On the evening of July 21,some radical demonstrators stormed the Liaison Office of the Central People's Govemment in Hong Kong Special Adrministrative Regjon(HKSAF),defaced the national emblerm and painted insulti...On the evening of July 21,some radical demonstrators stormed the Liaison Office of the Central People's Govemment in Hong Kong Special Adrministrative Regjon(HKSAF),defaced the national emblerm and painted insulting words on the wall.The vicious acts have trampled the rule of law in Hong Kong and challenged the authority of the Central Govemment,and are absolutely intolerable.展开更多
The purpose of this article is to provide a follow-up review of the impact of the SARS-CoV-2 Disease or Coronavirus Disease 2019(COVID-19)pandemic on human health and the role of physical activity(PA)during the 5-year...The purpose of this article is to provide a follow-up review of the impact of the SARS-CoV-2 Disease or Coronavirus Disease 2019(COVID-19)pandemic on human health and the role of physical activity(PA)during the 5-year pandemic.We aim to cover the immune system,the cardiopulmonary system,the musculoskeletal system,and the central nervous system(brain function),particularly among older adults,college students,and individuals with post-acute sequelae of COVID-19(Long-COVID).The COVID-19 pandemic has given us many lessons,learned from the death of six million lives and tremendous disturbance to human life.First,we need to continue to investigate cellular and molecular mechanisms that mediate various organistic failures resulting from the viral infection.Such investigations are the only way to completely understand the etiology of the diseases and to develop new drugs and vaccines.The molecular pathways that transmit the signals of viral infection to each organ system are different requiring both basic and clinical research.Available evidence suggests that mitochondrial dysfunction,reduced microcirculation and latent immune activation play a major role,eventually impairing cardiovascular tolerance and peripheral bioenergetics.Second,the COVID-19 pandemic has manifested major disturbances to human lifestyles with reduced PA and exercise standing out as a major factor.Conversely,physical inactivity due to social confinement and mental/psychological stresses has been clearly linked to intensified pathogenic symptoms and amplification of adverse effects on multiple physiological systems.If not intervened,this interaction can lead to Long-COVID,a dangerous futile circle to cause systemic failure.Finally,the COVID-19 pandemic has exerted differential impacts on different populations.Thus,the strategy to develop and conduct to cope with the negativity of pandemic needs to be specific,flexible and tailored to fit different patient populations.展开更多
In this editorial,we comment on an article by Liu et al.We focus specifically on the novel use of laparoscopic intracorporeal anastomosis(LIA)compared with open ileostomy reversal in patients with Crohn’s disease(CD)...In this editorial,we comment on an article by Liu et al.We focus specifically on the novel use of laparoscopic intracorporeal anastomosis(LIA)compared with open ileostomy reversal in patients with Crohn’s disease(CD),which is an innovative approach for improving postoperative outcomes and accelerating recovery in ileostomy reversal procedures.This study also highlights the limitations of the conventional open surgical technique,which is associated with higher rates of feeding intolerance,prolonged hospital stays,and delayed initiation of enteral nutrition.The chronic and recurrent nature of CD and the challenges posed by traditional surgical methods are issues addressed by LIA,which offers a minimally invasive approach that reduces surgical trauma,shortens recovery time,and improves tolerance to enteral nutrition,thereby enhancing postoperative outcomes.However,while LIA shows great promise,further prospective multicenter trials are needed to validate these findings and assess their broader application in other surgical scenarios.Overall,LIA represents a significant advancement in minimally invasive surgery for CD and has the potential to become the preferred standard approach for ileostomy reversal in patients requiring bowel reanastomosis.展开更多
BACKGROUND There is an increased maturation of laparoscopic intracorporeal anastomosis techniques.However,research on its application for small bowel stoma reversal in patients with Crohn's disease(CD)is limited.T...BACKGROUND There is an increased maturation of laparoscopic intracorporeal anastomosis techniques.However,research on its application for small bowel stoma reversal in patients with Crohn's disease(CD)is limited.Therefore,in this study,we compared the perioperative outcomes between laparoscopic intracorporeal ileostomy reversal(LIIR)and open ileostomy reversal(OIR).AIM To compare the safety,feasibility,bowel function recovery,and short-and longterm LIIR and OIR outcomes in patients with CD.METHODS This study included patients who underwent ileal reversal for CD between January 2021 and January 2023 at our institution.The baseline data,postoperative recovery,and complication indicators were retrospectively analyzed.Logistic regression analysis was conducted to explore factors that significantly influenced the development of enteral nutrition intolerance-related symptoms.RESULTS Notably,15 of the 45 patients in this study underwent OIR,and the remaining 30 received LIIR.Notably,no statistically significant differences were found between the two groups regarding clinical baseline characteristics,operation time,intraoperative hemorrhage,anastomotic site,enterolysis range,first postoperative flatus,postoperative complications,reoperation rate,or incidence of postoperative enteral nutrition intolerance.Compared with the OIR group,the LIIR group had a shorter postoperative hospital stay(P=0.045),lower incidence of enteral nutrition intolerance symptoms(P=0.019),and earlier postoperative total enteral nutrition initiation(P=0.033);however,it incurred higher total hospital costs(P=0.038).Furthermore,multivariate logistic regression analysis revealed that the duration of surgery and anastomotic technique were independent risk factors for postoperative symptoms of enteral nutrition intolerance(P<0.05).CONCLUSION Laparoscopic intracorporeal anastomosis for ileostomy reversal is safe and feasible.Patients who underwent this technique demonstrated improved tolerance to postoperative enteral nutrition and quicker resumption of total enteral nutrition.展开更多
Autism spectrum disorder(ASD)is a neurodevelopmental disorder where de novo mutations play a significant role.Although coding mutations in ASD have been extensively characterized,the impact of non-coding de novo mutat...Autism spectrum disorder(ASD)is a neurodevelopmental disorder where de novo mutations play a significant role.Although coding mutations in ASD have been extensively characterized,the impact of non-coding de novo mutations(ncDNMs)remains less understood.Here,we integrate cortex cell-specific cis-regulatory element annotations,a deep learning-based variant prediction model,and massively parallel reporter assays to systematically evaluate the functional impact of 227,878 ncDNMs from Simons Simplex Collection(SSC)and Autism Speaks MSSNG resource(MSSNG)cohorts.Our analysis identifies 238 ncDNMs with confirmed functional regulatory effects,including 137 down-regulated regulatory mutations(DrMuts)and 101 up-regulated regulatory mutations(UrMuts).Subsequent association analyses reveal that only DrMuts regulating loss-of-function(LoF)intolerant genes rather than other ncDNMs are significantly associated with the risk of ASD(Odds ratio=4.34;P=0.001).A total of 42 potential ASD-risk DrMuts across 41 candidate ASD-susceptibility genes are identified,including 12 recognized and 29 unreported genes.Interestingly,these noncoding disruptive mutations tend to be observed in genes extremely intolerant to LoF mutations.Our study introduces an optimized approach for elucidating the functional roles of ncDNMs,thereby expanding the spectrum of pathogenic variants and deepening our understanding of the complex molecular mechanisms underlying ASD.展开更多
Background:Patients with unrepaired Ebstein’s anomaly experience exercise intolerance,heart failure and premature mortality.Volumetric assessment of right ventricular function is difffcult due to the complex anatomy ...Background:Patients with unrepaired Ebstein’s anomaly experience exercise intolerance,heart failure and premature mortality.Volumetric assessment of right ventricular function is difffcult due to the complex anatomy of the right ventricle and tricuspid valve.Myocardial deformation indices are an early marker in other cardiac pathologies of ventricular dysfunction.Objectives:1.Assess myocardial deformation in unrepaired Ebstein’s compared to healthy controls.2.Investigate the relationships between myocardial deformation and exercise capacity.Methods:Myocardial deformation parameters(strain)were calculated using feature tracking from standard cardiac magnetic resonance cine images.Cardiopulmonary exercise results were included where available.Results:36 patients with unrepaired Ebstein’s and 36 matched controls were included.Right ventricular,right atrial,and left ventricular global longitudinal,as well as left ventricular circumferential strain were impaired in Ebstein’s patients compared to controls(p<0.05).In Ebstein’s patients right atrial peak strain correlated with their percentage predicted VO_(2) max(r=−0.448,p=0.022)and VE/VCO_(2) slope(r=0.435,p=0.026).There were no correlations between right ventricular ejection fraction and exercise parameters.When Ebstein’s patients were divided by severity into mild or severe according to the median total right/left index,those with severe demonstrated signiffcantly impaired right ventricular global longitudinal strain compared to those in the mild category(−17.5±5.4%vs.−21.4±4.4%,p=0.0017).Conclusions:Myocardial deformation parameters for both the right and left ventricle are impaired in patients with unrepaired Ebstein’s compared to healthy controls.Right atrial peak strain is related to impaired exercise capacity and warrants further investigation as an early prognostic marker in this patient cohort.展开更多
Cow milk protein allergy(CMPA)is a prevalent food allergy in infancy.It often presents with symptoms that overlap with other conditions,such as gastroeso-phageal reflux disease,lactose intolerance,food protein-induced...Cow milk protein allergy(CMPA)is a prevalent food allergy in infancy.It often presents with symptoms that overlap with other conditions,such as gastroeso-phageal reflux disease,lactose intolerance,food protein-induced enterocolitis syndrome,and eosinophilic esophagitis.This diagnostic overlap makes distin-guishing CMPA from its mimics difficult,resulting in potential misdiagnoses and unnecessary dietary restrictions.This review aims to comprehensively analyze CMPA and its mimicking conditions,highlighting their clinical presentations,diagnostic approaches,and management strategies to enhance diagnostic accu-racy and optimize patient care.A systematic literature search was conducted using PubMed,Scopus,Web of Science,and Google Scholar,focusing on studies published within the last 20 years.Articles addressing CMPA and its mimicking conditions were selected,with data synthesized into comparative analyses of diagnostic methods and management strategies.Accurate differentiation between CMPA and its mimics requires a thorough clinical evaluation supported by diagnostic tests such as skin prick tests,serum-specific IgE,and oral food challenges.Misdiagnosis can lead to nutritional deficiencies,psychological stress,and increased healthcare costs.Emerging diagnostic technologies,including component-resolved diagnostics and cytokine profiling,offer promising avenues for improving accuracy.A multidisciplinary approach involving pediatricians,allergists,and dietitians is essential for precise diagnosis and effective management.Ongoing research and education are crucial to enhancing clinical outcomes and reducing the burden on families.展开更多
This study investigates the role of Interleukin 17(IL-17)in exacerbating periapical lesions caused by Porphyromonas gingivalis(Pg)lipopolysaccharides(LPS)in the context of metabolic disease and its potential impact on...This study investigates the role of Interleukin 17(IL-17)in exacerbating periapical lesions caused by Porphyromonas gingivalis(Pg)lipopolysaccharides(LPS)in the context of metabolic disease and its potential impact on glucose tolerance.Researchers developed a unique mouse model where mice were monocolonized with Pg to induce periapical lesions.After 1 month,they were fed a highfat diet(HFD)for 2 months to simulate metabolic disease and oral microbiota dysbiosis.To explore the role of LPS from Pg,wildtype(WT)mice were challenged with purified LPS from Porphyromonas gingivalis,as well as with LPS-depleted and non-depleted Pg bacteria;IL-17 knockout(KO)mice were also included to assess the role of IL-17 signaling.The impact on bone lysis,periapical injury,glucose intolerance,and immune response was assessed.Results showed that in WT mice,the presence of LPS significantly worsened bone lysis,Th17 cell recruitment,and periapical injury.IL-17 KO mice exhibited reduced bone loss,glucose intolerance,and immune cell infiltration.Additionally,inflammatory markers in adipose tissue were lower in IL-17 KO mice,despite increased dysbiosis.The findings suggest that IL-17 plays a critical role in amplifying Pg-induced periapical lesions and systemic metabolic disturbances.Targeting IL-17 recruitment could offer a novel approach to improving glycemic control and reducing type 2 diabetes(T2D)risk in individuals with periapical disease.展开更多
Hepatitis C is an infection caused by the hepatitis C virus that attacks the liver and leads to inflammation. The current standard-of-care regimens include a protease inhibitor—telaprevir or boceprevir—in combinatio...Hepatitis C is an infection caused by the hepatitis C virus that attacks the liver and leads to inflammation. The current standard-of-care regimens include a protease inhibitor—telaprevir or boceprevir—in combination with pegylated interferon and ribavirin. Hepatitis?C treatment options on the horizon hold promise for better viral clearance with less toxicity than current regimens. There are new data about new drugs, both direct-acting antivirals while minimizing intolerable side effects or adverse events. Developed new data from 4 phase 3 trials with the hepatitis C drug sofosbuvir and ribavirin show that a 12-week regimen is effective in treating HCV genotypes 1 through 6. In the Annual Scientific Meeting and Postgraduate Course of the American College of Gastroenterology, different research was presented that was drawn from 4 phase 3 studies: NEUTRINO, FISSION, POSITRON and FUSION which enrolled different types of patients, who received Sofosbuvir with Peginterferon Alfa 2a and Ribavirin for 12 or 24 weeks in treatment;for all studies, the primary end point was sustained virologic response at 12 and 24 weeks posttreatment. In all studies, sofosbuvir was well tolerated, with a low incidence of adverse events. In conjunction with the suggested brief duration of this regimen, this indicates that drug combinations should improve treatment adherence compared with IFN-based treatment. In conclusion, 2 novel direct-acting antiviral agents—sofosbuvir and simeprevir—target various components of the HCV genome. Advantages of these drugs include a high barrier to viral resistance, a shorter duration of treatment, once-daily dosing, absence of food restrictions, few clinically significant drug interactions, and similar efficacy in all genotypes.展开更多
Lactose malabsorption is a very common condition characterized by intestinal lactase deficiency. Primary lactose malabsorption is an inherited deficit present in the majority of the world＇s population, while secondar...Lactose malabsorption is a very common condition characterized by intestinal lactase deficiency. Primary lactose malabsorption is an inherited deficit present in the majority of the world＇s population, while secondary hypolactasia can be the consequence of an intestinal disease. The presence of malabsorbed lactose in the colonic lumen causes gastrointestinal symptoms. The condition is known as lactose intolerance. In patients with lactase nonpersistence, treatment should be considered exclusively if intolerance symptoms are present. In the absence of guidelines, the common therapeutic approach tends to exclude milk and dairy products from the diet. However, this strategy may have serious nutritional disadvantages. Several studies have been carried out to find alternative approaches, such as exogenous β-galactosidase, yogurt and probiotics for their bacterial lactase activity, pharmacological and non pharmacological strategies that can prolong contact time between enzyme and substrate delaying gastrointestinal transit time, and chronic lactose ingestion to enhance colonic adaptation. In this review the usefulness of these approaches is discussed and a therapeutic management with a flow chart is proposed.展开更多
Hypervigilance and symptoms anticipation,visceral hypersensitivity and gastroduodenal sensorimotor abnormalities account for the varied clinical presentation of functional dyspepsia(FD)patients.Many patients recognize...Hypervigilance and symptoms anticipation,visceral hypersensitivity and gastroduodenal sensorimotor abnormalities account for the varied clinical presentation of functional dyspepsia(FD)patients.Many patients recognize meals as the main triggering factor;thus,dietary manipulations often represent the first-line management strategy in this cohort of patients.Nonetheless,scarce quality evidence has been produced regarding the relationship between specific foods and/or macronutrients and the onset of FD symptoms,resulting in nonstandardized nutritional approaches.Most dietary advises are indeed empirical and often lead to exclusion diets,reinforcing in patients the perception of“being intolerant”to food and self-perpetuating some of the very mechanisms underlying dyspepsia physiopathology(i.e.,hypervigilance and symptom anticipation).Clinicians are often uncertain regarding the contribution of specific foods to dyspepsia physiopathology and dedicated professionals(i.e.,dietitians)are only available in tertiary referral settings.This in turn,can result in nutritionally unbalanced diets and could even encourage restrictive eating behaviors in severe dyspepsia.In this review,we aim at evaluating the relationship between dietary habits,macronutrients and specific foods in determining FD symptoms.We will provide an overview of the evidence-based nutritional approach that should be pursued in these patients,providing clinicians with a valuable tool in standardizing nutritional advises and discouraging patients from engaging into indiscriminate food exclusions.展开更多
Celiac disease (CD) is a common autoimmune disorder characterized by an immune response to ingested gluten and has a strong HLA association with HLA- DQ2 and HLA-DQ8 molecules, but human HLA-DQ risk factors do not exp...Celiac disease (CD) is a common autoimmune disorder characterized by an immune response to ingested gluten and has a strong HLA association with HLA- DQ2 and HLA-DQ8 molecules, but human HLA-DQ risk factors do not explain the entire genetic susceptibility to gluten intolerance. CD is caused by the lack of immune tolerance (oral tolerance) to wheat gluten. In this sense, the expression of soluble HLA-G in CD is of special interest because the molecule plays an important role in the induction of immune tolerance. The enhanced expression of soluble HLA-G found in CD may be part of a mechanism to restore the gluten intolerance. In this editorial, we review recent progress in understanding CD in relation to its prevalence, diagnosis and possible mechanisms of pathogenesis.展开更多
AIM:To report preliminary results of the efficacy and safety of sunitinib in the management of Taiwan Residents gastrointestinal stromal tumors (GIST) patients facing imatinib mesylate (IM) intolerance or failure.METH...AIM:To report preliminary results of the efficacy and safety of sunitinib in the management of Taiwan Residents gastrointestinal stromal tumors (GIST) patients facing imatinib mesylate (IM) intolerance or failure.METHODS:Between 2001 and May 2010,199 Taiwan Residents patients with metastatic GIST were treated at Chang Gung Memorial Hospital.Among them,23 (11.6%) patients receiving sunitinib were investigated.RESULTS:Sixteen male and 7 female patients with a median age of 59 years (range:24-83 years) received sunitinib.Twenty-two GIST patients changed to sunitinib because of IM failure and 1 because of intolerance.The median duration of sunitinib administration was 6.0 mo (range:2-29 mo).The clinical benefit was 65.2% [2 complete response (CR),4 partial response (PR),and 9 stationary disease (SD);15/23].In 12 patients harboring mutations of the kit gene at exon 11,the clinical benefit rate (CR,PR,and SD) was 75.0% and 6 patients with tumors containing kit exon 9 mutations had a clinical benefit of 50.0% (not significant,P=0.344).The progression free survival (PFS) and overall survival (OS) did not differ between patients whose GISTs had wild type,KIT exon 9,or KIT exon 11 mutations.Hand-foot syndrome was the most common cause of grade Ⅲ adverse effect (26.1%),followed by anemia (17.4%),and neutropenia (13.0%).During the median 7.5-mo follow-up after sunitinib use,the median PFS and OS of these 23 GIST patients after sunitinib treatment were 8.4 and 14.1 mo,respectively.CONCLUSION:Sunitinib appears to be an effective treatment for Taiwan Residents with IM-resistant/intolerant GISTs and induced a sustained clinical benefit in more than 50% of Taiwan Residents advanced GIST patients.展开更多
Optimal bowel preparation increases the cecal intubation rate and detection of neoplastic lesions while decreasing the procedural time and procedural-related complications. Although high-volume polyethylene glycol(PEG...Optimal bowel preparation increases the cecal intubation rate and detection of neoplastic lesions while decreasing the procedural time and procedural-related complications. Although high-volume polyethylene glycol(PEG) solution is the most frequently used preparation for bowel cleansing, patients are often unwilling to take PEG solution due to its large volume, poor palatability, and high incidence of adverse events, such as abdominal bloating and nausea. Other purgatives include osmotic agents(e.g., sodium phosphate, magnesium citrate, and sodium sulfate), stimulant agents(e.g., senna, bisacodyl, and sodium picosulfate), and prokinetic agents(e.g., cisapride, mosapride, and itopride). A combination of PEG with an osmotic, stimulant, or prokinetic agent could effectively reduce the PEG solution volume and increase patients' adherence. Some such solutions have been found in several published studies to not be inferior to PEG alone in terms of bowel cleansing quality. Although combination methods showed similar efficacy and safety, the value of these studies is limited by shortcomings in study design. New effective and well-tolerated combination preparations are required, in addition to rigorous new validated studies.展开更多
During the last 100 years in medical literature,there are only 54 reports,including the report of Pasaoglu et al(World J Gastroenterol 2008;14:2915-2916),with clinical descriptions of agenesis of the dorsal pancreas i...During the last 100 years in medical literature,there are only 54 reports,including the report of Pasaoglu et al(World J Gastroenterol 2008;14:2915-2916),with clinical descriptions of agenesis of the dorsal pancreas in humans.Agenesis of the dorsal pancreas,a rare congenital pancreatic malformation,is associated with some other medical conditions such as hyperglycemia,abdominal pain,pancreatitis and a few other diseases.In approximately 50% of reported patients with this congenital malformation,hyperglycemia was demonstrated.Evaluation of hyperglycemia and diabetes mellitus in all patients with agenesis of the dorsal pancreas including description of fasting blood glucose,oral glucose tolerance test,glycated hemoglobin and medical treatment would be a future goal.Since autosomal dominant transmission has been suggested in single families,more family studies including imaging technologies with demonstration of the pancreatic duct system are needed for evaluation of this disease.With this letter to the editor,we aim to increase available information for the better understanding of this rare disease.展开更多
Irritable bowel syndrome(IBS) is one of the most common gastrointestinal disorders in Western countries. Despite the high prevalence of this disorders, the therapeutic management of these patients is often unsatisfact...Irritable bowel syndrome(IBS) is one of the most common gastrointestinal disorders in Western countries. Despite the high prevalence of this disorders, the therapeutic management of these patients is often unsatisfactory. A number of factors have been suggested to be involved in the pathogenesis of IBS, including impaired motility and sensitivity, increased permeability, changes in the gut microbiome and alterations in the brain-gut axis. Also food seems to play a critical role: the most of IBS patients report the onset or the exacerbation of their symptoms after the meals. Recently, an increasing attention has been paid to the role of food in IBS. In this review we summarize the most recent evidences about the role of diet on IBS symptoms. A diet restricted in fermentable, poorly absorbed carbohydrates and sugar alcohols has beneficial effects on IBS symptoms. More studies are needed to improve our knowledge about the relationship between food and IBS. However, in the foreseeable future, dietary strategies will represent one of the key tools in the therapeutic management of patients with IBS.展开更多
BACKGROUND Enteral nutrition(EN)is essential for critically ill patients.However,some patients will have enteral feeding intolerance(EFI)in the process of EN.AIM To develop a clinical prediction model to predict the r...BACKGROUND Enteral nutrition(EN)is essential for critically ill patients.However,some patients will have enteral feeding intolerance(EFI)in the process of EN.AIM To develop a clinical prediction model to predict the risk of EFI in patients receiving EN in the intensive care unit.METHODS A prospective cohort study was performed.The enrolled patients’basic information,medical status,nutritional support,and gastrointestinal(GI)symptoms were recorded.The baseline data and influencing factors were compared.Logistic regression analysis was used to establish the model,and the bootstrap resampling method was used to conduct internal validation.RESULTS The sample cohort included 203 patients,and 37.93%of the patients were diagnosed with EFI.After the final regression analysis,age,GI disease,early feeding,mechanical ventilation before EN started,and abnormal serum sodium were identified.In the internal validation,500 bootstrap resample samples were performed,and the area under the curve was 0.70(95%CI:0.63-0.77).CONCLUSION This clinical prediction model can be applied to predict the risk of EFI.展开更多
文摘On the evening of July 21,some radical demonstrators stormed the Liaison Office of the Central People's Govemment in Hong Kong Special Adrministrative Regjon(HKSAF),defaced the national emblerm and painted insulting words on the wall.The vicious acts have trampled the rule of law in Hong Kong and challenged the authority of the Central Govemment,and are absolutely intolerable.
文摘The purpose of this article is to provide a follow-up review of the impact of the SARS-CoV-2 Disease or Coronavirus Disease 2019(COVID-19)pandemic on human health and the role of physical activity(PA)during the 5-year pandemic.We aim to cover the immune system,the cardiopulmonary system,the musculoskeletal system,and the central nervous system(brain function),particularly among older adults,college students,and individuals with post-acute sequelae of COVID-19(Long-COVID).The COVID-19 pandemic has given us many lessons,learned from the death of six million lives and tremendous disturbance to human life.First,we need to continue to investigate cellular and molecular mechanisms that mediate various organistic failures resulting from the viral infection.Such investigations are the only way to completely understand the etiology of the diseases and to develop new drugs and vaccines.The molecular pathways that transmit the signals of viral infection to each organ system are different requiring both basic and clinical research.Available evidence suggests that mitochondrial dysfunction,reduced microcirculation and latent immune activation play a major role,eventually impairing cardiovascular tolerance and peripheral bioenergetics.Second,the COVID-19 pandemic has manifested major disturbances to human lifestyles with reduced PA and exercise standing out as a major factor.Conversely,physical inactivity due to social confinement and mental/psychological stresses has been clearly linked to intensified pathogenic symptoms and amplification of adverse effects on multiple physiological systems.If not intervened,this interaction can lead to Long-COVID,a dangerous futile circle to cause systemic failure.Finally,the COVID-19 pandemic has exerted differential impacts on different populations.Thus,the strategy to develop and conduct to cope with the negativity of pandemic needs to be specific,flexible and tailored to fit different patient populations.
文摘In this editorial,we comment on an article by Liu et al.We focus specifically on the novel use of laparoscopic intracorporeal anastomosis(LIA)compared with open ileostomy reversal in patients with Crohn’s disease(CD),which is an innovative approach for improving postoperative outcomes and accelerating recovery in ileostomy reversal procedures.This study also highlights the limitations of the conventional open surgical technique,which is associated with higher rates of feeding intolerance,prolonged hospital stays,and delayed initiation of enteral nutrition.The chronic and recurrent nature of CD and the challenges posed by traditional surgical methods are issues addressed by LIA,which offers a minimally invasive approach that reduces surgical trauma,shortens recovery time,and improves tolerance to enteral nutrition,thereby enhancing postoperative outcomes.However,while LIA shows great promise,further prospective multicenter trials are needed to validate these findings and assess their broader application in other surgical scenarios.Overall,LIA represents a significant advancement in minimally invasive surgery for CD and has the potential to become the preferred standard approach for ileostomy reversal in patients requiring bowel reanastomosis.
基金Supported by Chongqing Municipal Health Commission Medical Research Project,No.2023WSJK104.
文摘BACKGROUND There is an increased maturation of laparoscopic intracorporeal anastomosis techniques.However,research on its application for small bowel stoma reversal in patients with Crohn's disease(CD)is limited.Therefore,in this study,we compared the perioperative outcomes between laparoscopic intracorporeal ileostomy reversal(LIIR)and open ileostomy reversal(OIR).AIM To compare the safety,feasibility,bowel function recovery,and short-and longterm LIIR and OIR outcomes in patients with CD.METHODS This study included patients who underwent ileal reversal for CD between January 2021 and January 2023 at our institution.The baseline data,postoperative recovery,and complication indicators were retrospectively analyzed.Logistic regression analysis was conducted to explore factors that significantly influenced the development of enteral nutrition intolerance-related symptoms.RESULTS Notably,15 of the 45 patients in this study underwent OIR,and the remaining 30 received LIIR.Notably,no statistically significant differences were found between the two groups regarding clinical baseline characteristics,operation time,intraoperative hemorrhage,anastomotic site,enterolysis range,first postoperative flatus,postoperative complications,reoperation rate,or incidence of postoperative enteral nutrition intolerance.Compared with the OIR group,the LIIR group had a shorter postoperative hospital stay(P=0.045),lower incidence of enteral nutrition intolerance symptoms(P=0.019),and earlier postoperative total enteral nutrition initiation(P=0.033);however,it incurred higher total hospital costs(P=0.038).Furthermore,multivariate logistic regression analysis revealed that the duration of surgery and anastomotic technique were independent risk factors for postoperative symptoms of enteral nutrition intolerance(P<0.05).CONCLUSION Laparoscopic intracorporeal anastomosis for ileostomy reversal is safe and feasible.Patients who underwent this technique demonstrated improved tolerance to postoperative enteral nutrition and quicker resumption of total enteral nutrition.
基金supported by the National Natural Science of China(82322032 and 82221005)the Outstanding Youth Foundation of Jiangsu Province(BK20220050)+4 种基金the National Key Research&Development(R&D)Program of China(2024YFC2706800 and 2021YFC2700600)the Major Project of Changzhou Medical Center(CZKY1040101)the Major Project of Taizhou Clinical Medical College(TZKY20240003)the Major Program of Gusu School(GSKY20210102)the China Postdoctoral Science Foundation(2024M760296).
文摘Autism spectrum disorder(ASD)is a neurodevelopmental disorder where de novo mutations play a significant role.Although coding mutations in ASD have been extensively characterized,the impact of non-coding de novo mutations(ncDNMs)remains less understood.Here,we integrate cortex cell-specific cis-regulatory element annotations,a deep learning-based variant prediction model,and massively parallel reporter assays to systematically evaluate the functional impact of 227,878 ncDNMs from Simons Simplex Collection(SSC)and Autism Speaks MSSNG resource(MSSNG)cohorts.Our analysis identifies 238 ncDNMs with confirmed functional regulatory effects,including 137 down-regulated regulatory mutations(DrMuts)and 101 up-regulated regulatory mutations(UrMuts).Subsequent association analyses reveal that only DrMuts regulating loss-of-function(LoF)intolerant genes rather than other ncDNMs are significantly associated with the risk of ASD(Odds ratio=4.34;P=0.001).A total of 42 potential ASD-risk DrMuts across 41 candidate ASD-susceptibility genes are identified,including 12 recognized and 29 unreported genes.Interestingly,these noncoding disruptive mutations tend to be observed in genes extremely intolerant to LoF mutations.Our study introduces an optimized approach for elucidating the functional roles of ncDNMs,thereby expanding the spectrum of pathogenic variants and deepening our understanding of the complex molecular mechanisms underlying ASD.
基金This observational retrospective study was approved by the local Clinical Governance Committee(RRK6237)conformed to the principles of Good Clinical Practice guidelines.Additionally,healthy controls were identiffed from a national ethics board approved observational CMR study(NCT01028703).
文摘Background:Patients with unrepaired Ebstein’s anomaly experience exercise intolerance,heart failure and premature mortality.Volumetric assessment of right ventricular function is difffcult due to the complex anatomy of the right ventricle and tricuspid valve.Myocardial deformation indices are an early marker in other cardiac pathologies of ventricular dysfunction.Objectives:1.Assess myocardial deformation in unrepaired Ebstein’s compared to healthy controls.2.Investigate the relationships between myocardial deformation and exercise capacity.Methods:Myocardial deformation parameters(strain)were calculated using feature tracking from standard cardiac magnetic resonance cine images.Cardiopulmonary exercise results were included where available.Results:36 patients with unrepaired Ebstein’s and 36 matched controls were included.Right ventricular,right atrial,and left ventricular global longitudinal,as well as left ventricular circumferential strain were impaired in Ebstein’s patients compared to controls(p<0.05).In Ebstein’s patients right atrial peak strain correlated with their percentage predicted VO_(2) max(r=−0.448,p=0.022)and VE/VCO_(2) slope(r=0.435,p=0.026).There were no correlations between right ventricular ejection fraction and exercise parameters.When Ebstein’s patients were divided by severity into mild or severe according to the median total right/left index,those with severe demonstrated signiffcantly impaired right ventricular global longitudinal strain compared to those in the mild category(−17.5±5.4%vs.−21.4±4.4%,p=0.0017).Conclusions:Myocardial deformation parameters for both the right and left ventricle are impaired in patients with unrepaired Ebstein’s compared to healthy controls.Right atrial peak strain is related to impaired exercise capacity and warrants further investigation as an early prognostic marker in this patient cohort.
文摘Cow milk protein allergy(CMPA)is a prevalent food allergy in infancy.It often presents with symptoms that overlap with other conditions,such as gastroeso-phageal reflux disease,lactose intolerance,food protein-induced enterocolitis syndrome,and eosinophilic esophagitis.This diagnostic overlap makes distin-guishing CMPA from its mimics difficult,resulting in potential misdiagnoses and unnecessary dietary restrictions.This review aims to comprehensively analyze CMPA and its mimicking conditions,highlighting their clinical presentations,diagnostic approaches,and management strategies to enhance diagnostic accu-racy and optimize patient care.A systematic literature search was conducted using PubMed,Scopus,Web of Science,and Google Scholar,focusing on studies published within the last 20 years.Articles addressing CMPA and its mimicking conditions were selected,with data synthesized into comparative analyses of diagnostic methods and management strategies.Accurate differentiation between CMPA and its mimics requires a thorough clinical evaluation supported by diagnostic tests such as skin prick tests,serum-specific IgE,and oral food challenges.Misdiagnosis can lead to nutritional deficiencies,psychological stress,and increased healthcare costs.Emerging diagnostic technologies,including component-resolved diagnostics and cytokine profiling,offer promising avenues for improving accuracy.A multidisciplinary approach involving pediatricians,allergists,and dietitians is essential for precise diagnosis and effective management.Ongoing research and education are crucial to enhancing clinical outcomes and reducing the burden on families.
基金supported by the Paul Calas Award from the French Society of Endodontics(SFE)。
文摘This study investigates the role of Interleukin 17(IL-17)in exacerbating periapical lesions caused by Porphyromonas gingivalis(Pg)lipopolysaccharides(LPS)in the context of metabolic disease and its potential impact on glucose tolerance.Researchers developed a unique mouse model where mice were monocolonized with Pg to induce periapical lesions.After 1 month,they were fed a highfat diet(HFD)for 2 months to simulate metabolic disease and oral microbiota dysbiosis.To explore the role of LPS from Pg,wildtype(WT)mice were challenged with purified LPS from Porphyromonas gingivalis,as well as with LPS-depleted and non-depleted Pg bacteria;IL-17 knockout(KO)mice were also included to assess the role of IL-17 signaling.The impact on bone lysis,periapical injury,glucose intolerance,and immune response was assessed.Results showed that in WT mice,the presence of LPS significantly worsened bone lysis,Th17 cell recruitment,and periapical injury.IL-17 KO mice exhibited reduced bone loss,glucose intolerance,and immune cell infiltration.Additionally,inflammatory markers in adipose tissue were lower in IL-17 KO mice,despite increased dysbiosis.The findings suggest that IL-17 plays a critical role in amplifying Pg-induced periapical lesions and systemic metabolic disturbances.Targeting IL-17 recruitment could offer a novel approach to improving glycemic control and reducing type 2 diabetes(T2D)risk in individuals with periapical disease.
文摘Hepatitis C is an infection caused by the hepatitis C virus that attacks the liver and leads to inflammation. The current standard-of-care regimens include a protease inhibitor—telaprevir or boceprevir—in combination with pegylated interferon and ribavirin. Hepatitis?C treatment options on the horizon hold promise for better viral clearance with less toxicity than current regimens. There are new data about new drugs, both direct-acting antivirals while minimizing intolerable side effects or adverse events. Developed new data from 4 phase 3 trials with the hepatitis C drug sofosbuvir and ribavirin show that a 12-week regimen is effective in treating HCV genotypes 1 through 6. In the Annual Scientific Meeting and Postgraduate Course of the American College of Gastroenterology, different research was presented that was drawn from 4 phase 3 studies: NEUTRINO, FISSION, POSITRON and FUSION which enrolled different types of patients, who received Sofosbuvir with Peginterferon Alfa 2a and Ribavirin for 12 or 24 weeks in treatment;for all studies, the primary end point was sustained virologic response at 12 and 24 weeks posttreatment. In all studies, sofosbuvir was well tolerated, with a low incidence of adverse events. In conjunction with the suggested brief duration of this regimen, this indicates that drug combinations should improve treatment adherence compared with IFN-based treatment. In conclusion, 2 novel direct-acting antiviral agents—sofosbuvir and simeprevir—target various components of the HCV genome. Advantages of these drugs include a high barrier to viral resistance, a shorter duration of treatment, once-daily dosing, absence of food restrictions, few clinically significant drug interactions, and similar efficacy in all genotypes.
文摘Lactose malabsorption is a very common condition characterized by intestinal lactase deficiency. Primary lactose malabsorption is an inherited deficit present in the majority of the world＇s population, while secondary hypolactasia can be the consequence of an intestinal disease. The presence of malabsorbed lactose in the colonic lumen causes gastrointestinal symptoms. The condition is known as lactose intolerance. In patients with lactase nonpersistence, treatment should be considered exclusively if intolerance symptoms are present. In the absence of guidelines, the common therapeutic approach tends to exclude milk and dairy products from the diet. However, this strategy may have serious nutritional disadvantages. Several studies have been carried out to find alternative approaches, such as exogenous β-galactosidase, yogurt and probiotics for their bacterial lactase activity, pharmacological and non pharmacological strategies that can prolong contact time between enzyme and substrate delaying gastrointestinal transit time, and chronic lactose ingestion to enhance colonic adaptation. In this review the usefulness of these approaches is discussed and a therapeutic management with a flow chart is proposed.
文摘Hypervigilance and symptoms anticipation,visceral hypersensitivity and gastroduodenal sensorimotor abnormalities account for the varied clinical presentation of functional dyspepsia(FD)patients.Many patients recognize meals as the main triggering factor;thus,dietary manipulations often represent the first-line management strategy in this cohort of patients.Nonetheless,scarce quality evidence has been produced regarding the relationship between specific foods and/or macronutrients and the onset of FD symptoms,resulting in nonstandardized nutritional approaches.Most dietary advises are indeed empirical and often lead to exclusion diets,reinforcing in patients the perception of“being intolerant”to food and self-perpetuating some of the very mechanisms underlying dyspepsia physiopathology(i.e.,hypervigilance and symptom anticipation).Clinicians are often uncertain regarding the contribution of specific foods to dyspepsia physiopathology and dedicated professionals(i.e.,dietitians)are only available in tertiary referral settings.This in turn,can result in nutritionally unbalanced diets and could even encourage restrictive eating behaviors in severe dyspepsia.In this review,we aim at evaluating the relationship between dietary habits,macronutrients and specific foods in determining FD symptoms.We will provide an overview of the evidence-based nutritional approach that should be pursued in these patients,providing clinicians with a valuable tool in standardizing nutritional advises and discouraging patients from engaging into indiscriminate food exclusions.
文摘Celiac disease (CD) is a common autoimmune disorder characterized by an immune response to ingested gluten and has a strong HLA association with HLA- DQ2 and HLA-DQ8 molecules, but human HLA-DQ risk factors do not explain the entire genetic susceptibility to gluten intolerance. CD is caused by the lack of immune tolerance (oral tolerance) to wheat gluten. In this sense, the expression of soluble HLA-G in CD is of special interest because the molecule plays an important role in the induction of immune tolerance. The enhanced expression of soluble HLA-G found in CD may be part of a mechanism to restore the gluten intolerance. In this editorial, we review recent progress in understanding CD in relation to its prevalence, diagnosis and possible mechanisms of pathogenesis.
基金Supported by Chang Gung Medical Research Program 380711 Grant to Dr. Yeh CN
文摘AIM:To report preliminary results of the efficacy and safety of sunitinib in the management of Taiwan Residents gastrointestinal stromal tumors (GIST) patients facing imatinib mesylate (IM) intolerance or failure.METHODS:Between 2001 and May 2010,199 Taiwan Residents patients with metastatic GIST were treated at Chang Gung Memorial Hospital.Among them,23 (11.6%) patients receiving sunitinib were investigated.RESULTS:Sixteen male and 7 female patients with a median age of 59 years (range:24-83 years) received sunitinib.Twenty-two GIST patients changed to sunitinib because of IM failure and 1 because of intolerance.The median duration of sunitinib administration was 6.0 mo (range:2-29 mo).The clinical benefit was 65.2% [2 complete response (CR),4 partial response (PR),and 9 stationary disease (SD);15/23].In 12 patients harboring mutations of the kit gene at exon 11,the clinical benefit rate (CR,PR,and SD) was 75.0% and 6 patients with tumors containing kit exon 9 mutations had a clinical benefit of 50.0% (not significant,P=0.344).The progression free survival (PFS) and overall survival (OS) did not differ between patients whose GISTs had wild type,KIT exon 9,or KIT exon 11 mutations.Hand-foot syndrome was the most common cause of grade Ⅲ adverse effect (26.1%),followed by anemia (17.4%),and neutropenia (13.0%).During the median 7.5-mo follow-up after sunitinib use,the median PFS and OS of these 23 GIST patients after sunitinib treatment were 8.4 and 14.1 mo,respectively.CONCLUSION:Sunitinib appears to be an effective treatment for Taiwan Residents with IM-resistant/intolerant GISTs and induced a sustained clinical benefit in more than 50% of Taiwan Residents advanced GIST patients.
文摘Optimal bowel preparation increases the cecal intubation rate and detection of neoplastic lesions while decreasing the procedural time and procedural-related complications. Although high-volume polyethylene glycol(PEG) solution is the most frequently used preparation for bowel cleansing, patients are often unwilling to take PEG solution due to its large volume, poor palatability, and high incidence of adverse events, such as abdominal bloating and nausea. Other purgatives include osmotic agents(e.g., sodium phosphate, magnesium citrate, and sodium sulfate), stimulant agents(e.g., senna, bisacodyl, and sodium picosulfate), and prokinetic agents(e.g., cisapride, mosapride, and itopride). A combination of PEG with an osmotic, stimulant, or prokinetic agent could effectively reduce the PEG solution volume and increase patients' adherence. Some such solutions have been found in several published studies to not be inferior to PEG alone in terms of bowel cleansing quality. Although combination methods showed similar efficacy and safety, the value of these studies is limited by shortcomings in study design. New effective and well-tolerated combination preparations are required, in addition to rigorous new validated studies.
文摘During the last 100 years in medical literature,there are only 54 reports,including the report of Pasaoglu et al(World J Gastroenterol 2008;14:2915-2916),with clinical descriptions of agenesis of the dorsal pancreas in humans.Agenesis of the dorsal pancreas,a rare congenital pancreatic malformation,is associated with some other medical conditions such as hyperglycemia,abdominal pain,pancreatitis and a few other diseases.In approximately 50% of reported patients with this congenital malformation,hyperglycemia was demonstrated.Evaluation of hyperglycemia and diabetes mellitus in all patients with agenesis of the dorsal pancreas including description of fasting blood glucose,oral glucose tolerance test,glycated hemoglobin and medical treatment would be a future goal.Since autosomal dominant transmission has been suggested in single families,more family studies including imaging technologies with demonstration of the pancreatic duct system are needed for evaluation of this disease.With this letter to the editor,we aim to increase available information for the better understanding of this rare disease.
文摘Irritable bowel syndrome(IBS) is one of the most common gastrointestinal disorders in Western countries. Despite the high prevalence of this disorders, the therapeutic management of these patients is often unsatisfactory. A number of factors have been suggested to be involved in the pathogenesis of IBS, including impaired motility and sensitivity, increased permeability, changes in the gut microbiome and alterations in the brain-gut axis. Also food seems to play a critical role: the most of IBS patients report the onset or the exacerbation of their symptoms after the meals. Recently, an increasing attention has been paid to the role of food in IBS. In this review we summarize the most recent evidences about the role of diet on IBS symptoms. A diet restricted in fermentable, poorly absorbed carbohydrates and sugar alcohols has beneficial effects on IBS symptoms. More studies are needed to improve our knowledge about the relationship between food and IBS. However, in the foreseeable future, dietary strategies will represent one of the key tools in the therapeutic management of patients with IBS.
文摘BACKGROUND Enteral nutrition(EN)is essential for critically ill patients.However,some patients will have enteral feeding intolerance(EFI)in the process of EN.AIM To develop a clinical prediction model to predict the risk of EFI in patients receiving EN in the intensive care unit.METHODS A prospective cohort study was performed.The enrolled patients’basic information,medical status,nutritional support,and gastrointestinal(GI)symptoms were recorded.The baseline data and influencing factors were compared.Logistic regression analysis was used to establish the model,and the bootstrap resampling method was used to conduct internal validation.RESULTS The sample cohort included 203 patients,and 37.93%of the patients were diagnosed with EFI.After the final regression analysis,age,GI disease,early feeding,mechanical ventilation before EN started,and abnormal serum sodium were identified.In the internal validation,500 bootstrap resample samples were performed,and the area under the curve was 0.70(95%CI:0.63-0.77).CONCLUSION This clinical prediction model can be applied to predict the risk of EFI.
