Crizotinib in the treatment of ALK gene mutation positive children with inflammatory myofibroblastic tumor: a report of 4 cases / 中华实用儿科临床杂志

Objective:To investigate the efficacy and safety of targeted therapy with Crizotinib for children with ALK gene mutation positive inflammatory myofibroblastic tumor (IMT). Methods:A retrospective analysis was performed on 4 children with ALK gene mutation positive IMT admitted to Shanghai Children′s Hospital from January 2019 to June 2021.Among them, 3 cases were given the targeted drug Crizotinib[280 mg/(m 2· time), q12h] orally, and 1 case was observed after complete tumor resection to analyze the efficacy and adverse drug reactions. Results:All 4 cases were male, aged from 2 years and 3 months to 11 years and 3 months.The tumors originated from the abdominal cavity in 2 cases, the right orbit in 1 case, and the right lung in 1 case.Pathological immunohistochemistry and fluorescence in situ hybridization were both positive for ALK gene mutation, and complete remission was achieved after comprehensive treatment.Among them, 3 patients were treated with oral Crizotinib, and 2 patients were tried to stop taking the drug for 1 year, relapsed 1 month later, and still achieved complete remission after the second treatment.The 4 cases were followed up for 8-30 months, and all survived.All the cases showed no abnormalities in blood image, liver and kidney function, myocardial enzyme profile, cardiac function, hearing and vision, and 2 cases showed prolonged Q-T interval in the course of Crizotinib treatment, which could be recovered by temporary withdrawal of drug, and no abnormality in electrocardiogram was found in continued drug use. Conclusions:Crizotinib was used to treat ALK mutation positive IMT, shrink tumor and consolidate postoperative treatment, which is a good choice for IMT in children with difficult surgical resection and refractory recurrence.

Neonatal necrotizing enterocolitis:advance on mechanism of small-molecule drugs / 中国小儿急救医学

Necrotizing enterocolitis(NEC) is the most common disease of gastrointestinal tract in neonate,and is an important cause of neonatal death,especially in premature. Its pathogenesis has not be clear and tends to be multifactorial,leading to the lack of effective prevention and treatment strategies. With the de-velopment of neonatal intensive care unit and the gradually improvement of the nursing level,the diagnostic detection rate of NEC has increased significantly. In addition to conventional surgery and conservative treat-ment,the research and development of new drugs targeting at NEC has been carried out in-depth,including octreotide,erythropoietin,amino acid and all trans retinoic acid. Through the analysis and summary of the mechanism and clinical application of these small-molecule drugs in the treatment of NEC,this review aimed at retrospecting the research progress of NEC drug treatment in recent years to provide relevant background knowledge for clinical prevention,treatment and drug research and development of NEC.

Pediatric multiple magnetic foreign body ingestion:3 cases report and literature survey / 中华实用儿科临床杂志

Objective To enhance awareness of the dangerous of multiple magnets ingestion in children and to explore the optimal treatment of it.Methods The clinical data of 3 cases with multiple magnet ingestion were retrospectively studied based on literature review.Results Ingestion of multiple magnets (range:2-5 magnets) magnets occurred in 3 cases.Age ranged from 1 to 8 years old.Magnet sources included:2 from children's family,1 from their kindergarten.All patients had several bowel perforations(range:2-4).One case was completed by laparoscopic,1 case was converted to open suegery after laparoscopy,1 case was done by open surgery.All cases got complete recovery after surgical treatment,and no complications occurred by follow-up.Conclusions Ingestion of multiple magnets may show minimal initial physical manifestations at beginning but may result in significant complications later.Two or more magnets separated from each other along the gastrointestinal tract can attract each other across bowel walls,with may result in pressure necrosis,bowel perforation,and fistulas formation and even death.Early surgical consultation with an aggressive surgical approach is recommended.Family and society should be aware of the dangers of magnet ingestion.

Clinical analysis of obstructive infantile cholestasis / 中华普通外科杂志

Objective To summarize the etiology and surgical treatment of obstructive infantile cholestasis.Methods Clinical data of 108 cases of obstructive infantile cholestasis was studied retrospectively from April 2009 to April 2014.Results Correct diagnosis was established in all 108 patients by laparoscopic biliary tract exploration and cholangiography.Among those,there were noncorrectable biliary atresia in 81 cases (75.0％),correctable biliary atresia in 5 cases (4.6％),inspissated bile syndrome in 8 cases (7.4％),infantile hepatitis syndrome in 6 cases (5.6％),choledochal cyst in 4 cases (3.7％),biliary hypoplasia in 2 cases (1.9％),1 case (0.9％) suffered from spontaneous bile duct perforation,1 case (0.9％) suffered from oppression of lymph nodes in hepatic portal.Patients of nocorrectable biliary atresia were treated with open Kasai portoenterostomy or laparoscopic Kasai portoenterostomy,correctable biliary atresia and choledochal cyst underwent laparoscopic cyst excision and Roux-Y hepaticojejunostomy,inspissated bile syndrome,infantile hepatitis syndrome and biliary hypoplasia were treated by laparoscopic cholecystostomy and biliary tract irrigation.The patient of spontaneous bile duct perforation was treated with laparoscopic common bile duct exploration and T-tube drainage,the lymph node was excised in patient with oppression of lymph nodes in hepatic portal.All infants were followed-up for 3 months to 48 months,the clearance of jaundice rate varied in patients with Kasai portoenterostomy,patients with non-Kasai portoenterostomy were all in good condition and there were no symptom recurrence.Conclusion Biliary atresia,inspissated bile syndrome,infantile hepatitis syndrome,choledochal cyst and biliary hypoplasia are the most common cause of surgery-related infantile cholestasis.Kasai portoenterostomy,hepaticojejunostomy and cholecystostomy and biliary tract irrigation are the main surgical method for surgery-related infantile cholestasis.

Biobank development in the context of precision medicine:roadblocks and countermeasures / 中华医院管理杂志

Introduced in this paper are the current situation of biobank in China in the context of precision medicine.As a vital platform of precision medicine,biobank constitutes a resource support for this plan.Establishing high quality biobank has important implications for the implement of precision medicine in China.This paper focused on the problems existing in biobank development in the context of precision medicine and put forward corresponding countermeasures as well as suggestions.

Outcomes of surgical intervention for necrotizing enterocolitis within different pathological range / 中华实用儿科临床杂志

Objective To explore the surgical intervention outcomes of necrotizing enterocolitis (NEC)pa-tients with different extent of the disease.Methods The data of 25 pediatric patients with NEC who were treated with surgical intervention in Shanghai Children′s Hospital from December 201 1 to December 201 5 were retrospectively ana-lyzed.According to the extent of the disease,the patients were divided into 3 groups:focal disease(F),multisegmental disease(M),and pan -involvement(P).The information including operation style,survival rate and time for close osto-my was analyzed.Results There were 1 1 cases with F,8 cases with M,and 6 cases with P.All patients received lapa-rotomy surgery,colostomy,or peritoneal drainage.There were 1 2 patients with very low birth weight,7 patients with low birth weight,6 patients with normal birth weight in this study.There were 1 7 cases with gastrointestinal perforation (9 cases with pneumoperitoneum,8 cases without pneumoperitoneum),8 cases without digestive tract perforation (4 cases without pneumoperitoneum,4 cases with enterostenosis after conservative treatment).In this study,close ostomy was commonly conducted 3 -6 months after the operation,except for 3 cases who received 2 or more times of operation.The survival rate in F group was 1 00.0%(1 1 /1 1 cases),higher than those in the Mgroup with 62.5%(5 /8 cases)and P group with 1 6.7%(1 /6 cases)(χ2 =4.898,1 0.31 2,all P 0.05).Conclusions The extent of disease is correlated to the outcomes of surgical in-tervention,as F had a better outcome than Mand P.Low birth weight is a risk factor for NEC.Protecting the edge of the bowel is a key factor to ensure the survival and improve the quality of life of NEC patients.Close ostomy should be con-sidered when the patients are in a stable condition (liver function and intestinal function recovery,good nutrition condi-tion,etc),and under special circumstances to conduct early or delayed closure of fistula.

Intestinal barrier dysfunction and necrotizing enterocolitis / 国际儿科学杂志

Necrotizing enterocolitis ( NEC) is one of the most serious diseases of digestive system dur-ing neonatal period,which is one of the main cause of premature death. The components which maintain the in-testinal barrier function of newborns,especially the premature infants,are always underdeveloped,and easily to be damaged. Thus,the formation of tight junctions between epithelial cells is broken,the early intestinal peristal-sis established delayed,and the secretion of sIgA is reduced. These pathogenic factors induce serious complica-tions,such as intestinal barrier dysfunction,bacterial translocation and sepsis. Hypoxia ischemia,inflammation, infection can either cause intestinal mechanical barrier damage. The delay of micro ecological barrier establish-ment,the immature of immune barriers,intestinal microcirculation dysfunction are all involved in the occurrence of NEC. In addition,miRNA also plays an important role in the regulation of intestinal epithelial cell differentia-tion,structure and barrier function. Pathological changes of NEC are the result of intestinal barrier dysfunction, and the injury of intestinal barrier function will aggravate NEC pathological changes. Therefore, understanding the role of intestinal barrier dysfunction in the pathogenesis of NEC may improve the prevention and treatment of NEC.

Study on 13-cis retinoic acid inducing differentiation of three types of human neuroblastoma cell lines in vitro / 中华实用儿科临床杂志

Objective To investigate the effects of 13-cis retinoic acid (13-cis RA) in inducing differentiation of 3 types of human neuroblastoma (NB) cells in vitro.Methods The status of MYCN gene amplification of cultured SH-SY5Y,SK-N-SH and SK-N-BE2 cells was detected by fluorescence in situ hybridization.After treatment with different concentrations of 13-cis RA,morphological changes were observed by phase-contrast microscope,and neuron-specific enolase (NSE) concentrations were determined by enzyme linked immunosorbent assay.The cell viability was measured through cell counting kit-8 assay,and the cell apoptosis was assayed with flow cytometry (FCM).Results The morphological changes in differentiation were observed in all 3 types of NB cells after 13-cis RA treatment.MYCN amplification was detected in SK-N-BE2 cells even after 13-cis RA treatment,while the other 2 cell lines were amplification-null.After different concentrations of 13-cis RA treatment,NSE concentration increased with prolonged time,especially for SK-N-BE2 cell(F =27.00,P ＜ 0.000 1).13-cis RA stimulated cell proliferation within 48 hours of treatment,and then inhibited cell growth.FCM indicated that the degree of apoptosis in SH-SY5Y cell was significantly higher after 13-cis RA treatment of 10 μmol/L concentration for continuous 96 h and 120 h as compared to the control group (F =16.21,P =0.011;F =16.04,P =0.016).Cell apoptosis of SK-N-SH cell after 13-cis RA treatment of 1 μ mol/L and 10 μ mol/L concentration for 48 h,were significantly higher than those of the control group (F =15.05,P =0.012;F =31.18,P =0.005);while SK-N-BE2 cell with different concentrations of 13-cis RA(1 μmol/L,5 μmol/L,10 μ mol/L) for 120 h were significantly higher than those of the control group(F =9.05,P =0.030;F =11.38,P =0.028;F =7.88,P =0.041).Conclusions The present study showed that 13-cis RA could induce differentiation of human NB ceils in vitro.It induces cell proliferation within 48 hours of 13-cis RA,and thereafter suppresses cell growth.No improvement was found in MYCN amplification cells with the detection of DNA level after 13-cis RA treatment,which suggests that combined treatment is possibly needed.

The unduced effect of arsenic trioxide in different types of neuroblastoma cell lines / 中华实用儿科临床杂志

Objective To identify the effect of arsenic trioxide (As2O3) on the differentiation and apoptosis of different types of neuroblastoma(NB) cell lines.Methods The cell lines [SK-N-SH,SK-N-BE2,SH-SY5 Y] were induced with different concentrations (0 μmol/L,1 μmol/L,3 μmol/L,5 μ mol/L and 7 μ mol/L) of arsenic trioxide for 24 h,48 h,72 h under the same conditions.The expression of MYCN gene was examined by fluorescence in situ hybridization assay in SK-N-BE2,cell proliferation,cell cycle and cell apoptosis were detected with cell counting kit-8 (CCK-8) assay and flow cytometry.Results 5 μmol/L of As2O3 inhibited the expression of MYCN gene in SK-N-BE2;CCK-8 assay indicated that As2O3 inhibited the proliferation of NB cell in a dose-and time-dependent manner,the cell proliferation was significantly suppressed compared with the low concentration (1 μ mol/L) after treated with As2O3 by 1 μmol/L,3 μmol/L,5 μmol/L and 7 μmol/L in 24 h,48 h and 72 h,SH-SY5Y:24 h(chisq =9.666 7,P ＜ 0.05),48 h (chisq =9.666 7,P ＜ O.05),72 h (chisq =9.512 8,P ＜ 0.05);SK-N-SH,24 h (chisq =10.38,P＜0.054 6),48 h(chisq=8.641 0,P＜0.05),72 h(chisq=9.461 5,P＜0.05);SK-N-BE2:24 h (chisq =8.435 9,P ＜0.05),48 h(chisq =8.641 O,P ＜0.05),72 h(chisq =9.545 5,P ＜0.05);compared with the control group,the As2O3-treated cells showed increased apoptosis percentage,with the percentage of 1.6％ (0 μmol/L),3.8％ (1 μmol/L),6.1％ (3 μmol/L),10.4％ (5 μmol/L),40.2％ (7 μ mol/L);the cell cycle was arrested at G2/M phase,which prevented cell division.Conclusions (1) As2O3 play an important role on the NB cells proliferation,apoptosis which were dose-and time-dependent manner.(2)As2O3 can inhibit the expression of MYCN gene.(3)As2O3 also could block NB cell cycle at S and G2/M,and inhibit the cell nucleus replication and the As2O3 had different induced effect between different types of NB cell.

Progress in diagnosis and treatment of pyriform fistula in children / 国际儿科学杂志

Pyriform sinus fistula,owing to rare disease incidence and lacking of awareness,is always a puzzle to neck illness. At the mean time,The frequent delay in accurate diagnosis was reported in the literature. Pyriform sinus fistula should be considered in any children with repeated neck or thyroid infection/mass( mainly on the left side) . The combination of barium esophagography,CT scan and ultrasound is useful to establish the diagnosis. Intraoperative endoscopy-assisted intubation or methylene blue injection through the internal opening as a guide can facilitate identification of the tract during dissection,and it can effectively reduce the relapse rate.

Reoperation for patients with Hirschsprung's disease after a pull-through procedure / 中华实用儿科临床杂志

Most children with Hirschsprung's disease (HD) have a satisfactory outcome after a pull-through operation.However,a small group of patients develop severe postoperative complications,and a reoperation may be necessary.The most common and serious complications after definitive surgery are as follows:anastomotic stricture,a twist of the pull-through segment,retained aganglionosis,HD-associated enterocolitis,anastomotic leak,and fistulae.Using a well-defined treatment algorithm based on the clinical status as well as precise diagnostic workup can end the long suffering of patients with postoperative complications.Pull-through surgery can be safely performed with favorable outcomes after thorough history-taking,meticulous clinical examination,a thoughtful planning,adherence to basic surgical principles and under skillful hands.