The authors focused on the current surgical treatment of resectable gastric cancer, and significance of peri- and post-operative chemo or chemoradiation. Gastric cancer is the 4<sup>th</sup> most commonly ...The authors focused on the current surgical treatment of resectable gastric cancer, and significance of peri- and post-operative chemo or chemoradiation. Gastric cancer is the 4<sup>th</sup> most commonly diagnosed cancer and the second leading cause of cancer death worldwide. Surgery remains the only curative therapy, while perioperative and adjuvant chemotherapy, as well as chemoradiation, can improve outcome of resectable gastric cancer with extended lymph node dissection. More than half of radically resected gastric cancer patients relapse locally or with distant metastases, or receive the diagnosis of gastric cancer when tumor is disseminated; therefore, median survival rarely exceeds 12 mo, and 5-years survival is less than 10%. Cisplatin and fluoropyrimidine-based chemotherapy, with addition of trastuzumab in human epidermal growth factor receptor 2 positive patients, is the widely used treatment in stage IV patients fit for chemotherapy. Recent evidence supports the use of second-line chemotherapy after progression in patients with good performance status展开更多
Portal vein thrombosis (PVT) is a relatively common complication in patients with liver cirrhosis, but might also occur in absence of an overt liver disease. Several causes, either local or systemic, might play an imp...Portal vein thrombosis (PVT) is a relatively common complication in patients with liver cirrhosis, but might also occur in absence of an overt liver disease. Several causes, either local or systemic, might play an important role in PVT pathogenesis. Frequently, more than one risk factor could be identified; however, occasionally no single factor is discernable. Clinical examination, laboratory investigations, and imaging are helpful to provide a quick diagnosis, as prompt treatment might greatly affect a patient's outcome. In this review, we analyze the physiopathological mechanisms of PVT development, together with the hemodynamic and functional alterations related to this condition. Moreover, we describe the principal factors most frequently involved in PVT development and the recent knowledge concerning diagnostic and therapeutic procedures. Finally, we analyze the implications of PVT in the setting of liver transplantation and its possible influence on patients' future prognoses.展开更多
The revolution of genome sequencing is continuing after the successful secondgeneration sequencing （SGS） technology. The third-generation sequencing （TGS） technology, led by Pacific Biosciences （PacBio）, is prog...The revolution of genome sequencing is continuing after the successful secondgeneration sequencing （SGS） technology. The third-generation sequencing （TGS） technology, led by Pacific Biosciences （PacBio）, is progressing rapidly, moving from a technology once only capable of providing data for small genome analysis, or for performing targeted screening, to one that promises high quality de novo assembly and structural variation detection for human-sized genomes. In 2014, the MinION, the first commercial sequencer using nanopore technology, was released by Oxford Nanopore Technologies （ONT）. MiniON identifies DNA bases by measuring the changes in electrical conductivity generated as DNA strands pass through a biological pore. Its portability, affordability, and speed in data production makes it suitable for real-time applications, the release of the long read sequencer MiniON has thus generated much excitement and interest in the genomics community. While de novo genome assemblies can be cheaply produced from SGS data, assem- bly continuity is often relatively poor, due to the limited ability of short reads to handle long repeats. Assembly quality can be greatly improved by using TGS long reads, since repetitive regions can be easily expanded into using longer sequencing lengths, despite having higher error rates at the base level. The potential of nanopore sequencing has been demonstrated by various studies in genome surveillance at locations where rapid and reliable sequencing is needed, but where resources are limited.展开更多
Nonalcoholic fatty liver disease(NAFLD) is today considered the most common form of chronic liver disease, affecting a high proportion of the population worldwide. NAFLD encompasses a large spectrum of liver damage, r...Nonalcoholic fatty liver disease(NAFLD) is today considered the most common form of chronic liver disease, affecting a high proportion of the population worldwide. NAFLD encompasses a large spectrum of liver damage, ranging from simple steatosis to steatohepatitis, advanced fibrosis and cirrhosis. Obesity, hyperglycemia, type 2 diabetes and hypertriglyceridemia are the most important risk factors. The pathogenesis of NAFLD and its progression to fibrosis and chronic liver disease is still unknown. Accumulating evidence indicates that mitochondrial dysfunction plays a key role in the physiopathology of NAFLD, although the mechanisms underlying this dysfunction are still unclear. Oxidative stress is considered an important factor in producing lethal hepatocyte injury associated with NAFLD. Mitochondrial respiratory chain is the main subcellular source of reactive oxygen species(ROS), which may damage mitochondrial proteins, lipids and mitochondrial DNA. Cardiolipin, a phospholipid located at the level of the inner mitochondrial membrane, plays an important role in several reactions and processes involved in mitochondrial bioenergetics as well as in mitochondrial dependent steps of apoptosis. This phospholipid is particularly susceptible to ROS attack. Cardiolipin peroxidation has been associated with mitochondrial dysfunction in multiple tissues in several physiopathological conditions, including NAFLD. In this review, we focus on the potential roles played by oxidative stress and cardiolipin alterations in mitochondrial dysfunction associated with NAFLD.展开更多
Nowadays,hepatocellular carcinoma(HCC) is frequently diagnosed at an early stage,opening good perspectives to radical treatment by means of liver transplantation,surgical resection,or percutaneous ablation.Liver trans...Nowadays,hepatocellular carcinoma(HCC) is frequently diagnosed at an early stage,opening good perspectives to radical treatment by means of liver transplantation,surgical resection,or percutaneous ablation.Liver transplantation is considered the best option,but the lack of liver donors represents a major limitation.Therefore,surgical resection,offering a 5-year-survival rate of over 50%,is considered the first-choice treatment for patients with early stage HCC,whereas percutaneous ablation is usually reserved to patients who are not candidate to surgery.However,in the recent years some trials showed that percutaneous radiofrequency ablation(RFA) can be as effective as surgical resection in terms of overall survival and recurrencefree survival rates in patients with small HCC,and a retrospective comparative study reported 1-,3-,and 5-year overall survival rates and recurrence-free survival rates significantly better in patients with central HCC measuring 2 cm or smaller treated with RFA than in those treated with surgical resection.RFA is less expensive,less invasive,with lower complication rate and shorter hospital stay than surgical resection,and on the basis of the results of these studies it should be considered the first option in the treatment of very early HCC.However,RFA is size-dependent,so at present the need to achieve an adequate safety margin around the tumor limits to about 2 cm the diameter of the nodules that can be ablated with long-term outcomes comparable to or better than surgical resection.The main goal of the next technical developments of the thermal ablation systems should be the achievement of larger ablation areas with a single needle insertion.In this regard,the recent improvements in microwave energy delivery systems seem to open interesting perspectives to percutaneous microwave ablation,which could become the ablation technique of choice in the next future.展开更多
Inflammatory bowel disease （IBD） arises from disruption of immune tolerance to the gut commensal microbiota, leading to chronic intestinal inflammation and mucosal damage in genetically predisposed hosts. In healthy...Inflammatory bowel disease （IBD） arises from disruption of immune tolerance to the gut commensal microbiota, leading to chronic intestinal inflammation and mucosal damage in genetically predisposed hosts. In healthy individuals the intestinal microbiota have a symbiotic relationship with the host organism and possess important and unique functions, including a metabolic function （i.e. digestion of dietary compounds and xenobiotics, fermentation of undigestible carbohydrates with production of short chain fatty acids）, a mucosal barrier function （i.e. by inhibiting pathogen invasion and strengthening epithelial barrier integrity）, and an immune modula- tory function （i.e. mucosal immune system priming and maintenance of intestinal epithelium homeostasis）. A fine balance regulates the mechanism that allows co- existence of mammals with their commensal bacteria. In IBD this mechanism of immune tolerance is impaired because of several potential causative factors. The gut microbiota composition and activity of IBD patients are abnormal, with a decreased prevalence of dominant members of the human commensal microbiota （i.e. Clostridium IXa and IV groups, Bacteroides, bifldobacteria） and a concomitant increase in detrimental bacteria （i.e. sulphate-reducing bacteria, Escherichia coll. The observed dysbiosis is concomitant with defectiveinnate immunity and bacterial killing （i.e. reduced mucosal defensins and IgA, malfunctioning phagocytosis） and overaggressive adaptive immune response （due to ineffective regulatory T cells and antigen presenting cells）, which are considered the basis of IBD pathogen- esis. However, we still do not know how the interplay between these parameters causes the disease. Studies looking at gut microbial composition, epithelial integrity and mucosal immune markers in genotyped IBD populations are therefore warranted to shed light on this obscure pathogenesis.展开更多
The intimate connection and the strict mutual cooperation between the gut and the liver realizes a functional entity called gut-liver axis.The integrity of intestinal barrier is crucial for the maintenance of liver ho...The intimate connection and the strict mutual cooperation between the gut and the liver realizes a functional entity called gut-liver axis.The integrity of intestinal barrier is crucial for the maintenance of liver homeostasis.In this mutual relationship,the liver acts as a second firewall towards potentially harmful substances translocated from the gut,and is,in turn,is implicated in the regulation of the barrier.Increasing evidence has highlighted the relevance of increased intestinal permeability and consequent bacterial translocation in the development of liver damage.In particular,in patients with non-alcoholic fatty liver disease recent hypotheses are considering intestinal permeability impairment,diet and gut dysbiosis as the primary pathogenic trigger.In advanced liver disease,intestinal permeability is enhanced by portal hypertension.The clinical consequence is an increased bacterial translocation that further worsens liver damage.Furthermore,this pathogenic mechanism is implicated in most of liver cirrhosis complications,such as spontaneous bacterial peritonitis,hepatorenal syndrome,portal vein thrombosis,hepatic encephalopathy,and hepatocellular carcinoma.After liver transplantation,the decrease in portal pressure should determine beneficial effects on the gut-liver axis,although are incompletely understood data on the modifications of the intestinal permeability and gut microbiota composition are still lacking.How the modulation of the intestinal permeability could prevent the initiation and progression of liver disease is still an uncovered area,which deserves further attention.展开更多
Hepatocellular carcinoma is one of the most frequent malignant tumors worldwide:Portal vein tumor thrombosis(PVTT)occurs in about 35%-50%of patients and represents a strong negative prognostic factor,due to the increa...Hepatocellular carcinoma is one of the most frequent malignant tumors worldwide:Portal vein tumor thrombosis(PVTT)occurs in about 35%-50%of patients and represents a strong negative prognostic factor,due to the increased risk of tumor spread into the bloodstream,leading to a high recurrence risk.For this reason,it is a contraindication to liver transplantation and in several prognostic scores sorafenib represents its standard of care,due to its antiangiogenetic action,although it can grant only a poor prolongation of life expectancy.Recent scientific evidences lead to consider PVTT as a complex anatomical and clinical condition,including a wide range of patients with different prognosis and new treatment possibilities according to the degree of portal system involvement,tumor biological aggressiveness,complications caused by portal hypertension,patient’s clinical features and tolerance to antineoplastic treatments.The median survival has been reported to range between 2.7 and 4 mo in absence of therapy,but it can vary from 5 mo to 5 years,thus depicting an extremely variable scenario.For this reason,it is extremely important to focus on the most adequate strategy to be applied to each group of PVTT patients.展开更多
Portal vein thrombosis(PVT)represents a well-known complication during the natural course of liver cirrhosis(LC),ranging from asymptomatic cases to lifethreating conditions related to portal hypertension and hepatic d...Portal vein thrombosis(PVT)represents a well-known complication during the natural course of liver cirrhosis(LC),ranging from asymptomatic cases to lifethreating conditions related to portal hypertension and hepatic decompensation.Portal flow stasis,complex acquired hypercoagulable disorders and exogenous factors leading to endothelial dysfunction have emerged as key factors for PVT development.However,PVT occurrence remains unpredictable and many issues regarding its natural history,prognostic significance and treatment are still elusive.In particular although spontaneous resolution or disease stability occur in most cases of PVT,factors predisposing to disease progression or recurrence after spontaneous recanalization are not clarified as yet.Moreover,PVT impact on LC outcome is still debated,as PVT may represent itself a consequence of liver fibrosis and hepatic dysfunction progression.Anticoagulation and transjugular intrahepatic portosystemic shunt are considered safe and effective in this setting and are recommended in selected cases,even if the safer therapeutic option and the optimal therapy duration are still unknown.Nevertheless,their impact on mortality rates should be addressed more extensively.In this review we present the most debated questions regarding PVT,whose answers should come from prospective cohort studies and large sample-size randomized trials.展开更多
Dear Editor,Seed germination is a major developmental transition in a plant＇s life that involves the concerted action of several genetic and physiological pathways （Holdsworth et al., 2008）, and mostly consists of ...Dear Editor,Seed germination is a major developmental transition in a plant＇s life that involves the concerted action of several genetic and physiological pathways （Holdsworth et al., 2008）, and mostly consists of the resumption of embryo growth after a long quiescence imposed during seed maturation. In mature seeds, germination is repressed by abscisic acid （ABA）, while favorable environmental conditions promote gibberellin （GA） biosynthesis and decrease ABA （Holdsworth et al., 2008）. The increase in GA levels is essential for the rupture of testa and endosperm （Lee et al., 2002）. The activation of cell division in the embryo is an integral part of germination that precedes the protrusion of the root through the seed coat. In Arabidopsis, this activation has been linked to significant early changes in the expression of cell-cycle elements （Masubelele et al., 2005）. In the root apical meristem （RAM）, GAs regulate cell divisions （Achard et al., 2009; 0beda-Tomás et al., 2009）. Similarly, the transcription factors （TFs） TEOSINTE BRANCHED1/ CYCLOIDEA/PROLIFERATING CELL FACTOR14 （TCP14） and TCP15 have been proposed to regulate cell proliferation （Kieffer et al., 2011）. Moreover, the activity of TCP14 is necessary to undergo seed germination and, remarkably, seeds lacking this activity are hypersensitive to the negative effects on germination of GA biosynthesis inhibitor paclobutrazol, suggesting a functional relationship between this TF and GAs （Tatematsu et al., 2008）. Taking these observations into account, we hypothesized that TCP14 and TCP15 mediate GA-dependent activation of the cell cycle during germination.展开更多
Portal vein thrombosis(PVT) is one of the most common complications occurring during the natural course of liver cirrhosis.Even though PVT is often asymptomatic,the worsening of liver function,an unexpected episode of...Portal vein thrombosis(PVT) is one of the most common complications occurring during the natural course of liver cirrhosis.Even though PVT is often asymptomatic,the worsening of liver function,an unexpected episode of gastrointestinal bleeding or ascitic decompensation may be landmarks of PVT development.Beyond these clinical manifestations,it is debated whether PVT really has an impact on liver cirrhosis natural history or rather represents only one of its consequences.Probably PVT development should not only be considered as a matter of impaired blood flow or pro-coagulation tendency.On one hand,PVT seems a consequence of the worsening in portal vein outflow due to the increased hepatic resistance in cirrhotic livers.On the other hand,vascular microthrombosis secondary to necroinflammation may cause liver ischemia and infarction,with loss of hepatic tissue(parenchymal extinction) which is replaced by fibrotic tissue.Therefore,PVT might also be considered as the overt manifestation of the liver fibrosing process evolution and anticoagulant therapy may thus have microscopic indirect effects also on the progression of liver disease.At present,a connection between PVT development and the progression of liver fibrosis/cirrhosis has not yet been demonstrated.Nevertheless,it is not clear if PVT development may worsen cirrhotic patients' outcome by itself.Some authors tried to assess liver transplant benefit in PVT cirrhotic patients but data are contrasting.In this review,we will try to answer these questions,providing a critical analysis of data reported in literature.展开更多
AIM： To comparatively evaluate the long term efficacy of Rifaximin and dietary fibers in reducing symptoms and/or complication frequency in symptomatic, uncomplicated diverticular disease,METHODS： 307 patients （118...AIM： To comparatively evaluate the long term efficacy of Rifaximin and dietary fibers in reducing symptoms and/or complication frequency in symptomatic, uncomplicated diverticular disease,METHODS： 307 patients （118 males, 189 females, age range： 40-80 years） were enrolled in the study and randomly assigned to： Rifaximin （400 mg bid for 7 d every month） plus dietary fiber supplementation （at least 20 gr/d） or dietary fiber supplementation alone. The study duration was 24 mo; both clinical examination and symptoms＇ questionnaire were performed every two months. RESULTS： Both treatments reduced symptom frequency, but Rifaximin at a greater extent, when compared to basal values. Symptomatic score declined during both treatments, but a greater reduction was evident in the Rifaximin group （6.4±2.8 and 6.2 ± 2.6 at enrollment, P = NS, 1.0 ±0.7 and 2.4±1.7 after 24 mo, P 〈 0.001, respectively）. Probability of symptom reduction was higher and complication frequency lower （Kaplan-Meyer method） in the Rifaximin group （P 〈 0.0001 and 0.028, respectively）.CONCLUSION： In patients with symptomatic, uncomplicated diverticular disease, cyclic administration of RJfaximin plus dietary fiber supplementation is more effective in reducing both symptom and complication frequency than simple dietary fiber supplementation.Long term administration of the poorly absorbed antibiotic Rifaximin is safe and well tolerated by the patients,confirming the usefulness of this therapeutic strategy in the overall management of diverticular disease.展开更多
Several therapeutic procedures have been proposed as bridging treatments for patients with hepatocellular carcinoma(HCC)awaiting liver transplantation(LT).The most used treatments include transarterial chemoembolizati...Several therapeutic procedures have been proposed as bridging treatments for patients with hepatocellular carcinoma(HCC)awaiting liver transplantation(LT).The most used treatments include transarterial chemoembolization and radiofrequency ablation.Surgical resection has also been successfully used as a bridging procedure,and LT should be considered a rescue treatment in patients with previous HCC resection who experience tumor recurrence or post-treatment severe decompensation of liver function.The aims of bridging treatments include decreasing the waiting list dropout rate before transplantation,reducing HCC recurrence after transplantation,and improving post-transplant overall survival.To date,no data from prospective randomized studies are available;however,for HCC patients listed for LT within the Milan criteria,prolonging the waiting time over 6-12 mo is a risk factor for tumor spread.Bridging treatments are useful in containing tumor progression and decreasing dropout.Furthermore,the response to pre-LT treatments may represent a surrogate marker of tumor biological aggressiveness and could therefore be evaluated to prioritize HCC candidates for LT.Lastly,although a definitive conclusion can not be reached,the experiences reported to date suggest a positive impact of these treatments on both tumor recurrence and post-transplant patient survival.Advanced HCC may be downstaged to achieve and maintain the current conventional criteria for inclusion in the waiting list for LT.Recent studies have demonstrated that successfully downstaged patients can achieve a 5-year survival rate comparable to that of patients meeting the conventional criteria without requiring downstaging.展开更多
The hypothesis of an important role of gut microbiota in the maintenance of physiological state into the gastrointestinal(GI)system is supported by several studies that have shown a qualitative and quantitative altera...The hypothesis of an important role of gut microbiota in the maintenance of physiological state into the gastrointestinal(GI)system is supported by several studies that have shown a qualitative and quantitative alteration of the intestinal flora in a number of gastrointestinal and extra-gastrointestinal diseases.In the last few years,the importance of gut microbiota impairment in the etiopathogenesis of pathology such as autism,dementia and mood disorder,has been raised.The evidence of the inflammatory state alteration,highlighted in disorders such as schizophrenia,major depressive disorder and bipolar disorder,strongly recalls the microbiota alteration,highly suggesting an important role of the alteration of GI system also in neuropsychiatric disorders.Up to now,available evidences display that the impairment of gut microbiota plays a key role in the development of autism and mood disorders.The application of therapeutic modulators of gut microbiota to autism and mood disorders has been experienced only in experimental settings to date,with few but promising results.A deeper assessment of the role of gut microbiota in the development of autism spectrum disorder(ASD),as well as the advancement of the therapeutic armamentarium for the modulation of gut microbiota is warranted for a better management of ASD and mood disorders.展开更多
Nonalcoholic fatty liver disease(NAFLD) is emerging as the most common chronic liver disease, and is characterized by a wide spectrum of fat-liver disorders that can result in severe liver disease and cirrhosis. Infla...Nonalcoholic fatty liver disease(NAFLD) is emerging as the most common chronic liver disease, and is characterized by a wide spectrum of fat-liver disorders that can result in severe liver disease and cirrhosis. Inflammation and oxidative stress are the major risk factors involved in the pathogenesis of NAFLD. Currently, there is no consensus concerning the pharmacological treatment of NAFLD. However, lifestyle interventions based on exercise and a balanced diet for quality and quantity, are considered the cornerstone of NAFLD management. Mediterranean diet(MD), rich in polyunsaturated fats, polyphenols, vitamins and carotenoids, with their anti-inflammatory and antioxidant effects, has been suggested to be effective in preventing cardiovascular risk factors. In adults, MD has also been demonstrated to be efficacious in reducing the risk of metabolic syndrome. However, few studies are available on the effects of the MD in both adult and pediatric subjects with NAFLD. Thus, the aims of the present narrative review are to analyze the current clinical evidence on the impact of MD in patients with NAFLD, and to summarize the main mechanisms of action of MD components on this condition.展开更多
Antibiotics are usually prescribed to cure infections but they also have significant modulatory effects on the gut microbiota. Several alterations of the intestinal bacterial community have been reported during antibi...Antibiotics are usually prescribed to cure infections but they also have significant modulatory effects on the gut microbiota. Several alterations of the intestinal bacterial community have been reported during antibiotic treatment, including the reduction of beneficial bacteria as well as of microbial alpha-diversity. Although after the discontinuation of antibiotic therapies it has been observed a trend towards the restoration of the original condition, the new steady state is different from the previous one, as if antibiotics induced some kind of irreversible perturbation of the gut microbial community. The poorly absorbed antibiotic rifaximin seem to be different from the other antibiotics, because it exerts non-traditional effects additional to the bactericidal/bacteriostatic activity on the gut microbiota. Rifaximin is able to reduce bacterial virulence and translocation, has anti-inflammatory properties and has been demonstrated to positively modulate the gut microbial composition. Animal models, culture studies and metagenomic analyses have demonstrated an increase in Bifidobacterium, Faecalibacterium prausnitzii and Lactobacillus abundance after rifaximin treatment, probably consequent to the induction of bacterial resistance, with no major change in the overall gut microbiota composition. Antibiotics are therefore modulators of the symbiotic relationship between the host and the gut microbiota. Specific antibiotics, such as rifaximin, can also induce eubiotic changes in the intestinal ecosystem; this additional property may represent a therapeutic advantage in specific clinical settings.展开更多
Deep learning(DL)is one of the fastest-growing topics in materials data science,with rapidly emerging applications spanning atomistic,image-based,spectral,and textual data modalities.DL allows analysis of unstructured...Deep learning(DL)is one of the fastest-growing topics in materials data science,with rapidly emerging applications spanning atomistic,image-based,spectral,and textual data modalities.DL allows analysis of unstructured data and automated identification of features.The recent development of large materials databases has fueled the application of DL methods in atomistic prediction in particular.In contrast,advances in image and spectral data have largely leveraged synthetic data enabled by high-quality forward models as well as by generative unsupervised DL methods.In this article,we present a high-level overview of deep learning methods followed by a detailed discussion of recent developments of deep learning in atomistic simulation,materials imaging,spectral analysis,and natural language processing.For each modality we discuss applications involving both theoretical and experimental data,typical modeling approaches with their strengths and limitations,and relevant publicly available software and datasets.We conclude the review with a discussion of recent cross-cutting work related to uncertainty quantification in this field and a brief perspective on limitations,challenges,and potential growth areas for DL methods in materials science.展开更多
Hepatitis B virus(HBV)and hepatitis C virus(HCV)share common mode of transmission and both are able to induce a chronic infection.Dual HBV/HCV chronic coinfection is a fairly frequent occurrence,especially in high end...Hepatitis B virus(HBV)and hepatitis C virus(HCV)share common mode of transmission and both are able to induce a chronic infection.Dual HBV/HCV chronic coinfection is a fairly frequent occurrence,especially in high endemic areas and among individuals at high risk of parenterally transmitted infections.The intracellular interplay between HBV and HCV has not yet been sufficiently clarified,also due to the lack of a proper in vitro cellular model.Longitudinal evaluation of serum HBV DNA and HCV RNA amounts has revealed that complex virological profiles may be present in coinfected patients.Dual HBV/HCV infection has been associated to a severe course of the liver disease and to a high risk of developing hepatocellular carcinoma.Despite the clinical importance,solid evidence and clear guidelines for treatment of this special population are still lacking.This review summarizes the available data on the virological and clinical features as well as the therapeutic options of the dual HBV/HCV infection,and highlights the aspects that need to be better clarified.展开更多
To date,no vaccines or effective drugs have been approved to prevent or treat COVID-19 and the current standard care relies on supportive treatments.Therefore,based on the fast and global spread of the virus,urgent in...To date,no vaccines or effective drugs have been approved to prevent or treat COVID-19 and the current standard care relies on supportive treatments.Therefore,based on the fast and global spread of the virus,urgent investigations are warranted in order to develop preventive and therapeutic drugs.In this regard,treatments addressing the immunopathology of SARS-CoV-2 infection have become a major focus.Notably,while a rapid and well-coordinated immune response represents the first line of defense against viral infection,excessive inflammatory innate response and impaired adaptive host immune defense may lead to tissue damage both at the site of virus entry and at systemic level.Several studies highlight relevant changes occurring both in innate and adaptive immune system in COVID-19 patients.In particular,the massive cytokine and chemokine release,the so-called“cytokine storm”,clearly reflects a widespread uncontrolled dysregulation of the host immune defense.Although the prospective of counteracting cytokine storm is compelling,a major limitation relies on the limited understanding of the immune signaling pathways triggered by SARS-CoV-2 infection.The identification of signaling pathways altered during viral infections may help to unravel the most relevant molecular cascades implicated in biological processes mediating viral infections and to unveil key molecular players that may be targeted.Thus,given the key role of the immune system in COVID-19,a deeper understanding of the mechanism behind the immune dysregulation might give us clues for the clinical management of the severe cases and for preventing the transition from mild to severe stages.展开更多
The stomach is the most frequently involved site for extranodal lymphomas,accounting for nearly two-thirds of all gastrointestinal cases.It is widely accepted that gastric B-cell,low-grade mucosal-associated lymphoid ...The stomach is the most frequently involved site for extranodal lymphomas,accounting for nearly two-thirds of all gastrointestinal cases.It is widely accepted that gastric B-cell,low-grade mucosal-associated lymphoid tissue(MALT)-lymphoma is caused by Helicobacter pylori(H.pylori)infection.MALT-lymphomas may engender different clinical and endoscopic patterns.Often,diagnosis is confirmed in patients with only vague dyspeptic symptoms and without macroscopic lesions on gastric mucosa.H.pylori eradication leads to lymphoma remission in a large number of patients when treatment occurs at an early stage(Ⅰ-Ⅱ1).Neoplasia confined to the submucosa,localized in the antral region of the stomach,and without API2-MALT1 translocation,shows a high probability of remission following H.pylori eradication.When both bacterial infection and lymphoma recur,further eradication therapy is generally effective.Radiotherapy,chemotherapy and,in selected cases,surgery are the available therapeutic options with a high success rate for those patients who fail to achieve remission,while data on immunotherapy with monoclonal antibodies (rituximab)are still scarce.The 5-year survival rate is higher than 90%,but careful,long-term follow-up is required in these patients since lymphoma recurrence has been reported in some cases.展开更多
文摘The authors focused on the current surgical treatment of resectable gastric cancer, and significance of peri- and post-operative chemo or chemoradiation. Gastric cancer is the 4<sup>th</sup> most commonly diagnosed cancer and the second leading cause of cancer death worldwide. Surgery remains the only curative therapy, while perioperative and adjuvant chemotherapy, as well as chemoradiation, can improve outcome of resectable gastric cancer with extended lymph node dissection. More than half of radically resected gastric cancer patients relapse locally or with distant metastases, or receive the diagnosis of gastric cancer when tumor is disseminated; therefore, median survival rarely exceeds 12 mo, and 5-years survival is less than 10%. Cisplatin and fluoropyrimidine-based chemotherapy, with addition of trastuzumab in human epidermal growth factor receptor 2 positive patients, is the widely used treatment in stage IV patients fit for chemotherapy. Recent evidence supports the use of second-line chemotherapy after progression in patients with good performance status
文摘Portal vein thrombosis (PVT) is a relatively common complication in patients with liver cirrhosis, but might also occur in absence of an overt liver disease. Several causes, either local or systemic, might play an important role in PVT pathogenesis. Frequently, more than one risk factor could be identified; however, occasionally no single factor is discernable. Clinical examination, laboratory investigations, and imaging are helpful to provide a quick diagnosis, as prompt treatment might greatly affect a patient's outcome. In this review, we analyze the physiopathological mechanisms of PVT development, together with the hemodynamic and functional alterations related to this condition. Moreover, we describe the principal factors most frequently involved in PVT development and the recent knowledge concerning diagnostic and therapeutic procedures. Finally, we analyze the implications of PVT in the setting of liver transplantation and its possible influence on patients' future prognoses.
基金supported by the Wellcome Trust,the United Kingdom
文摘The revolution of genome sequencing is continuing after the successful secondgeneration sequencing （SGS） technology. The third-generation sequencing （TGS） technology, led by Pacific Biosciences （PacBio）, is progressing rapidly, moving from a technology once only capable of providing data for small genome analysis, or for performing targeted screening, to one that promises high quality de novo assembly and structural variation detection for human-sized genomes. In 2014, the MinION, the first commercial sequencer using nanopore technology, was released by Oxford Nanopore Technologies （ONT）. MiniON identifies DNA bases by measuring the changes in electrical conductivity generated as DNA strands pass through a biological pore. Its portability, affordability, and speed in data production makes it suitable for real-time applications, the release of the long read sequencer MiniON has thus generated much excitement and interest in the genomics community. While de novo genome assemblies can be cheaply produced from SGS data, assem- bly continuity is often relatively poor, due to the limited ability of short reads to handle long repeats. Assembly quality can be greatly improved by using TGS long reads, since repetitive regions can be easily expanded into using longer sequencing lengths, despite having higher error rates at the base level. The potential of nanopore sequencing has been demonstrated by various studies in genome surveillance at locations where rapid and reliable sequencing is needed, but where resources are limited.
文摘Nonalcoholic fatty liver disease(NAFLD) is today considered the most common form of chronic liver disease, affecting a high proportion of the population worldwide. NAFLD encompasses a large spectrum of liver damage, ranging from simple steatosis to steatohepatitis, advanced fibrosis and cirrhosis. Obesity, hyperglycemia, type 2 diabetes and hypertriglyceridemia are the most important risk factors. The pathogenesis of NAFLD and its progression to fibrosis and chronic liver disease is still unknown. Accumulating evidence indicates that mitochondrial dysfunction plays a key role in the physiopathology of NAFLD, although the mechanisms underlying this dysfunction are still unclear. Oxidative stress is considered an important factor in producing lethal hepatocyte injury associated with NAFLD. Mitochondrial respiratory chain is the main subcellular source of reactive oxygen species(ROS), which may damage mitochondrial proteins, lipids and mitochondrial DNA. Cardiolipin, a phospholipid located at the level of the inner mitochondrial membrane, plays an important role in several reactions and processes involved in mitochondrial bioenergetics as well as in mitochondrial dependent steps of apoptosis. This phospholipid is particularly susceptible to ROS attack. Cardiolipin peroxidation has been associated with mitochondrial dysfunction in multiple tissues in several physiopathological conditions, including NAFLD. In this review, we focus on the potential roles played by oxidative stress and cardiolipin alterations in mitochondrial dysfunction associated with NAFLD.
文摘Nowadays,hepatocellular carcinoma(HCC) is frequently diagnosed at an early stage,opening good perspectives to radical treatment by means of liver transplantation,surgical resection,or percutaneous ablation.Liver transplantation is considered the best option,but the lack of liver donors represents a major limitation.Therefore,surgical resection,offering a 5-year-survival rate of over 50%,is considered the first-choice treatment for patients with early stage HCC,whereas percutaneous ablation is usually reserved to patients who are not candidate to surgery.However,in the recent years some trials showed that percutaneous radiofrequency ablation(RFA) can be as effective as surgical resection in terms of overall survival and recurrencefree survival rates in patients with small HCC,and a retrospective comparative study reported 1-,3-,and 5-year overall survival rates and recurrence-free survival rates significantly better in patients with central HCC measuring 2 cm or smaller treated with RFA than in those treated with surgical resection.RFA is less expensive,less invasive,with lower complication rate and shorter hospital stay than surgical resection,and on the basis of the results of these studies it should be considered the first option in the treatment of very early HCC.However,RFA is size-dependent,so at present the need to achieve an adequate safety margin around the tumor limits to about 2 cm the diameter of the nodules that can be ablated with long-term outcomes comparable to or better than surgical resection.The main goal of the next technical developments of the thermal ablation systems should be the achievement of larger ablation areas with a single needle insertion.In this regard,the recent improvements in microwave energy delivery systems seem to open interesting perspectives to percutaneous microwave ablation,which could become the ablation technique of choice in the next future.
文摘Inflammatory bowel disease （IBD） arises from disruption of immune tolerance to the gut commensal microbiota, leading to chronic intestinal inflammation and mucosal damage in genetically predisposed hosts. In healthy individuals the intestinal microbiota have a symbiotic relationship with the host organism and possess important and unique functions, including a metabolic function （i.e. digestion of dietary compounds and xenobiotics, fermentation of undigestible carbohydrates with production of short chain fatty acids）, a mucosal barrier function （i.e. by inhibiting pathogen invasion and strengthening epithelial barrier integrity）, and an immune modula- tory function （i.e. mucosal immune system priming and maintenance of intestinal epithelium homeostasis）. A fine balance regulates the mechanism that allows co- existence of mammals with their commensal bacteria. In IBD this mechanism of immune tolerance is impaired because of several potential causative factors. The gut microbiota composition and activity of IBD patients are abnormal, with a decreased prevalence of dominant members of the human commensal microbiota （i.e. Clostridium IXa and IV groups, Bacteroides, bifldobacteria） and a concomitant increase in detrimental bacteria （i.e. sulphate-reducing bacteria, Escherichia coll. The observed dysbiosis is concomitant with defectiveinnate immunity and bacterial killing （i.e. reduced mucosal defensins and IgA, malfunctioning phagocytosis） and overaggressive adaptive immune response （due to ineffective regulatory T cells and antigen presenting cells）, which are considered the basis of IBD pathogen- esis. However, we still do not know how the interplay between these parameters causes the disease. Studies looking at gut microbial composition, epithelial integrity and mucosal immune markers in genotyped IBD populations are therefore warranted to shed light on this obscure pathogenesis.
文摘The intimate connection and the strict mutual cooperation between the gut and the liver realizes a functional entity called gut-liver axis.The integrity of intestinal barrier is crucial for the maintenance of liver homeostasis.In this mutual relationship,the liver acts as a second firewall towards potentially harmful substances translocated from the gut,and is,in turn,is implicated in the regulation of the barrier.Increasing evidence has highlighted the relevance of increased intestinal permeability and consequent bacterial translocation in the development of liver damage.In particular,in patients with non-alcoholic fatty liver disease recent hypotheses are considering intestinal permeability impairment,diet and gut dysbiosis as the primary pathogenic trigger.In advanced liver disease,intestinal permeability is enhanced by portal hypertension.The clinical consequence is an increased bacterial translocation that further worsens liver damage.Furthermore,this pathogenic mechanism is implicated in most of liver cirrhosis complications,such as spontaneous bacterial peritonitis,hepatorenal syndrome,portal vein thrombosis,hepatic encephalopathy,and hepatocellular carcinoma.After liver transplantation,the decrease in portal pressure should determine beneficial effects on the gut-liver axis,although are incompletely understood data on the modifications of the intestinal permeability and gut microbiota composition are still lacking.How the modulation of the intestinal permeability could prevent the initiation and progression of liver disease is still an uncovered area,which deserves further attention.
文摘Hepatocellular carcinoma is one of the most frequent malignant tumors worldwide:Portal vein tumor thrombosis(PVTT)occurs in about 35%-50%of patients and represents a strong negative prognostic factor,due to the increased risk of tumor spread into the bloodstream,leading to a high recurrence risk.For this reason,it is a contraindication to liver transplantation and in several prognostic scores sorafenib represents its standard of care,due to its antiangiogenetic action,although it can grant only a poor prolongation of life expectancy.Recent scientific evidences lead to consider PVTT as a complex anatomical and clinical condition,including a wide range of patients with different prognosis and new treatment possibilities according to the degree of portal system involvement,tumor biological aggressiveness,complications caused by portal hypertension,patient’s clinical features and tolerance to antineoplastic treatments.The median survival has been reported to range between 2.7 and 4 mo in absence of therapy,but it can vary from 5 mo to 5 years,thus depicting an extremely variable scenario.For this reason,it is extremely important to focus on the most adequate strategy to be applied to each group of PVTT patients.
文摘Portal vein thrombosis(PVT)represents a well-known complication during the natural course of liver cirrhosis(LC),ranging from asymptomatic cases to lifethreating conditions related to portal hypertension and hepatic decompensation.Portal flow stasis,complex acquired hypercoagulable disorders and exogenous factors leading to endothelial dysfunction have emerged as key factors for PVT development.However,PVT occurrence remains unpredictable and many issues regarding its natural history,prognostic significance and treatment are still elusive.In particular although spontaneous resolution or disease stability occur in most cases of PVT,factors predisposing to disease progression or recurrence after spontaneous recanalization are not clarified as yet.Moreover,PVT impact on LC outcome is still debated,as PVT may represent itself a consequence of liver fibrosis and hepatic dysfunction progression.Anticoagulation and transjugular intrahepatic portosystemic shunt are considered safe and effective in this setting and are recommended in selected cases,even if the safer therapeutic option and the optimal therapy duration are still unknown.Nevertheless,their impact on mortality rates should be addressed more extensively.In this review we present the most debated questions regarding PVT,whose answers should come from prospective cohort studies and large sample-size randomized trials.
文摘Dear Editor,Seed germination is a major developmental transition in a plant＇s life that involves the concerted action of several genetic and physiological pathways （Holdsworth et al., 2008）, and mostly consists of the resumption of embryo growth after a long quiescence imposed during seed maturation. In mature seeds, germination is repressed by abscisic acid （ABA）, while favorable environmental conditions promote gibberellin （GA） biosynthesis and decrease ABA （Holdsworth et al., 2008）. The increase in GA levels is essential for the rupture of testa and endosperm （Lee et al., 2002）. The activation of cell division in the embryo is an integral part of germination that precedes the protrusion of the root through the seed coat. In Arabidopsis, this activation has been linked to significant early changes in the expression of cell-cycle elements （Masubelele et al., 2005）. In the root apical meristem （RAM）, GAs regulate cell divisions （Achard et al., 2009; 0beda-Tomás et al., 2009）. Similarly, the transcription factors （TFs） TEOSINTE BRANCHED1/ CYCLOIDEA/PROLIFERATING CELL FACTOR14 （TCP14） and TCP15 have been proposed to regulate cell proliferation （Kieffer et al., 2011）. Moreover, the activity of TCP14 is necessary to undergo seed germination and, remarkably, seeds lacking this activity are hypersensitive to the negative effects on germination of GA biosynthesis inhibitor paclobutrazol, suggesting a functional relationship between this TF and GAs （Tatematsu et al., 2008）. Taking these observations into account, we hypothesized that TCP14 and TCP15 mediate GA-dependent activation of the cell cycle during germination.
文摘Portal vein thrombosis(PVT) is one of the most common complications occurring during the natural course of liver cirrhosis.Even though PVT is often asymptomatic,the worsening of liver function,an unexpected episode of gastrointestinal bleeding or ascitic decompensation may be landmarks of PVT development.Beyond these clinical manifestations,it is debated whether PVT really has an impact on liver cirrhosis natural history or rather represents only one of its consequences.Probably PVT development should not only be considered as a matter of impaired blood flow or pro-coagulation tendency.On one hand,PVT seems a consequence of the worsening in portal vein outflow due to the increased hepatic resistance in cirrhotic livers.On the other hand,vascular microthrombosis secondary to necroinflammation may cause liver ischemia and infarction,with loss of hepatic tissue(parenchymal extinction) which is replaced by fibrotic tissue.Therefore,PVT might also be considered as the overt manifestation of the liver fibrosing process evolution and anticoagulant therapy may thus have microscopic indirect effects also on the progression of liver disease.At present,a connection between PVT development and the progression of liver fibrosis/cirrhosis has not yet been demonstrated.Nevertheless,it is not clear if PVT development may worsen cirrhotic patients' outcome by itself.Some authors tried to assess liver transplant benefit in PVT cirrhotic patients but data are contrasting.In this review,we will try to answer these questions,providing a critical analysis of data reported in literature.
文摘AIM： To comparatively evaluate the long term efficacy of Rifaximin and dietary fibers in reducing symptoms and/or complication frequency in symptomatic, uncomplicated diverticular disease,METHODS： 307 patients （118 males, 189 females, age range： 40-80 years） were enrolled in the study and randomly assigned to： Rifaximin （400 mg bid for 7 d every month） plus dietary fiber supplementation （at least 20 gr/d） or dietary fiber supplementation alone. The study duration was 24 mo; both clinical examination and symptoms＇ questionnaire were performed every two months. RESULTS： Both treatments reduced symptom frequency, but Rifaximin at a greater extent, when compared to basal values. Symptomatic score declined during both treatments, but a greater reduction was evident in the Rifaximin group （6.4±2.8 and 6.2 ± 2.6 at enrollment, P = NS, 1.0 ±0.7 and 2.4±1.7 after 24 mo, P 〈 0.001, respectively）. Probability of symptom reduction was higher and complication frequency lower （Kaplan-Meyer method） in the Rifaximin group （P 〈 0.0001 and 0.028, respectively）.CONCLUSION： In patients with symptomatic, uncomplicated diverticular disease, cyclic administration of RJfaximin plus dietary fiber supplementation is more effective in reducing both symptom and complication frequency than simple dietary fiber supplementation.Long term administration of the poorly absorbed antibiotic Rifaximin is safe and well tolerated by the patients,confirming the usefulness of this therapeutic strategy in the overall management of diverticular disease.
文摘Several therapeutic procedures have been proposed as bridging treatments for patients with hepatocellular carcinoma(HCC)awaiting liver transplantation(LT).The most used treatments include transarterial chemoembolization and radiofrequency ablation.Surgical resection has also been successfully used as a bridging procedure,and LT should be considered a rescue treatment in patients with previous HCC resection who experience tumor recurrence or post-treatment severe decompensation of liver function.The aims of bridging treatments include decreasing the waiting list dropout rate before transplantation,reducing HCC recurrence after transplantation,and improving post-transplant overall survival.To date,no data from prospective randomized studies are available;however,for HCC patients listed for LT within the Milan criteria,prolonging the waiting time over 6-12 mo is a risk factor for tumor spread.Bridging treatments are useful in containing tumor progression and decreasing dropout.Furthermore,the response to pre-LT treatments may represent a surrogate marker of tumor biological aggressiveness and could therefore be evaluated to prioritize HCC candidates for LT.Lastly,although a definitive conclusion can not be reached,the experiences reported to date suggest a positive impact of these treatments on both tumor recurrence and post-transplant patient survival.Advanced HCC may be downstaged to achieve and maintain the current conventional criteria for inclusion in the waiting list for LT.Recent studies have demonstrated that successfully downstaged patients can achieve a 5-year survival rate comparable to that of patients meeting the conventional criteria without requiring downstaging.
文摘The hypothesis of an important role of gut microbiota in the maintenance of physiological state into the gastrointestinal(GI)system is supported by several studies that have shown a qualitative and quantitative alteration of the intestinal flora in a number of gastrointestinal and extra-gastrointestinal diseases.In the last few years,the importance of gut microbiota impairment in the etiopathogenesis of pathology such as autism,dementia and mood disorder,has been raised.The evidence of the inflammatory state alteration,highlighted in disorders such as schizophrenia,major depressive disorder and bipolar disorder,strongly recalls the microbiota alteration,highly suggesting an important role of the alteration of GI system also in neuropsychiatric disorders.Up to now,available evidences display that the impairment of gut microbiota plays a key role in the development of autism and mood disorders.The application of therapeutic modulators of gut microbiota to autism and mood disorders has been experienced only in experimental settings to date,with few but promising results.A deeper assessment of the role of gut microbiota in the development of autism spectrum disorder(ASD),as well as the advancement of the therapeutic armamentarium for the modulation of gut microbiota is warranted for a better management of ASD and mood disorders.
文摘Nonalcoholic fatty liver disease(NAFLD) is emerging as the most common chronic liver disease, and is characterized by a wide spectrum of fat-liver disorders that can result in severe liver disease and cirrhosis. Inflammation and oxidative stress are the major risk factors involved in the pathogenesis of NAFLD. Currently, there is no consensus concerning the pharmacological treatment of NAFLD. However, lifestyle interventions based on exercise and a balanced diet for quality and quantity, are considered the cornerstone of NAFLD management. Mediterranean diet(MD), rich in polyunsaturated fats, polyphenols, vitamins and carotenoids, with their anti-inflammatory and antioxidant effects, has been suggested to be effective in preventing cardiovascular risk factors. In adults, MD has also been demonstrated to be efficacious in reducing the risk of metabolic syndrome. However, few studies are available on the effects of the MD in both adult and pediatric subjects with NAFLD. Thus, the aims of the present narrative review are to analyze the current clinical evidence on the impact of MD in patients with NAFLD, and to summarize the main mechanisms of action of MD components on this condition.
文摘Antibiotics are usually prescribed to cure infections but they also have significant modulatory effects on the gut microbiota. Several alterations of the intestinal bacterial community have been reported during antibiotic treatment, including the reduction of beneficial bacteria as well as of microbial alpha-diversity. Although after the discontinuation of antibiotic therapies it has been observed a trend towards the restoration of the original condition, the new steady state is different from the previous one, as if antibiotics induced some kind of irreversible perturbation of the gut microbial community. The poorly absorbed antibiotic rifaximin seem to be different from the other antibiotics, because it exerts non-traditional effects additional to the bactericidal/bacteriostatic activity on the gut microbiota. Rifaximin is able to reduce bacterial virulence and translocation, has anti-inflammatory properties and has been demonstrated to positively modulate the gut microbial composition. Animal models, culture studies and metagenomic analyses have demonstrated an increase in Bifidobacterium, Faecalibacterium prausnitzii and Lactobacillus abundance after rifaximin treatment, probably consequent to the induction of bacterial resistance, with no major change in the overall gut microbiota composition. Antibiotics are therefore modulators of the symbiotic relationship between the host and the gut microbiota. Specific antibiotics, such as rifaximin, can also induce eubiotic changes in the intestinal ecosystem; this additional property may represent a therapeutic advantage in specific clinical settings.
基金Contributions from K.C.were supported by the financial assistance award 70NANB19H117 from the U.S.Department of CommerceNational Institute of Standards and Technology+5 种基金E.A.H.and R.C.(CMU)were supported by the National Science Foundation under grant CMMI-1826218the Air Force D3OM2S Center of Excellence under agreement FA8650-19-2-5209A.J.,C.C.,and S.P.O.were supported by the Materials Project,funded by the U.S.Department of Energy,Office of Science,Office of Basic Energy Sciences,Materials Sciences and Engineering Division under contract no,DE-AC02-05-CH11231Materials Project program KC23MP.S.J.L.B.was supported by the U.S.National Science Foundation through grant DMREF-1922234A.A.and A.C.were supported by NIST award 70NANB19H005NSF award CMMI-2053929.
文摘Deep learning(DL)is one of the fastest-growing topics in materials data science,with rapidly emerging applications spanning atomistic,image-based,spectral,and textual data modalities.DL allows analysis of unstructured data and automated identification of features.The recent development of large materials databases has fueled the application of DL methods in atomistic prediction in particular.In contrast,advances in image and spectral data have largely leveraged synthetic data enabled by high-quality forward models as well as by generative unsupervised DL methods.In this article,we present a high-level overview of deep learning methods followed by a detailed discussion of recent developments of deep learning in atomistic simulation,materials imaging,spectral analysis,and natural language processing.For each modality we discuss applications involving both theoretical and experimental data,typical modeling approaches with their strengths and limitations,and relevant publicly available software and datasets.We conclude the review with a discussion of recent cross-cutting work related to uncertainty quantification in this field and a brief perspective on limitations,challenges,and potential growth areas for DL methods in materials science.
文摘Hepatitis B virus(HBV)and hepatitis C virus(HCV)share common mode of transmission and both are able to induce a chronic infection.Dual HBV/HCV chronic coinfection is a fairly frequent occurrence,especially in high endemic areas and among individuals at high risk of parenterally transmitted infections.The intracellular interplay between HBV and HCV has not yet been sufficiently clarified,also due to the lack of a proper in vitro cellular model.Longitudinal evaluation of serum HBV DNA and HCV RNA amounts has revealed that complex virological profiles may be present in coinfected patients.Dual HBV/HCV infection has been associated to a severe course of the liver disease and to a high risk of developing hepatocellular carcinoma.Despite the clinical importance,solid evidence and clear guidelines for treatment of this special population are still lacking.This review summarizes the available data on the virological and clinical features as well as the therapeutic options of the dual HBV/HCV infection,and highlights the aspects that need to be better clarified.
基金supported by the University of Pavia(grants from FR&G 2019,Fondo Ricerca&Giovani,to C.L.).
文摘To date,no vaccines or effective drugs have been approved to prevent or treat COVID-19 and the current standard care relies on supportive treatments.Therefore,based on the fast and global spread of the virus,urgent investigations are warranted in order to develop preventive and therapeutic drugs.In this regard,treatments addressing the immunopathology of SARS-CoV-2 infection have become a major focus.Notably,while a rapid and well-coordinated immune response represents the first line of defense against viral infection,excessive inflammatory innate response and impaired adaptive host immune defense may lead to tissue damage both at the site of virus entry and at systemic level.Several studies highlight relevant changes occurring both in innate and adaptive immune system in COVID-19 patients.In particular,the massive cytokine and chemokine release,the so-called“cytokine storm”,clearly reflects a widespread uncontrolled dysregulation of the host immune defense.Although the prospective of counteracting cytokine storm is compelling,a major limitation relies on the limited understanding of the immune signaling pathways triggered by SARS-CoV-2 infection.The identification of signaling pathways altered during viral infections may help to unravel the most relevant molecular cascades implicated in biological processes mediating viral infections and to unveil key molecular players that may be targeted.Thus,given the key role of the immune system in COVID-19,a deeper understanding of the mechanism behind the immune dysregulation might give us clues for the clinical management of the severe cases and for preventing the transition from mild to severe stages.
文摘The stomach is the most frequently involved site for extranodal lymphomas,accounting for nearly two-thirds of all gastrointestinal cases.It is widely accepted that gastric B-cell,low-grade mucosal-associated lymphoid tissue(MALT)-lymphoma is caused by Helicobacter pylori(H.pylori)infection.MALT-lymphomas may engender different clinical and endoscopic patterns.Often,diagnosis is confirmed in patients with only vague dyspeptic symptoms and without macroscopic lesions on gastric mucosa.H.pylori eradication leads to lymphoma remission in a large number of patients when treatment occurs at an early stage(Ⅰ-Ⅱ1).Neoplasia confined to the submucosa,localized in the antral region of the stomach,and without API2-MALT1 translocation,shows a high probability of remission following H.pylori eradication.When both bacterial infection and lymphoma recur,further eradication therapy is generally effective.Radiotherapy,chemotherapy and,in selected cases,surgery are the available therapeutic options with a high success rate for those patients who fail to achieve remission,while data on immunotherapy with monoclonal antibodies (rituximab)are still scarce.The 5-year survival rate is higher than 90%,but careful,long-term follow-up is required in these patients since lymphoma recurrence has been reported in some cases.
