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Upregulation of cadherin-11 contributes to cholestatic liver fibrosis

pediatric Investigation 2022年第2期6卷 100-110页

作者： Bo Wu Xinbei Tian Weipeng Wang Jing Zhu Ying Lu Jun Du Yongtao Xiao department of pediatric Surgery Xin Hua HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Pediatric Gastroenterology and Nutrition Shanghai Institute of Pediatric ResearchShanghaiChina Shanghai Key Laboratory of pediatric gastroenterology and nutrition ShanghaiChina

Importance:Cadherin-11(CDH11),a cell-to-cell adhesion molecule,is implicated in the fibrotic process of several organs.Biliary atresia(BA)is a common cholestatic liver disease featuring cholestasis and progressive liver fibrosis in children.Cholestatic liver fibrosis may progress to liver cirrhosis and lacks effective therapeutic strategies.Currently,the role of CDH11 in cholestatic liver fibrosis remains unclear.Objective:This study aimed to explore the functions of CDH11 in cholestatic liver fibrosis.Methods:The expression ofCDH11 in BA livers was evaluated by database analysis and immunostaining.Seven BA liver samples were used for immunostaining.The wild type(Wt)andCDH11 knockout(CDH11^(-/-))mice were subjected to bile duct ligation(BDL)to induce cholestatic liver fibrosis.The serum biochemical analysis,liver histology,and western blotting were used to assess the extent of liver injury and fibrosis as well as activation of transforming growth factor-β(TGF-β)/Smad pathway.The effect of CDH11 on the activation of hepatic stellate cell line LX-2 cells was investigated.Results:Analysis of public RNA-seq datasets showed thatCDH11 expression levels were significantly increased in livers of BA,and CDH11 was correlated with liver fibrosis in BA.BDL-induced liver injury and liver fibrosis were attenuated inCDH11^(-/-)mice compared to Wt mice.The protein expression levels of phosphorylated Smad2/3 were decreased in livers ofCDH11^(-/-)BDL mice compared to Wt BDL mice.CDH11 knockdown inhibited the activation of LX-2 cells.Interpretation:CDH11 plays an important role in cholestatic liver fibrosis and may represent a potential therapeutic target for cholestatic liver disease,such as BA.

关键词： Cadherin-11 Biliary atresia Cholestatic liver fibrosis TGF-β/Smad

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Gastric electrical stimulation: An emerging therapy for children with intractable gastroparesis

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World Journal of gastroenterology 2019年第48期25卷 6880-6889页

作者： Aniruddh Setya Priyanka Nair Sam Xianjun Cheng department of pediatric gastroenterology Hepatology and Nutrition University of Florida

Management of gastroparesis remains challenging,particularly in pediatric patients.Supportive care and pharmacological therapies for symptoms remain the mainstay treatment.Although they are effective for mild and some moderately severe cases,often time they do not work for severe gastroparesis.There are a few prokinetics available,yet the use of these drugs is limited by a lack of persistent efficacy and/or safety concerns.Currently,the only modality for adult patients with severe intractable gastroparesis is surgery,e.g.,pyloroplasty and partial gastrectomy,however,this option is generally considered too radical for a growing child.Novel therapeutic approaches,particularly those which are less invasive,are needed.This article explores gastric electrical stimulation(GES),a new therapy for gastroparesis.Unlike others,it neither needs medications nor gastrectomy;rather,it treats through the use of microelectrodes to deliver high-frequency low energy electric stimulation to the pacemaker area of the stomach.Thus,it is tolerated and safe in children.Like in adult patients,GES appears to work in releasing symptoms,improving nutrition,and enhancing the quality of life;it also helps wean off medications and eliminate many needs for hospitalization.Considering the transient nature of gastroparesis in children in many occasions,GES is considered a“bridging”therapy after failed medical interventions and before surgery.

关键词： Gastroparesis Gastric electrical stimulation Nausea Vomiting Prokinetics

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Emerging role of regulated cell death in intestinal failure-associated liver disease

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 228-233页

作者： Si-Yang Cheng Lu Jiang Ying Wang Wei Cai department of pediatric Surgery Xinhua HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200092China Shanghai Key Laboratory of pediatric gastroenterology and nutrition Shanghai 200092China Shanghai Institute for pediatric Research Shanghai 200092China Division of pediatric gastroenterology and nutrition Xinhua HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200092China

Intestinal failure-associated liver disease(IFALD)is a common complication of long-term parenteral nutrition that is associated with significant morbidity and mortality.It is mainly characterized by cholestasis in children and steatohepatitis in adults.Unfortunately,there is no effective approach to prevent or reverse the disease.Regulated cell death(RCD)represents a fundamental biological paradigm that determines the outcome of a variety of liver diseases.Nowadays cell death is reclassified into several types,based on the mechanisms and morphological phenotypes.Emerging evidence has linked different modes of RCD,such as apoptosis,necroptosis,ferroptosis,and pyroptosis to the pathogenesis of liver diseases.Recent studies have shown that different modes of RCD are present in animal models and patients with IFALD.Understanding the pathogenic roles of cell death may help uncover the underlying mechanisms and develop novel therapeutic strategies in IFALD.In this review,we discuss the current knowledge on how RCD may link to the pathogenesis of IFALD.We highlight examples of cell death-targeted interventions aiming to attenuate the disease,and provide perspectives for future basic and translational research in the field.

关键词： Parenteral nutrition Apoptosis Necroptosis Cholestasis Steatosis

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Therapeutic developments in metabolic dysfunction-associated fatty liver disease

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Chinese Medical Journal 2022年第9期135卷 1009-1018页

作者： Yiwen Shi Jiangao Fan department of gastroenterology Xinhua Hospital Affiliated to Shanghai Jlao Tong University School of MedicineShanghai 200092China Shanghal Key Lab of pediatric gastroenterology and nutrition Shanghai 200092China

Metabolic dysfunction-associated fatty liver disease(MAFLD)has become one of the most prevalent chronic liver diseases worldwide,bringing risk of multiorgan disfunctions including cardiovascular events,complications of cirrhosis,and even malignance.In terms of health burden management,screening patients with high risk of MAFLD and providing individual comprehensive treatment is critical.Although there are numerous agents entering clinical trials for MAFLD treatment every year,there is still no effective approved drug.The nomenclature of MAFLD highlighted the concomitant metabolic disorders and obesity.MAFLD patients with type 2 diabetes had higher risk of developing liver cirrhosis and cancer,and would benefit from anti-hyperglycemic agents;overweight and obese patients may benefit more from weight loss therapies;for patients with metabolic syndrome,individual comprehensive management is needed to reduce the risk of adverse outcomes.In this review,we introduced the current status and advances of the treatment of MAFLD based on weight loss,improving insulin resistance,and management of cardiometabolic disorders,in order to provide individualized therapy approaches for patients with MAFLD.

关键词： Metabolic dysfunction-associated fatty liver disease Nonalcoholic fatty liver disease Metabolic disorder Pharmacological targets Management

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From NAFLD to MAFLD: Not just a change in the name

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Hepatobiliary & Pancreatic Diseases International 2022年第6期21卷 511-513页

作者： Jing Zeng Jian-Gao Fan department of gastroenterology Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200092China Shanghai Key Lab of pediatric gastroenterology and nutrition Shanghai 200092China

The names of many diseases have changed over time,and the criteria of successfully changing the name of a disease should make sense,be easy to say and write,get quick endorsement by professional societies,and keep the same acronym.In general,a change in the name of a disease usually represents an improve-ment in the understanding of the disease,whether on clinical set-tings and natural history or pathophysiological aspects.The suc-cessful renamed liver diseases in history include from non-A non-B hepatitis,non-B non-C hepatitis,primary biliary cirrhosis to hep-atitis C,hepatitis E and primary biliary cholangitis,respectively.Therefore,the rename of the disease that is finally used usually clearly indicates its main characteristics.

关键词： diseases NAFLD clinical

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Metabolic dysfunction-associated fatty liver disease: from basic research to clinical application

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Chinese Medical Journal 2022年第10期135卷 1138-1140页

作者： Ruixu Yang Qian Jin Jiangao Fan department of gastroenterology Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China Shanghai Key Lab of pediatric gastroenterology and nutrition Shanghai 200092China.

The increasing burden of non-alcoholic fatty liver disease:Non-alcoholic fatty liver disease(NAFLD)is the_most common causeofchronicliverdisease in the world.NAFLD encompasses,a spectrum of liver,disease,ranging from simple hepatic steatosis to non-alcoholic steatohepatitis(NASH),fibrosis,cirrhosis,and hepatocellular carcinoma(HCC).

关键词： liver NAFLD hepatic

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Clinical significance of low transaminase levels in children with inflammatory bowel disease

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World Journal of pediatrics 2019年第2期15卷 143-147页

作者： Murat Cakir Elif Sag Guzide Dogan Fatih Unal Erhun Kasirga department of pediatric gastroenterology Hepatology and nutrition Faculty of MedicineKaradeniz Technical UniversityTrabzonTurkey department of pediatric gastroenterology Hepatology and nutrition Faculty of MedicineManisa Celal Bayar UniversityManisaTurkey department of pediatric gastroenterology Hepatology and nutrition BursaTurkey

Background Low alanine aminotransaminase (LALT) levels may be seen in patients with inflammatory bowel disease (IBD),but there has been no study about the frequency and its clinical significance.We aimed to analyze the frequency of LALT,and its clinical significance in children with IBD.Methods The study included the 89 patients with IBD without hepatobiliary involvement.LALT was defined as ALT levels < 5 U/L.Demographic and clinical findings and outcome of the patients with and without LALT were compared.Results LALT was found 47.1% of the patients.At initial examination,it was more common in female patients (92.3 vs.41.3%,P < 0.001) and patients with CD (57.7 vs.30.2%,P=0.01).75% of the patients with penetrating Crohn's disease (CD) had LALT (P=0.002).Hemoglobin (10.4±2.1 vs.11.7± 1.9 g/dL,P=0.01),folic acid (5.2±3.3 vs.8.6±5.9 ng/mL,P =0.02) and serum albumin levels (3.6 ± 0.8 vs.4.7 ± 5 g/dL,P =0.002) were significantly low in patients with LALT.LALT was associted with the disease relapse within 2 weeks in 12 of the 16 patients with LALT whereas it was seen in 16 of the 73 patients without LALT during the follow-up (75 vs.21.9%,P < 0.001).Additionally,steroid dependency was more common in patients with LALT during the follow-up (62.5 vs.12.3%,P<0.001).Conclusions LALT is common in children with IBD especially in CD and associated with low hemoglobin,albumin and folic acid levels.It may be a marker of relapse and steroid dependency.

关键词： Children Inflammatory bowel disease Low transaminase levels Vitamin B6

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Serum ferritin in neonatal cholestasis: A specific and active molecule or a non-specific bystander marker?

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Hepatobiliary & Pancreatic Diseases International 2019年第2期18卷 173-180页

作者： Behairy El-Sayed Behairy Hatem Abd-Alsattar Konswa Hanaa Talaat Ahmed Dina Shehata El-Azab Nermin Mohamed Adawy Ahmad Mohamed Sira department of pediatric Hepatology Gastroenterology and Nutrition National Liver Institute Menofiya University department of Pathology National Liver Institute Menofiya University

Background: Serum ferritin(SF) and consequently hepatic iron have long been considered important in liver fibrosis progression. They have been studied in different liver diseases with no previous reports in neonatal cholestasis(NC). This study aimed to measure SF in different etiologies of NC and investigate its relation to hepatic iron and fibrosis. Methods: SF was measured in 75 infants, including 50 with NC and 25 with sepsis. SF was compared between these two groups. Biochemical parameters, hepatic iron grades, and liver fibrosis and other histopathological characteristics and correlated with SF were assessed in NC group. Finally, a comparison between intrahepatic cholestasis and obstructive etiology was performed. Results: SF was elevated in NC(1598 ± 2405 ng/mL) with no significant difference from those with sepsis( P = 0.445). NC and sepsis constituted augmenting factors leading to more elevation of SF(2589 ± 3511 ng/mL). SF was significantly correlated with hepatic iron grades( r = 0.536, P < 0.0 0 01) and a cut-off value of 803.5 ng/mL can predict higher grades( ≥ grade 3) of iron deposition with sensitivity of 100%, specificity of 70% and accuracy of 85%. Moreover, SF was significantly higher( P < 0.0 0 01) in those with intrahepatic cholestasis(2602 ± 3154 ng/mL) and their prevalent pathological findings of giant cell transformation( P = 0.009) and hepatocyte swelling( P = 0.023) than those with obstructive etiology(672 ± 566 ng/mL) and their prevalent pathological findings of ductular proliferation( P = 0.003) and bile plugs( P = 0.002). SF was unrelated to the grade of liver fibrosis( P = 0.058). Conclusions: SF is non-specifically elevated in NC, with positive correlation to hepatic iron grades. SF ≥ 803.5 ng/mL can predict higher grades( ≥ grade 3) of hepatic iron. However, an active role of increased SF and hepatic iron in disease progression remains questionable.

关键词： Biliary atresia Liver fibrosis Hepatic iron grade Intrahepatic cholestasis Iron

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Longitudinal changes in body weight of breastfeeding mothers in the first year after delivery and its relationship with human milk composition:a combined longitudinal and cross-sectional cohort study

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Food Science and Human Wellness 2024年第1期13卷 254-264页

作者： Huijuan Ruan Yajie Zhang Qingya Tang Xuan Zhao Xuelin Zhao Yi Xiang Wei Geng Yi Feng Wei Cai department of Clinical nutrition Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China Shanghai Key Laboratory of pediatric gastroenterology and nutrition Shanghai Institute of Pediatric ResearchShanghai 200092China department of pediatric Surgery Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China

Objective:Postpartum weight retention(PPWR)is a common problem among women after childbirth.The main objectives of this study are to understand the changes in body weight of breastfeeding mothers during long-term follow-up and preliminarily explore the relationship between maternal body weight and human milk composition,including macronutrients,leptin,and adiponectin.Methods:The study included a longitudinal cohort(122 mothers),and a cross-sectional cohort(37 mothers).The human milk,maternal weight,and dietary surveys were collected in the longitudinal cohort at different follow-up time points(1-14 days postpartum,2-4 months postpartum,5-7 months postpartum,and 12-17 months postpartum).The maternal body weight was analyzed using the responses in the survey questionnaires.A milk analyzer based on the mid-infrared spectroscopy(MIRS)was used to determine milk composition,and nutrition analysis software evaluated dietary intakes.In the cross-sectional cohort,participating mothers were asked to provide blood and human milk samples and pertinent information related to maternal body composition.Maternal body composition was measured by bioelectrical impedance analysis(BIA),while ELISA analyzed leptin and adiponectin in milk and serum.Results:At 5-7 months postpartum,the PPWR of breastfeeding mothers was(2.46±3.59)kg.At 12-17 months postpartum,the PPWR was(0.98±4.06)kg.PPWR was found to be negatively correlated with milk fat content within 14 days postpartum and positively correlated at 2-4 months postpartum.In addition,the maternal weight and body muscle mass were positively correlated with leptin and adiponectin in milk.Plasma leptin was positively correlated with the mother’s body weight,body mass index(BMI),FAT percentage,and body fat mass,while plasma adiponectin did not correlate with any parameter.The results also indicate that the PPWR did not correlate with leptin and adiponectin in plasma or milk.Conclusions:Breastfeeding mothers may retain considerable weight gain one year after delivery.Human milk composition

关键词： Human milk Milk composition Body weight Body mass index(BMI) Weight gain Postpartum weight retention

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Severe chest pain in a pediatric ulcerative colitis patient after 5-aminosalicylic acid therapy

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World Journal of gastroenterology 2008年第27期14卷 4400-4402页

作者： Orhan Atay Kadakkal Radhakrishnan Janine Arruda Robert Wyllie Department of Pediatric Gastroenterology and Nutrition The Children’s Hospital Cleveland Clinic

Severe reactions to mesalamine products are rarely seen in pediatric patients. We report a case of a 12-year-old boy who had a severe cardiac reaction to a mesalamine product Asacol. Past medical history is significant for ulcerative colitis (UC) diagnosed at 9 years of age. Colo- noscopy one week prior to admission revealed pancoli- tis. He was treated with Asacol 800 mg three times per day and prednisone 20 mg/d. He was subsequently ad- mitted to the hospital for an exacerbation of his UC and started on intravenous solumedrol. He had improvement of his abdominal pain and diarrhea. The patient com- plained of new onset of chest pain upon initiating Asacol therapy. Electrocardiogram (ECG) revealed non-specific ST-T wave changes with T-wave inversion in the lateral leads. Echocardiogram (ECHO) revealed low-normal to mildly depressed left ventricular systolic function. The left main coronary artery and left anterior descending artery were mildly prominent measuring 5 mm and 4.7 mm, respectively. His chest pain completely resolved within 24-36 h of discontinuing Asacol. A repeat echo- cardiogram performed two days later revealed normal left ventricular function with normal coronary arteries (< 3.5 mm). Onset of chest pain after Asacol and im- mediate improvement of chest pain, as well as improve- ment of echocardiogram and ECG findings after discon- tinuing Asacol suggests that our patient suffered from a rare drug-hypersensitivity reaction to Asacol.

关键词： 5-对氨基水杨酸溃疡性结肠炎心包炎小儿胸痛

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