Objective:To investigate the therapeutic effectiveness of endoscopic retrograde cholangiopancreatography (ERCP) and stent implantation in the treatment of pancreaticobiliary injuries in children.Methods:A retrospective analysis was conducted on the clinical data of children diagnosed with pancreaticobiliary injury and undergoing ERCP and stent implantation at Beijing Children′s Hospital, Capital Medical University from January 2021 to December 2022. Demographic information, clinical data, endoscopic treatment methods, postoperative complications and clinical prognosis of the children were collected. The etiology, location of pancreaticobiliary injury, occurrence of complications after endoscopic treatment, and the time for improvement and recovery after endoscopic treatment were analyzed. The patients were divided into five groups according to the etiologies of pancreaticobiliary duct injuries: post-surgical, pancreatic trauma, acute pancreatitis, chronic pancreatitis, and systemic lupus erythematosus groups. They were also classified into four groups according to the sites of pancreaticobiliary duct injuries: common bile duct, pancreatic head, pancreatic body, and pancreatic tail groups. Multi-factor analysis of variance was used for comparing the time of improvement and recovery among different groups.Results:Among 22 patients, there were 8 males and 14 females, and the age was 7.5 (3.3,10.8) years. There were 19 cases of pancreatic or bile duct fistula, and 3 cases of pancreatic or bile duct stenosis. A total of 33 endoscopic procedures were performed on the 22 patients, out of which, 3 duct stenosis were failed to insert the stent because the catheter failed to pass through the stenosis site. The success rate was 91% (30/33). The pancreatic duct or bile duct stent was inserted, with the stent located at pancreatic or bile duct fistula. Postoperative complications included pancreatitis in 3 cases (9%, 3/33), hyperamylasemia in 5 cases (15%, 5/33), and postoperative infection in 4 cases (12%, 4/33). All patients were followed up for more than 1 year. Significant improvement was observed in external drainage and imaging monitoring among patients with successfully placed stents. There was no significant difference in the improvement time of ERCP in the treatment of pancreaticobile duct injury caused by different etiology ( F=0.65, P=0.637). However, there were significant differences in healing time ( F=6.46, P=0.004), among which the healing time of injuries caused by systemic lupus erythematosus was significantly different from that after surgery, trauma, acute pancreatitis and chronic pancreatitis (all P<0.05). There was no significant difference in the improvement and healing time among different injury sites (all P>0.05). Conclusions:ERCP and stent implantation can safely and effectively improve the clinical symptoms of children with pancreaticobiliary injury. Early intervention can improve long-term prognosis.

Radiation-induced thrombocytopenia (RIT) faces a perplexing challenge in the clinical treatment of cancer patients, and current therapeutic approaches are inadequate in the clinical settings. In this research, oxymatrine, a new molecule capable of healing RIT was screened out, and the underlying regulatory mechanism associated with magakaryocyte (MK) differentiation and thrombopoiesis was demonstrated. The capacity of oxymatrine to induce MK differentiation was verified in K-562 and Meg-01 cells in vitro. The ability to induce thrombopoiesis was subsequently demonstrated in Tg (cd41:enhanced green fluorescent protein (eGFP)) zebrafish and RIT model mice. In addition, we carried out network pharmacological prediction, drug affinity responsive target stability assay (DARTS) and cellular thermal shift assay (CETSA) analyses to explore the potential targets of oxymatrine. Moreover, the pathway underlying the effects of oxymatrine was determined by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, Western blot (WB), and immunofluorescence. Oxymatrine markedly promoted MK differentiation and maturation in vitro. Moreover, oxymatrine induced thrombopoiesis in Tg (cd41:eGFP) zebrafish and accelerated thrombopoiesis and platelet function recovery in RIT model mice. Mechanistically, oxymatrine directly binds to toll-like receptor 2 (TLR2) and further regulates the downstream pathway stimulator of interferon genes (STING)/nuclear factor-kappaB (NF-κB), which can be blocked by C29 and C-176, which are specific inhibitors of TLR2 and STING, respectively. Taken together, we demonstrated that oxymatrine, a novel TLR2 agonist, plays a critical role in accelerating MK differentiation and thrombopoiesis via the STING/NF-κB axis, suggesting that oxymatrine is a promising candidate for RIT therapy.

Objective:To investigate the pathogenic mechanism and clinical characteristics of the novel splicing variant of ATP-binding cassette subfamily B member 4 (ABCB4) and provide a basis for subsequent genetic diagnosis.Methods:The clinical data of a 5-year-old child with cholestatic liver disease admitted to the Beijing Children′s Hospital of Capital Medical University was retrospectively analyzed. The pathogenic variations were detected by whole exome sequencing and verified by Sanger sequencing, and bioinformatics was used to predict the pathogenicity of the mutation sites. Possible pathogenic variations were verified in vitro by Minigene assay. The clinical outcome was followed after discharge from hospital.Results:The 5-year-old boy had developed cholestasis at the age of 11 months. His physical examination showed obvious enlargement of the liver and spleen. Cholestatic cirrhosis was diagnosed by liver function tests, abdominal ultrasonography, liver biopsy and pathology. The results of genetic analysis showed that the patient was a complex heterozygote of the ABCB4 gene, with a pathogenic mutation c.2860G>A and a novel mutation c.2065-8T>G, derived from the mother and father respectively. The conservative prediction of the c.2065-8T>G site showed that this region was highly conserved and may affect splicing. Minigene assay results confirmed that the c.2065-8T>G mutation resulted in a 7 bp retention of intron 16 in the mature mRNA. In the absence of nonsense-mediated mRNA decay, the amino acid frameshift forms a truncated protein, which is represented by p.Glu689ValfsTer19. The patient was diagnosed as progressive familial intrahepatic cholestasis type 3 (PFIC3) and treated with ursodeoxycholic acid (UDCA). His clinical symptoms improved during 18 months of follow-up.Conclusions:The c.2065-8T>G variant is confirmed to affect the splicing process and exhibits complex heterozygosity with c.2860G>A, which is identified as the cause of the disease. PFIC3 children with this variant showed cholestatic liver disease as the main manifestation with a slow progression and was sensitive to treatment with UDCA.

Objective To evaluate the efficacy and safety of ozone injection therapy for lumbar disc hemiation(LDH).Methods A computerized retrieval of academic papers concerning the randomized controlled trial(RCT)on ozone injection therapy for LDH from the databases of Embase,PubMed,Cochrane library and Web of science was conducted.The retrieval time period was from the establishment of the database to February 2023.The literature retrieval,screening,and data extraction were independently performed by two researchers.Cochrane bias risk assessment tool was used to assess the quality of the included literature.Stata 17.0 software was used to make meta-analysis.Results A total of 9 RCTs including 702 patients were finally included in this study.The results of meta-analysis showed that compared with radiofrequency thermocoagulation,percutaneous rotation and other treatments for LDH,the combination use of ozone injection could signifiicantly improve the effective rate based on Macnab efficacy evaluation criteria(RR=1.097,95％CI:1.038～1.159,P=0.001)and the excellent rate(RR=1.185～95％CI:1.074～1.309,P=0.001),and decrease the visual analog scale(VAS)pain score(WMD=-0.810～95％CI:-1.205～-0.414,P=0.000),and the differences in the above indexes were statistically significant.Conclusion Compared with the simple use of radiofrequency thermocoagulation,percutaneous rotation,and other treatment for LDH,the combination use of ozone injection therapy can significantly improve the effective rate and excellent rate based on Macnab efficacy evaluation criteria,decrease VAS score,with a high clinical safety.Limited by the quantity and quality of the original studies included in this study,the above conclusions need to be further verified by multi-center,large-sample and high-quality studies.

Objective:To analyze the etiology of chronic pancreatitis(CP) and evaluate the impact of different intervention methods on the prognosis.Methods:This is a retrospective analysis conducted on clinical data of pediatric patients with CP admitted to Beijing Children's Hospital between January 2010 and December 2023,including etiology,clinical manifestations,imaging data and treatments.Follow-up assessments included height,weight,complications occurrence,and long-term nutritional status evaluated by using Z scores.Results:A total of 98 patients with CP were included in the study,containing 51 males and 47 females,with an age range of 1.95 to 15.96 years (median 8.49 years).The etiological contained the gene mutation (39.8%,39/98) (involving PRSS1, SPINK1, CFTR),the anatomical abnormality (26/98,26.5%),idiopathic pancreatitis (33.7%,33/98).Predominant clinical manifestations included abdominal pain (79/98,79.6%),nausea/vomit(48/98,49.0%),chest tightness/chest pain (10/98,10.2%),with malnutrition (44/98,44.9%) and the serum amylase increased in some patients.Imaging findings revealed heterogeneous pancreatic echoes,dilated pancreatic ducts and pancreatic stones via abdominal ultrasound,and a full or atrophic pancreas with irregular margins,tortuous or dilated pancreatic ducts through abdominal magnetic resonance imaging.Compared with CP caused by other reasons,hereditdry CP had a higher rate of pancreatic morphological changes(100.0% vs.88.1%, P<0.05).By March 2024,follow-up showed all 98 patients underwent initial medical treatment,followed by surgical intervention in 13 cases,endoscopic retrograde cholangiopancreatography intervention in 51 cases,and no surgical or endoscopic intervention in 34 cases.Six children developed diabetes,six had reduced fecal pancreatic elastase-1 but without fat diarrhea.Long-term follow-up indicated improved nutritional status among children who underwent endoscopic retrograde cholangiopancreatography intervention(Z score,-1.22 vs.0.74, P<0.001). Conclusion:Gene mutations and anatomical abnormalities is the main etiological factors in pediatric patients with CP.Early endoscopic intervention can significantly improve the long-term prognosis of the children.

Objective:To investigate the effects of compound Duzhong Jiangu Granules on joint function and gut microbiota in patients with Kashin-Beck disease.Methods:A single group pre- and post-experimental design was conducted, the patients with Kashin-Beck disease were selected as the subjects in Xunyi County, Xianyang City, Shaanxi Province; and treated with oral administration of compound Duzhong Jiangu Granules (12 g/bag, 1 bag/time, 3 times/day) for a period of 1 month. The improvement of joint function was evaluated using the joint dysfunction index scoring method before and after treatment. Morning stool samples of patients were collected and the changes in gut microbiota were analyzed before and after treatment using 16S rDNA sequencing technology.Results:A total of 87 patients with Kashin-Beck disease were included, including 44 males and 43 females; the age was (60.38 ± 7.12) years old, and the body mass index was (23.67 ± 3.59) kg/m 2. The comprehensive scores of joint dysfunction index for patients with Kashin-Beck disease before and after treatment were (7.27 ± 2.05) and (5.86 ± 2.01) points, respectively, and the difference was statistically significant ( t = 5.88, P < 0.001). The sequencing results of gut microbiota showed that there were statistically significant differences in the alpha diversity (chao1, observed species index) and beta diversity of gut microbiota in patients with Kashin-Beck disease before and after treatment ( Z = - 5.08, - 5.03, R = 0.09, P < 0.001). In the distribution of gut microbiota, Firmicutes was the dominant phylum, with relative abundances of 50.21% and 52.09% before and after treatment, respectively; the Bifidobacterium was the dominant bacterial genus, with relative abundances of 16.83% and 18.81% before and after treatment, respectively. At the genus level, a total of 17 gut microbiota genera were screened out, among which the relative abundances of Hafnia-Obesumbacterium, Gammaproteobacteria_unclassified, Acinetobacter, Pantoea, Leuconostoc, and Akkermanisia were significantly higher than before treatment ( Z = - 2.40, - 2.24, - 2.06, - 3.59, - 2.24, - 2.11, P < 0.05). The relative abundances of Dubosiella, Selenomonas, Anaeroplasma, Lachnospiraceae_ NK4A136_group, Rikenella, Prevotella, Megasphaera, Lactobacillus, Prevotella-9, Phascolarctobacterium, and Desulfovibrio were significantly lower than before treatment ( Z = - 9.38, - 2.61, - 2.18, - 8.43, - 2.45, - 2.46, - 2.49, - 7.29, - 2.29, - 2.55, - 2.08, P < 0.05). Conclusions:Compound Duzhong Jiangu Granules can effectively improve the joint function of patients with Kashin-Beck disease, and alter the diversity and richness of the gut microbiota community. It may reduce clinical symptoms in patients by regulating the structure of gut microbiota.

Objective:To assess the value of double-balloon enteroscopy(DBE)in the treatment of Peutz-Jeghers syndrome(PJS)polyp with intussusception in children.Methods:A total of 14 cases with PJS polyp with intussusception were collected in Gastroenterology Department of Beijing Children′s Hospital Affiliated to Capital Medical University from July 2019 to January 2023.The general information, clinical manifestations, history of surgeries, abdominal ultrasound, enteroscopy and postoperative outcomes were retrospectively analyzed.Results:Fourteen cases with intussusception of PJS(including nine boys and five girls) were enrolled, and the average age was(10.25±2.52)years.There were 21 small intestinal intussusceptions in 14 cases, including eight cases of single intussusception and six cases of multiple intussusceptions.All the patients underwent DBE examination and treatment.A total of 215 small intestinal polyps were removed, no direct complications such as bleeding or perforation were found during the operation.Twelve cases were confirmed intussusception relieved by DBE, and the average maximum diameter of polyps causing intussusception was(4.38±1.43)cm.In addition, DBE did not reach the site of intussusception polyp in one case, and another case developed intestinal obstruction after DBE operation, which were treated by surgery.Conclusion:DBE provides a relatively effective method for the treatment of PJS polyps with intussusception without complete ileus in children.

Objective:To investigate the clinical features and risk factors of the extraintestinal manifestations(EIM)in children with ulcerative colitis(UC).Methods:A retrospective case-control study was conducted.The clinical data of 99 children with UC diagnosed in Department of Gastroenterology, Beijing Children′s Hospital, Capital Medical University from January 2016 to December 2021 were analyzed.According to whether the patients had EIM or not, they were divided into EIM-positive group and EIM-negative group.Rank sum test, χ2test or Fisher′s exact test were used to compare the variables between the 2 groups, including the clinical features, laboratory examination results and treatments.The Logistic regression was used to analyze the risk factors of EIM in children with UC. Results:A total of 99 children with UC were enrolled, including 57 males and 42 females; the age of onset was 10.3(6.4, 12.6)years, and the course of disease was 4.2(1.6, 10.1)months.The patients were mainly characterized by extensive disease(E3)and pancolitis(E4)(69/99, 69.7%), moderate to severe activity(63/99, 63.6%)and moderate to severe inflammation of colonic mucosa(89/99, 89.9%). There were 77 patients(77.8%)in the EIM-negative group and 22 patients(22.2%)in the EIM-positive group, of which 5 patients had two types of EIMs; the most common EIMs were oral ulcers(9 cases), joint lesions(7 cases), and skin lesions(6 cases). Compared with the EIM-negative group, those in the EIM-positive group, such as the E4 type(77.3% vs 44.2%, χ2=7.513, P=0.006), moderate to severe activity(81.8% vs 58.4%, χ2=4.041, P=0.044), pediatric ulcerative colitis activity index score[47.5(35.0, 57.5)score vs 35.0(25.0, 50.0)score, Z=-2.260, P=0.024], the proportion of C-reactive protein≥8mg/L at diagnosis(54.5% vs 19.5%, χ2=10.607, P=0.001), erythrocyte sedimentation rate[30.0(13.8, 47.8)mm/h vs 10.0(4.0, 19.5)mm/h, Z=-3.918, P<0.001], the proportion of glucocorticoid treatment within one year after diagnosis(77.3% vs 49.4%, χ2=5.403, P=0.020)and the proportion of biological agents treatment(45.5% vs 23.4%, χ2=4.112, P=0.043)were significantly higher; the E3 type were significantly lower than those in the EIM-negative group(0 vs 23.4%, χ2=4.813, P=0.028), and the differences were statistically significant.Multivariate Logistic regression analysis showed that erythrocyte sedimentation rate at diagnosis was an independent risk factor of EIM in children with UC( OR=1.063, 95% CI: 1.025~1.103, P=0.001). Conclusion:The UC patients with EIM had more extensive lesions, more severe disease activity, significantly increased inflammatory indicators, and more commom glucocorticoid and biologic therapy.Increased erythrocyte sedimentation rate was an high risk factor of EIM in children with UC.

Objective:To investigate the value of endoscopic retrograde cholangiopancreatography(ERCP)and related techniques in the diagnosis and treatment of chronic pancreatitis in children.Methods:The clinical data of 16 children with chronic pancreatitis diagnosed in the Department of Gastroenterology at Beijing Children′s Hospital from January 2021 to January 2022, who had ERCP indications were analyzed retrospectively, including age, sex, operation time, postoperative complications and follow-up data.Results:Thirty nine ERCP operations were performed in 16 children, with the age of (7.20±2.51) years old, and the minimum weight of 13 kg.There were 7 males and 9 females.The clinical manifestations were upper abdominal pain in all cases, 3 patients with dyspnea, 1 patient with gastrointestinal bleeding, and 1 patient with diabetes.In terms of etiology, 16 cases were diagnosed by ERCP including, 7 cases with pancreatic divisum, 1 case with abnormal pancreaticobile duct confluence.Among the 16 children, 11 had gene examination with 9 gene mutations (including 7 cases SPINK1 mutation, 1 case PRSS mutation, and 1 case CFTR mutation).The operation time was 30 to 65 minutes, and the median was 43 minutes.The operation time was negative correlation with age, while there was no correlation with the anatomical structure abnormality or the gene mutation.Among the 16 children, 15 were placed with pancreatic duct stents, with a success rate of 93.8%.Three children had postoperative pancreatitis, the rest had hyperamylasemia.Postoperative complications were not related with the age, the anatomical structure abnormality or the gene mutation.All children had been followed up for more than one year.All children have not suffered from pancreatitis again, and the body mass index had increased significantly after operation than before( P<0.05).The ERCP operation was performed 2 to 4 times in children after stent replacement, and the time of stent replacement ranged from 3 months to 12 months. Conclusion:The main causes of chronic pancreatitis in children are anatomical abnormalities or gene mutations.ERCP and related techniques are minimally invasive, safe and effective in the treatment of chronic pancreatitis.

Objective To study influencing factors of renal blunt impact injury by using finite element (FE) method. Methods Based on CT images of the kidney, the kidney FE models for different age groups were constructed. The renal blunt impact test was reconstructed, and the influence of kidney material constitutive parameters, kidney tissue structure, kidney size, impact position and impact velocity on injury severity were analyzed. Results Under the same impact condition, the stress of renal cortex decreased with the kidney mass increasing, and increased with the impact velocity of the hammer increasing. The renal capsule had a certain energy absorption effect, so as to reduce the kidney stress. When the kidney was impacted, the stress of renal cortex under side impact was significantly higher than that under frontal impact. Conclusions Compared with viscoelastic constitutive model, Mooney Rivlin material constitutive model is more suitable for FE evaluation on renal injury severity. The renal injury decreases with the kidney mass increasing. The increase of impact velocity will intensify the renal injury severity. Renal capsule will reduce renal injury to a certain extent, so the existence of renal capsule structure must be considered in FE modeling of the kidney. Compared with frontal and rear impact, the renal injury severity is greater when the kidney is impacted from the lateral side.