切波弹性成像(SWE)技术的彩色多普勒超声诊断仪对400名志愿者睾丸、附睾进行检查,获得弹性模量值进行统计学分析。结果睾丸中心部与周边部的纵切面弹性平均值分别为(4.236±0.315)k Pa和(4.176±0.149)k Pa,横切面弹性平均值分别为(4.105±0.158)k Pa和(4.121±0.182)k Pa。附睾头及附睾尾纵切面的弹性平均值分别为(5.629±0.275)k Pa和(5.371±0.111)k Pa,横切面的弹性平均值分别为(5.743±0.237)k Pa和(5.500±0.141)k Pa。结论睾丸及附睾测量的不同部位、不同切面不是影响睾丸及附睾弹性模量值的显著因素。