Effect of Jianpi Xiaowei Decoction on Gastric Function and Quality of Life in Elderly Patients with Chronic Atrophic Gastritis of Liver-Stomach Stagnation Heat Type

[Objectives]To observe the effect of Jianpi Xiaowei Decoction on gastric function and quality of life in elderly patients with chronic atrophic gastritis(CAG)of liver-stomach heat stagnation type.[Methods]Seventy-two elderly patients with CAG of liver-stomach stagnation-heat type were randomly divided into study group and control group.The two groups were treated with Jianpi Xiaowei Decoction and Rabeprazole Enteric-coated Tablets respectively.The curative effect of TCM syndromes,serum pepsinogen I and II(PG-I and PG-II),gastrin-17(G-17)and quality of life(SF-36 table)scores of gastric function indicators before and after treatment were observed.[Results]After treatment,the total effective rate of the study group was 97.22%(35/36),which was significantly higher than that of the control group 77.78%(28/36)(P<0.05).Before treatment,there was no significant difference in the levels of gastric function indicators between the two groups(P>0.05).After treatment,the indicators of the study group were significantly lower than those of the control group(t=12.239,6.010,5.928,10.420,P<0.05).Before treatment,there was no significant difference in SF-36 scores between the two groups(P>0.05).After treatment,the SF-36 scores in the study group were significantly lower than those in the control group(t=3.520,10.335,11.300,9.693,P<0.05).[Conclusions]Jianpi Xiaowei Decoction can achieve significant curative effect in the treatment of CAG with liver and stomach stagnation heat type in the elderly,and can significantly improve the key gastrointestinal hormone levels and quality of life of elderly patients.It is worthy of promotion in the same clinical cases.

Silymarin in non alcoholic fatty liver disease

AIM: This study was undertaken to evaluate the hepatic effects of silybum marianum on non alcoholic fatty liver disease (NAFLD). METHODS: In 72 patients affected by NAFLD, main metabolic, hepatic and anti-inflammatory parameters were assayed after 3 mo of a restricted diet and before silymarin treatment (twice a day orally). The brightness of liver echography texture (hepatorenal ratio brightness) was also defined at same time. These evaluations were repeated after 6 mo of treatment. RESULTS: Serum levels of some metabolic and anti-inflammatory data nonsignificantly lowered after 6 mo of silymarin. On the contrary, Steato test, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase were significantly (P < 0.001) reduced. Instead, the AST/ALT ratio unchanged. Finally, the hepatorenal brightness ratio, as an index of hepatic steatosis, significantly (P < 0.05) dropped. CONCLUSION: The obtained results indicate that silymarin appears to be effective to reduce the biochemical, inflammatory and ultrasonic indices of hepatic steatosis. Some parameters indicative of early stage of atherosclerosis were also lowered.

An enriched environment promotes synaptic plasticity and cognitive recovery after permanent middle cerebral artery occlusion in mice

Cerebral ischemia activates an endogenous repair program that induces plastic changes in neurons. In this study, we investigated the effects of environmental enrichment on spatial learning and memory as well as on synaptic remodeling in a mouse model of chronic cerebral ischemia, produced by subjecting adult male C57 BL/6 mice to permanent left middle cerebral artery occlusion. Three days postoperatively, mice were randomly assigned to the environmental enrichment and standard housing groups. Mice in the standard housing group were housed and fed a standard diet. Mice in the environmental enrichment group were housed in a cage with various toys and fed a standard diet. Then, 28 days postoperatively, spatial learning and memory were tested using the Morris water maze. The expression levels of growth-associated protein 43, synaptophysin and postsynaptic density protein 95 in the hippocampus were analyzed by western blot assay. The number of synapses was evaluated by electron microscopy. In the water maze test, mice in the environmental enrichment group had a shorter escape latency, traveled markedly longer distances, spent more time in the correct quadrant(northeast zone), and had a higher frequency of crossings compared with the standard housing group. The expression levels of growth-associated protein 43, synaptophysin and postsynaptic density protein 95 were substantially upregulated in the hippocampus in the environmental enrichment group compared with the standard housing group. Furthermore, electron microscopy revealed that environmental enrichment increased the number of synapses in the hippocampal CA1 region. Collectively, these findings suggest that environmental enrichment ameliorates the spatial learning and memory impairment induced by permanent middle cerebral artery occlusion. Environmental enrichment in mice with cerebral ischemia likely promotes cognitive recovery by inducing plastic changes in synapses.

Team players in the pathogenesis of metabolic dysfunctionsassociated steatotic liver disease:The basis of development of pharmacotherapy

Nutrient metabolism is regulated by several factors.Social determinants of health with or without genetics are the primary regulator of metabolism,and an unhealthy lifestyle affects all modulators and mediators,leading to the adaptation and finally to the exhaustion of cellular functions.Hepatic steatosis is defined by presence of fat in more than 5%of hepatocytes.In hepatocytes,fat is stored as triglycerides in lipid droplet.Hepatic steatosis results from a combination of multiple intracellular processes.In a healthy individual nutrient metabolism is regulated at several steps.It ranges from the selection of nutrients in a grocery store to the last step of consumption of ATP as an energy or as a building block of a cell as structural component.Several hormones,peptides,and genes have been described that participate in nutrient metabolism.Several enzymes participate in each nutrient metabolism as described above from ingestion to generation of ATP.As of now several publications have revealed very intricate regulation of nutrient metabolism,where most of the regulatory factors are tied to each other bidirectionally,making it difficult to comprehend chronological sequence of events.Insulin hormone is the primary regulator of all nutrients’metabolism both in prandial and fasting states.Insulin exerts its effects directly and indirectly on enzymes involved in the three main cellular function processes;metabolic,inflammation and repair,and cell growth and regeneration.Final regulators that control the enzymatic functions through stimulation or suppression of a cell are nuclear receptors in especially farnesoid X receptor and peroxisome proliferator-activated receptor/RXR ligands,adiponectin,leptin,and adiponutrin.Insulin hormone has direct effect on these final modulators.Whereas blood glucose level,serum lipids,incretin hormones,bile acids in conjunction with microbiota are intermediary modulators which are controlled by lifestyle.The purpose of this review is to overview the key players in the pathogenesis of metabolic dysfunction-associated steatotic liver disease(MASLD)that help us understand the disease natural course,risk stratification,role of lifestyle and pharmacotherapy in each individual patient with MASLD to achieve personalized care and target the practice of precision medicine.PubMed and Google Scholar databases were used to identify publication related to metabolism of carbohydrate and fat in states of health and disease states;MASLD,cardiovascular disease and cancer.More than 1000 publications including original research and review papers were reviewed.

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.

Improving the radiological diagnosis of hepatic artery thrombosis after liver transplantation: Current approaches and future challenges

Hepatic artery thrombosis(HAT)is a devastating vascular complication following liver transplantation,requiring prompt diagnosis and rapid revascularization treatment to prevent graft loss.At present,imaging modalities such as ultrasound,computed tomography,and magnetic resonance play crucial roles in diagnosing HAT.Although imaging techniques have improved sensitivity and specificity for HAT diagnosis,they have limitations that hinder the timely diagnosis of this complication.In this sense,the emergence of artificial intelligence(AI)presents a transformative opportunity to address these diagnostic limitations.The development of machine learning algorithms and deep neural networks has demonstrated the potential to enhance the precision diagnosis of liver transplant complications,enabling quicker and more accurate detection of HAT.This article examines the current landscape of imaging diagnostic techniques for HAT and explores the emerging role of AI in addressing future challenges in the diagnosis of HAT after liver transplant.

Spontaneous Paravesical and Broad Ligament Hematoma after Vaginal Delivery Had Uterine Artery Embolization after Evacuating the Hematoma

Broad ligament hematoma is typically seen during cesarean section due to rupture of branches of uterine and vaginal vessels and it’s rare to be seen post-normal vaginal delivery. Addressing puerperal hematomas postpartum presents considerable challenges for obstetric care providers. While hematomas such as those affecting the vulva, vulvovaginal region, or paravaginal area are frequently encountered, retroperitoneal hematomas are rare and notably pose a greater risk to the life of the patient. The medical literature contains scant case reports on retroperitoneal hematomas, with no consensus on a definitive treatment approach. Pelvic arterial embolization has emerged as both a sensible and increasingly preferred method for treating these hematomas recently, but its application is contingent upon the patient maintaining hemodynamic stability and the availability of a specialized interventional embolization unit. In our case, we are presenting a very rare case of a 31-year-old primigravida female with a history of in vitro fertilization pregnancy. She delivered a normal vaginal delivery at 31 weeks gestation. Unfortunately, she experienced multiple complications intrapartum, including preeclampsia and placental abruption. These complications increased her risk of developing a broad ligament hematoma.

Relevance of ADAMTS13 to liver transplantation and surgery

A disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13(ADAMTS13) specifically cleaves unusually-large von Willebrand factor(VWF) multimers under high shear stress,and down-regulates VWF function to form platelet thrombi.Deficiency of plasma ADAMTS13 activity induces a life-threatening systemic disease,termed thrombotic microangiopathy(TMA) including thrombotic thrombocytopenic purpura(TTP).Children with advanced biliary cirrhosis due to congenital biliary atresia sometimes showed pathological features of TMA,with a concomitant decrease of plasma ADAMTS13 activity.Disappearance of their clinical findings of TTP after successful liver transplantation suggested that the liver is a major organ producing plasma ADAMTS13.In situ hybridization analysis showed that ADAMTS13 was produced by hepatic stellate cells.Subsequently,it was found that ADADTS13 was not merely responsible to development of TMA and TTP,but also related to some kinds of liver dysfunction after liver transplantation.Ischemia-reperfusion injury and acute rejection in liver transplant recipients were often associated with marked decrease of ADAMTS13 and concomitant formation of unusually large VWF multimers without findings of TMA/TTP.The similar phenomenon was observed also in patients who underwent hepatectomy for liver tumors.Imbalance between ADAMTS13 and VWF in the hepatic sinusoid might cause liver damage due to microcirculatory disturbance.It can be called as "local TTP like mechanism" which plays a crucial role in liver dysfunction after liver transplantation and surgery.

Update in lean metabolic dysfunction-associated steatotic liver disease

BACKGROUND A new nomenclature consensus has emerged for liver diseases that were previously known as non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated fatty liver disease(MAFLD).They are now defined as metabolic dysfunction-associated steatotic liver disease(MASLD),which includes cardiometabolic criteria in adults.This condition,extensively studied in obese or overweight patients,constitutes around 30%of the population,with a steady increase worldwide.Lean patients account for approximately 10%-15%of the MASLD population.However,the pathogenesis is complex and is not well understood.AIM To systematically review the literature on the diagnosis,pathogenesis,characteristics,and prognosis in lean MASLD patients and provide an interpretation of these new criteria.METHODS We conducted a comprehensive database search on PubMed and Google Scholar between January 2012 and September 2023,specifically focusing on lean NAFLD,MAFLD,or MASLD patients.We include original articles with patients aged 18 years or older,with a lean body mass index categorized according to the World Health Organization criteria,using a cutoff of 25 kg/m2 for the general population and 23 kg/m2 for the Asian population.RESULTS We include 85 studies in our analysis.Our findings revealed that,for lean NAFLD patients,the prevalence rate varied widely,ranging from 3.8%to 34.1%.The precise pathogenesis mechanism remained elusive,with associations found in genetic variants,epigenetic modifications,and adaptative metabolic response.Common risk factors included metabolic syndrome,hypertension,and type 2 diabetes mellitus,but their prevalence varied based on the comparison group involving lean patients.Regarding non-invasive tools,Fibrosis-4 index outperformed the NAFLD fibrosis score in lean patients.Lifestyle modifications aided in reducing hepatic steatosis and improving cardiometabolic profiles,with some medications showing efficacy to a lesser extent.However,lean NAFLD patients exhibited a worse prognosis compared to the obese or overweight counterpart.CONCLUSION MASLD is a complex disease comprising epigenetic,genetic,and metabolic factors in its pathogenesis.Results vary across populations,gender,and age.Limited data exists on clinical practice guidelines for lean patients.Future studies employing this new nomenclature can contribute to standardizing and generalizing results among lean patients with steatotic liver disease.

Role of gut-liver axis and glucagon-like peptide-1 receptor agonists in the treatment of metabolic dysfunction-associated fatty liver disease

Metabolic dysfunction-associated fatty liver disease(MAFLD)is a hepatic manifestation of the metabolic syndrome.It is one of the most common liver diseases worldwide and shows increasing prevalence rates in most countries.MAFLD is a progressive disease with the most severe cases presenting as advanced fibrosis or cirrhosis with an increased risk of hepatocellular carcinoma.Gut microbiota play a significant role in the pathogenesis and progression of MAFLD by disrupting the gut-liver axis.The mechanisms involved in maintaining gut-liver axis homeostasis are complex.One critical aspect involves preserving an appropriate intestinal barrier permeability and levels of intestinal lumen metabolites to ensure gutliver axis functionality.An increase in intestinal barrier permeability induces metabolic endotoxemia that leads to steatohepatitis.Moreover,alterations in the absorption of various metabolites can affect liver metabolism and induce liver steatosis and fibrosis.Glucagon-like peptide-1 receptor agonists(GLP-1 RAs)are a class of drugs developed for the treatment of type 2 diabetes mellitus.They are also commonly used to combat obesity and have been proven to be effective in reversing hepatic steatosis.The mechanisms reported to be involved in this effect include an improved regulation of glycemia,reduced lipid synthesis,β-oxidation of free fatty acids,and induction of autophagy in hepatic cells.Recently,multiple peptide receptor agonists have been introduced and are expected to increase the effectiveness of the treatment.A modulation of gut microbiota has also been observed with the use of these drugs that may contribute to the amelioration of MAFLD.This review presents the current understanding of the role of the gutliver axis in the development of MAFLD and use of members of the GLP-1 RA family as pleiotropic agents in the treatment of MAFLD.

Effects of resveratrol in experimental and clinical non-alcoholic fatty liver disease

The prevalence of obesity and related conditions like non-alcoholic fatty liver disease(NAFLD) is increasing worldwide and therapeutic options are limited.Alternative treatment options are therefore intensively sought after.An interesting candidate is the natural polyphenol resveratrol(RSV) that activates adenosinmonophosphate-activated protein kinase(AMPK) and silent information regulation-2 homolog 1(SIRT1).In addition,RSV has known anti-oxidant and anti-inflammatory effects.Here,we review the current evidence for RSVmediated effects on NAFLD and address the different aspects of NAFLD and non-alcoholic steatohepatitis(NASH) pathogenesis with respect to free fatty acid(FFA) flux from adipose tissue,hepatic de novo lipogenesis,inadequate FFA β-oxidation and additional intra- and extrahepatic inflammatory and oxidant hits.We review the in vivo evidence from animal studies and clinical trials.The abundance of animal studies reports a decrease in hepatic triglyceride accumulation,liver weight and a general improvement in histological fatty liver changes,along with a reduction in circulating insulin,glucose and lipid levels.Some studies document AMPK or SIRT1 activation,and modulation of relevant markers of hepatic lipogenesis,inflammation and oxidation status.However,AMPK/SIRT1-independent actions are also likely.Clinical trials are scarce and have primarily been performed with a focus on overweight/obese participants without a focus on NAFLD/NASH and histological liver changes.Future clinical studies with appropriate design are needed to clarify the true impact of RSV treatment in NAFLD/NASH patients.

Studies on mechanism of Sialy Lewis-X antigen in liver metastases of human colorectal carcinoma

INTRODUCTIONSialyl Lewis-X antigen ,correlated with carcinoma, is a group of carbohydrate antigen containing oligosaccharide expressed of embryonic tisue and glycoproteins on cell surface of embryonic tissue[1].The SLeX antigen located on cell surface is synthesized principally by two enzymes ,al ,3fucosyltransfrease and a2, 3sialyctransferase.In adults ,SLeX antigen is expressed principally on the surfaces of granulocytic cells and some tumor cells .

BioLiverⅠ型生物人工肝支持系统治疗两种急性肝衰竭犬的实验研究

目的评价BioLiver-Ⅰ型生物人工肝支持系统(BALSS)治疗两种急性肝衰竭(ALF)犬的效应.方法采用多次皮下注射醋氨酚的方法建立急性药物中毒ALF模型犬;应用手术切除80%的肝脏建立少肝ALF犬模型.分离中国实验用小型猪肝细胞并培养于BALSS中,对两种ALF犬进行6h的交叉灌流,观察治疗前后犬生理、生化和组织学的变化.结果注射醋氨酚48h后可建立ALF犬模型,模型成功率为63.3%;肝大部分切除手术后24h可建立ALF模型,模型成功率为84.2%.应用作者改进的酶消化法,从每只小型猪的肝脏平均可获得(1.0～3.0)×1010个肝细胞且存活率较高.应用BioLiver-Ⅰ型BALSS对两种ALF犬进行治疗后,相关的血液生化指标明显改善,肝脏的病理损伤得以修复.药物诱发的ALF犬长期存活率高于手术组.BALSS治疗对其他脏器无明显损伤.结论 BioLiver-Ⅰ型BALSS能够安全有效地为两种ALF犬提供肝功能支持,可望成为救治ALF的重要方法.

Prediction of hepatic artery occlusion after liver transplantation by ultrasound characteristics and clinical risk factors

BACKGROUND Hepatic artery occlusion(HAO)after liver transplantation(LT)is a devastating complication,resulting in early graft loss and reduced overall survival.Ultra-sound is an established assessment method for HAO in patients following LT,especially those with complex hepatic artery reconstruction.METHODS We retrospectively analyzed the ultrasound characteristics and the clinic risk factors associated with HAO in 400 adult LT patients who were enrolled and treated at the Third People's Hospital of Shenzhen between November 2016 and July 2022.Fourteen patients diagnosed with acute HAO(A-HAO)by surgery and fifteen diagnosed with chronic HAO(C-HAO)were included.A control group of 33 patients without HAO complications during the same period were randomly selected using a random number table.All patients underwent an ultrasono-graphy examination.Parameters including resistance index(RI),peak systolic velocity(PSV),and portal vein velocity(PVV)were compared across the groups.Additionally,basic clinical data were collected for all patients,including gender,age,primary diagnosis,D-dimer concentration,total operation time,cold ischemia time,hot ischemia time,intraoperative blood loss and transfusion,intraoperative urine volume,infusion,model for end-stage liver disease(MELD)score,and whether complex hepatic artery reconstructions were performed.Furthermore,risk factors influencing HAO formation after LT were analyzed.RESULTS Compared to the non-HAO group,PVV and RI were higher in the A-HAO group,while PSV was lower.Conversely,both PSV and RI were lower in the C-HAO group compared to the non-HAO group.The proportion of patients undergoing complex hepatic artery reconstructions and the gamma-glutamyltransferase(GGT)level before occlusion were significantly higher in the A-HAO group compared to the non-HAO group.However,there were no distinct differences between the two groups in D-dimer,MELD score,pre-occlusion alanine transaminase and aspartate transaminase levels,or intraoperative conditions.CONCLUSION Ultrasound features of the hepatic artery before occlusion are significantly associated with postoperative HAO development.Additionally,complex hepatic artery reconstructions,defined as revascularization of the graft requiring additional anastomosis between donor hepatic arteries,constitute a risk factor for A-HAO.Besides,abnormal pre-occlusion GGT elevation is an important biochemical indicator.Therefore,ultrasound examination serves as an important tool for screening HAO,especially in patients with the identified risk factors.

Successful treatment of acute liver failure due to Wilson’s disease: Serendipity or fortuity?

BACKGROUND Acute liver failure(ALF)may be the first and most dramatic presentation of Wilson’s disease(WD).ALF due to WD(WD-ALF)is difficult to distinguish from other causes of liver disease and is a clear indication for liver transplantation.There is no firm recommendation on specific and supportive medical treatment for this condition.AIM To critically evaluate the diagnostic and therapeutic management of WD-ALF patients in order to improve their survival with native liver.METHODS A retrospective analysis of patients with WD-ALF was conducted in two pediatric liver units from 2018 to 2023.RESULTS During the study period,16 children(9 males)received a diagnosis of WD and 2 of them presented with ALF.The first was successfully treated with an unconventional combination of low doses of D-penicillamine and zinc plus steroids,and survived without liver transplant.The second,exclusively treated with supportive therapy,needed a hepatotransplant to overcome ALF.CONCLUSION Successful treatment of 1 WD-ALF patient with low-dose D-penicillamine and zinc plus steroids may provide new perspectives for management of this condition,which is currently only treated with liver transplantation.

Liver as a new target organ in Alzheimer's disease:insight from cholesterol metabolism and its role in amyloid-beta clearance

Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primary characteristic of Alzheimer's disease in the central nervous system and peripheral organs,targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer's disease treatment.Metabolic abnormalities are commonly observed in patients with Alzheimer's disease.The liver is the primary peripheral organ involved in amyloid-beta metabolism,playing a crucial role in the pathophysiology of Alzheimer's disease.Notably,impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer's disease.In this review,we explore the underlying causes of Alzheimer's disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol metabolism.Furthermore,we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer's disease.

Parasites of the liver:A global problem?

Parasitic liver diseases can be caused by trematodes,cestodes,nematodes,and protozoa.This pathology is significant because millions of people in different parts of the world have liver parasites,which can manifest themselves in the development of inflammation,liver cysts,cholecystitis,cholelithiasis,pancreatitis and liver cirrhosis that are often threatening their lives.The International Agency for Research on Cancer considers three species of trematodes,Schistosoma haematobium,Opisthorchis viverrini and Clonorchis sinensis,to be carcinogens.Complex modern examination methods,in some cases including extensive screening of large populations,are required for diagnosing liver parasites.Treatment of parasitic liver diseases is differentiated and can involve a combination of surgical and therapeutic measures.There is no doubt that the clinical and epidemiological scale allows one to regard parasitic liver diseases as a global healthcare problem.

Treatment of Atherosclerotic Disease of the Femoral Artery: Randomized Controlled Trials and Meta-Analyses. Should You Be Sceptical?

A narrative review of the data provided by Randomised Controlled clinical trials and meta-analyses was undertaken to assess how much reliance a clinician could place on these in selecting a treatment for patients with disease of the Femoral artery. An attempt was made to detect and review every clinical trial and meta-analysis published on treatments relating to disease of the femoral artery but not relating to drug treatment. Disease of the femoral artery in >65 years age group occurs in approximately 20% of the population but symptomatology was present in 40%. In almost all trials the predominant (>90%) indication for treatment was intermittent claudication. In this setting, clinical benefit was limited and did not extend beyond 12 months. Mortality, from co-morbidities was high. The Basil Trial was the only one to examine intervention for critical limb ischemia. The results for Bypass surgery and Percutaneous transarterial balloon angioplasty (PTA) were equivalent. There is little evidence to support the use of PTA or stenting other than in the treatment of patients with critical limb ischemia.

Giant saphenous vein graft pseudoaneurysm to right posterior descending artery presenting with superior vena cava syndrome

Saphenous vein grafts(SVG) pseudoaneurysms,especially giant ones,are rare and occur as a late complication of coronary artery bypass grafting. This condition affects both genders and typically occurs within the sixth decade of life. The clinical presentation ranges from an asymptomatic incidental finding on imaging studies to new onset angina,dyspnea,myocardial infarction or symptoms related to compression of neighboring structures. An 82-year-old woman presented with acute onset back pain,dyspnea and was noted to have significantly engorged neck veins. In the emergency department,a chest computed tomographic angiogram with intravenous contrast revealed a ruptured giant bilobed SVG pseudoaneurysm to the right posterior descending artery(RPDA). This imaging modality also demonstrated compression of the superior vena cava(SVC) by the SVG pseudoaneurysm. Coronary angiogram with bypass study was performed to establish the patency of this graft. Endovascular coiling and embolization of the SVG to RPDA was initially considered but disfavored after the coronary angiogram revealed preserved flow from the graft to this arterial branch. After reviewing the angiogram films,a surgical strategy was favored over a percutaneous intervention with a Nitinol self-expanding stent since the latter would have not addressed the superior vena cava compression caused by the giant pseudoaneurysm. Intraoperative transesophageal echocardiogram demonstrated SVCcompression by the giant pseudoaneurysm cranial lobe. Our patient underwent surgical ligation and excision of the giant pseudoaneurysm and the RPDA was regrafted successfully. In summary,saphenous vein grafts pseudoaneurysms can be life-threatening and its therapy should be guided based on the presence of mechanical complications,the patency of the affected vein graft and the involved myocardial territory viability.

Adeno-associated virus mediated endostatin gene therapy in combination with topoisomerase inhibitor effectively controls liver tumor in mouse model

AIM:rAAV mediated endostatin gene therapy has been examined as a new method for treating cancer.However, a sustained and high protein delivery is required to achieve the desired therapeutic effects.We evaluated the impact of topoisomerase inhibitors in rAAV delivered endostatin gene therapy in a liver tumor model. METHODS:rAAV containing endostatin expression cassettes were transduced into hepatoma cell lines.To test whether the topoisomerase inhibitor pretreatment increased the expression of endostatin,Western blotting and ELISA were performed.The biologic activity of endostatin was confirmed by endothelial cell proliferation and tube formation assays. The anti-tumor effects of the rAAV-endostatin vector combined with a topoisomerase inhibitor,etoposide,were evaluated in a mouse liver tumor model. RESULTS:Topoisomerase inhibitors,including camptothecin and etoposide,were found to increase the endostatin exPression level in vitro.The over-expressed endostatin, as a result of pretreatment with a topoisomerase inhibitor, was also biologically active.In animal experiments,the combined therapy of topoisomerase inhibitor,etoposide with the rAAV-endostatin vector had the best tumor- suppressive effect and tumor foci were barely observed in livers of the treated mice.Pretreatment with an etoposide increased the level of endostatin in the liver and serum of rAAV-endostatin treated mice.Finally,the mice treated With rAAV-endostatin in combination with etoposide showed the longest survival among the experimental models. CONCLUSION:rAAV delivered endostatin gene therapy in combination with a topoisomerase inhibitor pretreatment is an effective modality for anticancer gene therapy.