BACKGROUND Blue rubber bleb naevus syndrome(BRBNS)is a rare disease that usually presents with multiple venous malformations in the skin and gastrointestinal tract.Lesions located in the gastrointestinal tract always ...BACKGROUND Blue rubber bleb naevus syndrome(BRBNS)is a rare disease that usually presents with multiple venous malformations in the skin and gastrointestinal tract.Lesions located in the gastrointestinal tract always result in chronic gastrointestinal bleeding and severe anemia.The successful management of BRBNS with sirolimus had been reported in many institutions,due to its impact on signaling pathways of angiogenesis.However,the experience in treatment of neonates with BRBNS was limited.CASE SUMMARY A 38-day-old premature female infant born with multiple skin lesions,presented to our center complaining of severe anemia and hematochezia.Laboratory examination demonstrated that hemoglobin was 5.3 g/dL and contrast-enhanced abdominal computed tomography showed multiple low-density space-occupying lesions in the right lobe of the liver.She was diagnosed as having BRBNS based on typical clinical and examination findings.The patient was treated by transfusions twice and hemostatic drugs but symptoms of anemia were difficult to alleviate.A review of BRBNS case reports found that patients had been successfully treated with sirolimus.Then the patient was treated with sirolimus at an average dose of 0.95 mg/m2/d with a target drug level of 10-15 ng/mL.During 28 mo of treatment,the lesion was reduced,hemoglobin returned to normal,and there were no adverse drug reactions.CONCLUSION This case highlights the dosing regimen and plasma concentration in neonates,for the current common empiric dose is high.展开更多
AIM： To investigate the genetic relationship between Hirschsprung＇s disease （HD） and intestinal neuronal dysplasia （IND） in Chinese population.METHODS： Peripheral blood samples were obtained from 30 HD patients...AIM： To investigate the genetic relationship between Hirschsprung＇s disease （HD） and intestinal neuronal dysplasia （IND） in Chinese population.METHODS： Peripheral blood samples were obtained from 30 HD patients, 20 IND patients, 18 HD/IND combined patients and 20 normal individuals as control. Genomic DNA was extracted according to standard procedure. Exons 11,13,15,i7 of RET proto-oncogene were amplified by polymerase chain reaction （PCR）. The mutations of RET proto-oncogene were analyzed by single strand conformational polymorphism （SSCP） and sequencing of the positive amplified products was performed.RESULTS： Eight germline sequence variants were detected. In HD patients, 2 missense mutations in exon 11 at nucleotide 15165 G→A （G667S）, 2 frameshifc mutations in exon 13 at nucleotide 18974 （18974insG）, 1 missense mutation in exon 13 at nucleotide 18919 A→G （K756E） and 1 silent mutation in exon 15 at nucleotide 20692 G→A（Q916Q） were detected. In HD/IND combined patients, 1 missense mutation in exon 11 at nucleotide 15165 G→A and 1 silent mutation in exon 13 at nucleotide 18888 T→G （L745L） were detected. No mutation was found in IND patients and controls.CONCLUSION： Mutation of RET proto-oncogene is involved in the etiopathogenesis of HD. The frequency of REr proto-oncogene mutation is quite different between IND and HD in Chinese population, IND is a distinct clinical entity genetically different from HD.展开更多
Background Macrophages are involved in various immune inflammatory disease conditions.This study aimed to investigate the role and mechanism of macrophages in regulating acute intestinal injury in neonatal necrotizing...Background Macrophages are involved in various immune inflammatory disease conditions.This study aimed to investigate the role and mechanism of macrophages in regulating acute intestinal injury in neonatal necrotizing enterocolitis(NEC).Methods CD68,nucleotide-binding oligomerization domain,leucine-rich repeat,and pyrin domain-containing 3(NLRP3),cysteine aspartate-specific protease-1(caspase-1),and interleukin-1β(IL-1β)in paraffin sections of intestinal tissues from NEC and control patients were detected with immunohistochemistry,immunofluorescence,and western blot.Hypertonic pet milk,hypoxia and cold stimulation were used to establish a mouse(wild type and Nlrp3^(-/-))model of NEC.The mouse macrophage(RAW 264.7)and rat intestinal epithelial cell-6 lines were also cultured followed by various treatments.Macrophages,intestinal epithelial cell injuries,and IL-1β release were determined.Results Compared to the gut“healthy”patients,the intestinal lamina propria of NEC patients had high macrophage infiltration and high NLRP3,caspase-1,and IL-1β levels.Furthermore,in vivo,the survival rate of Nlrp3^(-/-)NEC mice was dramatically improved,the proportion of intestinal macrophages was reduced,and intestinal injury was decreased compared to those of wild-type NEC mice.NLRP3,caspase-1,and IL-1β derived from macrophages or supernatant from cocultures of macrophages and intestinal epithelial cells also caused intestinal epithelial cell injuries.Conclusions Macrophage activation may be essential for NEC development.NLRP3/caspase-1/IL-1β cellular signals derived from macrophages may be the underlying mechanism of NEC development,and all these may be therapeutic targets for developing treatments for NEC.展开更多
Background:Congenital duodenal obstruction(CDO)is one of the most common anomalies in newborns,and accounting for nearly half of all cases of neonatal intestinal obstruction.This study aimed to review our single-cente...Background:Congenital duodenal obstruction(CDO)is one of the most common anomalies in newborns,and accounting for nearly half of all cases of neonatal intestinal obstruction.This study aimed to review our single-center experience in managing congenital duodenal obstruction while evaluate the outcomes.Methods:We conducted a retrospective analysis of the records of all neonates dianogsed with congenital duodenal obstruction admitted to our center between January 2003 and December 2012.We analyzed demographic criteria,clinical manifestations,associated anomalies,radiologic findings,surgical methods,postoperative complications,and fi nal outcomes.Results:The study comprised 287 newborns(193 boys and 94 girls).Birth weight ranged from 950 g to 4850 g.Fifty-three patients were born prematurely between 28 and 36 weeks'gestation.Malrotation was diagnosed in 174 patients,annular pancreas in 66,duodenal web in 55,duodenal atresia or stenosis in 9,preduodenal portal vein in 2,and congenital band compression in 1.Twenty patients had various combinations of these conditions.Presenting symptoms included bilious vomiting,dehydration,and weight loss.X-rays of the upper abdomen demonstrated the presence of a typical double-bubble sign or air-fluid levels in 68.64%of patients,and confi rmatory upper and/or lower gastrointestinal contrast studies were obtained in 64.11%.Multiple associated abnormalities were observed in 50.52%of the patients.Various surgical approaches were used,including Ladd's procedure,duodenoplasty,duodenoduodenostomy,duodenojejunostomy,or a combination of these.Seventeen patients died postoperatively and 14 required re-operation.Conclusions:Congenital duodenal obstruction is a complex entity with various etiologies and often includes multiple concomitant disorders.Timely diagnosis and aggressive surgery are key to improving prognosis.Care should be taken to address all of the causes of duodenal obstruction and/or associated alimentary tract anomalies during surgery.展开更多
Background The pathogenesis of biliary atresia (BA) is associated with an inflammatory process involving the biliary tree. This study aimed to investigate the association of T-helper cell cytokine levels with age in p...Background The pathogenesis of biliary atresia (BA) is associated with an inflammatory process involving the biliary tree. This study aimed to investigate the association of T-helper cell cytokine levels with age in patients with BA. Methods Twenty-eight patients with BA were divided into three groups according to their age (< 2 months, 2–3 months, and ≥ 3 months). All the patients underwent Kasai portoenterostomy. Blood samples were collected from the patients pre-operatively, and the liver tissue specimens were obtained during surgery. We detected serum levels of interleukin (IL)-1β, IL-12p70, interferon (IFN)-γ, IL-6, IL-10, and transforming growth factor (TGF)-β1 and liver expression of IL-1β, IL-6, and TGF-β1. Results The serum levels of IL-1β, IL-12p70, IL-6, and IL-10 in patients aged ≥ 3 months were significantly higher than those in patients aged < 2 months. There were no significant age-related differences in the IL-1β, IL-6 and TGF-β1 expres-sion levels in the liver tissue of patients with BA. Conclusions The serum levels of IL-1β, IL-6, IL-10 and IL-12p70 showed significant age-related differences in patients with BA. Interpretation of the role of cytokines in BA needs to take patient's age into consideration.展开更多
Background Biliary atresia(BA)is a rare fatal liver disease in children,and the aim of this study was to develop a method to diagnose BA early.Methods We determined serum levels of matrix metalloproteinase-7(MMP-7),th...Background Biliary atresia(BA)is a rare fatal liver disease in children,and the aim of this study was to develop a method to diagnose BA early.Methods We determined serum levels of matrix metalloproteinase-7(MMP-7),the results of 13 liver tests,and the levels of 20 bile acids,and integrated computational models were constructed to diagnose BA.Results Our findings demonstrated that MMP-7 expression levels,as well as the results of four liver tests and levels of ten bile acids,were significantly different between 86 BA and 59 non-BA patients(P<0.05).The computational prediction model revealed that MMP-7 levels alone had a higher predictive accuracy[area under the receiver operating characteristic curve(AUC)=0.966,95%confidence interval(CI):0.942,0.989]than liver test results and bile acid levels.The AUC was 0.890(95%CI 0.837,0.943)for liver test results and 0.825(95%CI 0.758,0.892)for bile acid levels.Furthermore,bile levels had a higher contribution to enhancing the predictive accuracy of MMP-7 levels(AUC=0.976,95%CI 0.953,1.000)than liver test results.The AUC was 0.983(95%CI 0.962,1.000)for MMP-7 levels combined with liver test results and bile acid levels.In addition,we found that MMP-7 levels were highly correlated with gamma-glutamyl transferase levels and the liver fibrosis score.Conclusion The innovative integrated models based on a large number of indicators provide a noninvasive and cost-effective approach for accurately diagnosing BA in children.展开更多
文摘BACKGROUND Blue rubber bleb naevus syndrome(BRBNS)is a rare disease that usually presents with multiple venous malformations in the skin and gastrointestinal tract.Lesions located in the gastrointestinal tract always result in chronic gastrointestinal bleeding and severe anemia.The successful management of BRBNS with sirolimus had been reported in many institutions,due to its impact on signaling pathways of angiogenesis.However,the experience in treatment of neonates with BRBNS was limited.CASE SUMMARY A 38-day-old premature female infant born with multiple skin lesions,presented to our center complaining of severe anemia and hematochezia.Laboratory examination demonstrated that hemoglobin was 5.3 g/dL and contrast-enhanced abdominal computed tomography showed multiple low-density space-occupying lesions in the right lobe of the liver.She was diagnosed as having BRBNS based on typical clinical and examination findings.The patient was treated by transfusions twice and hemostatic drugs but symptoms of anemia were difficult to alleviate.A review of BRBNS case reports found that patients had been successfully treated with sirolimus.Then the patient was treated with sirolimus at an average dose of 0.95 mg/m2/d with a target drug level of 10-15 ng/mL.During 28 mo of treatment,the lesion was reduced,hemoglobin returned to normal,and there were no adverse drug reactions.CONCLUSION This case highlights the dosing regimen and plasma concentration in neonates,for the current common empiric dose is high.
文摘AIM： To investigate the genetic relationship between Hirschsprung＇s disease （HD） and intestinal neuronal dysplasia （IND） in Chinese population.METHODS： Peripheral blood samples were obtained from 30 HD patients, 20 IND patients, 18 HD/IND combined patients and 20 normal individuals as control. Genomic DNA was extracted according to standard procedure. Exons 11,13,15,i7 of RET proto-oncogene were amplified by polymerase chain reaction （PCR）. The mutations of RET proto-oncogene were analyzed by single strand conformational polymorphism （SSCP） and sequencing of the positive amplified products was performed.RESULTS： Eight germline sequence variants were detected. In HD patients, 2 missense mutations in exon 11 at nucleotide 15165 G→A （G667S）, 2 frameshifc mutations in exon 13 at nucleotide 18974 （18974insG）, 1 missense mutation in exon 13 at nucleotide 18919 A→G （K756E） and 1 silent mutation in exon 15 at nucleotide 20692 G→A（Q916Q） were detected. In HD/IND combined patients, 1 missense mutation in exon 11 at nucleotide 15165 G→A and 1 silent mutation in exon 13 at nucleotide 18888 T→G （L745L） were detected. No mutation was found in IND patients and controls.CONCLUSION： Mutation of RET proto-oncogene is involved in the etiopathogenesis of HD. The frequency of REr proto-oncogene mutation is quite different between IND and HD in Chinese population, IND is a distinct clinical entity genetically different from HD.
基金supported by the National Natural Science Foundation of China(81901989 to LDM,82272191 to SQ,and 82171699 to TJF)Natural Science Foundation of Zhejiang Province(LY21H150005 to LDM,LY22H040006 to TJF)+1 种基金Foundation for The Top-Notch Youth Talent Cultivation Project of Independent Design Project of National Clinical Research Center for Child Health(Q21B0007 to LDM)Special Fund for the Incubation of Young Clinical Scientist,Children's Hospital,Zhejiang University School of Medicine(CHZJU2022YS002 to LDM).
文摘Background Macrophages are involved in various immune inflammatory disease conditions.This study aimed to investigate the role and mechanism of macrophages in regulating acute intestinal injury in neonatal necrotizing enterocolitis(NEC).Methods CD68,nucleotide-binding oligomerization domain,leucine-rich repeat,and pyrin domain-containing 3(NLRP3),cysteine aspartate-specific protease-1(caspase-1),and interleukin-1β(IL-1β)in paraffin sections of intestinal tissues from NEC and control patients were detected with immunohistochemistry,immunofluorescence,and western blot.Hypertonic pet milk,hypoxia and cold stimulation were used to establish a mouse(wild type and Nlrp3^(-/-))model of NEC.The mouse macrophage(RAW 264.7)and rat intestinal epithelial cell-6 lines were also cultured followed by various treatments.Macrophages,intestinal epithelial cell injuries,and IL-1β release were determined.Results Compared to the gut“healthy”patients,the intestinal lamina propria of NEC patients had high macrophage infiltration and high NLRP3,caspase-1,and IL-1β levels.Furthermore,in vivo,the survival rate of Nlrp3^(-/-)NEC mice was dramatically improved,the proportion of intestinal macrophages was reduced,and intestinal injury was decreased compared to those of wild-type NEC mice.NLRP3,caspase-1,and IL-1β derived from macrophages or supernatant from cocultures of macrophages and intestinal epithelial cells also caused intestinal epithelial cell injuries.Conclusions Macrophage activation may be essential for NEC development.NLRP3/caspase-1/IL-1β cellular signals derived from macrophages may be the underlying mechanism of NEC development,and all these may be therapeutic targets for developing treatments for NEC.
基金supported by grants from Zhejiang Province Science and Technology Programs(no.2012C13G2010119,2012C13024-1 and 2012C23096)Zhejiang Provincial Program for the Cultivation of High-level Innovative Health talents(Qiang Shu).
文摘Background:Congenital duodenal obstruction(CDO)is one of the most common anomalies in newborns,and accounting for nearly half of all cases of neonatal intestinal obstruction.This study aimed to review our single-center experience in managing congenital duodenal obstruction while evaluate the outcomes.Methods:We conducted a retrospective analysis of the records of all neonates dianogsed with congenital duodenal obstruction admitted to our center between January 2003 and December 2012.We analyzed demographic criteria,clinical manifestations,associated anomalies,radiologic findings,surgical methods,postoperative complications,and fi nal outcomes.Results:The study comprised 287 newborns(193 boys and 94 girls).Birth weight ranged from 950 g to 4850 g.Fifty-three patients were born prematurely between 28 and 36 weeks'gestation.Malrotation was diagnosed in 174 patients,annular pancreas in 66,duodenal web in 55,duodenal atresia or stenosis in 9,preduodenal portal vein in 2,and congenital band compression in 1.Twenty patients had various combinations of these conditions.Presenting symptoms included bilious vomiting,dehydration,and weight loss.X-rays of the upper abdomen demonstrated the presence of a typical double-bubble sign or air-fluid levels in 68.64%of patients,and confi rmatory upper and/or lower gastrointestinal contrast studies were obtained in 64.11%.Multiple associated abnormalities were observed in 50.52%of the patients.Various surgical approaches were used,including Ladd's procedure,duodenoplasty,duodenoduodenostomy,duodenojejunostomy,or a combination of these.Seventeen patients died postoperatively and 14 required re-operation.Conclusions:Congenital duodenal obstruction is a complex entity with various etiologies and often includes multiple concomitant disorders.Timely diagnosis and aggressive surgery are key to improving prognosis.Care should be taken to address all of the causes of duodenal obstruction and/or associated alimentary tract anomalies during surgery.
文摘Background The pathogenesis of biliary atresia (BA) is associated with an inflammatory process involving the biliary tree. This study aimed to investigate the association of T-helper cell cytokine levels with age in patients with BA. Methods Twenty-eight patients with BA were divided into three groups according to their age (< 2 months, 2–3 months, and ≥ 3 months). All the patients underwent Kasai portoenterostomy. Blood samples were collected from the patients pre-operatively, and the liver tissue specimens were obtained during surgery. We detected serum levels of interleukin (IL)-1β, IL-12p70, interferon (IFN)-γ, IL-6, IL-10, and transforming growth factor (TGF)-β1 and liver expression of IL-1β, IL-6, and TGF-β1. Results The serum levels of IL-1β, IL-12p70, IL-6, and IL-10 in patients aged ≥ 3 months were significantly higher than those in patients aged < 2 months. There were no significant age-related differences in the IL-1β, IL-6 and TGF-β1 expres-sion levels in the liver tissue of patients with BA. Conclusions The serum levels of IL-1β, IL-6, IL-10 and IL-12p70 showed significant age-related differences in patients with BA. Interpretation of the role of cytokines in BA needs to take patient's age into consideration.
基金supported by a grant from the Key Program of the Independent Design Project of National Clinical Research Center for Child Health(Grant no.S20C0004)Shanghai Pujiang Program(21PJ1423100)Ministry of Industry and Information Technology Artificial Intelligence Medical Devices Innovation Program.
文摘Background Biliary atresia(BA)is a rare fatal liver disease in children,and the aim of this study was to develop a method to diagnose BA early.Methods We determined serum levels of matrix metalloproteinase-7(MMP-7),the results of 13 liver tests,and the levels of 20 bile acids,and integrated computational models were constructed to diagnose BA.Results Our findings demonstrated that MMP-7 expression levels,as well as the results of four liver tests and levels of ten bile acids,were significantly different between 86 BA and 59 non-BA patients(P<0.05).The computational prediction model revealed that MMP-7 levels alone had a higher predictive accuracy[area under the receiver operating characteristic curve(AUC)=0.966,95%confidence interval(CI):0.942,0.989]than liver test results and bile acid levels.The AUC was 0.890(95%CI 0.837,0.943)for liver test results and 0.825(95%CI 0.758,0.892)for bile acid levels.Furthermore,bile levels had a higher contribution to enhancing the predictive accuracy of MMP-7 levels(AUC=0.976,95%CI 0.953,1.000)than liver test results.The AUC was 0.983(95%CI 0.962,1.000)for MMP-7 levels combined with liver test results and bile acid levels.In addition,we found that MMP-7 levels were highly correlated with gamma-glutamyl transferase levels and the liver fibrosis score.Conclusion The innovative integrated models based on a large number of indicators provide a noninvasive and cost-effective approach for accurately diagnosing BA in children.
