肠道微生态影响动脉粥样硬化发生发展的机制

动脉粥样硬化(AS)不仅是一种炎症性疾病,而且属于一种代谢性疾病。肠道微生态的改变可对AS的发生发展产生双面影响。一方面,肠道菌群紊乱可以通过影响机体的胆碱代谢、氧化应激、炎症反应等机制直接促进AS产生发展,此外,可通过导致AS危险因素肥胖、高脂血症、糖尿病等的产生这些间接机制促AS的进展。另一方面,益生菌及益生元的增加则可有效地降低肠道微生物内毒素产生、增强肠道屏障、减轻机体质量、缓解炎症反应、改善胰岛素抵抗,进而在AS的进展方面发挥重要作用。因此,合理调控机体肠道微生态环境成为AS防治的新型重要手段。     

PNPLA3 I148M polymorphism and progressive liver disease

The 148 Isoleucine to Methionine protein variant(I148M)of patatin-like phospholipase domain-containing 3(PNPLA3),a protein is expressed in the liver and is involved in lipid metabolism,has recently been identified as a major determinant of liver fat content.Several studies confirmed that the I148M variant predisposes towards the full spectrum of liver damage associated with fatty liver:from simple steatosis to steatohepatitis and progressive fibrosis.Furthermore,the I148M variant represents a major determinant of progression of alcohol related steatohepatitis to cirrhosis,and to influence fibrogenesis and related clinical outcomes in chronic hepatitis C virus hepatitis,and possibly chronic hepatitis B virus hepatitis,hereditary hemochromatosis and primary sclerosing cholangitis.All in all,studies suggest that the I148M polymorphism may represent a general modifier of fibrogenesis in liver diseases.Remarkably,the effect of the I148M variant on fibrosis was independent of that on hepatic steatosis and inflammation,suggesting that it may affect both the quantity and quality of hepatic lipids and the biology of non-parenchymal liver cells besides hepatocytes,directly promoting fibrogenesis.Therefore,PNPLA3 is a key player in liver disease progression.Assessment of the I148M polymorphism will possibly inform clinical practice in the future,whereas the determination of the effect of the 148M variant will reveal mechanisms involved in hepatic fibrogenesis.     

瓣膜性房颤定义及抗凝治疗研究进展

现阶段对于"瓣膜病变型"房颤(AF)与"非瓣膜病变型"AF的定义尚未达成共识,不仅如此,各指南在表述这些概念时也存在差异。临床试验对于"瓣膜病变型"AF与"非瓣膜病变型"AF定义的阐述不甚理想。两类AF血栓栓塞风险差异较大,抗凝治疗策略也有所不同。本文将对瓣膜性AF定义及抗凝治疗的研究进展予以综述。     

Endoscopic resection techniques for colorectal neoplasia:Current developments

Endoscopic polypectomy and endoscopic mucosal resection(EMR) are the established treatment standards for colorectal polyps. Current research aims at the reduction of both complication and recurrence rates as well as on shortening procedure times. Cold snare resection is the emerging standard for the treatment of smaller(< 5 mm) polyps and is possibly also suitable for the removal of noncancerous polyps up to 9 mm. The method avoids thermal damage, has reduced procedure times and probably also a lower risk for delayed bleeding. On the other end of the treatment spectrum, endoscopic submucosal dissection(ESD)offers en bloc resection of larger flat or sessile lesions. The technique has obvious advantages in the treatment of high-grade dysplasia and early cancer. Due to its minimal recurrence rate, it may also be an alternative to fractionated EMR of larger flat or sessile lesions. However, ESD is technically demanding and burdened by longer procedure times and higher costs. It should therefore be restricted to lesions suspicious for high-grade dysplasia or early invasive cancer.The latest addition to endoscopic resection techniques is endoscopic fullthickness resection with specifically developed devices for flexible endoscopy.This method is very useful for the treatment of smaller difficult-to-resect lesions,e.g., recurrence with scar formation after previous endoscopic resections.     

Lymph node staging in colorectal cancer:Old controversies and recent advances

Outcome prediction based on tumor stage reflected by the American Joint Committee on Cancer(AJCC)/Union for International Cancer Control(UICC)tumor node metastasis(TNM)system is currently regarded as the strongest prognostic parameter for patients with colorectal cancer.For affected patients,the indication for adjuvant therapy is mainly guided by the presence of regional lymph node metastasis.In addition to the extent of surgical lymph node removal and the thoroughness of the pathologist in dissecting the resection specimen,several parameters that are related to the pathological work-up of the dissected nodes may affect the clinical significance of lymph node staging.These include changing definitions of lymph nodes,involved lymph nodes,and tumor deposits in different editions of the AJCC/UICC TNM system as well as the minimum number of nodes to be dissected.Methods to increase the lymph node yield in the fatty tissue include methylene blue injection and acetone compression.Outcome prediction based on the lymph node ratio,defined as the number of positive lymph nodes divided by the total number of retrieved nodes,may be superior to the absolute numbers of involved nodes.Extracapsular invasion has been identified as additional prognostic factor.Adding step sectioning and immunohistochemistry to the pathological work-up may result in higher accuracy of histological diagnosis.The clinical value of more recent technical advances,such as sentinel lymph node biopsy and molecular analysis of lymph nodes tissue still remains to be defined.     

Acute kidney injury spectrum in patients with chronic liver disease:Where do we stand?

Acute kidney injury (AKI) is a common complication of liver cirrhosis and is of the utmost clinical and prognostic relevance. Patients with cirrhosis, especially decompensated cirrhosis, are more prone to develop AKI than those without cirrhosis. The hepatorenal syndrome type of AKI (HRS–AKI), a spectrum of disorders in prerenal chronic liver disease, and acute tubular necrosis (ATN) are the two most common causes of AKI in patients with chronic liver disease and cirrhosis. Differentiating these conditions is essential due to the differences in treatment. Prerenal AKI, a more benign disorder, responds well to plasma volume expansion, while ATN requires more specific renal support and is associated with substantial mortality. HRS–AKI is a facet of these two conditions, which are characterized by a dysregulation of the immune response. Recently, there has been progress in better defining this clinical entity, and studies have begun to address optimal care. The present review synopsizes the current diagnostic criteria, pathophysiology, and treatment modalities of HRS–AKI and as well as AKI in other chronic liver diseases (non-HRS–AKI) so that early recognition of HRS–AKI and the appropriate management can be established.     

Prophecy about post-endoscopic retrograde cholangiopancreatography pancreatitis:From divination to science

One unresolved issue of endoscopic retrograde cholangiopancreatography(ERCP)is post-ERCP pancreatitis (PEP),which occurs in up to 40%of patients.Identification of risk factors for PEP is especially important in the field of ERCP practice because it may assist physicians in taking protective measures in situations with high risk.A decade ago,Freeman et al meticulously evaluated a large number of potentially relevant risk factors for PEP,which can be divided into patient-relat-ed and procedure-related issues.In this commentary, we summarize this classic article and reevaluate the risk factors for PEP from the current point of view.This is followed by assessment of strategies for prevention of PEP that can be divided into mechanical and pharmacologic methods.     

Role of endoscopic ultrasound in the screening and follow-up of high-risk individuals for familial pancreatic cancer

Managing familial pancreatic cancer(FPC)is challenging for gastroenterologists,surgeons and oncologists.High-risk individuals(HRI)for pancreatic cancer(PC)(FPC or with germline mutations)are a heterogeneous group of subjects with a theoretical lifetime cumulative risk of PC over 5%.Screening is mainly based on annual magnetic resonance imaging(MRI)and endoscopic ultrasound(EUS).The goal of screening is to identify early-stage operable cancers or high-risk precancerous lesions(pancreatic intraepithelial neoplasia or intraductal papillary mucinous neoplasms with high-grade dysplasia).In the literature,target lesions are identified in 2%-5%of HRI who undergo screening.EUS appears to provide better identification of small solid lesions(0%-46%of HRI)and chronicpancreatitis-like parenchymal changes(14%-77%of HRI),while MRI is probably the best modality to identify small cystic lesions(13%-49%of HRI).There are no specific studies in HRI on the use of contrast-enhanced harmonic EUS.EUS can also be used to obtain tissue samples.Nevertheless,there is still limited evidence on the accuracy of imaging procedures used for screening or agreement on which patients to treat.The cost-effectiveness of screening is also unclear.Certain new EUS-related techniques,such as searching for DNA abnormalities or protein markers in pancreatic fluid,appear to be promising.     

Issues and controversies in esophageal inlet patch

The proximal esophagus is rarely examined,and its inspection is often inadequate.Optical chromoendoscopy techniques such as narrow band imaging improve the detection rate of inlet patches in the proximal esophagus,a region in which their prevalence is likely underestimated.Various studies have reported correlations between these esophageal marks with different issues such as Barrett’s esophagus,but these findings remain controversial.Conflicting reports complicate the process of interpreting the clinical features of esophageal inlet patches and underestimate their importance.Unfortunately,the limited clinical data and statistical analyses make reaching any conclusions difficult.It is hypothesized that inlet patches are correlated with various esophageal and extraesophageal symptoms,diagnoses and the personalized therapeutic management of patients with inlet patches as well as the differential diagnosis for premalignant lesions or early cancers.Due to its potential underdiagnosis,there are no consensus guidelines for the management and follow up of inlet patches.This review focuses on questions that were raised from published literature on esophageal inlet patches in adults.     

Sleep,immunity and inflammation in gastrointestinal disorders

Sleep disorders have become a global issue,and discovering their causes and consequences are the focus of many research endeavors.An estimated 70 million Americans suffer from some form of sleep disorder.Certain sleep disorders have been shown to cause neurocognitive impairment such as decreased cognitive ability,slower response times and performance detriments.Recent research suggests that individuals with sleep abnormalities are also at greater risk of serious adverse health,economic consequences,and most importantly increased all-cause mortality.Several research studies support the associations among sleep,immune function and inflammation.Here,we review the current research linking sleep,immune function,and gastrointestinal diseases and discuss the interdependent relationship between sleep and these gastrointestinal disorders.Different physiologic processes including immune system and inflammatory cytokines help regulate the sleep.The inflammatory cytokines such as tumor necrosis factor,interleukin-1(IL-1),and IL-6 have been shown to be a significant contributor of sleep disturbances.On the other hand,sleep disturbances such as sleep deprivation have been shown to up regulate these inflammatory cytokines.Alterations in these cytokine levels have been demonstrated in certain gastrointestinal diseases such as inflammatory bowel disease,gastro-esophageal reflux,liver disorders and colorectal cancer.In turn,abnormal sleep brought on by these diseases is shown to contribute to the severity of these same gastrointestinal diseases.Knowledge of these relationships will allow gastroenterologists a great opportunity to enhance the care of their patients.     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

MUTATION FREQUENCY IN NURSES AND PHARMACISTS WORKING WITH CYTOTOXIC DRUGS

Individuals occupationally exposed to cytotoxic drugs may be at risk owing to the effects of these agents on DNA. As an index of DNA damage, in vivo mutations were measured in lymphocytes from 24 oncology nurses or pharmacists and 24 matched controls. Mutation frequency was significantly increased in exposed individuals and appeared to be related to duration of exposure. However, the overall magnitude of the increase was small and its biological significance remains to be determined.     

A single injection of adrenergic agonists enhances pineal melatonin production in Turkish hamsters

Abstract: The purpose of this study was to determine whether the pineal gland of Turkish hamsters (Mesocricetus brandti) responds to adrenergic agonists with an increase in melatonin production, and, if it does, whether the sensitivity of the pineal gland to agonists would differ throughout the dark phase. Adult Turkish hamsters weighing 110–210 g received a subcutaneous injection of isoproterenol (ISO, 1 mg/kg B.W.) or norepinephrine (NE, 1 mg/kg B.W.) at different times of night. Animals exposed to LD 16:8 responded to ISO or NE with increased pineal melatonin content only when injected at dawn, when endogenous melatonin is at basal or near-basal levels. When the 8 hr scotophase was entirely replaced with light, the responsiveness to ISO injections at dawn disappeared. In animals exposed to light from 30 min prior to injection to the time of sacrifice, ISO injections increased pineal melatonin content (P < 0.005, three-way ANOVA), which varied, depending on the specific time of injection (effect of time of night, P < 0.05, three-way ANOVA). These results demonstrate that (1) adrenergic agonists enhance the production of pineal melatonin in Turkish hamsters, (2) this stimulatory effect takes place late, but not early in the 8 hr scotophase, and (3) the adrenergic induction of pineal melatonin production in Turkish hamsters requires priming by darkness during the appropriate circadian phase.     

Immune effector mechanisms in malaria: An update focusing on human immunity

The past decade has witnessed dramatic decreases in malaria‐associated mortality and morbidity around the world. This progress has largely been due to intensified malaria control measures, implementation of rapid diagnostics and establishing a network to anticipate and mitigate antimalarial drug resistance. However, the ultimate tool for malaria prevention is the development and implementation of an effective vaccine. To date, malaria vaccine efforts have focused on determining which of the thousands of antigens expressed by Plasmodium falciparum are instrumental targets of protective immunity. The antigenic variation and antigenic polymorphisms arising in parasite genes under immune selection present a daunting challenge for target antigen selection and prioritization, and is a given caveat when interpreting immune recall responses or results from monovalent vaccine trials. Other immune evasion strategies executed by the parasite highlight the myriad of ways in which it can become a recurrent infection. This review provides an update on immune effector mechanisms in malaria and focuses on our improved ability to interrogate the complexity of human immune system, accelerated by recent methodological advances. Appreciating how the human immune landscape influences the effectiveness and longevity of antimalarial immunity will help explain which conditions are necessary for immune effector mechanisms to prevail.     

Secondary aortoduodenal fistula

Aorto-duodenal fistulae （ADF） are the most frequent aorto-enteric fistulae （80%）, presenting with upper gastrointestinal bleeding. We report the first case of a man with a secondary aorto-duodenal fistula presenting with a history of persistent occlusive syndrome. A 59-year old man who underwent an aortic-bi-femoral bypass 5 years ago, presented with dyspepsia and biliary vomiting. Computed tomography scan showed in the third duodenal segment the presence of inflammatory tissue with air bubbles between the duodenum and prosthesis, adherent to the duodenum. The patient was submitted to surgery, during which the prosthesis was detached from the duodenum, the intestine failed to close and a gastro-jejunal anastomosis was performed. The post-operative course was simple, secondary ADF was a complication （0.3%-2%） of aortic surgery. Mechanical erosion of the prosthetic material into the bowel was due to the lack of interposed retroperitoneal tissue or the excessive pulsation of redundantly placed grafts or septic procedures. The third or fourth duodenal segment was most frequently involved. Diagnosis of ADF was difficult. Surgical treatment is always recommended by explorative laparotomy. ADF must be suspected whenever a patient with aortic prosthesis has digestive bleeding or unexplained obstructive syndrome. Rarely the clinical picture of ADF is subtle presenting as an obstructive syndrome and in these cases the principal goal is to effectively relieve the mechanical bowel obstruction.     

Serological survey of HIV and syphilis in pregnant women in Madagascar

Objectives Peripartal transmission of human immunodeficiency virus (HIV) and Treponema pallidum, the causative agent of syphilis, leads to severe consequences for newborns. Preventive measures require awareness of the maternal infection. Although HIV and syphilis testing in Madagascar could be theoretically carried out within the framework of the national pregnancy follow‐up scheme, the required test kits are rarely available at peripheral health centres. In this study, we screened blood samples of pregnant Madagascan women for HIV and syphilis seroprevalence to estimate the demand for systemic screening in pregnancy. Methods Retrospective anonymous serological analysis for HIV and syphilis was performed in plasma samples from 1232 pregnant women that were taken between May and July 2010 in Ambositra, Ifanadiana, Manakara, Mananjary, Moramanga and Tsiroanomandidy (Madagascar) during pregnancy follow‐up. Screening was based on Treponema pallidum haemagglutination tests for syphilis and rapid tests for HIV, with confirmation of positive screening results on line assays. Results Out of 1232 pregnant women, none were seropositive for HIV and 37 (3%) were seropositive for Treponema pallidum. Conclusions Our findings are in line with previous studies that describe considerable syphilis prevalence in the rural Madagascan population. The results suggest a need for screening to prevent peripartal Treponema pallidum transmission, while HIV is still rare. If they are known, Treponema pallidum infections can be easily, safely and inexpensively treated even in pregnancy to reduce the risk of transmission.     

Married to M. tuberculosis: risk of infection and disease in spouses of smear-positive tuberculosis patients

Objectives To quantify the risk of infection and disease in spouses of tuberculosis patients and the extent to which intervention could reduce the risk in this highly exposed group. Methods We compared HIV prevalence, TB prevalence and incidence and tuberculin skin test (TST) results in spouses of TB patients and community controls. HIV‐positive spouses were offered isoniazid preventive therapy (IPT), and TST was repeated at 6, 12 and 24 months. Results We recruited 148 spouses of smear‐positive patients ascertained prospectively and 3% had active TB. We identified 203 spouses of previously diagnosed smear‐positive patients, 11 had already had TB, and the rate of TB was 2.4 per 100 person years(py) over 2 years (95% CI 1.15–5.09). 116 were found alive and recruited. HIV prevalence was 37% and 39% in the prospective and retrospective spouse groups and 17% in controls. TST was ≥10 mm in 80% of HIV negative and in 57% of HIV‐positive spouses ascertained retrospectively; 74% HIV negative and 62% HIV‐positive spouses ascertained prospectively, and 48% HIV negative and 26% HIV‐positive community controls. Of 54 HIV‐positive spouses, 18 completed 6‐month IPT. At 2 year follow‐up, 87% of surviving spouses had TST ≥10 mm and the rate of TB was 1.1 per 100 py (95% CI 0.34–3.29). Conclusions Spouses are a high‐risk group who should be screened for HIV and active TB. TST prevalence was already high by the time the spouses were approached but further infections were seen to occur. Uptake and adherence to IPT was disappointing, lessening the impact of short‐duration therapy.