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 compare the efficacy of combination therapy on cyclic vomiting syndrome(CVS)in children, and improve the efficacy of CVS treatment in the future.Methods:This study retrospectively analyzed patients′ medical records of CVS, which were admitted to Digestive Department of Beijing Children′s Hospital from 2012 to 2019.The treatment regimen was A(Cyproheptadine+ Doxepin+ Valproate), B(Propranolol+ Cyproheptadine), or C(Propranolol+ Amitriptyline). Meanwhile, the patients should take drugs more than three months.The clinical data of 42 cases were analyzed retrospectively, and the treatment effect after discharge was followed up by telephone until October, 2020.Results:Among the 42 cases, 17 were male and 25 were female, whose mean age of onset was (4.65±3.23) years, and the age of diagnosis was (6.79±3.58) years.The main accompanied symptoms were abdominal pain and upper gastrointestinal bleeding.Forty-two patients were moderate/severe CVS.The regimens A, B and C were observed in 7, 11, and 24 patients, respectively.The age at improvement was(8.17±4.12)years.The course of treatment was(1.37±0.96)years.The age at follow-up was(10.32±4.03)years.During the 1-year follow-up, 35 cases were effective, and the efficiency was 83.3%.Among them, 23 cases had no paroxysmal vomiting and 7 cases had no effect.There was no significant difference in therapy effects among group A, B and C. Between the effective group and non-effective group, there were statistical differences in the personal history of hiatus hernia( P=0.024), the weight at follow-up ( P=0.042), and the course of medication( P=0.020). Conclusion:The combination regimen has a higher effective rate in the treatment of CVS.There was no significant difference among the three regimens in the treatment of CVS.For children with refractory CVS, who can not be treated with combination therapy, individualized therapy should be further developed.

Objective:To evaluate the efficacy and safety of infliximab(IFX)in pediatric patients with ulcerative colitis(UC).Methods:The clinical data of 17 UC patients who received IFX treatment at Beijing Children′s Hospital, Capital Medical University from January 2017 to December 2021 were retrospectively analyzed, and the pediatric ulcerative colitis activity index(PUCAI)and laboratory data were compared before and after treatment to evaluate the efficacy and safety of IFX.Results:A total of 17 UC patients were included, and among them there were 9 boys and 8 girls.The age of onset was 12.1(10.7, 12.8)years old, and median age at IFX initiation was 12.5(11.8, 13.6)years old.The duration of IFX medication was 46.1(17.4, 56.9)weeks, and the times of IFX injections was 8.0(4.5, 10.5). The mean PUCAI score of the 17 UC patients at start of IFX treatment was (50.6±21.2) points, and the Mayo endoscopic score showed: ten severe activity, six moderate activity, and one mild activity.IFX efficacy analysis: the clinical response rate was 87.5%(14/16), and the clinical remission rate was 56.3%(9/16) at the 14th week.The sustained response rate was 81.8%(9/11), and the sustained remission rate was 36.4%(4/11) at the 30th week.At the 14th week of IFX treatment, PUCAI score[2.5(0, 10.0)points vs.50.0(41.3, 70.0)points] and white blood cell count[5.7(4.8, 8.6)×10 9/L vs.8.7(6.4, 13.5)×10 9/L] significantly decreased(all P<0.05), hemoglobin[(113.8±20.4)g/L vs.(99.3 ± 19.4)g/L] and albumin level[42.2(40.0, 44.4)g/L vs.36.6(28.6, 40.2)g/L] significantly increased compared with those before IFX treatment, and the differences were statistically significant(all P<0.05). The Mayo endoscopic scores at 14 weeks of IFX treatment in 12 active UC patients showed: only 2 patients achieved mucosal healing, 5 patients had reduced from severe to moderate mucosal inflammation, and 5 patients had no improvement.Seven patients had 10 adverse events, 2 cases had 4 times acute infusion reactions, and 5 cases had 6 times infections. Conclusion:IFX is effective and relatively safe in inducing and maintaining clinical remission in pediatric UC patients.

Objective:To investigate the clinical features of pediatric ulcerative colitis (UC) and analyze the risk factors of disease relapse.Methods:The clinical data of 79 children with UC diagnosed in Beijing Children′s Hospital, Capital Medical University from January 2016 to February 2021 were retrospectively analyzed. They were divided into early relapse group and non-early relapse group according to the clinical relapse within 12 months after diagnosis. T-test, rank sum test, χ 2 test 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 early relapse. The cumulative relapse rate during follow-up was calculated by Kaplan-Meier method. Results:Among the 79 UC children, 46 were males and 33 were females, and the age of onset was 10.6 (6.4, 12.7) years. The children were mainly characterized by extensive disease (E3) and pancolitis (E4) (51/79, 65%), moderate to severe activity (48/79, 61%) and moderate to severe inflammation of colonic mucosa (71/79, 90%). Thirty-eight (48%) patients had atypical phenotype and 17 (22%) had extraintestinal manifestations. The follow-up period was 43.9 (22.8, 61.3) months, and of the 41 patients rechecked with colonoscopy, 7 (17%) had disease progression. According to Kaplan-Meier analysis, the cumulative relapse rate of the 79 cases at 3 months, 6 months, 1 year and 2 years after diagnosis were 27% (21/79), 47% (37/79), 57% (45/79) and 73% (53/73), respectively. There were 45 children (57%) in early relapse group and 34 (43%) in non-early relapse group. In early relapse group, hemoglobin and mucosal healing rate were both significantly lower (105 (87, 122) vs. 120 (104, 131) g/L, 28% (7/25) vs. 7/9, Z=-2.38, χ2=4.87, both P<0.05). The rate of steroid-dependent, E3 and step-up therapy during the induction period were all significantly higher than those in non-early relapse group (11/19 vs. 1/12, 24% (11/45) vs. 6% (2/34), 29% (13/45) vs. 6% (2/34), χ2=5.67, 4.85, 6.66, all P<0.05). Multivariate Logistic regression analysis showed that extraintestinal manifestations ( OR=4.33, 95% CI 1.05-17.83), E3 ( OR=8.27, 95% CI 1.47-46.46) and step-up therapy during the induction period ( OR=5.58, 95% CI 1.01-30.77) were independent risk factors for early relapse. Conclusions:Pediatric UC is usually extensive and severe, with atypical phenotype, a high rate of relapse and a risk of disease progression. Extraintestinal manifestations, E3 and step-up therapy during the induction period are independent risk factors for early relapse.

Objective:To evaluate the clinical efficacy and safety of Infliximab (IFX) in pediatric Crohn′s disease (CD).Methods:The efficacy of IFX therapy in 30 patients suffering from active CD who were not completely improved with traditional medicine and enteral nutrition or had intolerance to the medicine in Beijing Children′s Hospital Affiliated to Capital Medical University from December 2014 to December 2019 were retrospectively analyzed.Pediatric Crohn′s Disease Activity Index (PCDAI), blood biochemistry indices, mucosal healing, nutritional status, and adverse reactions were compared and evaluated.Results:Thirty active CD cases, with 18 males and 12 females, were enrolled, and the average age was (8.63±4.76) years old.Three cases who didn′t complete 3 times of IFX injection and 1 case who lost to be followed up were excluded.A total of 26 cases of CD in active period were enrolled in this study on efficacy.The clinical remission and response rate of 26 cases were 61.5% and 84.6%, respectively, at 14-week of IFX therapy.The clinical remission and response rate of 21 cases were 71.4% and 85.7%, respectively, at 30-week.The clinical remission and response rate of 15 cases were 86.7% and 93.3%, respectively, at 54-week.At week 14 th, PCDAI score [(9.56±8.05) scores vs.(29.02±10.86) scores] decreased compared with before treatment ( t=7.339, P<0.05). The levels of erythrocyte sedimentation rate [(15.54±10.26) mm/1 h vs.(33.77±21.30) mm/1 h] and C-reactive protein [(4.79±12.94 ) mg/L vs.(16.33±23.43) mg/L] were obviously decreased, and the hemoglobin [(126.27±16.51) g/L vs.(110.58±16.45) g/L], hematocrit [(37.03±3.95)% vs.(33.52±4.32)%], and albumin levels [(42.30±3.03) g/L vs.(37.13±5.68) g/L] were remarkably increased compared with those before treatment ( t=3.932, 1.993, -3.398, -3.060, -4.009, all P<0.05). Height for age Z score and body mass index Z score were increased after IFX treatment, without statistically significant differences (all P>0.05). Conclusions:IFX therapy had good clinical efficacy in controlling inflammatorys and inducing clinical remission in pediatric CD.

Objective:To summarize the clinical features and therapeutic outcomes of patients with hyperinsulinemic hypoglycemia (HH) auxiliarily diagnosed by 18F-DOPA positron emission tomography (PET) CT scanning. Methods:The clinical data of 123 patients who were diagnosed with hyperinsulinemic hypoglycemia by comprehensive clinical diagnostic procedures in the Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children′s Hospital of Fudan University between January 2016 and December 2020 were retrospectively analyzed. Clinical data such as gender, age of onset, province, concurrent serum insulin level measured during hypoglycemia, lesion type of pancreas by 18F-DOPA-PET CT scanning, genetic test results, and treatment were collected successively. The clinical features and therapeutic outcomes were compared between patients with focal and diffuse pancreatic lesions. T test, Rank sum test, and χ2 test were used for comparison between groups. Results:A total of 123 patients with hyperinsulinemic hypoglycemia (72 males and 51 females), whose average age of onset was 3 days (ranging from 1 day to 4 860 days), were recruited from 24 provinces. The concurrent serum insulin level was 7.1 (0.4-303.0) mU/L during hypoglycemia. 18F-DOPA-PET CT scanning identified focal lesions in 25.2% (31/123) and diffuse lesions in 74.8% (92/123) of the patients; 64.2% (79/123) of the HH cases were found to have pathogenic gene variants, in which 88.6% (70/79) were found to have K ATP channel related genes (61 in ABCC8 and 9 in KCNJ11 mutations). Thirty-seven patients (17 focal and 20 diffuse) received surgical treatment with a success rate of 67.6% (25/37). The effective rate of diazoxide for children with diffuse type was significantly higher than that of children with focal group (28.3% (26/92) vs. 9.7% (3/31), χ2=10.31, P=0.001). Conclusions:18F-DOPA-PET CT scan can improve the success rate of surgery. Comprehensive diagnosis of the etiology of hyperinsulinemic hypoglycemia by genetic analysis and 18F-DOPA-PET CT scanning can result in better treatment and prognosis.

Intrahepatic cholangiocellular carcinoma (ICC) has become the second common malignant tumors of the liver, with its incidence being next only to hepatocellular carcinoma (HCC). Due to the lack of targeted screening methods and specific clinical manifestations, most intrahepatic cholangiocarcinoma(ICC)is clearly diagnosed as advanced, which brings great difficulties to the treatment of ICC. At present, radical surgical resection is still the most effective method to ICC. However, for some patients who had a positive-margin (R1) resection or positive lymph node metastasis, multidisciplinary comprehensive treatment including transcatheter arterial chemoembolization (TACE), local ablation, systemic chemotherapy, targeted therapy and immunotherapy, etc. can effectively improve the prognosis of these patients.

Objective:To summarize clinical and genetic features of infantile-onset inflammatory bowel disease(IO-IBD) patients.Methods:The clinical data of 48 IO-IBD patients from Beijing Children′s Hospital, Capital Medical University, including age of onset, family history, clinical manifestations and drug efficacy were retrospectively analyzed.Based on target gene panel, next generation sequencing (NGS) was performed for 43 patients, and further compared clinical features between gene mutation and non-gene mutation IO-IBD groups.Results:Among the 48 IO-IBD patients, 41 cases suffered from Crohn′s disease (CD) and 7 cases were ulcerative colitis (UC). The median age of onset was 2.00(0.24-6.00) months, and 45.8%(22/48 cases) of patients′ onset age was within 1 month.Diarrhea (48/48 cases, 100%), fever (45/48 cases, 93.8%) and hematochezia (37/48 cases, 77.1%) were the main clinical symptoms.Perianal lesions and rashes were common extraintestinal manifestations, accounting for 43.8%(21/48 cases) each.Among 41 CD patients, 73.2%(30/41 cases) had predominantly colonic disease (L2 type), and disease behavior was mainly nonstricturing and nonpenetrating (B1 type) (33/41 cases, 80.5%). Among 7 UC patients, 57.1%(4/7 cases) had predominantly pancolonic (E4 type). The surgical rate of the 48 IO-IBD patients was 12.5%(6/48 cases), the clinical remission rate was 50.0%(24/48 cases), and the mortality rate was 25.0%(12/48 cases). Among the 43 IO-IBD patients, 23 (23/43 cases, 53.5%) had meaningful gene mutations, of which 22 cases had mutations in interleukin-10 receptor A ( IL-10 RA) and 1 case with mutation in TTC37.A total of 11 mutation sites were detected in 22 patients with IL-10 RA mutations, including one novel mutation site c. 635G>C (p.R212P); 19 cases c. 301C>T (p.R101W) and 8 cases c. 537G>A (p.T179T) that were common mutation sites.Compared with non-gene mutation IO-IBD group, patients in gene mutation IO-IBD group had earlier onset age [0.3 (0.1-1.0) months vs.(6.27±5.64) months, P<0.001], higher proportion of malnutrition [14 cases(60.9%) vs.5 cases(25.0%), P=0.018], oral ulcers [14 cases(60.9%) vs. 30 cases(15.0%), P=0.006] and perianal lesions [17 cases(73.9%) vs.3 cases(15.0%), P<0.001], and the lower rate of clinical remission[7 cases(30.4%) vs.15 cases(75.0%), P=0.004]. Conclusions:IO-IBD patients had a high rate of monogenic mutation, and IL-10 RA gene mutation was the common mutation.IO-IBD patients developing with gene mutation were characterized by early age of onset, higher incidence of malnutrition, oral ulcers, perianal lesions, and the lower clinical remission rate.

Objective To summarize the clinical data of the children with inflammatory bowel diseases (IBD),including Crohn's disease (CD) and ulcerative colitis (UC),and to analyze and compare the clinical features of very early-onset IBD (VEO-IBD) and late-onset IBD (LO-IBD).Methods A retrospective analysis of the clinical data of 184 cases of IBD hospitalized children diagnosed at Beijing Children's Hospital,Capital Medical University from January 2000 to December 2014.According to their ages of onset,the patients were divided into VEO-IBD group (＜6 years old) and LO-IBD group (6-16 years old);the patients with CD were divided into VEO-CD group (＜ 6 years old) and LO-CD group (6-16 years old);UC were divided into VEO-UC group (＜ 6 years old) and LO-UC group (6-16 years old).The clinical features among each group were analyzed and compared.Results A total of 184 IBD patients were included in the study,77 cases(41.8％) were VEO-IBD and 107 cases(58.2％) were LO-IBD.Comparison between VEO-CD group and LO-CD group indicated that abdominal pain was more common in LO-CD group (P ＜ 0.05),while diarrhea and hematochezia were more common in VEO-CD group (all P ＜ 0.05).In addition,comparison between VEO-UC group and LO-UC group indicated that abdominal pain was more common in LO-UC group(P ＜ 0.001),while diarrhea,fever,and oral ulcers were more common in VEO-UC group (all P ＜0.05).Both VEO-CD and LO-CD group were mainly ileocolonic[15/27 cases (55.6％),20/47 cases (42.6％)],non-narrow,non-penetrating [20/27 cases (74.1％),30/47 cases (63.8％)] and moderate-to-severe activity[23/27 cases(85.2％),37/47 cases (78.7％)].The incidence of perianal lesions in the VEO-CD group was as high as 51.9％ (14/27 cases),which was significantly higher than that in the LO-CD group (9/47 cases,19.1％) (P ＜ 0.05).Left-sided UC and severe UC were more common in VEO-UC group(all P ＜ 0.05),while pancolitis and mild UC were more common in LO-UC group (all P ＜ 0.05).The incidence of intestinal perforation in the VEO-UC group was significantly higher than that in the LO-UC group (P ＜0.05).The incidence of surgical rate,intestinal obstruction,and intestinal perforation in the LO-CD group were significantly higher than those in the LO-UC group (all P ＜ 0.05).Conclusions Compared between VEO-IBD and LO-IBD,VEO-IBD patients are more severe,with perianal lesions more common,and the incidence of intestinal perforation is higher.

Objective: To investigate the antibiotic resistance of Helicobacter pylori(Hp) isolates cultured from endoscopic gastric mucosal samples and influencing factors for antibiotic resistance in children. Methods: From April 2013 to February 2016, Hp cultured from mucosa samples of the gastric antrum and the body of stomach was investigated in 246 patients with ¹³C breath test positive examined by gastroscopy.Resistance to Amoxicillin, Clarithromycin, Metronidazole, Tetracycline was tested for Hp by using E-test.The clinical data were collected from the patients, and the relationship among age, gender, endoscopic diagnosis, histological performance, eradication number factors and antibiotic resistance rate were analyzed. Results: Of 246 specimens, 174 cases (70.7%) were positive.The overall antibiotic resistance rates of isolates obtained were 96.55% (168/174 cases), 57.47% (100/174 cases), 4.02% (7/174 cases), 1.15%(2/174 cases) with respect to Clarithromycin, Metronidazole, Tetracycline and Amoxicillin.An antibiotic resistance rate was 43.10% (75/174 strains), among which the Clarithromycin resistance rate was 93.33% (70/75 strains), and the Metronidazole resistance rate was 6.67% (5/75 strains). Double resistance rate was of 54.02%(94/174 strains), among which the resistances rate of Clarithromycin+ Metronidazole was 52.30%(91/94 strains), and the resistances rate of Clarithromycin+ Tetracycline was 1.72%(3/94 strains). Triple resistance rate of Clarithromycin+ Metronidazole+ Tetracycline was 1.15%(2/174 strains). Quadruple resistance rate of Clarithromycin+ Metronidazole+ Amoxicillin+ Tetracycline was 1.15%(2/174 strains). Factor analysis showed that the resistance rate of Clarithromycin in children who had failed in eradication therapy [98.7%(148/150 cases)] was higher than that in children who had not undergone eradication therapy [83.3%(20/24 cases)], and the difference was statistically significant(χ²=14.610, P<0.05). There was no significant difference in the relationship between Hp resistance to Metronidazole and Clarithromycin and the age, gender, endoscopic diagnosis and histological manifestations(all P>0.05). Conclusions Hp resistance rate to Clarithromycin, Metronidazole is very high in children, but it is relatively low to Amoxicillin and Tetracycline, and multiple antibiotic resistance is at high prevalence.