Impact of apolipoprotein E isoforms on sporadic Alzheimer's disease:beyond the role of amyloid beta

The impact of apolipoprotein E(ApoE)isoforms on sporadic Alzheimer's disease has long been studied;however,the influences of apolipoprotein E gene(APOE)on healthy and pathological human brains are not fully understood.ApoE exists as three common isoforms(ApoE2,ApoE3,and ApoE4),which differ in two amino acid residues.Traditionally,ApoE binds cholesterol and phospholipids and ApoE isoforms display diffe rent affinities for their receptors,lipids transport and distribution in the brain and periphery.The role of ApoE in the human depends on ApoE isoforms,brain regions,aging,and neural injury.APOE E4 is the strongest genetic risk factor for sporadic Alzheimer's disease,considering its role in influencing amyloid-beta metabolism.The exact mechanisms by which APOE gene variants may increase or decrease Alzheimer's disease risk are not fully understood,but APOE was also known to affect directly and indirectly tau-mediated neurodegeneration,lipids metabolism,neurovascular unit,and microglial function.Consistent with the biological function of ApoE,ApoE4 isoform significantly alte red signaling pathways associated with cholesterol homeostasis,transport,and myelination.Also,the rare protective APOE variants confirm that ApoE plays an important role in Alzheimer's disease pathogenesis.The objectives of the present mini-review were to describe classical and new roles of various ApoE isoforms in Alzheimer's disease pathophysiology beyond the deposition of amyloid-beta and to establish a functional link between APOE,brain function,and memory,from a molecular to a clinical level.APOE genotype also exerted a heterogeneous effect on clinical Alzheimer's disease phenotype and its outcomes.Not only in learning and memory but also in neuro psychiatric symptoms that occur in a premorbid condition.Cla rifying the relationships between Alzheimer's disease-related pathology with neuropsychiatric symptoms,particularly suicidal ideation in Alzheimer's disease patients,may be useful for elucidating also the underlying pathophysiological process and its prognosis.Also,the effects of anti-amyloid-beta drugs,recently approved for the treatment of Alzheimer's disease,could be influenced by the APOE genotype.

Prediction,prevention and management of gastroesophageal reflux after per-oral endoscopic myotomy:An update

Achalasia cardia,the most prevalent primary esophageal motility disorder,is predominantly characterized by symptoms of dysphagia and regurgitation.The principal therapeutic approaches for achalasia encompass pneumatic dilatation(PD),Heller's myotomy,and the more recent per-oral endoscopic myotomy(POEM).POEM has been substantiated as a safe and efficacious modality for the management of achalasia.Although POEM demonstrates superior efficacy compared to PD and an efficacy parallel to Heller's myotomy,the incidence of gastroesophageal reflux disease(GERD)following POEM is notably higher than with the aforementioned techniques.While symptomatic reflux post-POEM is relatively infrequent,the significant occurrence of erosive esophagitis and heightened esophageal acid exposure necessitates vigilant monitoring to preclude long-term GERD-related complications.Contemporary advancements in the field have enhanced our comprehension of the risk factors,diagnostic methodologies,preventative strategies,and therapeutic management of GERD subsequent to POEM.This review focuses on the limitations inherent in the 24-h pH study for evaluating post-POEM reflux,potential modifications in the POEM technique to mitigate GERD risk,and the strategies for managing reflux following POEM.

Bridging the gap:Unveiling the crisis of physical inactivity in inflammatory bowel diseases

In this editorial we comment on the article titled“Inflammatory bowel diseases patients suffer from significant low levels and barriers to physical activity:The BE-FIT-IBD study”published in a recent issue of the World Journal of Gastroen-terology 2023;29(41):5668-5682.Inflammatory bowel diseases(IBD)are emerging as a significant global health concern as their incidence continues to rise on a global scale,with detrimental impacts on quality of life.While many advances have been made regarding the management of the disease,physical inactivity in these patients represents an underexplored issue that may hold the key for further and better understanding the ramifications of IBD.Chronic pain,fatigue,and fear of exacerbating symptoms promotes physical inactivity among IBD patients,while the lack of clear guidelines on safe exercise regimens contributes to a norm of physical inactivity.Physical activity(PA)is accepted to have a positive effect on disease outcomes and quality of life,while inactivity exacerbates comorbidities like cardiovascular disease and mental health disorders.The“BE-FIT-IBD”study,focusing on PA levels and barriers in IBD patients of Southern Italy,revealed that a significant proportion(42.9%)were physically inactive.This lack of PA is attributed to barriers such as fear of flare-ups and misconceptions about exercise exacerbating the disease.The study also highlighted the need for better communication between healthcare providers and patients regarding the benefits of PA and safe incorporation into lifestyles.Moreover,physical inactivity may also contribute to disability in IBD patients,having a great impact on employment status.Of note is the fact that IBD also comes with an important psychological burden with relevant evidence suggesting that regular PA can improve mood,reduce anxiety,and enhance mental health.The“BE-FIT-IBD”study advocated for the integration of PA into IBD management,emphasizing the bidirectional link between PA and IBD.Regular exercise can influence the course of IBD,potentially reducing symptom severity and prolonging remission periods.As such,it is mandatory that healthcare providers actively educate patients,dispel misconceptions,and tailor exercise recommendations to improve the quality of life and reduce IBD-related complications.

The outcomes and safety of patients undergoing endoscopic retrograde cholangiopancreatography combining a single-use cholangioscope and a single-use duodenoscope:A multicenter retrospective international study

Background: Duodenoscope-related multidrug-resistant organism(MDRO) infections raise concerns. Disposable duodenoscopes have been recently introduced in the market and approved by regulatory agencies with the aim to reduce the risk of endoscopic retrograde cholangiopancreatography(ERCP) associated infections. The aim of this study was to evaluate the outcome of procedures performed with single-use duodenoscopes in patients with clinical indications to single-operator cholangiopancreatoscopy. Methods: This is a multicenter international, retrospective study combining all patients who underwent complex biliopancreatic interventions using the combination of a single-use duodenoscope and a single-use cholangioscope. The primary outcome was technical success defined as ERCP completion for the intended clinical indication. Secondary outcomes were procedural duration, rate of cross-over to reusable duodenoscope, operator-reported satisfaction score(1 to 10) on performance rating of the single-use duodenoscope, and adverse event(AE) rate. Results: A total of 66 patients(26, 39.4% female) were included in the study. ERCP was categorized according to ASGE ERCP grading system as 47(71.2%) grade 3 and 19(28.8%) grade 4. The technical success rate was 98.5%(65/66). Procedural duration was 64(interquartile range 15-189) min, cross-over rate to reusable duodenoscope was 1/66(1.5%). The satisfaction score of the single-use duodenoscope classified by the operators was 8.6 ± 1.3 points. Four patients(6.1%) experienced AEs not directly related to the single-use duodenoscope, namely 2 post-ERCP pancreatitis(PEP), 1 cholangitis and 1 bleeding.Conclusions: Single-use duodenoscope is effective, reliable and safe even in technically challenging procedures with a non-inferiority to reusable duodenoscope, making these devices a viable alternative to standard reusable equipment.

Dietary Green Tea Extract and Antioxidants Improve Insulin Secretory Functions of Pancreatic β-Cells in Mild and Severe Experimental Rodent Model of Chronic Pancreatitis

Chronic pancreatitis (CP) is a progressive inflammatory disorder of the pancreas. It is predominantly idiopathic (with an unknown cause) in India and mostly due to alcohol in the West. Diabetes that occur secondary to chronic pancreatitis (T3c Diabetes) is often brittle, and is difficult to attain normoglycemia with conventional treatment requiring multiple doses of insulin. Mild and severe model of CP was induced in mice by repeated intraperitoneal injections of cerulein and L-arginine respectively with an intent to study islet dysfunction and develop therapeutic strategy in animal models of CP. Dietary intervention of epigallocatechin-3-gallate (EGCG) was tested in both the models of CP for its beneficial effects on insulin secretory functions. Pancreata collected upon euthanasia were used to study alterations in the morphology of pancreatic parenchyma and inflammation by staining with H&E and fibrotic changes by Masson’s trichrome and picrosirius staining. Insulin secretory functions of islets were evaluated to test the efficacy of the dietary intervention on β-cell functions. Intraperitoneal glucose tolerance test was performed to monitor the glucose homeostasis before and after the dietary intervention. Both the models resulted in CP with dispersed acini, inflammation and fibrosis. The loss of acini and extent of fibrosis was more in L-arginine model. 2-fold improvement in glucose-stimulated insulin secretory functions of islets was observed with 0.5% EGCG dietary intervention in cerulein model of CP and 1.6-fold in L-arginine model of CP. A further improvement in insulin secretion by 3.2-fold was observed with additional dietary supplements like N-acetyl cysteine, curcumin in combination with EGCG. Our results thus demonstrate and highlight the therapeutic potential of dietary green tea (EGCG) supplementation in reversing islet dysfunction and improving glucose homeostasis in experimental chronic pancreatitis in mice.

Scope and caveats:Artificial intelligence in gastroenterology

The use of Artificial intelligence(AI)has evolved from its mid-20th century origins to playing a pivotal tool in modern medicine.It leverages digital data and computational hardware for diverse applications,including diagnosis,prognosis,and treatment responses in gastrointestinal and hepatic conditions.AI has had an impact in diagnostic techniques,particularly endoscopy,ultrasound,and histopathology.AI encompasses machine learning,natural language processing,and robotics,with machine learning being central.This involves sophisticated algorithms capable of managing complex datasets,far surpassing traditional statistical methods.These algorithms,both supervised and unsupervised,are integral for interpreting large datasets.In liver diseases,AI's non-invasive diagnostic applications,particularly in non-alcoholic fatty liver disease,and its role in characterizing hepatic lesions is promising.AI aids in distinguishing between normal and cirrhotic livers and improves the accuracy of lesion characterization and prognostication of hepatocellular carcinoma.AI enhances lesion identification during endoscopy,showing potential in the diagnosis and management of early-stage esophageal carcinoma.In peptic ulcer disease,AI technologies influence patient management strategies.AI is useful in colonoscopy,particularly in detecting smaller colonic polyps.However,its applicability in nonacademic settings requires further validation.Addressing these issues is vital for harnessing the potential of AI.In conclusion,while AI offers transformative possibilities in gastroenterology,careful integration and balancing of technical possibilities with ethical and practical application,is essential for optimal use.

Diagnostic value of conventional endoscopic ultrasound for lymph node metastasis in upper gastrointestinal neoplasia:A metaanalysis

BACKGROUND Upper gastrointestinal neoplasia mainly includes esophageal cancer and gastric cancer,both of which have high morbidity and mortality.Lymph node metastasis(LNM),as the most common metastasis mode of both diseases,is an important factor affecting tumor stage,treatment strategy and clinical prognosis.As a new fusion technology,endoscopic ultrasound(EUS)is becoming increasingly used in the diagnosis and treatment of digestive system diseases,but its use in detecting LNM in clinical practice remains limited.AIM To evaluate the diagnostic value of conventional EUS for LNM in upper gastrointestinal neoplasia.METHODS Using the search mode of“MeSH+Entry Terms”and according to the predetermined inclusion and exclusion criteria,we conducted a comprehensive search and screening of the PubMed,EMBASE and Cochrane Library databases from January 1,2000 to October 1,2022.Study data were extracted according to the predetermined data extraction form.The quality of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool,and the results of the quality assessment were presented using Review Manager 5.3.5 software.Finally,Stata14.0 software was used for a series of statistical analyses.RESULTS A total of 22 studies were included in our study,including 2986 patients.The pooled sensitivity,specificity,positive likelihood ratio,negative likelihood ratio,diagnostic score and diagnostic odds ratio of conventional EUS in the diagnosis of upper gastrointestinal neoplasia LNM were 0.62[95%confidence interval(CI):0.50-0.73],0.80(95%CI:0.73-0.86),3.15(95%CI:2.46-4.03),0.47(95%CI:0.36-0.61),1.90(95%CI:1.51-2.29)and 6.67(95%CI:4.52-9.84),respectively.The area under the summary receiver operating characteristic curve was 0.80(95%CI:0.76-0.83).Sensitivity analysis indicated that the results of the meta-analysis were stable.There was considerable heterogeneity among the included studies,and the threshold effect was an important source of heterogeneity.Univariable meta-regression and subgroup analysis showed that tumor type,sample size and EUS diagnostic criteria were significant sources of heterogeneity in specificity(P<0.05).No significant publication bias was found.CONCLUSION Conventional EUS has certain clinical value and can assist in the detection of LNM in upper gastrointestinal neoplasia,but it cannot be used as a confirmatory or exclusionary test.

Factors affecting the quality of bowel preparation for colonoscopy in hard-to-prepare patients:Evidence from the literature

Adequate bowel cleansing is critical for a high-quality colonoscopy because it affects diagnostic accuracy and adenoma detection.Nevertheless,almost a quarter of procedures are still carried out with suboptimal preparation,resulting in longer procedure times,higher risk of complications,and higher likelihood of missing lesions.Current guidelines recommend high-volume or low-volume polyethylene glycol(PEG)/non-PEG-based split-dose regimens.In patients who have had insufficient bowel cleansing,the colonoscopy should be repeated the same day or the next day with additional bowel cleansing as a salvage option.A strategy that includes a prolonged low-fiber diet,a split preparation regimen,and a colonoscopy within 5 h of the end of preparation may increase cleansing success rates in the elderly.Furthermore,even though no specific product is specifically recommended in the other cases for difficult-to-prepare patients,clinical evidence suggests that 1-L PEG plus ascorbic acid preparation are associated with higher cleansing success in hospitalized and inflammatory bowel disease patients.Patients with severe renal insufficiency(creatinine clearance<30 mL/min)should be prepared with isotonic high volume PEG solutions.Few data on cirrhotic patients are currently available,and no trials have been conducted in this population.An accurate characterization of procedural and patient variables may lead to a more personalized approach to bowel preparation,especially in patients undergoing resection of left colon lesions,where intestinal preparation has a poor outcome.The purpose of this review was to summarize the evidence on the risk factors influencing the quality of bowel cleansing in difficult-to-prepare patients,as well as strategies to improve colonoscopy preparation in these patients.

Efficacy and safety of modified tetracycline dosing in a quadruple therapy for Helicobacter pylori:A retrospective single center study

BACKGROUND Although highly effective as a component of Helicobacter pylori(H.pylori)treatment regimen,tetracycline is associated with a high incidence of medicationrelated adverse events.Modified dosing of tetracycline as part of quadruple therapy may improve safety while providing comparable eradication rates.AIM To evaluate the efficacy and safety of modified dosing of tetracycline in patients receiving tetracycline and furazolidone-containing quadruple therapy in patients with H.pylori infection.METHODS Consecutive patients(10/2020-12/2021)who received tetracycline and furazolidone quadruple therapy for H.pylori infection at Sir Run Run Shaw Hospital were identified.All patients received tetracycline,furazolidone,proton pump inhibitor,and bismuth for 14 d as primary or rescue therapy.Modified tetracycline dose group received tetracycline 500 mg twice daily while standard group received 750 mg twice daily or 500 mg three times daily.RESULTS Three hundred and ninety-four patients[mean age=46.3±13.9,male=137(34.8%),and 309(78.4%)primary therapy]completed tetracycline and furazolidone quadruple therapy for H.pylori infection including those who received modified tetracycline dose in 157 and standard doses in 118(750 mg twice daily)and 119(500 mg three times daily).Eradication rates in the modified tetracycline dose group were 92.40%and in the standard groups,eradication rates were 93.20%for 750 mg twice daily group and 92.43%for 500 mg three times daily group,respectively,without statistical difference(P=0.959).The incidence of adverse events was lower in the modified tetracycline dose(15.3%vs 32.3%and 29.4%;P=0.002)compared to the standard dose group.CONCLUSION In a real-world experience,modified tetracycline dosing as part of tetracycline and furazolidone quadruple therapy for 14 d demonstrated high efficacy,comparable to standard tetracycline dose regimens,with a favorable safety profile.

Manipulation of the intestinal microbiome-a slow journey to primetime

The gut microbiota has important functions in the regulation of normal body functions.Alterations of the microbiota are being increasingly linked to various disease states.The microbiome has been manipulated via the administration of stool from animals or humans,for more than 1000 years.Currently,fecal microbiota transplantation can be performed via endoscopic administration of fecal matter to the duodenum or colon or via capsules of lyophilized stools.More recently fecal microbial transplantation has been shown to be very effective for recurrent Clostridoides difficile infection(CDI).In addition there is some evidence of efficacy in the metabolic syndrome and its hepatic manifestation,metabolic associated fatty liver disease(MAFLD),irritable bowel syndrome(IBS)and inflammatory bowel disease(IBD).We review the current literature regarding the microbiome and the pathogenesis and treatment of CDI,MAFLD,IBS and IBD.

Assessing the Burden of Choledochian Lithiasis and Cholangiocarcinoma in Patients Undergoing Endoscopic Retrograde Cholangiopancreatography, Using Disability-Adjusted Life Years

Exact estimates of the current and future burden of gastroenterological pathology can support the national public health policy. In order to have a possible comparison between the impact and burden of some diseases, a series of health measurements were developed, simultaneously including morbidity and mortality. The aim of the study was to evaluate the burden of gastrointestinal pathology that requires therapeutic endoscopy, such as choledochian lithiasis and cholangiocarcinoma in a tertiary centre between 2019 and 2020. The scientific research was carried out as a retrospective study, intending to analyze the macroeconomic indicator-Disability-Adjusted-Life Year (DALY) in patients who underwent endoscopic retrograde cholangiopancreatography (ERCP), for the diagnosis of choledochian lithiasis or cholangiocarcinoma. The study included the cases diagnosed based on clinical, biological and imaging criteria. Our study showed that the values of DALY indicator are higher in men than in women. The DALY approach has a strong methodological framework and a firm theoretical grounding. It has been widely accepted by public health experts and employed to measure the global and regional burdens of the disease.

Fundus photography,fundus fluorescein angiography,and optical coherence tomography of healthy cynomolgus monkey,New Zealand rabbit,Sprague Dawley rat,and BALB/c mouse retinas

Background:A variety of experimental animal models are used in basic ophthalmological research to elucidate physiological mechanisms of vision and disease pathogenesis.The choice of animal model is based on the measurability of specific parameters or structures,the applicability of clinical measurement technologies,and the similarity to human eye function.Studies of eye pathology usually compare optical parameters between a healthy and altered state,so accurate baseline assessments are critical,but few reports have comprehensively examined the normal anatomical structures and physiological functions in these models.Methods:Three cynomolgus monkeys,six New Zealand rabbits,ten Sprague Dawley(SD)rats,and BALB/c mice were examined by fundus photography(FP),fundus fluorescein angiography(FFA),and optical coherence tomography(OCT).Results:Most retinal structures of cynomolgus monkey were anatomically similar to the corresponding human structures as revealed by FP,FFA,and OCT.New Zealand rabbits have large eyeballs,but they have large optic disc and myelinated retinal nerve fibers in their retinas,and the growth pattern of retinal vessels were also different to the human retinas.Unlike monkeys and rabbits,the retinal vessels of SD rats and BALB/c mice were widely distributed and clear.The OCT performance of them were similar with human beings except the macular.Conclusions:Monkey is a good model to study changes in retinal structure associated with fundus disease,rabbits are not suitable for studies on retinal vessel diseases and optic nerve diseases,and rats and mice are good models for retinal vascular diseases.These measures will help guide the choice of model and measurement technology and reduce the number of experimental animals required.

Surgical management of hydatid cyst disease of the liver: An improvement from our previous experience?

BACKGROUND Hydatid liver disease remains an important issue in endemic areas,which may require immediate surgery.Although laparoscopic surgery is on the rise,the presence of certain complications may require conversion to the open approach.AIM To compare the results of laparoscopic treatment and the open approach in the context of a 12-year single institution experience,and to perform a further comparison between results from the current study and those from a previous study.METHODS Between January 2009 and December 2020,247 patients underwent surgery for hydatic disease of the liver in our department.Of the 247 patients,70 underwent laparoscopic treatment.A retrospective analysis between the two groups was performed,as well as a comparison between current and previous laparoscopic experience(1999-2008).RESULTS There were statistically significant differences between the laparoscopic and open approaches regarding the cyst dimension,location,and presence of cystobiliary fistula.There were no intraoperative complications in the laparoscopic group.The cutoff value for the cyst size regarding the presence of cystobiliary fistula was 6.85 cm(P=0.001).CONCLUSION Laparoscopic surgery still plays an important role in the treatment of hydatid disease of the liver,with an increase in its usage over the course of years that has shown benefits regarding the postoperative recovery with a decreased rate of intraoperative complications.Although experienced surgeons can perform laparoscopic surgery in the most difficult conditions,there are some selection criteria that need to be maintained for higher quality results.

role of the normal gut microbiota

Relation between the gut microbiota and human health is being increasingly recognised. It is now well established that a healthy gut flora is largely responsible for overall health of the host. The normal human gut microbiota comprises of two major phyla, namely Bacteroidetes and Firmicutes. Though the gut microbiota in an infant appears haphazard, it starts resembling the adult flora by the age of 3 years. Nevertheless, there exist temporal and spatial variations in the microbial distribution from esophagus to the rectum all along the individual's life span. Developments in genome sequencing technologies and bioinformatics have now enabled scientists to study these microorganisms and their function and microbehost interactions in an elaborate manner both in health and disease. The normal gut microbiota imparts specific function in host nutrient metabolism, xenobiotic and drug metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Several factors play a role in shaping the normal gut microbiota. They include(1) the mode of delivery(vaginal or caesarean);(2) diet during infancy(breast milk or formula feeds) and adulthood(vegan based or meat based); and(3) use of antibiotics or antibiotic like molecules that are derived from the environment or the gut commensal community. A major concern of antibiotic use is the long-term alteration of the normal healthy gut microbiota and horizontal transfer of resistance genes that could result in reservoir of organisms with a multidrug resistant gene pool.

Single center experience of capsule endoscopy in patients with obscure gastrointestinal bleeding

AIM:To identify optimum timing to maximize diagnostic yield by capsule endoscopy (CE) in patients with obscure gastrointestinal bleeding (OGIB).METHODS:We identified patients who underwent CE at our institution from August 2003 to December 2009.Patient medical records were reviewed to determine type of OGIB (occult,overt),CE results and complications,and timing of CE with respect to onset of bleeding.RESULTS:Out of 385 patients investigated for OGIB,284 (74%) had some lesion detected by CE.In 222 patients (58%),definite lesions were detected that could unequivocally explain OGIB.Small bowel ulcer/erosions secondary to Crohn's disease,tuberculosis or non-steroidal anti-inflammatory agent use were the commonest lesions detected.Patients with overt GI bleeding for < 48 h before CE had the highest diagnostic yield (87%).This was significantly greater (P < 0.05) compared to that in patients with overt bleeding prior to 48 h (68%),as well as those with occult OGIB (59%).CONCLUSION:We established the importance of early CE in management of OGIB.CE within 48 h of overt bleeding has the greatest potential for lesion detection.

Epidural anesthesia is effective for extracorporeal shock wave lithotripsy of pancreatic and biliary calculi

AIM: To evaluate the efficacy of thoracic epidural analgesia for extracorporeal shock wave lithotripsy (ESWL). METHODS: ESWL is an effective, non-invasive technique for the treatment of difficult pancreatic and large bile duct calculi. The procedure is often painful and requires large doses of analgesics. Many different anesthetic techniques have been used. Patients with either large bile duct calculi or pancreatic duct calculi which could not be extracted by routine endoscopic methods were selected. Thoracic epidural anesthesia (TEA) was routinely used in all the subjects unless contraindicated. Bupivacaine 0.25% with or without clonidine was used to block the segments D6 to D12. The dose was calculated depending on the age, height and weight of the patient. It was usually 1-2 mL per segment blocked.RESULTS: Ninety eight percent of the 1509 patients underwent ESWL under TEA. The subjects selected were within American Society of Anesthesiologists grade Ⅰ to Ⅲ. ESWL using EA permitted successful elimination of bile duct or pancreatic calculi with minimal morbidity. The procedure time was shorter in patients with TEA than in those who underwent ESWL under total intravenous anesthesia. CONCLUSION: Almost all patients undergoing ESWL with EA had effective blocks with a single catheter insertion and local anesthetic injection.

Role of oxygen free radicals in patients with acute pancreatitis

The generation of oxygen free radicals has been implicated in the pathogenesis of experimental pancreatitis.The aim of this study was to determine the role of oxygen free radicals in patients with acute pancreatitis.METHODS: The plasma levels of C-reactive protein (CRP),lipid peroxide (LPO), myeloperoxidase (MPO) and superoxide dismutase (SOD) were measured in 13 patients with acute pancreatitis and 14 healthy volunteers.RESULTS: Among the patients with acute pancreatitis, there were higher plasma levels of LPO and MPO and lower SOD activity in patients with severe pancreatitis than in those with mild pancreatitis. However, there was no significant difference in the serum marker of oxidative stress no matter what the etiology was. The LPO level was especially correlated with the concentration of serum CRP and CT severity index.CONCLUSION: The oxygen free radicals may be closely associated with inflammatory process and the severity of acute pancreatitis. Especially, the concentration of plasma LPO is a meaningful index for determining the severity of the disease.

Tumor growth inhibition effect of hIL-6 on colon cancer cells transfected with the target gene by retroviral vector

AIM To observe the tumor inhibitory effects bytransfecting IL-6 cDNA into colon cancer cell lineHT-29 with retroviral vector pZIP cDNA.METHODS Human IL-6 gene was reconstructedin retrovirus vector and transfected into incasingcells PA317 by lipofectamine mediated method,the clones of the cells transferred with hlL-6were selected by G418,and targeted HT-29 cellswere infected with the virus granules secretedfrom PA317 and also selected by G418.Test genetranscription and expression level byhybridization,ELISA and MTT assay,etc.Analyze tumor inhibitory effects according to thecell growth curve,plating forming rate andtumorigenicity in nude mice.RESULT Successfully constructed andtransfected recombinant expressing vectorspZIPIL-6 cDNA and got positive transfected celllines.The colon cancer cell line(HT-29 IL-5)transfected with the hlL-5 gene by retroviralvector was established.The log proliferationperiod and the doubling time of this cell line wasbetween 4 to 7 days and 2.5 days according tothe direct cell count,the cell proliferation wasobviously inhibited with MTT assay,the platinginhibitory rate was 50% by plating efficiencytest.When HT-29 IL-6 cells were inoculated intothe nude mice subcutaneously,carcinogenicactivity of the solid tumor was found superior tothe control group and the size of tumor was notsignificantly enlarged.Injection of combinationvirus fluid containing 11.-6 gene intotransplantation tumors could inhibit the growthand development of the tumor.CONCLUSION IL-6 could inhibit the growth andproliferation of colon cancer cells by retroviralvector-mediated transduction.

LY294002 potentiates the anti-cancer effect of oxaliplatin for gastric cancer via death receptor pathway

AIM:To examine the effects of combined treatment of oxaliplatin and phosphatidylinositol 3'-kinase inhibitor,2-(4-morpholinyl) -8-phenyl-4H-1-benzopyran-4-one(LY294002) for gastric cancer. METHODS:Cell viability was evaluated by 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide assay.Apoptotic cells were detected by flow cytometric analysis and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay.Western blotting and immuno-precipitation were used to examine protein expression and recruitment,respectively.Nuclear factorκB(NFκB) binding activities were investigated using electrophoretic mobility shift assay.Nude mice were used to investigate tumor growth. RESULTS:Treatment with combined oxaliplatin and LY294002 resulted in increased cell growth inhibi-tion and cell apoptosis in vitro,and increased tumor growth inhibition and cell death in the tumor mass in vivo.In MKN45 and AGS cells,oxaliplatin treatment promoted both protein kinase B(Akt) and NFκB activation,while pretreatment with LY294002 significantly attenuated oxaliplatin-induced Akt activity and NFκB binding.LY294002 promoted oxaliplatin-induced Fas ligand(FasL) expression,Fas-associated death domain protein recruitment,caspase-8,Bid,and caspase-3 activation,and the short form of cellular caspase-8/FLICEinhibitory protein(c-FLIPS) inhibition.In vivo,LY294002 inhibited oxaliplatin-induced activation of Akt and NFκB,and increased oxaliplatin-induced expression of FasL,inhibition of c-FLIPS,and activation of caspase-8,Bid,and caspase-3. CONCLUSION:Combination of oxaliplatin and LY294002 was therapeutically promising for gastric cancer treatment.The enhanced sensitivity of the combined treatment was associated with the activation of the death receptor pathway.

Diagnostic performance of magnifying narrow-band imaging for early gastric cancer: A meta-analysis

AIM: To investigate the performance of magnifying endoscopy with narrow-band imaging(ME-NBI) in the diagnosis of early gastric cancer(EGC).METHODS: Systematic literature searches were conducted until February 2014 in Pub Med, EMBASE, Web of Science, Ovid, Scopus and the Cochrane Library databases by two independent reviewers. Meta-analysis was performed to calculate the pooled sensitivity, specificity and diagnostic odds ratio and to construct a summary receiver operating characteristic(ROC) curve. Subgroup analyses were performed based on the morphology type of lesions, diagnostic standard, the size of lesions, type of assessment, country and sample size to explore possible sources of heterogeneity. A Deeks' asymmetry test was used to evaluate the publication bias.RESULTS: Fourteen studies enrolling 2171 patients were included. The pooled sensitivity, specificity and diagnostic odds ratio for ME-NBI diagnosis of EGC were 0.86(95%CI: 0.83-0.89), 0.96(95%CI: 0.95-0.97) and 102.75(95%CI: 48.14-219.32), respectively, with the area under ROC curve being 0.9623. Among the 14 studies, six also evaluated the diagnostic value of conventional white-light imaging, with a sensitivityof 0.57(95%CI: 0.50-0.64) and a specificity of 0.79(95%CI: 0.76-0.81). When using "VS"(vessel plus surface) ME-NBI diagnostic systems in gastric lesions of depressed macroscopic type, the pooled sensitivity and specificity were 0.64(95%CI: 0.52-0.75) and 0.96(95%CI: 0.95-0.98). For the lesions with a diameter less than 10 mm, the sensitivity and specificity were 0.74(95%CI: 0.65-0.82) and 0.98(95%CI: 0.97-0.98).CONCLUSION: ME-NBI is a promising endoscopic tool in the diagnosis of early gastric cancer and might be helpful in further target biopsy.