从现有波动量法出发,研究用户波动与背景谐波变化对公共联结点谐波电流、谐波电压的影响,提出一种基于用户主导波动量筛选原理的用户谐波发射水平估计方法。提出公共连接点(point of common coupling,PCC)谐波波动伏安特性比的概念,研...从现有波动量法出发,研究用户波动与背景谐波变化对公共联结点谐波电流、谐波电压的影响,提出一种基于用户主导波动量筛选原理的用户谐波发射水平估计方法。提出公共连接点(point of common coupling,PCC)谐波波动伏安特性比的概念,研究系统侧、用户侧谐波波动对其变化的影响;利用统计学筛选方法从PCC点谐波电流测量值中筛选出用户主导谐波电流波动量,以此估计系统谐波阻抗;采用用户谐波电压发射水平修正公式消除背景谐波的影响。对理论模型和实际工程算例的仿真证明该文方法的正确性和有效性。展开更多
Objective: To investigate the effects of exogenous recombinant human brain natriuretic peptide(rh BNP) after primary percutaneous coronary intervention(PCI) on non-invasive hemodynamic in acute myocardial infarction p...Objective: To investigate the effects of exogenous recombinant human brain natriuretic peptide(rh BNP) after primary percutaneous coronary intervention(PCI) on non-invasive hemodynamic in acute myocardial infarction patients with left ventricular failure. Methods: A number of 96 acute myocardial infarction patients accompanied with heart failure after PCI hospitalized in the People's Hospital of Sanya during February 2012 to October 2015 were selected. They were randomly divided into the therapy group(n = 50) and control group(n = 46). On the basis of routine treatment, patients in the therapy group were treated with intravenous rh BNP(1.5 μg/kg was intravenous injection with uniform speed of 3 min, followed by continuous infusion 0.007 5 μg/kg·min for 72 h), while the control group received conventional treatment. Bio Z-2011 non-invasive hemodynamic real-time monitoring system was used to monitor the hemodynamic parameters changes and the leves of plasma pro-BNP, serum creatinine, serum potassium, serum sodium and urine volume of each group before and after treating for 30 min, 1 h, 3 h, 6 h, 12 h, 24 h, 48 h, 72 h. Results: Patients in the therapy group showed no effect on heart rate, while after 30 min of intravenous injection of rh BNP, CO, CI, SV, and SI increased significantly and LVET and TFC reduced at the same time, which had certain effect on blood pressure(SBP/DBP). Compared with the control group, the therapy group showed a faster and more effective improvement on haemodynamics. Conclusions: Acute myocardial infarction patients complicated with left heart failure after primary PCI can significantly improve hemodynamics by treating with rh BNP.展开更多
The current epidemic of non-alcoholic fatty liver disease(NAFLD) is reshaping the field of hepatology all around the world.The widespread diffusion of metabolic risk factors such as obesity,type2-diabetes mellitus,and...The current epidemic of non-alcoholic fatty liver disease(NAFLD) is reshaping the field of hepatology all around the world.The widespread diffusion of metabolic risk factors such as obesity,type2-diabetes mellitus,and dyslipidemia has led to a worldwide diffusion of NAFLD.In parallel to the increased availability of effective anti-viral agents,NAFLD is rapidly becoming the most common cause of chronic liver disease in Western Countries,and a similar trend is expected in Eastern Countries in the next years.This epidemic and its consequences have prompted experts from all over the word in identifying effective strategies for the diagnosis,management,and treatment of NAFLD.Different scientific societies from Europe,America,and Asia-Pacific regions have proposed guidelines based on the most recent evidence about NAFLD.These guidelines are consistent with the key elements in the management of NAFLD,but still,show significant difference about some critical points.We reviewed the current literature in English language to identify the most recent scientific guidelines about NAFLD with the aim to find and critically analyse the main differences.We distinguished guidelines from 5 different scientific societies whose reputation is worldwide recognised and who are representative of the clinical practice in different geographical regions.Differences were noted in: the definition of NAFLD,the opportunity of NAFLD screening in high-risk patients,the noninvasive test proposed for the diagnosis of NAFLD and the identification of NAFLD patients with advanced fibrosis,in the follow-up protocols and,finally,in the treatment strategy(especially in the proposed pharmacological management).These difference have been discussed in the light of the possible evolution of the scenario ofNAFLD in the next years.展开更多
Liver fibrosis is an important pathological precondition for hepatocellular carcinoma.The degree of hepatic fibrosis is positively correlated with liver cancer.Liver fibrosis is a series of pathological and physiologi...Liver fibrosis is an important pathological precondition for hepatocellular carcinoma.The degree of hepatic fibrosis is positively correlated with liver cancer.Liver fibrosis is a series of pathological and physiological process related to liver cell necrosis and degeneration after chronic liver injury,which finally leads to extracellular matrix and collagen deposition.The early detection and precise staging of fibrosis and cirrhosis are very important for early diagnosis and timely initiation of appropriate therapeutic regimens.The risk of severe liver fibrosis finally progressing to liver carcinoma is＆gt;50%.It is known that biopsy is the gold standard for the diagnosis and staging of liver fibrosis.However,this method has some limitations,such as the potential for pain,sampling variability,and low patient acceptance.Furthermore,the necessity of obtaining a tissue diagnosis of liver fibrosis still remains controversial.An increasing number of reliable non-invasive approaches are now available that are widely applied in clinical practice,mostly in cases of viral hepatitis,resulting in a significantly decreased need for liver biopsy.In fact,the noninvasive detection and evaluation of liver cirrhosis now has good accuracy due to current serum markers,ultrasound imaging,and magnetic resonance imaging quantification techniques.A prominent advantage of the non-invasive detection and assessment of liver fibrosis is that liver fibrosis can be monitored repeatedly and easily in the same patient.Serum biomarkers have the advantages of high applicability（〉95%）and good reproducibility.However,their results can be influenced by different patient conditions because none of these markers are liver-specific.The most promising techniques appear to be transient elastography and magnetic resonance elastography because they provide reliable results for the detection of fibrosis in the advanced stages,and future developments promise to increase the reliability and accuracy of the staging of hepatic fibrosis.This article aim展开更多
The evaluation and follow up of liver fibrosis and cirrhosis have been traditionally performed by liver biopsy. However, during the last 20 years, it has become evident that this "gold-standard" is imperfect...The evaluation and follow up of liver fibrosis and cirrhosis have been traditionally performed by liver biopsy. However, during the last 20 years, it has become evident that this "gold-standard" is imperfect; even according to its proponents, it is only "the best" among available methods. Attempts at uncovering non-invasive diagnostic tools have yielded multiple scores, formulae, and imaging modalities. All are better tolerated, safer, more acceptable to the patient, and can be repeated essentially as often as required. Most are much less expensive than liver biopsy. Consequently, their use is growing, and in some countries the number of biopsies performed, at least for routine evaluation of hepatitis B and C, has declined sharply. However, the accuracy and diagnostic value of most, if not all, of these methods remains controversial. In this review for the practicing physician, we analyze established and novel biomarkers and physical techniques. We may be witnessing in recent years the beginning of the end of the first phase for the development of non-invasive markers. Early evidence suggests that they might be at least as good as liver biopsy. Novel experimental markers and imaging techniques could produce a dramatic change in diagnosis in the near future.展开更多
To assess “predictors” of esophageal varices (EV) and variceal bleeding using non-invasive markers in Albanian patients diagnosed with liver cirrhosis. METHODSOne hundred thirty-nine newly diagnosed cirrhotic patien...To assess “predictors” of esophageal varices (EV) and variceal bleeding using non-invasive markers in Albanian patients diagnosed with liver cirrhosis. METHODSOne hundred thirty-nine newly diagnosed cirrhotic patients without variceal bleeding were included in this analysis. Model for end-stage liver disease (MELD), aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AST/ALT), AST to platelet ratio index (APRI), platelet count to spleen diameter (PC/SD), fibrosis-4-index (FIB-4), fibrosis index (FI) and King’s Score were measured for all participants. All patients underwent endoscopic assessment within two days of hospitalization. The major end point was the first esophageal variceal bleeding (EVB) event. The diagnostic performance of “predictors” for the presence of EV and EVB were assessed by sensitivity and specificity values obtained from the receiver operating characteristics procedure. RESULTSFIB-4 was the only strong and significant “predictor” of esophageal varices (multivariable-adjusted OR = 1.57 for one unit increment; 95%CI: 1.15-2.14). Furthermore, a cut-off value of 3.23 for FIB-4 was a significant predictor of esophageal varices, with a sensitivity of 72%, a specificity of 58% and a proportion of area under the curve (AUC) of 66% (P = 0.01). During the follow-up (median: 31.5 mo; interquartile range: 11-59 mo), 34 patients (24%) experienced a first EVB. FIB-4 was a poor predictor of EVB (the AUC was only 51%) for a cut-off value of 5.02. Furthermore, the AUC of AST/ALT, APRI, PC/SD, FI, MELD and King’s Score ranged from 45% to 55%. None of the non-invasive markers turned out to be a useful predictor of EVB. CONCLUSIONDespite the low diagnostic accuracy, FIB-4 appears the most efficient non-invasive liver fibrosis marker which can be used as an initial screening tool for cirrhotic patients.展开更多
Since the discovery of Helicobacter pylori (H. pylori) in 1983, numerous detection methods for the presence of the bacterium have been developed. Each one of them has been associated with advantages and disadvantages....Since the discovery of Helicobacter pylori (H. pylori) in 1983, numerous detection methods for the presence of the bacterium have been developed. Each one of them has been associated with advantages and disadvantages. Noninvasive tests such as serology, <sup>13</sup>C urea breath test (UBT) and stool antigen tests are usually preferred by the clinicians. Serology has its own limitation especially in endemic areas while <sup>13</sup>C UBT is technically very demanding. The stool antigen detection method, although specific, is usually associated with poor sensitivity. The <sup>13</sup>C UBT is believed to be specific, but with present revelation of the fact that stomach is colonized by many other urease producing bacteria makes it questionable. Histology, culture, rapid urease test and polymerase chain reaction (PCR) are the tests which are carried out on antral biopsies collected by invasive means. Histology has been proposed to be very sensitive and specific but the question is how by simply looking the morphology of the bacteria in the microscope, one can claim that the curved bacterium is exclusively H. pylori. Rapid urease test (RUT), the doctor’s test, is also challenged because the presence of other urease producing bacteria in the stomach cannot be denied. Moreover, RUT has been reported with poor sensitivity specially, when density of the bacterium is low. Isolation of H. pylori is essential to investigate its growth requirements, antibiotic susceptibility testing, studying virulence factor to develop vaccine and many more explorations. It has also got several disadvantages i.e., special condition for transporting, media, incubation and few days waiting for the colonies to appear, apart from the speed essentially needed to process the specimens. Till date, majority of the microbiological laboratories in the world are not equipped and trained to isolate such fastidious bacterium. The option left is PCR methods to detect H. pylori’s DNA in gastric mucosa, gastric juice, saliva, dental plaques展开更多
Liver cirrhosis is a common and growing public health problem globally.The diagnosis of cirrhosis portends an increased risk of morbidity and mortality.Liver biopsy is considered the gold standard for diagnosis of cir...Liver cirrhosis is a common and growing public health problem globally.The diagnosis of cirrhosis portends an increased risk of morbidity and mortality.Liver biopsy is considered the gold standard for diagnosis of cirrhosis and staging of fibrosis.However,despite its universal use,liver biopsy is an invasive and inaccurate gold standard with numerous drawbacks.In order to overcome the limitations of liver biopsy,a number of non-invasive techniques have been investigated for the assessment of cirrhosis.This review will focus on currently available non-invasive markers of cirrhosis.The evidence behind the use of these markers will be highlighted,along with an assessment of diagnostic accuracy and performance characteristics of each test.Non-invasive markers of cirrhosis can be radiologic or serum-based.Radiologic techniques based on ultrasound,magnetic resonance imaging and elastography have been used to assess liver fibrosis.Serum-based biomarkers of cirrhosis have also been developed.These are broadly classified into indirect and direct markers.Indirect biomarkers reflect liver function,which may decline with the onset of cirrhosis.Direct biomarkers,reflect extracellular matrix turnover,and include molecules involved in hepatic fibrogenesis.On the whole,radiologic and serum markers of fibrosis correlate well with biopsy scores,especially when excluding cirrhosis or excluding fibrosis.This feature is certainly clinically useful,and avoids liver biopsy in many cases.展开更多
AIM： To assess the performance of several noninvasive markers and of our recently proposed stepwise combination algorithms to diagnose significant fibrosis （F ≥ 2 by METAVIR） and cirrhosis （F4 by METAVIR） in chr...AIM： To assess the performance of several noninvasive markers and of our recently proposed stepwise combination algorithms to diagnose significant fibrosis （F ≥ 2 by METAVIR） and cirrhosis （F4 by METAVIR） in chronic hepatitis B （CHB）.METHODS： One hundred and ten consecutive patients （80 males, 30 females, mean age： 42.6 ± 11.3） with CHB undergoing diagnostic liver biopsy were included. AST-to-Platelet ratio （APRI）, Forns＇ index, AST-to-ALT Ratio, Goteborg University Cirrhosis Index （GUCD, Hui＇s model and Fibrotest were measured on the day of liver biopsy. The performance of these methods and of sequential algorithms combining Fibrotest, APRI and biopsy was defined by positive （PPV） and negative （NPV） predictive values, accuracy and area under the curve （AUC）. RESULTS： PPV for significant fibrosis was excellent （100%） with Forns and high （〉 92%） with APR1, GUCI, Fibrotest and Hui. However, significant fibrosis could not be excluded by any marker （NPV 〈 65%）. Fibretest had the best PPV and NPV for cirrhosis （87% and 90%, respectively）. Fibrotest showed the best AUC for both significant fibrosis and cirrhosis （0.85 and 0.76, respectively）. Stepwise combination algorithms of APR1, Fibrotest and biopsy showed excellent performance （0.96 AUC, 100% NPV） for significant fibrosis and 0.95 AUC, 98% NPV for cirrhosis, with 50%-80% reduced need for liver biopsy. CONCLUSION： In CHB sequential combination of APRI, Fibrotest and liver biopsy greatly improves the diagnostic performance of the single non-invasive markers. Need for liver biopsy is reduced by 50%-80% but cannot be completely avoided. Non-invasive markers and biopsy should be considered as agonists and not antagonists towards the common goal of estimating liver fibrosis.展开更多
The development of gastritis is associated with an increased risk of gastric cancer. Current invasive gastritis diagnostic methods are not suitable for monitoring progressIn this work based on 78 gastritis patients an...The development of gastritis is associated with an increased risk of gastric cancer. Current invasive gastritis diagnostic methods are not suitable for monitoring progressIn this work based on 78 gastritis patients and 50 healthy individuals, we observed that the variation of tongue-coating microbiota was associated with the occurrenee and development of gastritis. Twenty-one microbial species were identified for differentiating tongue-coating microbiomes of gastritis and healthy individuals. Pathways such as microbial metabolism in diverse environments, biosynthesis of antibiotics and bacterial chemotaxis were up-regulated in gastritis patients. The abundance of Campylobacter concisus was found associated with the gastric precancerous cascade. Furthermore, Campylobacter concisus could be detected in tongue coating and gastric fluid in a validation cohort containing 38 gastritis patients. These observations provided biological evidence of tongue diagnosis in traditional Chinese medicine, and indicated that tongue-coating microbiome could be a potential non-invasive biomarker, which might be suitable for long-term monitoring of gastritis.展开更多
Various Ionic and molecular activities in the extraceUular environment are vital to plant cell physiological processes. A noninvasive microsensing system （NMS） based on either the scanning ion-selective electrode te...Various Ionic and molecular activities in the extraceUular environment are vital to plant cell physiological processes. A noninvasive microsensing system （NMS） based on either the scanning ion-selective electrode technique （SIET） or the scanning polarographlc electrode technique （SPET） is able to obtain information regarding the transportation of various Ions/molecules in Intact samples under normal physiological conditions. The two-probe simultaneous test system （2STS） Is an Integrated system composed of SIET, SPET, and a Xu-Kunkel sampling protocol. In the present study, 2STS was able to simultaneously measure fluxes of H^＋ and O2 of the Uly （Lillum Iongiflorum Thunb. cv. Ace） pollen tube while avoiding interference between the two probes. The results Indicate that the proton fluxes were effluxes, whereas the oxygen fluxes were Influxes, and they were closely correlated to each other surrounding the constitutive alkaline band region. Specifically, when the proton effluxes increased, the oxygen Influxes also increased. Therefore, the hypothesis of condensed active mitochondria existing in the alkalized area of the pollen tube proposed by Hepler＇s group is supported.展开更多
AIM To investigate the value of ultrasound elastography combined with serological indexes in diagnosing liver fibrosis and assessing its severity.METHODS A total of 338 chronic hepatitis B(CHB) patients were divided i...AIM To investigate the value of ultrasound elastography combined with serological indexes in diagnosing liver fibrosis and assessing its severity.METHODS A total of 338 chronic hepatitis B(CHB) patients were divided into a disease group(patients with hepatic fibrosis) and control group(subjects without hepatic fibrosis). The disease group was further divided into S1-S4 according to the degree of fibrosis. Independent risk factors for hepatic fibrosis were analyzed using multivariate logistic regression. The diagnostic values of hepatic fibrosis from different indicators were compared using receiver operating characteristic(ROC) curves. The combination of elastography and serological indexes was explored to assess the severity of hepatic fibrosis.RESULTS The multivariate logistic regression analysis results revealed that shear wave velocity(SWV), hyaluronic acid(HA), type Ⅳ collagen(CⅣ) and aspartate aminotransferase-to-platelet ratio index(APRI) significantly affected the occurrence of hepatic fibrosis. The ROC curve revealed that the accuracy of the diagnosis of hepatic fibrosis for SWV and HA were 87.3% and 84.8%, respectively. The accuracy of SWV combined with HA was 88.9%. The multiple linear regression analysis revealed that SWV, aspartate aminotransferase(AST)/alanine aminotransferase(ALT), HA, CⅣ, APRI and fibrosis index based on the 4 factor(FIB-4) were screened as statistically significant independent factors. The established regression equation was: Fibrosis level =-4.046 + 1.024 × SWV + 1.170 × AST/ALT + 0.011 × HA + 0.020 × CⅣ + 0.719 × APRI + 0.379 × FIB-4. CONCLUSION SWV combined with serological indexes can improve the accuracy of diagnosis for CHB hepatic fibrosis. Serum indexes can help diagnose the degree of hepatic fibrosis.展开更多
Current neuromodulation techniques such as optogenetics and deep-brain stimulation are transforming basic and translational neuroscience. These two neuro- modulation approaches are, however, invasive since surgical im...Current neuromodulation techniques such as optogenetics and deep-brain stimulation are transforming basic and translational neuroscience. These two neuro- modulation approaches are, however, invasive since surgical implantation of an optical fiber or wire electrode is required. Here, we have invented a non-invasive magnetogenetics that combines the genetic targeting of a mag- netoreceptor with remote magnetic stimulation. The noninvasive activation of neurons was achieved by neuronal expression of an exogenous magnetoreceptor, an iron-sulfur cluster assembly protein 1 （Iscal）. In HEK-293 cells and cultured hippocampal neurons expressing this magnetoreceptor, application of an external magnetic field resulted in membrane depolarization and calcium influx in a reproducible and reversible manner, as indicated by the ultrasensitive fluorescent calcium indicator GCaMP6s.Moreover, the magnetogenetic control of neuronal activity might be dependent on the direction of the magnetic field and exhibits on-response and off-response patterns for the external magnetic field applied. The activation of this magnetoreceptor can depolarize neurons and elicit trains of action potentials, which can be triggered repetitively with a remote magnetic field in whole-cell patch-clamp recording. In transgenic Caenorhabditis elegans expressing this magnetoreceptor in myo-3-specific muscle cells or mec-4- specific neurons, application of the external magnetic field triggered muscle contraction and withdrawal behavior of the worms, indicative of magnet-dependent activation of muscle cells and touch receptor neurons, respectively. The advantages of magnetogenetics over optogenetics are its exclusive non-invasive, deep penetration, long-term continuous dosing, unlimited accessibility, spatial uniformity and relative safety. Like optogenetics that has gone through decade-long improvements, magnetogenetics, with continuous modification and maturation, will reshape the current landscape of neuromodulation toolboxes and will have a broad range 展开更多
文摘从现有波动量法出发,研究用户波动与背景谐波变化对公共联结点谐波电流、谐波电压的影响,提出一种基于用户主导波动量筛选原理的用户谐波发射水平估计方法。提出公共连接点(point of common coupling,PCC)谐波波动伏安特性比的概念,研究系统侧、用户侧谐波波动对其变化的影响;利用统计学筛选方法从PCC点谐波电流测量值中筛选出用户主导谐波电流波动量,以此估计系统谐波阻抗;采用用户谐波电压发射水平修正公式消除背景谐波的影响。对理论模型和实际工程算例的仿真证明该文方法的正确性和有效性。
基金supported by Science and Education Project of Hainan Province Health and Family Planning administrationand Sanya Health and Technology Innovation Project(NO.2015YW19)
文摘Objective: To investigate the effects of exogenous recombinant human brain natriuretic peptide(rh BNP) after primary percutaneous coronary intervention(PCI) on non-invasive hemodynamic in acute myocardial infarction patients with left ventricular failure. Methods: A number of 96 acute myocardial infarction patients accompanied with heart failure after PCI hospitalized in the People's Hospital of Sanya during February 2012 to October 2015 were selected. They were randomly divided into the therapy group(n = 50) and control group(n = 46). On the basis of routine treatment, patients in the therapy group were treated with intravenous rh BNP(1.5 μg/kg was intravenous injection with uniform speed of 3 min, followed by continuous infusion 0.007 5 μg/kg·min for 72 h), while the control group received conventional treatment. Bio Z-2011 non-invasive hemodynamic real-time monitoring system was used to monitor the hemodynamic parameters changes and the leves of plasma pro-BNP, serum creatinine, serum potassium, serum sodium and urine volume of each group before and after treating for 30 min, 1 h, 3 h, 6 h, 12 h, 24 h, 48 h, 72 h. Results: Patients in the therapy group showed no effect on heart rate, while after 30 min of intravenous injection of rh BNP, CO, CI, SV, and SI increased significantly and LVET and TFC reduced at the same time, which had certain effect on blood pressure(SBP/DBP). Compared with the control group, the therapy group showed a faster and more effective improvement on haemodynamics. Conclusions: Acute myocardial infarction patients complicated with left heart failure after primary PCI can significantly improve hemodynamics by treating with rh BNP.
文摘The current epidemic of non-alcoholic fatty liver disease(NAFLD) is reshaping the field of hepatology all around the world.The widespread diffusion of metabolic risk factors such as obesity,type2-diabetes mellitus,and dyslipidemia has led to a worldwide diffusion of NAFLD.In parallel to the increased availability of effective anti-viral agents,NAFLD is rapidly becoming the most common cause of chronic liver disease in Western Countries,and a similar trend is expected in Eastern Countries in the next years.This epidemic and its consequences have prompted experts from all over the word in identifying effective strategies for the diagnosis,management,and treatment of NAFLD.Different scientific societies from Europe,America,and Asia-Pacific regions have proposed guidelines based on the most recent evidence about NAFLD.These guidelines are consistent with the key elements in the management of NAFLD,but still,show significant difference about some critical points.We reviewed the current literature in English language to identify the most recent scientific guidelines about NAFLD with the aim to find and critically analyse the main differences.We distinguished guidelines from 5 different scientific societies whose reputation is worldwide recognised and who are representative of the clinical practice in different geographical regions.Differences were noted in: the definition of NAFLD,the opportunity of NAFLD screening in high-risk patients,the noninvasive test proposed for the diagnosis of NAFLD and the identification of NAFLD patients with advanced fibrosis,in the follow-up protocols and,finally,in the treatment strategy(especially in the proposed pharmacological management).These difference have been discussed in the light of the possible evolution of the scenario ofNAFLD in the next years.
文摘Liver fibrosis is an important pathological precondition for hepatocellular carcinoma.The degree of hepatic fibrosis is positively correlated with liver cancer.Liver fibrosis is a series of pathological and physiological process related to liver cell necrosis and degeneration after chronic liver injury,which finally leads to extracellular matrix and collagen deposition.The early detection and precise staging of fibrosis and cirrhosis are very important for early diagnosis and timely initiation of appropriate therapeutic regimens.The risk of severe liver fibrosis finally progressing to liver carcinoma is＆gt;50%.It is known that biopsy is the gold standard for the diagnosis and staging of liver fibrosis.However,this method has some limitations,such as the potential for pain,sampling variability,and low patient acceptance.Furthermore,the necessity of obtaining a tissue diagnosis of liver fibrosis still remains controversial.An increasing number of reliable non-invasive approaches are now available that are widely applied in clinical practice,mostly in cases of viral hepatitis,resulting in a significantly decreased need for liver biopsy.In fact,the noninvasive detection and evaluation of liver cirrhosis now has good accuracy due to current serum markers,ultrasound imaging,and magnetic resonance imaging quantification techniques.A prominent advantage of the non-invasive detection and assessment of liver fibrosis is that liver fibrosis can be monitored repeatedly and easily in the same patient.Serum biomarkers have the advantages of high applicability（〉95%）and good reproducibility.However,their results can be influenced by different patient conditions because none of these markers are liver-specific.The most promising techniques appear to be transient elastography and magnetic resonance elastography because they provide reliable results for the detection of fibrosis in the advanced stages,and future developments promise to increase the reliability and accuracy of the staging of hepatic fibrosis.This article aim
文摘The evaluation and follow up of liver fibrosis and cirrhosis have been traditionally performed by liver biopsy. However, during the last 20 years, it has become evident that this "gold-standard" is imperfect; even according to its proponents, it is only "the best" among available methods. Attempts at uncovering non-invasive diagnostic tools have yielded multiple scores, formulae, and imaging modalities. All are better tolerated, safer, more acceptable to the patient, and can be repeated essentially as often as required. Most are much less expensive than liver biopsy. Consequently, their use is growing, and in some countries the number of biopsies performed, at least for routine evaluation of hepatitis B and C, has declined sharply. However, the accuracy and diagnostic value of most, if not all, of these methods remains controversial. In this review for the practicing physician, we analyze established and novel biomarkers and physical techniques. We may be witnessing in recent years the beginning of the end of the first phase for the development of non-invasive markers. Early evidence suggests that they might be at least as good as liver biopsy. Novel experimental markers and imaging techniques could produce a dramatic change in diagnosis in the near future.
文摘To assess “predictors” of esophageal varices (EV) and variceal bleeding using non-invasive markers in Albanian patients diagnosed with liver cirrhosis. METHODSOne hundred thirty-nine newly diagnosed cirrhotic patients without variceal bleeding were included in this analysis. Model for end-stage liver disease (MELD), aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AST/ALT), AST to platelet ratio index (APRI), platelet count to spleen diameter (PC/SD), fibrosis-4-index (FIB-4), fibrosis index (FI) and King’s Score were measured for all participants. All patients underwent endoscopic assessment within two days of hospitalization. The major end point was the first esophageal variceal bleeding (EVB) event. The diagnostic performance of “predictors” for the presence of EV and EVB were assessed by sensitivity and specificity values obtained from the receiver operating characteristics procedure. RESULTSFIB-4 was the only strong and significant “predictor” of esophageal varices (multivariable-adjusted OR = 1.57 for one unit increment; 95%CI: 1.15-2.14). Furthermore, a cut-off value of 3.23 for FIB-4 was a significant predictor of esophageal varices, with a sensitivity of 72%, a specificity of 58% and a proportion of area under the curve (AUC) of 66% (P = 0.01). During the follow-up (median: 31.5 mo; interquartile range: 11-59 mo), 34 patients (24%) experienced a first EVB. FIB-4 was a poor predictor of EVB (the AUC was only 51%) for a cut-off value of 5.02. Furthermore, the AUC of AST/ALT, APRI, PC/SD, FI, MELD and King’s Score ranged from 45% to 55%. None of the non-invasive markers turned out to be a useful predictor of EVB. CONCLUSIONDespite the low diagnostic accuracy, FIB-4 appears the most efficient non-invasive liver fibrosis marker which can be used as an initial screening tool for cirrhotic patients.
基金Supported by Council of Scientific and Industrial Research,New Delhi,India in the form of Senior Research Fellowship awarded to Patel SK
文摘Since the discovery of Helicobacter pylori (H. pylori) in 1983, numerous detection methods for the presence of the bacterium have been developed. Each one of them has been associated with advantages and disadvantages. Noninvasive tests such as serology, <sup>13</sup>C urea breath test (UBT) and stool antigen tests are usually preferred by the clinicians. Serology has its own limitation especially in endemic areas while <sup>13</sup>C UBT is technically very demanding. The stool antigen detection method, although specific, is usually associated with poor sensitivity. The <sup>13</sup>C UBT is believed to be specific, but with present revelation of the fact that stomach is colonized by many other urease producing bacteria makes it questionable. Histology, culture, rapid urease test and polymerase chain reaction (PCR) are the tests which are carried out on antral biopsies collected by invasive means. Histology has been proposed to be very sensitive and specific but the question is how by simply looking the morphology of the bacteria in the microscope, one can claim that the curved bacterium is exclusively H. pylori. Rapid urease test (RUT), the doctor’s test, is also challenged because the presence of other urease producing bacteria in the stomach cannot be denied. Moreover, RUT has been reported with poor sensitivity specially, when density of the bacterium is low. Isolation of H. pylori is essential to investigate its growth requirements, antibiotic susceptibility testing, studying virulence factor to develop vaccine and many more explorations. It has also got several disadvantages i.e., special condition for transporting, media, incubation and few days waiting for the colonies to appear, apart from the speed essentially needed to process the specimens. Till date, majority of the microbiological laboratories in the world are not equipped and trained to isolate such fastidious bacterium. The option left is PCR methods to detect H. pylori’s DNA in gastric mucosa, gastric juice, saliva, dental plaques
文摘Liver cirrhosis is a common and growing public health problem globally.The diagnosis of cirrhosis portends an increased risk of morbidity and mortality.Liver biopsy is considered the gold standard for diagnosis of cirrhosis and staging of fibrosis.However,despite its universal use,liver biopsy is an invasive and inaccurate gold standard with numerous drawbacks.In order to overcome the limitations of liver biopsy,a number of non-invasive techniques have been investigated for the assessment of cirrhosis.This review will focus on currently available non-invasive markers of cirrhosis.The evidence behind the use of these markers will be highlighted,along with an assessment of diagnostic accuracy and performance characteristics of each test.Non-invasive markers of cirrhosis can be radiologic or serum-based.Radiologic techniques based on ultrasound,magnetic resonance imaging and elastography have been used to assess liver fibrosis.Serum-based biomarkers of cirrhosis have also been developed.These are broadly classified into indirect and direct markers.Indirect biomarkers reflect liver function,which may decline with the onset of cirrhosis.Direct biomarkers,reflect extracellular matrix turnover,and include molecules involved in hepatic fibrogenesis.On the whole,radiologic and serum markers of fibrosis correlate well with biopsy scores,especially when excluding cirrhosis or excluding fibrosis.This feature is certainly clinically useful,and avoids liver biopsy in many cases.
文摘AIM： To assess the performance of several noninvasive markers and of our recently proposed stepwise combination algorithms to diagnose significant fibrosis （F ≥ 2 by METAVIR） and cirrhosis （F4 by METAVIR） in chronic hepatitis B （CHB）.METHODS： One hundred and ten consecutive patients （80 males, 30 females, mean age： 42.6 ± 11.3） with CHB undergoing diagnostic liver biopsy were included. AST-to-Platelet ratio （APRI）, Forns＇ index, AST-to-ALT Ratio, Goteborg University Cirrhosis Index （GUCD, Hui＇s model and Fibrotest were measured on the day of liver biopsy. The performance of these methods and of sequential algorithms combining Fibrotest, APRI and biopsy was defined by positive （PPV） and negative （NPV） predictive values, accuracy and area under the curve （AUC）. RESULTS： PPV for significant fibrosis was excellent （100%） with Forns and high （〉 92%） with APR1, GUCI, Fibrotest and Hui. However, significant fibrosis could not be excluded by any marker （NPV 〈 65%）. Fibretest had the best PPV and NPV for cirrhosis （87% and 90%, respectively）. Fibrotest showed the best AUC for both significant fibrosis and cirrhosis （0.85 and 0.76, respectively）. Stepwise combination algorithms of APR1, Fibrotest and biopsy showed excellent performance （0.96 AUC, 100% NPV） for significant fibrosis and 0.95 AUC, 98% NPV for cirrhosis, with 50%-80% reduced need for liver biopsy. CONCLUSION： In CHB sequential combination of APRI, Fibrotest and liver biopsy greatly improves the diagnostic performance of the single non-invasive markers. Need for liver biopsy is reduced by 50%-80% but cannot be completely avoided. Non-invasive markers and biopsy should be considered as agonists and not antagonists towards the common goal of estimating liver fibrosis.
基金National Natural Science Foundation of China (Grant Nos. 81630103, 91729301, 91229201 and 81225025)the Project of Tsinghua-Fuzhou Insititute for Data Technology (TFIDT2018001)to S. Li and grants 61673231 and 61721003 to X. Zhang.
文摘The development of gastritis is associated with an increased risk of gastric cancer. Current invasive gastritis diagnostic methods are not suitable for monitoring progressIn this work based on 78 gastritis patients and 50 healthy individuals, we observed that the variation of tongue-coating microbiota was associated with the occurrenee and development of gastritis. Twenty-one microbial species were identified for differentiating tongue-coating microbiomes of gastritis and healthy individuals. Pathways such as microbial metabolism in diverse environments, biosynthesis of antibiotics and bacterial chemotaxis were up-regulated in gastritis patients. The abundance of Campylobacter concisus was found associated with the gastric precancerous cascade. Furthermore, Campylobacter concisus could be detected in tongue coating and gastric fluid in a validation cohort containing 38 gastritis patients. These observations provided biological evidence of tongue diagnosis in traditional Chinese medicine, and indicated that tongue-coating microbiome could be a potential non-invasive biomarker, which might be suitable for long-term monitoring of gastritis.
基金Supported by the National Natural Science Foundation of China （30170552）, Beijing Natural Science Foundation （5042004）, Beijing Education Committee Science and Technology Development Project （KM200410028015） and Applicable Electronics Inc. （Forestdale, MA, USA）.
文摘Various Ionic and molecular activities in the extraceUular environment are vital to plant cell physiological processes. A noninvasive microsensing system （NMS） based on either the scanning ion-selective electrode technique （SIET） or the scanning polarographlc electrode technique （SPET） is able to obtain information regarding the transportation of various Ions/molecules in Intact samples under normal physiological conditions. The two-probe simultaneous test system （2STS） Is an Integrated system composed of SIET, SPET, and a Xu-Kunkel sampling protocol. In the present study, 2STS was able to simultaneously measure fluxes of H^＋ and O2 of the Uly （Lillum Iongiflorum Thunb. cv. Ace） pollen tube while avoiding interference between the two probes. The results Indicate that the proton fluxes were effluxes, whereas the oxygen fluxes were Influxes, and they were closely correlated to each other surrounding the constitutive alkaline band region. Specifically, when the proton effluxes increased, the oxygen Influxes also increased. Therefore, the hypothesis of condensed active mitochondria existing in the alkalized area of the pollen tube proposed by Hepler＇s group is supported.
基金Supported by the Natural Science Research Project of Minhang District,No.2013MHZ003
文摘AIM To investigate the value of ultrasound elastography combined with serological indexes in diagnosing liver fibrosis and assessing its severity.METHODS A total of 338 chronic hepatitis B(CHB) patients were divided into a disease group(patients with hepatic fibrosis) and control group(subjects without hepatic fibrosis). The disease group was further divided into S1-S4 according to the degree of fibrosis. Independent risk factors for hepatic fibrosis were analyzed using multivariate logistic regression. The diagnostic values of hepatic fibrosis from different indicators were compared using receiver operating characteristic(ROC) curves. The combination of elastography and serological indexes was explored to assess the severity of hepatic fibrosis.RESULTS The multivariate logistic regression analysis results revealed that shear wave velocity(SWV), hyaluronic acid(HA), type Ⅳ collagen(CⅣ) and aspartate aminotransferase-to-platelet ratio index(APRI) significantly affected the occurrence of hepatic fibrosis. The ROC curve revealed that the accuracy of the diagnosis of hepatic fibrosis for SWV and HA were 87.3% and 84.8%, respectively. The accuracy of SWV combined with HA was 88.9%. The multiple linear regression analysis revealed that SWV, aspartate aminotransferase(AST)/alanine aminotransferase(ALT), HA, CⅣ, APRI and fibrosis index based on the 4 factor(FIB-4) were screened as statistically significant independent factors. The established regression equation was: Fibrosis level =-4.046 + 1.024 × SWV + 1.170 × AST/ALT + 0.011 × HA + 0.020 × CⅣ + 0.719 × APRI + 0.379 × FIB-4. CONCLUSION SWV combined with serological indexes can improve the accuracy of diagnosis for CHB hepatic fibrosis. Serum indexes can help diagnose the degree of hepatic fibrosis.
基金supported by Tsinghua-Peking Center for Life SciencesIDG/Mc Govern Foundationthe National Natural Science Foundation of China
文摘Current neuromodulation techniques such as optogenetics and deep-brain stimulation are transforming basic and translational neuroscience. These two neuro- modulation approaches are, however, invasive since surgical implantation of an optical fiber or wire electrode is required. Here, we have invented a non-invasive magnetogenetics that combines the genetic targeting of a mag- netoreceptor with remote magnetic stimulation. The noninvasive activation of neurons was achieved by neuronal expression of an exogenous magnetoreceptor, an iron-sulfur cluster assembly protein 1 （Iscal）. In HEK-293 cells and cultured hippocampal neurons expressing this magnetoreceptor, application of an external magnetic field resulted in membrane depolarization and calcium influx in a reproducible and reversible manner, as indicated by the ultrasensitive fluorescent calcium indicator GCaMP6s.Moreover, the magnetogenetic control of neuronal activity might be dependent on the direction of the magnetic field and exhibits on-response and off-response patterns for the external magnetic field applied. The activation of this magnetoreceptor can depolarize neurons and elicit trains of action potentials, which can be triggered repetitively with a remote magnetic field in whole-cell patch-clamp recording. In transgenic Caenorhabditis elegans expressing this magnetoreceptor in myo-3-specific muscle cells or mec-4- specific neurons, application of the external magnetic field triggered muscle contraction and withdrawal behavior of the worms, indicative of magnet-dependent activation of muscle cells and touch receptor neurons, respectively. The advantages of magnetogenetics over optogenetics are its exclusive non-invasive, deep penetration, long-term continuous dosing, unlimited accessibility, spatial uniformity and relative safety. Like optogenetics that has gone through decade-long improvements, magnetogenetics, with continuous modification and maturation, will reshape the current landscape of neuromodulation toolboxes and will have a broad range
