Clinicopathological features and mucosal microbiota in gastric mucosal damage between nodular and non-nodular gastritis in children with Helicobacter pylori infection.

AIMS: Nodular gastritis (NG) represents a frequently observed clinical presentation of Helicobacter pylori (H. pylori) infection in pediatric patients. This investigation aimed to explore the microbiota and histological features of the gastric mucosa in children with H. pylori colonized NG. MAIN METHODS: The current investigation examined a sample of 120 children who underwent gastroscopy due to symptoms of gastrointestinal distress, which showed that 64 were patients with H. pylori infection. Endoscopic procedures were conducted to acquire mucosal biopsies for the purpose of DNA extraction and histopathological analysis. The 16S rRNA profiling was utilized to examine the gastric mucosal microbiota. KEY FINDINGS: In conjunction with endoscopic evaluation, 26 of 64 patients were diagnosed with NG. The NG group had significantly higher inflammation scores and activity scores on histological assessment than the non-NG group. The NG group exhibited a significant reduction in the richness levels of the five genera. In terms of the predicted functions, the pathways of synthesis and degradation of ketone bodies and phagosome in the NG group were less abundant compared with the non-NG group, while the Wnt signaling pathway was significantly enriched. NG does not increase a microbial community that possesses genotoxic potential within the gastric mucosa. SIGNIFICANCE: In conclusion, NG group exhibited significant severe inflammation and reduced abundance levels of several bacterial genera compared to the non-NG group. However, individuals with NG did not have a dysregulated microbial community with genotoxic potential.

Impacts of a new diagnosis-related group point payment system on children's medical services in China: Length of stay and costs.

BACKGROUND: Paediatric healthcare is always highlighted in medical and health care system reform in China. Zhejiang Province established a new diagnosis-related group (DRG) point payment reform in 2020 to regulate provider behaviours and control medical costs. We conducted this study to evaluate impacts of the DRG point payment policy on provider behaviours and resource usage in children's medical services. METHODS: Data from patients' discharge records from July 2019 to December 2020 in Children's Hospital, Zhejiang University School of Medicine were collected for analysis. We employed the interrupted time series approach to reveal the trend before and after the DRG point payment reform and the difference-in-differences analysis to estimate the independent outcome changes attributed to the reform. RESULTS: We found that the upward trend of length of stay slightly slowed, and the total costs began to decrease at the post-policy stage. Although independent effects of the reform were not presented among the whole sample, the length of stay and hospitalisation costs of moderate-hospital-stay paediatric patients, non-surgical patients, and infant patients were found to decrease rapidly after the reform. CONCLUSION: DRG point payments can changed the provider behaviours and eventually reduce healthcare resource usage in children's medical services.

The Effects of Helicobacter pylori Infection on Gastric Microbiota in Children With Duodenal Ulcer.

Background: Helicobacter pylori (H. pylori) infection is the main cause of chronic gastritis and duodenal ulcer in children. Little is known about the effect of H. pylori on gastric microbiota in children with duodenal ulcer. This study is aimed at the characteristics of gastric microbiota in children with duodenal ulcer on H. pylori infection. Methods: We studied 23 children diagnosed with duodenal ulcer by gastric endoscopy because of the gastrointestinal symptoms, 15 children were diagnosed with H. pylori infection, while 8 children were without H. pylori infection. Endoscopic mucosal biopsy samples were obtained for DNA extraction. Microbiomes were analyzed by 16S rRNA profiling and microbial functions were predicted using the software Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). Results: Bacterial richness and diversity of gastric microbiota in duodenal ulcer with H. pylori-positive were lower than those negative. The gastric microbiota in H. pylori-positive group significantly reduced proportions of six phyla and fifteen genera; only Helicobacter taxa were more abundant in H. pylori-positive group. Co-expression network analysis showed a more complex network of interactions in the H. pylori-positive group than that in the H. pylori-negative group. For the predicted functions, lower abundance in the pathways of carbohydrate metabolism, signal transduction, amino acid metabolism, and lipid metabolism were found in H. pylori-positive group than the H. pylori-negative group. H. pylori colonization reduces a microbial community with genotoxic potential in the gastric mucosa of children with duodenal ulcer. Conclusions: The presence of H. pylori significantly influences gastric microbiota and results in a lower abundance of multiple taxonomic levels in children with duodenal ulcer. Children with duodenal ulcer exhibit a dysbiotic microbial community with genotoxic potential, which is distinct from that of children with H. pylori infection. Clinical Trial Registration: [http://www.chictr.org.cn], identifier [ChiCTR1800015190].

The Effects of Helicobacter pylori Infection on Microbiota Associated With Gastric Mucosa and Immune Factors in Children.

Background: Helicobacter pylori infection is the main cause of chronic gastritis in children. Little is known about the effect of Helicobacter pylori on microbiota and immunity. This study was aimed at characterizing stomach microbiota and immune-regulatory properties of children with Helicobacter pylori colonization. Methods: We studied 122 children who had undergone gastric endoscopy due to gastrointestinal symptoms, 57 were diagnosed with Helicobacter pylori infection. Endoscopic mucosal biopsy samples were obtained for DNA and RNA extraction. Microbiomes were analyzed by 16S rRNA profiling, with the differentially expressed genes analyzed using RNA sequencing. The RNA-sequencing results of selected genes were validated by qRT-PCR. Results: Bacterial diversity of Helicobacter pylori-positive gastric specimens were lower than those of negative, and both groups were clearly separated according to beta diversity. Helicobacter pylori-positive group significantly reduced proportions of six phyla and eight genera; only Helicobacter taxa were more abundant in Helicobacter pylori-negative group. Gastric tissues RNA sequencing showed increased expression of multiple immune response genes in Helicobacter pylori -infection. Helicobacter pylori -infected children with restructured gastric microbiota had higher levels of FOXP3, IL-10, TGF-ß1 and IL-17A expressions, which were consistent with increased CD4+T cell and macrophagocyte, compared with non-infected children. Conclusions: Presence of Helicobacter pylori significantly influences gastric microbiota and results in lower abundance of multiple taxonomic levels in children. Meanwhile, it affects gastric immune environment and promotes the occurrence of gastritis. Clinical Trial Registration: [http://www.chictr.org.cn], identifier [ChiCTR1800015190].

[Diagnosis and treatment recommendation for pediatric COVID-19 (the second edition)].

The coronavirus disease 2019 (COVID-19) has caused a global pandemic. All people including children are generally susceptible to COVID-19, but the condition is relatively mild for children. The diagnosis of COVID-19 is largely based on the epidemiological evidence and clinical manifestations, and confirmed by positive detection of virus nucleic acid in respiratory samples. The main symptoms of COVID-19 in children are fever and cough; the total number of white blood cell count is usually normal or decreased; the chest imaging is characterized by interstitial pneumonia, which is similar to other respiratory virus infections and Mycoplasma pneumoniae infections. Early identification, early isolation, early diagnosis and early treatment are important for clinical management. The treatment of mild or moderate type of child COVID-19 is mainly symptomatic. For severe and critical ill cases, the oxygen therapy, antiviral drugs, antibacterial drugs, glucocorticoids, mechanical ventilation or even extracorporeal membrane oxygenation (ECMO) may be adopted, and the treatment plan should be adjusted timely through multi-disciplinary cooperation.

Diagnosis and treatment recommendations for pediatric respiratory infection caused by the 2019 novel coronavirus.

Since December 2019, an epidemic caused by novel coronavirus (2019-nCoV) infection has occurred unexpectedly in China. As of 8 pm, 31 January 2020, more than 20 pediatric cases have been reported in China. Of these cases, ten patients were identified in Zhejiang Province, with an age of onset ranging from 112 days to 17 years. Following the latest National recommendations for diagnosis and treatment of pneumonia caused by 2019-nCoV (the 4th edition) and current status of clinical practice in Zhejiang Province, recommendations for the diagnosis and treatment of respiratory infection caused by 2019-nCoV for children were drafted by the National Clinical Research Center for Child Health, the National Children's Regional Medical Center, Children's Hospital, Zhejiang University School of Medicine to further standardize the protocol for diagnosis and treatment of respiratory infection in children caused by 2019-nCoV.

Application of gene chip technology in the diagnostic and drug resistance detection of Helicobacter pylori in children.

BACKGROUND AND AIMS: Helicobacter pylori (HP) culture for diagnosing HP infection is time-consuming and technologically complex. This study evaluated the clinical significance of gastric mucosal gene chip technology in the rapid diagnosis of HP infection and detection of drug resistance in children. METHODS: Patients (between the age of 2.5 and 16.0 years old) manifesting gastrointestinal symptoms were enrolled in this study. HP culture of gastric mucosa and drug sensitivity test were performed. A gene chip of gastric mucosa was used to detect the presence of HP infection, some single nucleotide polymorphisms in HP drug resistance genes, or associated gene mutation. DNA sequencing was investigated and compared with the gene chip test results. RESULTS: Out of 267 cases, HP culture was positive in 169 cases and negative in 98 cases. HP detection by the gene chip method was positive in 208 cases and negative in 59 cases. The sensitivity, specificity, and accuracy of the gene chip technology for diagnosing HP infection were 96.1, 85.0, and 93.6%, respectively. HP resistance gene locus using the gene chip showed the main mutation locus of clarithromycin to be 2143A/G, levofloxacin at locus GyrA 91 and GyrA 87, and amoxicillin at PBP1 556ser. Concordance rates between gene chip and DNA sequencing for VacA-S/M, 16S rRNA, 23S rRNA, and GyrA were greater than 95%, and that of PBP1 was greater than 82%. CONCLUSION: Gastric mucosal gene chip technology can be used for rapid diagnosis and drug resistance detection of HP infection in children.

Association of T-helper cell cytokine level with age in patients with biliary atresia: a preliminary study.

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 preoperatively, and the liver tissue specimens were obtained during surgery. We detected serum levels of interleukin (IL)-1ß, IL-12p70, interferon (IFN)-γ, IL-6, IL-10, and transforming growth factor (TGF)-ß1 and liver expression of IL-1ß, IL-6, and TGF-ß1. RESULTS: The serum levels of IL-1ß, 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-1ß, IL-6 and TGF-ß1 expression levels in the liver tissue of patients with BA. CONCLUSIONS: The serum levels of IL-1ß, 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.

[Timing of nasojejunal feeding tube placement and enteral nutrition in children with acute pancreatitis].

OBJECTIVE: To investigate the impact of timing of nasojejunal feeding tube placement and enteral nutrition on clinical outcomes in children with acute pancreatitis. METHODS: A retrospective analysis was performed on the clinical data of 31 children with acute pancreatitis, who received nasojejunal feeding between January 2008 and July 2013, to investigate the relationship of abdominal symptoms/signs and serum amylase level with the tolerability of catheterization and success rate of enteral nutrition. The treatment outcome and incidence of adverse reactions and complications were compared between the early enteral nutrition group ( ≤7 days from the onset of the disease) and late enteral nutrition group (>7 days from the onset of the disease). RESULTS: Abdominal symptoms/signs and serum amylase level were independent of the tolerable rate of catheterization and success rate of enteral nutrition. Compared with the late enteral nutrition group, the early enteral nutrition group had a shortened time to normal serum amylase level, significantly reduced incidence of systemic complications, length of hospital stay, and hospitalization expenses, and less weight gain. The tolerable rate of catheterization and success rate of enteral nutrition showed no significant difference between the two groups. Similarly, no significant differences were found in the increase in albumin level after enteral nutrition, duration of enteral nutrition, incidence of adverse reactions, and incidence of local complications. CONCLUSIONS: Abdominal symptoms/signs and serum amylase level cannot be used as a measure of whether nasojejunal feeding tube placement and enteral nutrition can be performed. Early enteral nutrition can better improve clinical outcomes in children with acute pancreatitis, and it is feasible.

[Value of nasojejunal nutrition in the treatment of children with acute pancreatitis].

OBJECTIVE: To evaluate the feasibility and effectiveness of placement of nasojejunal feeding tube and nasojejunal nutrition feeding in children with acute pancreatitis. METHOD: Twenty-two patients (of whom 13 had severe acute pancreatitis and 9 acute mild pancreatitis) who needed nutritional intervention were selected. They were from Department of Gastroenterology and Surgery during the years 2009 - 2012, and they were at high nutritional risk after STONGkid nutrition risk screening. The average age of them was 5 - 15 years (9.1 years ± 2.8 years). Assisted by endoscopy, the nasojejunal feeding tube was placed in 22 of 24 patients (in 2 cases of recurrent pancreatitis the tubes were placed again after extubation). Besides the use of regular fasting, antacids, inhibitors of trypsin secretion, and anti-infective treatment, 23 cases of all children got nasojejunal nutrition treatment as well. The outcome measures included the success rate, complications of endoscope-assisted nasojejunal tube placement. The children's tolerance and nutrition indicators (weight, blood lymphocytes count, erythrocytes count, serum albumin, serum creatinine, blood urea nitrogen) were observed before and after enteral nutrition therapy. RESULT: Malnutrition evaluation was done 24 times before treatment among 22 patients, incidence of malnutrition was 33% in 22 cases. Placement of nasojejunal tube placement was attempted for a total of 24 times and was successful on first placement in 22 cases, in two cases the placement was successful on the second placement, so the success rate of the first attempt for placement was 92%. No significant complications were observed in any of the cases. Twenty-three of 24 cases were given standardized enteral nutrition (one case was not given enteral nutrition therapy but underwent ERCP due to obstructive jaundice). Twenty-two of 23 cases could tolerate enteral nutrition well, only 1 case was unable to tolerate enteral nutrition due to the pancreas schizophrenia, paralytic ileus. The treatment of jejunal feeding success rate was 96%. The feeding duration was 2 - 74 d (27.0 d ± 18.3 d). The adverse reactions include plugging of the tube in two cases, constipation in two cases, five cases had abdominal pain, diarrhea in 2 cases, vomiting in 2 cases and 1 case of jejunum retention. No case had nasopharynx ulcers, gastrointestinal perforation, gastrointestinal bleeding, re-feeding syndrome and infection etc. Blood erythrocytes count, serum creatinine, blood urea nitrogen were not significantly changed. Twenty of 23 cases were cured, 2 cases were improved and 1 case was unchanged. CONCLUSION: Endoscope-assisted nasojejunal tube placement for children with acute pancreatitis is safe and feasible. Nasojejunal nutrition therapy is effective for acute pancreatitis patients who are at severe nutritional risk, especially for the improvement of the nutritional status of children.

A Chinese girl molecularly diagnosed with Alagille syndrome.

BACKGROUND: Alagille syndrome (AGS) is a rare or fatal disease affecting multiple systems including the liver, heart, eyes, skeleton and face. It has been considered a genetically heterogeneous disorder of the Notch signaling pathway. METHODS: A 28-month-old Chinese girl with congenital heart disease and jaundice was diagnosed with Alagille syndrome by liver biopsy showing a paucity of the intrahepatic bile ducts. Variants of the JAG1 gene were detected by DNA sequencing in the patient and her unaffected father. RESULTS: A heterozygous missense mutation was identified in exon 2 of the JAG1 gene in the proband but not in exon 2, 4, 6, 9, 17, 23, 24 by DNA sequencing in her father. The mutation G-->T change was seen at position 133 in the cDNA sequence (c.133 G-->T), causing a substitution of a leucine for a valine (V45L) residue in the N terminus between signal peptide and DSL domain of the Notch ligand. This mutation, however, was absent in her father. CONCLUSION: Genes in the Notch signaling pathway should be further studied in AGS, and used to confirm clinical or prenatal diagnosis and facilitate genetic counseling.

[Clinical value of wireless capsule endoscopy in diagnosis of small bowel disease in children].

OBJECTIVE: The pathological change of small bowel is difficult to examine because it is anatomically unique. The development of wireless capsule endoscopy provides an unique opportunity to visualize the entire small bowel in a minimally invasive manner. The aim of this study was to assess the safety and clinical value of wireless capsule endoscopy in children. METHODS: During the last 4 years (June, 2004-June, 2008), 46 times of wireless capsule endoscopy were performed in 43 patients with suspected small bowel disease, including obscure gastrointestinal bleeding (n = 11), recurrent abdominal pain (n = 20), chronic diarrhea (n = 9), protein losing enteropathy (n = 2), recurrent vomiting (n = 1). Of the 43 cases, 28 were male and 15 were female, the age ranged from 6 to 18 years, 8 of these cases were < 10 years old. The weight of the patients ranged between 15 kg and 60 kg. The average time of capsule passing through the stomach and the small intestine, the tolerance to and complication of wireless capsule endoscopy in patients, the image quality of capsule endoscopy, and the cleanliness of small intestine after fasting for 8 hours were observed and recorded. RESULT: All the patients could easily swallow the capsule and had good tolerance. The overall success rate was 94% (43/46). The median time of capsule passing through the stomach and small intestine was 73 min (range, 3 - 600 min) and 246 min (range, 73 - 413 min), respectively. The diagnostic yield of pathological change in small intestine was 90% (37/41), and the diagnostic accordance rate was 84% (31/37). Based on the wireless capsule endoscopy, diagnostic findings included Crohn's diseases (15), lymph follicular hyperplasia (4), nonspecific enteritis (4), vascular malformations (3), small bowel tumour (2), primary intestinal lymphangiectasia (2), gastrointestinal motility disorders (2), Meckel's diverticulum (1), angioma (1), small intestinal worm disease (1), duodenal ulcer (1), and polyposis syndromes (1). The capsule of 1 patient remained in the stomach. The cleanliness of small intestine after 8 hours fasting was good. And the capsule endoscopy can show high quality small intestine image. CONCLUSION: Wireless capsule endoscopy is a noninvasive, safe and useful tool for the investigation of the small intestine in children, especially for obscure gastrointestinal bleeding and Crohn's disease.