By Invoking symmetry principle, we present a self-consistent interpretation of the existing quantum theory which explains why our world is fundamentally indeterministic and that why non-local quantum jumps occur. Symm...By Invoking symmetry principle, we present a self-consistent interpretation of the existing quantum theory which explains why our world is fundamentally indeterministic and that why non-local quantum jumps occur. Symmetry principle dictates that the concept of probability is more fundamental than the notion of the wave function in that the former can be derived directly from symmetries rather than have to be assumed as an additional axiom. It is argued that the notion of quantum probability and that of the wavefunction are intimately connected.展开更多
Free will is difficult to classify with respect to determinism or indeterminism, and its phenomenology in consciousness often shows both aspects. Initially, it is felt as unlimited and indeterminate will power, with t...Free will is difficult to classify with respect to determinism or indeterminism, and its phenomenology in consciousness often shows both aspects. Initially, it is felt as unlimited and indeterminate will power, with the potentiality of multiple choices. Thereafter, reductive deliberation is led by determinism to the final decision, which realises only one of the potential choices. The reductive deliberation phase tries to find out the best alternative and simultaneously satisfying vague motivations, contextual conditions and personal preferences. The essential sense of free will is the introduction of personal preferences, which allows a higher diversity of reactions to vague motivations. With an oversimplified model of determinism as a chain of events, incompatibilists define ＂free＂ as ＂undetermined＂ so that determinism becomes incompatible with any free choice between alternatives. In consciousness, free will requires a more complex model of network determinism as well as the consideration of unconsciousness as a causal factor. When ＂free＂ defined as ＂undetermined＂ is applied to the context of consciousness, it should be reinterpreted as ＂unconscious of being determined＂ or not aware of underlying determinism. Lacking information on determinism generates a feeling of ＂free＂ in consciousness and, therefore, gives the impression of indeterminism. Lacking information may be induced by an uncertain future without determined events--an unconscious past with biological reactions suddenly emerging from the unconsciousness or an unknown present unable to distinguish determinism of complex events. Therefore, at the level of human consciousness, the experience of free will is associated with apparent indeterminism although it is based on unconscious determinism. The concepts of compatibilism and incompatibilism are only two different aspects of the same phenomenon and correspond to consciousness and unconsciousness. Nevertheless, they can be considered together with a free will concept based on relativity depending on two different reference frames--the first person＇s experience frame or the Laplace＇s demon frame with knowledge on every molecule of the universe. Only relativity of the free will concept avoids the contradiction between ＂free＂ and ＂unfree＂ for the same phenomenon and could be a compromise for considering compatibilism and incompatibilism equally.展开更多
Irreducible indeterminism is considered by most physicists as an ontological interpretation of quantum mechanics, which attributes inherent indeterminism to elementary paJcticles. This view was extrapolated by von Neu...Irreducible indeterminism is considered by most physicists as an ontological interpretation of quantum mechanics, which attributes inherent indeterminism to elementary paJcticles. This view was extrapolated by von Neumann from the atomocosm to the entire universe. Heisenberg proposed an epistemic interpretation, postulating that indeterminism stems from ambivalent detection systems, rather than being a characteristic of elementary particles Transformative detection that inherently affects the measured phenomena is responsible for the indeterminism in the atomocosm. As the same does not generally hold true in the macrocosm, this discrepancy has led to the notion of the Heisenberg cut. As explained by Heisenberg＇s microscope example, high-energy light can displace electrons from their atomic shells in the atomocosm, but would not induce the same effect on objects in the macrocosm, thus rendering such detection neutral. Therefore, detection systems are ambivalent in that they can be transformative under the cut and neutral otherwise. Device variation is found under and above the cut and is the essential cause of outcome variability in the macrocosm. Thus, two completely different categories of indeterminism exist simultaneously under the Heisenberg cut, but only one is found above the cut, known as measurement variations of devices. Experimental exploration of elementary paJcticle behaviors is possible only with the help of detection systems. If these systems affect particle characteristics in any way, this would be sufficient to explain the irreducible quantum mechanical indeterminism. Consequently, the true behavior of elementary particles, whether indeterminist or determinist, would never be detectable. Above the cut, on the other hand, variations in device performance are inevitable, due to reducible perturbing factors, inducing measurement wJciation of devices Heisenberg discovered a general principle of ambivalent detection systems, which can also be found in the macrocosm. In the Wilson Cloud Chamber, vapor is an ambivalent detection system, since high-energy charged particles would produce straight tracks, whereas those of lower energy would leave an irregular trace. According to the epistemic interpretation, von Neumann＇s extrapolation of irreducible quantum mechanical indeterminism to the entire universe would not be necessary, thereby avoiding the uncomfortable conclusion that the entire universe is based on indeterminism展开更多
Estimating causal effects is a principal goal in epidemiology and other branches of science. Nonetheless, what constitutes an effect and which measure of effect is pre-ferred are unsettled questions. I argue that, und...Estimating causal effects is a principal goal in epidemiology and other branches of science. Nonetheless, what constitutes an effect and which measure of effect is pre-ferred are unsettled questions. I argue that, under indeterminism, an effect is a change in the tendency of the outcome variable to take each of its values, and then present a critical analysis of commonly used measures of effect and the measures of frequency from which they are calculated. I conclude that all causal effects should be quantified using a unifying measure of effect called the log likelihood ratio (which is the log probability ratio when the outcome is a discrete variable). Furthermore, I suggest that effects should be estimated for all causal contrasts of the causal variable (i.e., expo-sure), on all values of the outcome variable, and for all time intervals between the cause and the outcome. This goal should be kept in mind in practical approximations.展开更多
Many real⁃world machine learning applications face the challenge of dealing with changing data over time,known as concept drift,and the issue of data indeterminacy,where all the true labels available are unrealistic.T...Many real⁃world machine learning applications face the challenge of dealing with changing data over time,known as concept drift,and the issue of data indeterminacy,where all the true labels available are unrealistic.This can lead to a decrease in the accuracy of the prediction models.The aim of this study is to introduce a new approach for detecting drift,which is based on neutrosophic set theory.This approach takes into account uncertainty in the prediction model and is able to handle indeterminate information,considering its impact on the models performance.The proposed method reads data into windows and calculates a set of values based on the concept of neutrosophic membership.These values are then used in the Neutrosophic Support Vector Machine(N⁃SVM).To address the issue of indeterminate true label data,the values issued by N⁃SVM are expressed as entropy and used as input for the ADWIN(Adaptive Windowing)change detector.When a drift is detected,the prediction model is retrained by including only the most recent instances with the original training data set.The proposed method gives promising results in terms of drift detection accuracy compared to the state of existing drift detection methods such as KSWIN,ADWIN,and DWM.展开更多
This paper reveals the origin of nonlinear dynamics and presents a solution for nonlinear systematic problems based on other science. Generally, physical phenomena are divided into linear static logical problems and n...This paper reveals the origin of nonlinear dynamics and presents a solution for nonlinear systematic problems based on other science. Generally, physical phenomena are divided into linear static logical problems and nonlinear dynamic systematic problems, but all scientists have solved both problems using the same algebraic logical solution in statistical physics based on determinism such as chaos theory. Surprisingly, this is a contradiction and a serious mistake because there is a perfect solution such as the system analysis theory exist<span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">ing</span></span></span><span><span><span style="font-family:;" "=""><span style="font-family:Verdana;"> in other science. Unfortunately, it has developed in the 20</span><sup><span style="font-family:Verdana;">th</span></sup><span style="font-family:Verdana;"> century by engineers. Thus, classical physicists could not solve it. Meanwhile, the author achieved the systematic solution for many unsolved nonlinear systematical, further, proved the research result through simulation using specially designed simulation device. Thus, this is a revolutionary achievement because it</span></span><span> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">can easily solve the unsolved nonlinear dynamics that exists in all fields of science</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">. </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Ironically most determinists do not welcome and reject it. However, it has no matter, it will be separated from current physics and other scientists studied it in the second physics. Therefore, it would be contributed to solve the unsolved nonlinear dynamics in complex science</span></span></span><span style="font-family:Verdana;">.</span>展开更多
One of the most intriguing problems of philosophy and of mankind is the question whether humans have a free will. This question is heavily disputed between natural scientists and especially neuroscientists, who deny f...One of the most intriguing problems of philosophy and of mankind is the question whether humans have a free will. This question is heavily disputed between natural scientists and especially neuroscientists, who deny free will, and philosophers and other groups, who insist on free will. It is perplexing that both sides base their premise on the same precondition, namely naturalism. We will prove that naturalism automatically leads to physicalism, to materialism, and to reductionism. We will also prove here that it is logically not possible to have a free will if naturalism is true. Free will definitely requires an additional substance, a non-material soul, which cannot be part of our universe. This must not be in contradiction to our current knowledge of natural sciences.展开更多
HIV-indeterminate Western blotting(WB)results are typically obtained in WB confirmatory assays,and the number of indeterminate samples may increase with the detection of HIV infections,which will present considerable ...HIV-indeterminate Western blotting(WB)results are typically obtained in WB confirmatory assays,and the number of indeterminate samples may increase with the detection of HIV infections,which will present considerable challenges for the management of HIV/AIDS.Nucleic acid detection has been used as a laboratory test for screening suspected or indeterminate samples.However,the effectiveness of these assays for the differential diagnosis of HIV-indeterminate WB samples remained undetermined.In this study,210 subjects with HIV-indeterminate WB results were detected from 6360 positive HIV screening samples between 2015 and 2016 in southeastern China,in which HIV-indeterminate WB results accounted for 3.30%.The highest proportion of indeterminate results was observed in pregnant and lying-in women receiving physical examinations(16.67%),followed by that in voluntary blood donors(8.82%).The most common WB band patterns were p24,gpl60 and p24,and gpl60.The follow-up study revealed that the highest negative and positive conversion rates of HIV antibodies were in samples with a single p24 band(80.28%),and with gpl60 and p24 bands(86.21%),respectively.Among the Env,Gag,and Pol antibodies,samples with a Gag band showed the highest negative conversion rate(81.25%),whereas the highest positive conversion rate was observed in samples with an Env band(56.76%).In addition,quantitative and qualitative HIV nucleic acid testing exhibited the highest sensitivity(96.3%)and specificity(97.85%),respectively.Our results indicate a lower proportion of HIV indeterminate WB results in southeastern China compared to previous reports,and the follow-up re-examination of patients with HIV indeterminate results should be performed.Nucleic acid testing facilitates the identification of HIV infections.展开更多
Due to the need for improvement in the diagnosis and minimally invasive therapy of the bile duct disorders new technologies for cholangioscopy have been recently developed. Per-oral cholangioscopy has become an import...Due to the need for improvement in the diagnosis and minimally invasive therapy of the bile duct disorders new technologies for cholangioscopy have been recently developed. Per-oral cholangioscopy has become an important diagnostic and therapeutic tool leading to avoidance of aggressive and unnecessary surgery in many clinical scenarios. This paper focuses on the newly developed SpyGlass DS technology, its advantages, and the technique of single-operator cholangioscopy(SOC), biliary indications and possible adverse events. We also review the available literature; discuss the limitations and future expectations.Digital SOC(D-SOC) is a useful technique, which provides endoscopic imaging of the biliary tree, optical diagnosis, biopsy under direct vision and therapeutic interventions. The implementations are diagnostic and therapeutic. Diagnostic indications are indeterminate biliary strictures, unclear filling defects, staging of cholangiocarcinoma, staging of ampullary tumors(extension into the common bile duct), unclear bile duct dilation, exploring cystic lesions of the biliary tree,unexplained hemobilia, posttransplant biliary complications. Therapeutic indications are lithotripsy of difficult stones, retrieval of migrated stents, foreign body removal, guide wire placement, transpapillary gallbladder drainage and endoscopic tumor ablative therapy. Most studied and established indications are the diagnosis of indeterminate biliary stricture and intraductal lithotripsy of difficult stones. The adverse events are not different and more common compared to those of Endoscopic retrograde cholangiopancreatography(ERCP)alone. D-SOC is a safe and effective procedure, adjunct to the standard ERCP and the newly available digital technology overcomes many of the limitations of the previous generations of cholangioscopes.展开更多
AIM:To investigate the clinicopathologic parameters of pulmonary metastasis in colorectal cancer(CRC) patients after lung operation of indeterminate pulmonary nodules(IPNs).METHODS:From a prospective database of CRCpa...AIM:To investigate the clinicopathologic parameters of pulmonary metastasis in colorectal cancer(CRC) patients after lung operation of indeterminate pulmonary nodules(IPNs).METHODS:From a prospective database of CRCpatients,40 cases that underwent lung operation between November 2008 and December 2012 for suspicious metastatic pulmonary nodules on chest computed tomography(CT)were enrolled.The decision to perform a lung operation was made if the patient met the following criteria:(1)completely resected or resectable primary CRC;(2)completely resectable IPNs;(3)controlled or controllable extrapulmonary metastasis;and(4)adequate general condition and pulmonary function to tolerate pulmonary operation.Lung operation was performed by a thoracic surgeon without CT-guided biopsy for pathologic confirmation.RESULTS:A total of 40 cases of lung resection was performed in 29 patients.Five patients underwent repeated lung resection.The final pathology result showed metastasis from the CRC in 30 cases(75%)and benign pathology in 10 cases(25%).The primary tumor site was the rectum in 26/30(86.6%)cases with pulmonary metastasis,but only 3/10(30%)cases in the benign group had a primary rectal cancer(P=0.001).Positron emission tomography(PET)-CT was performed for 22/30(73.4%)patients in the lung metastasis group and for 6/10(60.0%)patients in the benign group.PET-CT revealed hot uptake of18fluorine 2-fluoro-2-deoxy-D-glucose with all IPNs in both groups.The group with pulmonary metastasis had a higher incidence of primary rectal cancer(P=0.001),a more advanced tumor stage(P=0.011),and more frequent lymphatic invasion of tumor cells(P=0.005).Six cases with previous liver metastasectomy were present in the lung metastasis group.Serum carcinoembryonic antigen levels before lung operation were not elevated in any of the patients.CONCLUSION:The stage and location of the primary tumor and tumor cell infiltration of lymphatics provide useful indicators for deciding on lung resection of IPNs in CRC.展开更多
Patients with indeterminate colitis(IC) are significantly younger at diagnosis with onset of symptoms before the age of 18 years with significant morbidity in the interim. The successful care of IC is based on microsc...Patients with indeterminate colitis(IC) are significantly younger at diagnosis with onset of symptoms before the age of 18 years with significant morbidity in the interim. The successful care of IC is based on microscopic visual predict precision of eventual ulcerative colitis(UC) or Crohn's colitis(CC) which is not offered in 15%-30% of inflammatory bowel disease(IBD) patients even after a combined state-of-the-art classification system of clinical, visual endoscopic, radiologic and histologic examination. These figures have not changed over the past 3 decades despite the introduction of newer diagnostic modalities. The patient outcomes after restorative proctocolectomy and ileal pouch-anal anastomosis may be painstaking if IC turns into CC. Our approach is aiming at developing a single sensitive and absolute accurate diagnostic test tool during the first clinic visit through endoscopic biopsy derived proteomic patterns. Matrix-assisted-laser desorption/ionization mass spectrometry(MS) and/or imaging MS technologies permit a histology-directed cellular test of endoscopy biopsy which identifies phenotype specific proteins, as biomarker that would assist clinicians more accurately delineate IC as beingeither a UC or CC or a non-IBD condition. These novel studies are underway on larger cohorts and are highly innovative with significances in differentiating a UC from CC in patients with IC and could lend mechanistic insights into IBD pathogenesis.展开更多
AIM:To assess the diagnostic ability of endoscopic ultrasonography(EUS)for evaluating causes of dista biliary strictures shown on endoscopic retrograde chol angiopancreatography(ERCP)or magnetic resonance cholangiopan...AIM:To assess the diagnostic ability of endoscopic ultrasonography(EUS)for evaluating causes of dista biliary strictures shown on endoscopic retrograde chol angiopancreatography(ERCP)or magnetic resonance cholangiopancreatography(MRCP),even without iden tifiable mass on computed tomography(CT). METHODS:The diagnostic ability of EUS was retro spectively analyzed and compared with that of routine cytology(RC)and tumor markers in 34 patients with distal biliary strictures detected by ERCP or MRCP a Dokkyo Medical School Hospital from December 2005 to December 2008,without any adjacent mass or ec centric thickening of the bile duct on CT that could cause biliary strictures.Findings considered as benign strictures on EUS included preservation of the normasonographic layers of the bile duct wall,irrespective of the presence of a mass lesion.Other strictures were considered malignant.Final diagnosis of underlying diseases was made by pathological examination in 18 cases after surgical removal of the samples,and by clinical follow-up for>10 mo in 16 cases. RESULTS:Seventeen patients(50%)were finally di- agnosed with benign conditions,including 6"normal" subjects,while 17 patients(50%)were diagnosed with malignant disease.In terms of diagnostic ability,EUS showed 94.1%sensitivity,82.3%specificity,84.2% positive predictive value,93.3%negative predictive value(NPV)and 88.2%accuracy for identifying ma- lignant and benign strictures.EUS was more sensi- tive than RC(94.1%vs 62.5%,P=0.039).NPV was also better for EUS than for RC(93.3%vs 57.5%,P= 0.035).In addition,EUS provided significantly higher sensitivity than tumor markers using 100 U/mL as the cutoff level of carbohydrate antigen 19-9(94.1%vs 53%,P=0.017).On EUS,biliary stricture that was fi- nally diagnosed as malignant showed as a hypoechoic, irregular mass,with obstruction of the biliary duct and invasion to surrounding tissues. CONCLUSION:EUS can diagnose biliary strictures caused by malignant tumors that are undetectable on CT.Earlier detection by EUS would provide more therapeutic options for patients with early-stage pancreaticobiliary cancer.展开更多
Biliary strictures are considered indeterminate when basic work-up, including transabdominal imaging and endoscopic retrograde cholangiopancreatography with routine cytologic brushing, are non-diagnostic. Indeterminat...Biliary strictures are considered indeterminate when basic work-up, including transabdominal imaging and endoscopic retrograde cholangiopancreatography with routine cytologic brushing, are non-diagnostic. Indeterminate biliary strictures can easily be mischaracterized which may dramatically affect patient's outcome. Early and accurate diagnosis of malignancy impacts not only a patient's candidacy for surgery, but also potential timely targeted chemotherapies. A significant portion of patients with indeterminate biliary strictures have benign disease and accurate diagnosis is, thus, paramount to avoid unnecessary surgery. Current sampling strategies have suboptimal accuracy for the diagnosis of malignancy. Emerging data on other diagnostic modalities, such as ancillary cytology techniques, single operator cholangioscopy, and endoscopic ultrasonography-guided fine needle aspiration, revealed promising results with much improved sensitivity.展开更多
In order to solve the problems of excess ovality and cross-section distortion of longitudinally submerged arc welding pipes after forming,a new three-roller continuous setting round process was proposed.This process c...In order to solve the problems of excess ovality and cross-section distortion of longitudinally submerged arc welding pipes after forming,a new three-roller continuous setting round process was proposed.This process can be divided into three stages:loading stage,roll bending stage and unloading stage.Based on the discretization idea,the mechanical model of the primary statically indeterminate problem of the longitudinally submerged arc welding pipes at the roll bending stage was established,and the deformation response was obtained.The simulation and theoretical results show that there are three positive bending regions and three reverse bending regions along the circumference of the pipe.The loading force of each roller shows growth,stability and downward trend with time.The error between the theoretical fitting curve and the simulated data point is very small,and the simulation results verify the reliability of the theoretical calculation.The experimental results show that the residual ovality decreases with the increase of the reduction,and the reduction of the turning point is the optimum reduction.In addition,the residual ovality of the pipe is less than 0.7%without cross-section distortion,which verifies the feasibility of this process.展开更多
There is currently no gold standard test for the diagnosis of inflammatory bowel disease (IBD). Physicians must rely on a number of diagnostic tools including clinical and endoscopic evaluation as well as histologic, ...There is currently no gold standard test for the diagnosis of inflammatory bowel disease (IBD). Physicians must rely on a number of diagnostic tools including clinical and endoscopic evaluation as well as histologic, serologic and radiologic assessment. The real difficulty for physicians in both primary and secondary care is differentiating between patients suffering from functional symptoms and those with true underlying IBD. Alongside this, there is always concern regarding the possibility of a missed, or delayed diagnosis of ulcerative colitis (UC) or Crohn’s disease. Even once the diagnosis of IBD has been made, there is often uncertainty in distinguishing between cases of UC or Crohn’s. As a consequence, in cases of incorrect diagnosis, optimal treatment and management may be adversely affected. Endoscopic evaluation can be uncomfortable and inconvenient for patients. It carries significant risks including perforation and in terms of monetary cost, is expensive. The use of biomarkers to help in the diagnosis and differentiation of IBD has been increasing over time. However, there is not yet one biomarker, which is sensitive of specific enough to be used alone in diagnosing IBD. Current serum testing includes C-reactive protein and erythrocyte sedimentation rate, which are cheap, reliable but non-specific and thus not ideal. Stool based testing such as faecal calprotectin is a much more specific tool and is currently in widespread clinical use. Non-invasive sampling is of the greatest clinical value and with the recent advances in metabolomics, genetics and proteomics, there are now more tools available to develop sensitive and specific biomarkers to diagnose and differentiate between IBD. Many of these new advances are only in early stages of development but show great promise for future clinical use.展开更多
Peroral cholangioscopy(POC) is an important tool for the management of a selected group of biliary diseases. Because of its direct visualization, POC allows targeted diagnostic and therapeutic procedures. POC can be p...Peroral cholangioscopy(POC) is an important tool for the management of a selected group of biliary diseases. Because of its direct visualization, POC allows targeted diagnostic and therapeutic procedures. POC can be performed using a dedicated cholangioscope that is advanced through the accessory channel of a duodenoscope or via the insertion of a small-diameter endoscope directly into the bile duct. POC was first described in the 1970 s, but the use of earlier generation devices was substantially limited by the cumbersome equipment setup and high repair costs. For nearly ten years, several technical improvements, including the single-operator system, high-quality images, the development of dedicated accessories and the increased size of the working channel, have led to increased diagnostic accuracy, thus assisting in the differentiation of benign and malignant intraductal lesions, targeting biopsies and the precise delineation of intraductal tumor spread before surgery. Furthermore, lithotripsy of difficult bile duct stones, ablative therapies for biliary malignancies and direct biliary drainage can be performed under POC control. Recent developments of new types of conventional POCs allow feasible, safe and effective procedures at reasonable costs. In the current review, we provide an updated overview of POC, focusing our attention on the main current clinical applications and on areas for future research.展开更多
BACKGROUND Histological changes after direct-acting antivirals(DAAs)therapy in hepatitis C virus(HCV)patients has not been elucidated.Whether the predominantly progressive,indeterminate and predominately regressive(P-...BACKGROUND Histological changes after direct-acting antivirals(DAAs)therapy in hepatitis C virus(HCV)patients has not been elucidated.Whether the predominantly progressive,indeterminate and predominately regressive(P-I-R)score,evaluating fibrosis activity in hepatitis B virus patients has predictive value in HCV patients has not been investigated.AIM To identify histological changes after DAAs therapy and to evaluate the predictive value of the P-I-R score in HCV patients.METHODS Chronic HCV patients with paired liver biopsy specimens before and after DAAs treatment were included.Sustained virologic response(SVR)was defined as an undetectable serum HCV RNA level at 24 wk after treatment cessation.The Ishak system and P-I-R score were assessed.Inflammation improvement and fibrosis regression were defined as a≥2-points decrease in the histology activity index(HAI)score and a≥1-point decrease in the Ishak fibrosis score,respectively.Fibrosis progression was defined as a≥1-point increase in the Ishak fibrosis score.Histologic improvement was defined as a≥2-points decrease in the HAI score without worsening of the Ishak fibrosis score after DAAs therapy.The P-I-R score was also assessed.“absolutely reversing or advancing”was defined as the same directionality implied by both change in the Ishak score and posttreatment P-I-R score;and“probably reversing or advancing”was defined as only one parameter showing directionality.RESULTS Thirty-eight chronic HCV patients with paired liver biopsy specimens before and after DAAs treatment were included.The mean age of these patients was 40.9±14.6 years and there were 53%(20/38)males.Thirty-four percent(13/38)of patients were cirrhotic.Eighty-two percent(31/38)of patients achieved inflammation improvement.The median HAI score decreased significantly after SVR(pretreatment 7.0 vs posttreatment 2.0,Z=-5.146,P=0.000).Thirty-seven percent(14/38)of patients achieved fibrosis improvement.The median Ishak score decreased significantly after SVR(pretreatment 4.0 vs posttreatment 3.0,Z=-2.354,P=0.019).Eighty-two percent(31/38)of patients showed histological improvement.The P-I-R score was evaluated in 61%(23/38)of patients.The progressive group showed lower platelet(P=0.024)and higher HAI scores(P=0.070)before treatment.In patients with stable Ishak stage after treatment:Progressive injury was seen in 22%(4/18)of patients,33%(6/18)were classified as indeterminate and regressive changes were seen in 44%(8/18)of patients who were judged as probably reversing by the Ishak and P-I-R systems.CONCLUSION Significant improvement of necroinflammation and partial remission of fibrosis in HCV patients occurred shortly after DAAs therapy.The P-I-R score has potential in predicting fibrosis in HCV patients.展开更多
The introduction of wireless capsule endoscopy in 2000 has revolutionized our ability to visualize parts of the small bowel mucosa classically unreached by the conventional endoscope, and since the recent introduction...The introduction of wireless capsule endoscopy in 2000 has revolutionized our ability to visualize parts of the small bowel mucosa classically unreached by the conventional endoscope, and since the recent introduction of colon capsule endoscopy, a promising alternative method has been available for the evaluation of large bowel mucosa. The advantages of wireless capsule endoscopy include its non-invasive character and its ability to visualize proximal and distal parts of the intestine, while important disadvantages include the procedure's inability of tissue sampling and significant incompletion rate. Its greatest limitation is the prohibited use in cases of known or suspected stenosis of the intestinal lumen due to high risk of retention. Wireless capsule endoscopy plays an important role in the early recognition of recurrence, on Crohn's disease patients who have undergone ileocolonic resection for the treatment of Crohn's disease complications, and in patients' management and therapeutic strategy planning, before obvious clinical and laboratory relapse. Although capsule endoscopy cannot replace traditional endoscopy, it offers valuable information on the evaluation of intestinal disease and has a significant impact on disease reclassification of patients with a previous diagnosis of ulcerative colitis or inflammatory bowel disease unclassified/indeterminate colitis. Moreover, it may serve as an effective alternative where colonoscopy is contraindicated and in cases with incomplete colonoscopy studies. The use of patency capsule maximizes safety and is advocated in cases of suspected small or large bowel stenosis.展开更多
Different histopathological manifestations of focal liver lesions show varying common and uncommon imaging findings and some pathologies may show similar appearance despite of different histopathology.It is necessary ...Different histopathological manifestations of focal liver lesions show varying common and uncommon imaging findings and some pathologies may show similar appearance despite of different histopathology.It is necessary to characterise focal liver lesions accurately as not only benign and malignant lesions are managed differently,but also certain benign lesions have differing management.These lesions are increasingly being detected due to rapid growth of use of crosssectional imaging as well as improvement in image quality and new imaging techniques.Contrast enhanced magnetic resonance imaging(MRI)is considered the gold standard technique in characterising focal liver lesions.Addition of gadoxetic acid has been shown to significantly increase diagnostic accuracy in the detection and characterization of liver abnormalities.Classic imaging characteristics of common liver lesions,including their behaviour on gadoxetic acid enhanced MRI,have been described in literature over recent years.It is important to be familiar with the typical aspects of these lesions as well as know the uncommon and overlapping imaging features to reach an accurate diagnosis.In this article,we will review the well-described characteristic imaging findings of common and rare focal liver lesions and present several challenging cases encountered in the clinical setting,namely hepatocellular adenoma,focal nodular hyperplasia,hepatic angiomyolipoma,hepatocellular carcinoma,intrahepatic cholangiocarcinoma,neuroendocrine tumours as well as a pleomorphic liposarcoma of the liver.展开更多
Sheath blight disease (ShB) has a severe impact on the production of rice. ABI3/VP1-like 1(RAVL1) negatively regulated the rice defense mechanism against ShB, however, this regulatorymechanism is not clearly understoo...Sheath blight disease (ShB) has a severe impact on the production of rice. ABI3/VP1-like 1(RAVL1) negatively regulated the rice defense mechanism against ShB, however, this regulatorymechanism is not clearly understood. In this study, we identified that indeterminate domain 3 (IDD3) waspositively regulated by RAVL1. Further, chromatin immunoprecipitation (ChIP) assay, yeast one-hybridassay and transient expression assay indicated a direct binding between RAVL1 and the IDD3 promoterregion. IDD3 was ubiquitously expressed in different tissues and at different stages, and its expressionwas significantly enhanced by Rhizoctonia solani infection. IDD3 exhibited transcription activation activityin yeast and IDD3-GFP was found to be localized in the nucleus. IDD3 mutants exhibited no significantdifferences in response to ShB, while IDD3 overexpressors were more susceptible to ShB compared withwild type (WT) plants. Furthermore, IDD3 repressors were less susceptible to R. solani than WT plants.Interestingly, the expression of brassinosteroid-related genes (D2, D11 and BRI1) was lower in IDD3repressors and higher in IDD3 overexpressors compared with WT. However, the ChIP assay revealedthat IDD3 did not directly bind to the D2 and D11 promoters. Overexpression of IDD3 in BRI1 mutantd61-1 inhibited the activity of IDD3, reducing its susceptibility to ShB compared with IDD3 overexpressorand WT plants, indicating that IDD3 negatively regulated the rice defense mechanism against ShB by activatingthe BR signaling pathway. Thus, our analyses provided information to enhance the understanding of therice defense mechanism against ShB.展开更多
文摘By Invoking symmetry principle, we present a self-consistent interpretation of the existing quantum theory which explains why our world is fundamentally indeterministic and that why non-local quantum jumps occur. Symmetry principle dictates that the concept of probability is more fundamental than the notion of the wave function in that the former can be derived directly from symmetries rather than have to be assumed as an additional axiom. It is argued that the notion of quantum probability and that of the wavefunction are intimately connected.
文摘Free will is difficult to classify with respect to determinism or indeterminism, and its phenomenology in consciousness often shows both aspects. Initially, it is felt as unlimited and indeterminate will power, with the potentiality of multiple choices. Thereafter, reductive deliberation is led by determinism to the final decision, which realises only one of the potential choices. The reductive deliberation phase tries to find out the best alternative and simultaneously satisfying vague motivations, contextual conditions and personal preferences. The essential sense of free will is the introduction of personal preferences, which allows a higher diversity of reactions to vague motivations. With an oversimplified model of determinism as a chain of events, incompatibilists define ＂free＂ as ＂undetermined＂ so that determinism becomes incompatible with any free choice between alternatives. In consciousness, free will requires a more complex model of network determinism as well as the consideration of unconsciousness as a causal factor. When ＂free＂ defined as ＂undetermined＂ is applied to the context of consciousness, it should be reinterpreted as ＂unconscious of being determined＂ or not aware of underlying determinism. Lacking information on determinism generates a feeling of ＂free＂ in consciousness and, therefore, gives the impression of indeterminism. Lacking information may be induced by an uncertain future without determined events--an unconscious past with biological reactions suddenly emerging from the unconsciousness or an unknown present unable to distinguish determinism of complex events. Therefore, at the level of human consciousness, the experience of free will is associated with apparent indeterminism although it is based on unconscious determinism. The concepts of compatibilism and incompatibilism are only two different aspects of the same phenomenon and correspond to consciousness and unconsciousness. Nevertheless, they can be considered together with a free will concept based on relativity depending on two different reference frames--the first person＇s experience frame or the Laplace＇s demon frame with knowledge on every molecule of the universe. Only relativity of the free will concept avoids the contradiction between ＂free＂ and ＂unfree＂ for the same phenomenon and could be a compromise for considering compatibilism and incompatibilism equally.
文摘Irreducible indeterminism is considered by most physicists as an ontological interpretation of quantum mechanics, which attributes inherent indeterminism to elementary paJcticles. This view was extrapolated by von Neumann from the atomocosm to the entire universe. Heisenberg proposed an epistemic interpretation, postulating that indeterminism stems from ambivalent detection systems, rather than being a characteristic of elementary particles Transformative detection that inherently affects the measured phenomena is responsible for the indeterminism in the atomocosm. As the same does not generally hold true in the macrocosm, this discrepancy has led to the notion of the Heisenberg cut. As explained by Heisenberg＇s microscope example, high-energy light can displace electrons from their atomic shells in the atomocosm, but would not induce the same effect on objects in the macrocosm, thus rendering such detection neutral. Therefore, detection systems are ambivalent in that they can be transformative under the cut and neutral otherwise. Device variation is found under and above the cut and is the essential cause of outcome variability in the macrocosm. Thus, two completely different categories of indeterminism exist simultaneously under the Heisenberg cut, but only one is found above the cut, known as measurement variations of devices. Experimental exploration of elementary paJcticle behaviors is possible only with the help of detection systems. If these systems affect particle characteristics in any way, this would be sufficient to explain the irreducible quantum mechanical indeterminism. Consequently, the true behavior of elementary particles, whether indeterminist or determinist, would never be detectable. Above the cut, on the other hand, variations in device performance are inevitable, due to reducible perturbing factors, inducing measurement wJciation of devices Heisenberg discovered a general principle of ambivalent detection systems, which can also be found in the macrocosm. In the Wilson Cloud Chamber, vapor is an ambivalent detection system, since high-energy charged particles would produce straight tracks, whereas those of lower energy would leave an irregular trace. According to the epistemic interpretation, von Neumann＇s extrapolation of irreducible quantum mechanical indeterminism to the entire universe would not be necessary, thereby avoiding the uncomfortable conclusion that the entire universe is based on indeterminism
文摘Estimating causal effects is a principal goal in epidemiology and other branches of science. Nonetheless, what constitutes an effect and which measure of effect is pre-ferred are unsettled questions. I argue that, under indeterminism, an effect is a change in the tendency of the outcome variable to take each of its values, and then present a critical analysis of commonly used measures of effect and the measures of frequency from which they are calculated. I conclude that all causal effects should be quantified using a unifying measure of effect called the log likelihood ratio (which is the log probability ratio when the outcome is a discrete variable). Furthermore, I suggest that effects should be estimated for all causal contrasts of the causal variable (i.e., expo-sure), on all values of the outcome variable, and for all time intervals between the cause and the outcome. This goal should be kept in mind in practical approximations.
文摘Many real⁃world machine learning applications face the challenge of dealing with changing data over time,known as concept drift,and the issue of data indeterminacy,where all the true labels available are unrealistic.This can lead to a decrease in the accuracy of the prediction models.The aim of this study is to introduce a new approach for detecting drift,which is based on neutrosophic set theory.This approach takes into account uncertainty in the prediction model and is able to handle indeterminate information,considering its impact on the models performance.The proposed method reads data into windows and calculates a set of values based on the concept of neutrosophic membership.These values are then used in the Neutrosophic Support Vector Machine(N⁃SVM).To address the issue of indeterminate true label data,the values issued by N⁃SVM are expressed as entropy and used as input for the ADWIN(Adaptive Windowing)change detector.When a drift is detected,the prediction model is retrained by including only the most recent instances with the original training data set.The proposed method gives promising results in terms of drift detection accuracy compared to the state of existing drift detection methods such as KSWIN,ADWIN,and DWM.
文摘This paper reveals the origin of nonlinear dynamics and presents a solution for nonlinear systematic problems based on other science. Generally, physical phenomena are divided into linear static logical problems and nonlinear dynamic systematic problems, but all scientists have solved both problems using the same algebraic logical solution in statistical physics based on determinism such as chaos theory. Surprisingly, this is a contradiction and a serious mistake because there is a perfect solution such as the system analysis theory exist<span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">ing</span></span></span><span><span><span style="font-family:;" "=""><span style="font-family:Verdana;"> in other science. Unfortunately, it has developed in the 20</span><sup><span style="font-family:Verdana;">th</span></sup><span style="font-family:Verdana;"> century by engineers. Thus, classical physicists could not solve it. Meanwhile, the author achieved the systematic solution for many unsolved nonlinear systematical, further, proved the research result through simulation using specially designed simulation device. Thus, this is a revolutionary achievement because it</span></span><span> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">can easily solve the unsolved nonlinear dynamics that exists in all fields of science</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">. </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Ironically most determinists do not welcome and reject it. However, it has no matter, it will be separated from current physics and other scientists studied it in the second physics. Therefore, it would be contributed to solve the unsolved nonlinear dynamics in complex science</span></span></span><span style="font-family:Verdana;">.</span>
文摘One of the most intriguing problems of philosophy and of mankind is the question whether humans have a free will. This question is heavily disputed between natural scientists and especially neuroscientists, who deny free will, and philosophers and other groups, who insist on free will. It is perplexing that both sides base their premise on the same precondition, namely naturalism. We will prove that naturalism automatically leads to physicalism, to materialism, and to reductionism. We will also prove here that it is logically not possible to have a free will if naturalism is true. Free will definitely requires an additional substance, a non-material soul, which cannot be part of our universe. This must not be in contradiction to our current knowledge of natural sciences.
基金supported by grants from the Cultivation of Young Talents Project Fund from the Fujian Provincial Health and Family Planning Commission (Grant No. 2015-ZQN-ZD11)the Pilot Project of Fujian Provincial Department of Science and Technology (Grant No. 2016Y0010)+2 种基金the Jiangsu Provincial Project of Invigorating Health Care through Science, Technology and EducationJiangsu Provincial Medical Youth Talentthe Project of Invigorating Health Care through Science, Technology and Education (Grant No. QNRC2016621)
文摘HIV-indeterminate Western blotting(WB)results are typically obtained in WB confirmatory assays,and the number of indeterminate samples may increase with the detection of HIV infections,which will present considerable challenges for the management of HIV/AIDS.Nucleic acid detection has been used as a laboratory test for screening suspected or indeterminate samples.However,the effectiveness of these assays for the differential diagnosis of HIV-indeterminate WB samples remained undetermined.In this study,210 subjects with HIV-indeterminate WB results were detected from 6360 positive HIV screening samples between 2015 and 2016 in southeastern China,in which HIV-indeterminate WB results accounted for 3.30%.The highest proportion of indeterminate results was observed in pregnant and lying-in women receiving physical examinations(16.67%),followed by that in voluntary blood donors(8.82%).The most common WB band patterns were p24,gpl60 and p24,and gpl60.The follow-up study revealed that the highest negative and positive conversion rates of HIV antibodies were in samples with a single p24 band(80.28%),and with gpl60 and p24 bands(86.21%),respectively.Among the Env,Gag,and Pol antibodies,samples with a Gag band showed the highest negative conversion rate(81.25%),whereas the highest positive conversion rate was observed in samples with an Env band(56.76%).In addition,quantitative and qualitative HIV nucleic acid testing exhibited the highest sensitivity(96.3%)and specificity(97.85%),respectively.Our results indicate a lower proportion of HIV indeterminate WB results in southeastern China compared to previous reports,and the follow-up re-examination of patients with HIV indeterminate results should be performed.Nucleic acid testing facilitates the identification of HIV infections.
文摘Due to the need for improvement in the diagnosis and minimally invasive therapy of the bile duct disorders new technologies for cholangioscopy have been recently developed. Per-oral cholangioscopy has become an important diagnostic and therapeutic tool leading to avoidance of aggressive and unnecessary surgery in many clinical scenarios. This paper focuses on the newly developed SpyGlass DS technology, its advantages, and the technique of single-operator cholangioscopy(SOC), biliary indications and possible adverse events. We also review the available literature; discuss the limitations and future expectations.Digital SOC(D-SOC) is a useful technique, which provides endoscopic imaging of the biliary tree, optical diagnosis, biopsy under direct vision and therapeutic interventions. The implementations are diagnostic and therapeutic. Diagnostic indications are indeterminate biliary strictures, unclear filling defects, staging of cholangiocarcinoma, staging of ampullary tumors(extension into the common bile duct), unclear bile duct dilation, exploring cystic lesions of the biliary tree,unexplained hemobilia, posttransplant biliary complications. Therapeutic indications are lithotripsy of difficult stones, retrieval of migrated stents, foreign body removal, guide wire placement, transpapillary gallbladder drainage and endoscopic tumor ablative therapy. Most studied and established indications are the diagnosis of indeterminate biliary stricture and intraductal lithotripsy of difficult stones. The adverse events are not different and more common compared to those of Endoscopic retrograde cholangiopancreatography(ERCP)alone. D-SOC is a safe and effective procedure, adjunct to the standard ERCP and the newly available digital technology overcomes many of the limitations of the previous generations of cholangioscopes.
文摘AIM:To investigate the clinicopathologic parameters of pulmonary metastasis in colorectal cancer(CRC) patients after lung operation of indeterminate pulmonary nodules(IPNs).METHODS:From a prospective database of CRCpatients,40 cases that underwent lung operation between November 2008 and December 2012 for suspicious metastatic pulmonary nodules on chest computed tomography(CT)were enrolled.The decision to perform a lung operation was made if the patient met the following criteria:(1)completely resected or resectable primary CRC;(2)completely resectable IPNs;(3)controlled or controllable extrapulmonary metastasis;and(4)adequate general condition and pulmonary function to tolerate pulmonary operation.Lung operation was performed by a thoracic surgeon without CT-guided biopsy for pathologic confirmation.RESULTS:A total of 40 cases of lung resection was performed in 29 patients.Five patients underwent repeated lung resection.The final pathology result showed metastasis from the CRC in 30 cases(75%)and benign pathology in 10 cases(25%).The primary tumor site was the rectum in 26/30(86.6%)cases with pulmonary metastasis,but only 3/10(30%)cases in the benign group had a primary rectal cancer(P=0.001).Positron emission tomography(PET)-CT was performed for 22/30(73.4%)patients in the lung metastasis group and for 6/10(60.0%)patients in the benign group.PET-CT revealed hot uptake of18fluorine 2-fluoro-2-deoxy-D-glucose with all IPNs in both groups.The group with pulmonary metastasis had a higher incidence of primary rectal cancer(P=0.001),a more advanced tumor stage(P=0.011),and more frequent lymphatic invasion of tumor cells(P=0.005).Six cases with previous liver metastasectomy were present in the lung metastasis group.Serum carcinoembryonic antigen levels before lung operation were not elevated in any of the patients.CONCLUSION:The stage and location of the primary tumor and tumor cell infiltration of lymphatics provide useful indicators for deciding on lung resection of IPNs in CRC.
基金Supported by NIH/NIDDK R21DK095186-01A1,Nos.3U54 CA091408–09S1,U54RR026140/U54MD007593,and UL1 RR024975Research Foundation,American Society of Colon and Rectal Surgeons,Limited Project Grant(LPG-086)
文摘Patients with indeterminate colitis(IC) are significantly younger at diagnosis with onset of symptoms before the age of 18 years with significant morbidity in the interim. The successful care of IC is based on microscopic visual predict precision of eventual ulcerative colitis(UC) or Crohn's colitis(CC) which is not offered in 15%-30% of inflammatory bowel disease(IBD) patients even after a combined state-of-the-art classification system of clinical, visual endoscopic, radiologic and histologic examination. These figures have not changed over the past 3 decades despite the introduction of newer diagnostic modalities. The patient outcomes after restorative proctocolectomy and ileal pouch-anal anastomosis may be painstaking if IC turns into CC. Our approach is aiming at developing a single sensitive and absolute accurate diagnostic test tool during the first clinic visit through endoscopic biopsy derived proteomic patterns. Matrix-assisted-laser desorption/ionization mass spectrometry(MS) and/or imaging MS technologies permit a histology-directed cellular test of endoscopy biopsy which identifies phenotype specific proteins, as biomarker that would assist clinicians more accurately delineate IC as beingeither a UC or CC or a non-IBD condition. These novel studies are underway on larger cohorts and are highly innovative with significances in differentiating a UC from CC in patients with IC and could lend mechanistic insights into IBD pathogenesis.
文摘AIM:To assess the diagnostic ability of endoscopic ultrasonography(EUS)for evaluating causes of dista biliary strictures shown on endoscopic retrograde chol angiopancreatography(ERCP)or magnetic resonance cholangiopancreatography(MRCP),even without iden tifiable mass on computed tomography(CT). METHODS:The diagnostic ability of EUS was retro spectively analyzed and compared with that of routine cytology(RC)and tumor markers in 34 patients with distal biliary strictures detected by ERCP or MRCP a Dokkyo Medical School Hospital from December 2005 to December 2008,without any adjacent mass or ec centric thickening of the bile duct on CT that could cause biliary strictures.Findings considered as benign strictures on EUS included preservation of the normasonographic layers of the bile duct wall,irrespective of the presence of a mass lesion.Other strictures were considered malignant.Final diagnosis of underlying diseases was made by pathological examination in 18 cases after surgical removal of the samples,and by clinical follow-up for>10 mo in 16 cases. RESULTS:Seventeen patients(50%)were finally di- agnosed with benign conditions,including 6"normal" subjects,while 17 patients(50%)were diagnosed with malignant disease.In terms of diagnostic ability,EUS showed 94.1%sensitivity,82.3%specificity,84.2% positive predictive value,93.3%negative predictive value(NPV)and 88.2%accuracy for identifying ma- lignant and benign strictures.EUS was more sensi- tive than RC(94.1%vs 62.5%,P=0.039).NPV was also better for EUS than for RC(93.3%vs 57.5%,P= 0.035).In addition,EUS provided significantly higher sensitivity than tumor markers using 100 U/mL as the cutoff level of carbohydrate antigen 19-9(94.1%vs 53%,P=0.017).On EUS,biliary stricture that was fi- nally diagnosed as malignant showed as a hypoechoic, irregular mass,with obstruction of the biliary duct and invasion to surrounding tissues. CONCLUSION:EUS can diagnose biliary strictures caused by malignant tumors that are undetectable on CT.Earlier detection by EUS would provide more therapeutic options for patients with early-stage pancreaticobiliary cancer.
文摘Biliary strictures are considered indeterminate when basic work-up, including transabdominal imaging and endoscopic retrograde cholangiopancreatography with routine cytologic brushing, are non-diagnostic. Indeterminate biliary strictures can easily be mischaracterized which may dramatically affect patient's outcome. Early and accurate diagnosis of malignancy impacts not only a patient's candidacy for surgery, but also potential timely targeted chemotherapies. A significant portion of patients with indeterminate biliary strictures have benign disease and accurate diagnosis is, thus, paramount to avoid unnecessary surgery. Current sampling strategies have suboptimal accuracy for the diagnosis of malignancy. Emerging data on other diagnostic modalities, such as ancillary cytology techniques, single operator cholangioscopy, and endoscopic ultrasonography-guided fine needle aspiration, revealed promising results with much improved sensitivity.
基金supported by the National Natural Science Foundation of China (Nos. 52005431, 51705449 and 51975509)the Natural Science Foundation of Hebei Province of China (No. E2020203086)the National Major Science and Technology Projects of China (No. 2018ZX04007002)
文摘In order to solve the problems of excess ovality and cross-section distortion of longitudinally submerged arc welding pipes after forming,a new three-roller continuous setting round process was proposed.This process can be divided into three stages:loading stage,roll bending stage and unloading stage.Based on the discretization idea,the mechanical model of the primary statically indeterminate problem of the longitudinally submerged arc welding pipes at the roll bending stage was established,and the deformation response was obtained.The simulation and theoretical results show that there are three positive bending regions and three reverse bending regions along the circumference of the pipe.The loading force of each roller shows growth,stability and downward trend with time.The error between the theoretical fitting curve and the simulated data point is very small,and the simulation results verify the reliability of the theoretical calculation.The experimental results show that the residual ovality decreases with the increase of the reduction,and the reduction of the turning point is the optimum reduction.In addition,the residual ovality of the pipe is less than 0.7%without cross-section distortion,which verifies the feasibility of this process.
文摘There is currently no gold standard test for the diagnosis of inflammatory bowel disease (IBD). Physicians must rely on a number of diagnostic tools including clinical and endoscopic evaluation as well as histologic, serologic and radiologic assessment. The real difficulty for physicians in both primary and secondary care is differentiating between patients suffering from functional symptoms and those with true underlying IBD. Alongside this, there is always concern regarding the possibility of a missed, or delayed diagnosis of ulcerative colitis (UC) or Crohn’s disease. Even once the diagnosis of IBD has been made, there is often uncertainty in distinguishing between cases of UC or Crohn’s. As a consequence, in cases of incorrect diagnosis, optimal treatment and management may be adversely affected. Endoscopic evaluation can be uncomfortable and inconvenient for patients. It carries significant risks including perforation and in terms of monetary cost, is expensive. The use of biomarkers to help in the diagnosis and differentiation of IBD has been increasing over time. However, there is not yet one biomarker, which is sensitive of specific enough to be used alone in diagnosing IBD. Current serum testing includes C-reactive protein and erythrocyte sedimentation rate, which are cheap, reliable but non-specific and thus not ideal. Stool based testing such as faecal calprotectin is a much more specific tool and is currently in widespread clinical use. Non-invasive sampling is of the greatest clinical value and with the recent advances in metabolomics, genetics and proteomics, there are now more tools available to develop sensitive and specific biomarkers to diagnose and differentiate between IBD. Many of these new advances are only in early stages of development but show great promise for future clinical use.
文摘Peroral cholangioscopy(POC) is an important tool for the management of a selected group of biliary diseases. Because of its direct visualization, POC allows targeted diagnostic and therapeutic procedures. POC can be performed using a dedicated cholangioscope that is advanced through the accessory channel of a duodenoscope or via the insertion of a small-diameter endoscope directly into the bile duct. POC was first described in the 1970 s, but the use of earlier generation devices was substantially limited by the cumbersome equipment setup and high repair costs. For nearly ten years, several technical improvements, including the single-operator system, high-quality images, the development of dedicated accessories and the increased size of the working channel, have led to increased diagnostic accuracy, thus assisting in the differentiation of benign and malignant intraductal lesions, targeting biopsies and the precise delineation of intraductal tumor spread before surgery. Furthermore, lithotripsy of difficult bile duct stones, ablative therapies for biliary malignancies and direct biliary drainage can be performed under POC control. Recent developments of new types of conventional POCs allow feasible, safe and effective procedures at reasonable costs. In the current review, we provide an updated overview of POC, focusing our attention on the main current clinical applications and on areas for future research.
基金The National Natural Science Foundation of China,No.81870406the Beijing Natural Science Foundation,No.7182174and the China National Science and Technology Major Project for Infectious Diseases Control during the 13th Five-Year Plan Period,No.2017ZX10202202.
文摘BACKGROUND Histological changes after direct-acting antivirals(DAAs)therapy in hepatitis C virus(HCV)patients has not been elucidated.Whether the predominantly progressive,indeterminate and predominately regressive(P-I-R)score,evaluating fibrosis activity in hepatitis B virus patients has predictive value in HCV patients has not been investigated.AIM To identify histological changes after DAAs therapy and to evaluate the predictive value of the P-I-R score in HCV patients.METHODS Chronic HCV patients with paired liver biopsy specimens before and after DAAs treatment were included.Sustained virologic response(SVR)was defined as an undetectable serum HCV RNA level at 24 wk after treatment cessation.The Ishak system and P-I-R score were assessed.Inflammation improvement and fibrosis regression were defined as a≥2-points decrease in the histology activity index(HAI)score and a≥1-point decrease in the Ishak fibrosis score,respectively.Fibrosis progression was defined as a≥1-point increase in the Ishak fibrosis score.Histologic improvement was defined as a≥2-points decrease in the HAI score without worsening of the Ishak fibrosis score after DAAs therapy.The P-I-R score was also assessed.“absolutely reversing or advancing”was defined as the same directionality implied by both change in the Ishak score and posttreatment P-I-R score;and“probably reversing or advancing”was defined as only one parameter showing directionality.RESULTS Thirty-eight chronic HCV patients with paired liver biopsy specimens before and after DAAs treatment were included.The mean age of these patients was 40.9±14.6 years and there were 53%(20/38)males.Thirty-four percent(13/38)of patients were cirrhotic.Eighty-two percent(31/38)of patients achieved inflammation improvement.The median HAI score decreased significantly after SVR(pretreatment 7.0 vs posttreatment 2.0,Z=-5.146,P=0.000).Thirty-seven percent(14/38)of patients achieved fibrosis improvement.The median Ishak score decreased significantly after SVR(pretreatment 4.0 vs posttreatment 3.0,Z=-2.354,P=0.019).Eighty-two percent(31/38)of patients showed histological improvement.The P-I-R score was evaluated in 61%(23/38)of patients.The progressive group showed lower platelet(P=0.024)and higher HAI scores(P=0.070)before treatment.In patients with stable Ishak stage after treatment:Progressive injury was seen in 22%(4/18)of patients,33%(6/18)were classified as indeterminate and regressive changes were seen in 44%(8/18)of patients who were judged as probably reversing by the Ishak and P-I-R systems.CONCLUSION Significant improvement of necroinflammation and partial remission of fibrosis in HCV patients occurred shortly after DAAs therapy.The P-I-R score has potential in predicting fibrosis in HCV patients.
文摘The introduction of wireless capsule endoscopy in 2000 has revolutionized our ability to visualize parts of the small bowel mucosa classically unreached by the conventional endoscope, and since the recent introduction of colon capsule endoscopy, a promising alternative method has been available for the evaluation of large bowel mucosa. The advantages of wireless capsule endoscopy include its non-invasive character and its ability to visualize proximal and distal parts of the intestine, while important disadvantages include the procedure's inability of tissue sampling and significant incompletion rate. Its greatest limitation is the prohibited use in cases of known or suspected stenosis of the intestinal lumen due to high risk of retention. Wireless capsule endoscopy plays an important role in the early recognition of recurrence, on Crohn's disease patients who have undergone ileocolonic resection for the treatment of Crohn's disease complications, and in patients' management and therapeutic strategy planning, before obvious clinical and laboratory relapse. Although capsule endoscopy cannot replace traditional endoscopy, it offers valuable information on the evaluation of intestinal disease and has a significant impact on disease reclassification of patients with a previous diagnosis of ulcerative colitis or inflammatory bowel disease unclassified/indeterminate colitis. Moreover, it may serve as an effective alternative where colonoscopy is contraindicated and in cases with incomplete colonoscopy studies. The use of patency capsule maximizes safety and is advocated in cases of suspected small or large bowel stenosis.
文摘Different histopathological manifestations of focal liver lesions show varying common and uncommon imaging findings and some pathologies may show similar appearance despite of different histopathology.It is necessary to characterise focal liver lesions accurately as not only benign and malignant lesions are managed differently,but also certain benign lesions have differing management.These lesions are increasingly being detected due to rapid growth of use of crosssectional imaging as well as improvement in image quality and new imaging techniques.Contrast enhanced magnetic resonance imaging(MRI)is considered the gold standard technique in characterising focal liver lesions.Addition of gadoxetic acid has been shown to significantly increase diagnostic accuracy in the detection and characterization of liver abnormalities.Classic imaging characteristics of common liver lesions,including their behaviour on gadoxetic acid enhanced MRI,have been described in literature over recent years.It is important to be familiar with the typical aspects of these lesions as well as know the uncommon and overlapping imaging features to reach an accurate diagnosis.In this article,we will review the well-described characteristic imaging findings of common and rare focal liver lesions and present several challenging cases encountered in the clinical setting,namely hepatocellular adenoma,focal nodular hyperplasia,hepatic angiomyolipoma,hepatocellular carcinoma,intrahepatic cholangiocarcinoma,neuroendocrine tumours as well as a pleomorphic liposarcoma of the liver.
基金the Science and Technology Innovation Talents of Shenyang,China(Grant No.RC190489).
文摘Sheath blight disease (ShB) has a severe impact on the production of rice. ABI3/VP1-like 1(RAVL1) negatively regulated the rice defense mechanism against ShB, however, this regulatorymechanism is not clearly understood. In this study, we identified that indeterminate domain 3 (IDD3) waspositively regulated by RAVL1. Further, chromatin immunoprecipitation (ChIP) assay, yeast one-hybridassay and transient expression assay indicated a direct binding between RAVL1 and the IDD3 promoterregion. IDD3 was ubiquitously expressed in different tissues and at different stages, and its expressionwas significantly enhanced by Rhizoctonia solani infection. IDD3 exhibited transcription activation activityin yeast and IDD3-GFP was found to be localized in the nucleus. IDD3 mutants exhibited no significantdifferences in response to ShB, while IDD3 overexpressors were more susceptible to ShB compared withwild type (WT) plants. Furthermore, IDD3 repressors were less susceptible to R. solani than WT plants.Interestingly, the expression of brassinosteroid-related genes (D2, D11 and BRI1) was lower in IDD3repressors and higher in IDD3 overexpressors compared with WT. However, the ChIP assay revealedthat IDD3 did not directly bind to the D2 and D11 promoters. Overexpression of IDD3 in BRI1 mutantd61-1 inhibited the activity of IDD3, reducing its susceptibility to ShB compared with IDD3 overexpressorand WT plants, indicating that IDD3 negatively regulated the rice defense mechanism against ShB by activatingthe BR signaling pathway. Thus, our analyses provided information to enhance the understanding of therice defense mechanism against ShB.
