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06 January 2024, Volume 39 Issue 1 Previous Issue   

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Evidence-based guideline for pediatric clinical application of probiotics （2023）   Society of Microecology, Chinese Preventive Medical Association 2024, 39(1): 1-15.  DOI: 10.19538/j.ek2024010601 Abstract ( )   The efficacy and safety of probiotics as drugs, foods or dietary supplements for the prevention and treatment of pediatric diseases have been widely confirmed. In recent years, research on probiotics has been continuously updated. To help physicians better understand and use probiotics, pediatric experts from the Microecology Branch of the Chinese Society of Preventive Medicine have developed this guideline based on the "Evidence-Based Guideline for Pediatric Clinical Application of Probiotics" published in 2017, combined newly published literature from China and abroad, and considered the current actual situation in China, with a view to guiding the standard clinical application of probiotics in pediatrics in China.

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Focusing on microecological preparations in children ZHENG Yue-jie, HUANG Zhi-hua 2024, 39(1): 16-20.  DOI: 10.19538/j.ek2024010602 Abstract ( )   With the deepening of research on the relationship between intestinal microbiota and human health and disease，microecological preparations have attracted more and more attention from pediatric medical staff and the public.Microecological preparations include probiotics，prebiotics，synbiotics and postbiotics，of which probiotics are currently the most widely used preparations.Probiotics play a role in the prevention and treatment of certain diseases and health promotion by antagonizing potential pathogenic bacteria，enhancing mucosal immune function and intestinal barrier function，activating and regulating systemic immune response，and improving intestinal metabolism.Probiotics can be given in the form of drugs，formula supplements，dietary supplements and health care supplements.Probiotics have the characteristics of strain specificity，dose dependence and individual or population differences，which are the main basis for clinical application selection，recommendation and evaluation of probiotics.

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Progress in the application of probiotics in neonatal diseases SUN Qian, HUA Zi-yu 2024, 39(1): 21-24.  DOI: 10.19538/j.ek2024010603 Abstract ( )   Probiotics are a category of live microorganisms that，when consumed in adequate amounts，exert beneficial effects on health.Research has demonstrated their crucial role in regulating the composition of the gut microbiota，enhancing its barrier function， suppressing inflammation， and participating in immune modulation.The digestive and immune systems of newborns are immature， supplementation with probiotics may improve clinical outcomes of necrotizing enterocolitis and pathological jaundice in the newborn. This review aims to elucidate the role of probiotics in assisting the management of neonatal digestive system disorders and systemic diseases.However， the effectiveness and safety of probiotics in neonates require large clinical researches and long-term follow-up observations for further reliable evaluation.

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Progress in the application of probiotics in the digestive system diseases of children XIONG Jing-jing, HUANG Yong-kun 2024, 39(1): 25-28.  DOI: 10.19538/j.ek2024010604 Abstract ( )   Probiotics are a type of live microorganisms that have been proven to be beneficial to human health.They can regulate intestinal micro-ecological balance.Recent research has shown that probiotics have varying degrees of efficacy in the treatment digestive system diseases in children，and their safety and effectiveness have been clinically verified to a certain extent. This article focuses on the clinical applications and research progress of some probiotics in the prevention and treatment of pediatric Helicobacter pylori infection，acute diarrhea，infantile colic，necrotizing enterocolitis，constipation，lactose intolerance，inflammatory bowel disease，pediatric non-alcoholic fatty liver and pancreatitis.

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Progress in the application of probiotics in respiratory diseases in children GOU Yuan, WANG Wen-jian 2024, 39(1): 28-32.  DOI: 10.19538/j.ek2024010605 Abstract ( )   The gut microbiota carries acquired genes， participates in normal physiological and pathological processes， and is closely related to human health. Probiotics have functions such as antagonizing pathogenic microorganisms， enhancing epithelial barriers or nutrient metabolism， and stimulating and promoting immune maturation in the body. They are currently widely used in various diseases such as childhood diarrhea， functional gastrointestinal diseases， and metabolic diseases. In recent years， probiotics have also been used as adjunctive therapies for respiratory diseases， with the main mechanism of action being achieved by regulating lung immunity through the mucosal immune system. The article briefly introduces the mechanism of probiotics in the prevention and treatment of  respiratory diseases and their clinical progress in children's respiratory diseases.

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Advances in the application of probiotics in pediatric allergic diseases JI Ruo-chen, ZHANG Lin 2024, 39(1): 32-35.  DOI: 10.19538/j.ek2024010606 Abstract ( )   In recent years，the prevalence of allergic diseases among children in China has been increasing year by year.Changes in modern lifestyle and diet，as well as the increase in the rate of cesarean section and the use of antibiotics in the early stage of life directly or indirectly affect the development direction of intestinal flora colonization，succession and immunity in early life.These factors are closely associated with the long-term health and risk of diseases，particularly allergic diseases of infants. The“hygiene hypothesis”theory has been widely supported by research，suggesting that dysbiosis of the gut microbiota serves as a prerequisite and foundation for the development of allergic diseases.Therefore，microbial ecological strategies can be considered important approaches to the prevention and treatment of allergic diseases.This article provides a systematic review and discussion on the role of early-life gut microbiota development in the occurrence and development of allergic diseases，as well as the research progress on the application of probiotics in children with allergic diseases，aiming to provide a basis for primary prevention and targeted treatment of allergic diseases.

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Application progress of probiotics in the antibiotic-associated diarrhea in children ZOU Biao, SHU Sai-nan 2024, 39(1): 36-42.  DOI: 10.19538/j.ek2024010607 Abstract ( )   Antibiotic-associated diarrhea（AAD）is a common complication of antibiotic treatment.It is characterized by the disruption of the gut microbiota，causing the decrease of  intestinal short chain fatty acid（SCFA）concentrations，accumulation of luminal carbohydrates and colonic bile acids，changes in water and electrolyte absorption，and ultimately diarrhea. Many randomized controlled trials have shown the benefits of probiotics in preventing AAD. Although adverse events have been reported for probiotics，they still are broadly considered to be a safe and inexpensive preventative treatment option for AAD and other gastrointestinal disorders.This review summarized the effects of probiotics on children's AAD，in order to guide its rational application.

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Research progress in fecal microbiota transplantation in children HUANG Ying, DONG Fang 2024, 39(1): 42-47.  DOI: 10.19538/j.ek2024010608 Abstract ( )   The normal and stable intestinal microbiota plays a key role in maintaining body health，and treatment methods based on intestinal microecology have gradually attracted attention.In recent years，fecal microbiota transplantation therapy，which restructures intestinal homeostasis in patients by transplanting intestinal microbiota in healthy people，has developed rapidly.Many studies have confirmed that fecal microbiota transplantation has a certain effect on children with clostridium difficile infection，inflammatory bowel disease，irritable bowel syndrome，constipation，nervous system diseases，allergic diseases and endocrine and metabolic diseases.This article reviews the donor selection，fecal preparation，delivery methods，and the present status and prospect of clinical application of fecal microbiota transplantation in children，in order to provide better guidance for clinical practice.

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Prebiotics and postbiotics in pediatric clinical application WANG Wei, WU Qing-bin 2024, 39(1): 47-50.  DOI: 10.19538/j.ek2024010609 Abstract ( )   Prebiotics are substrates that can be selectively utilized by host microorganisms to confer health benefits.Postbiotics are preparations of inanimate microorganisms and/or their related components that provide health benefits to the host. Although the ingredients of the two formulations are different，the mechanism of action is the interaction of prebiotics or postbiotics with the gut microbiota，which endows the host with health benefits.This is particularly important for children，especially for infant disease prevention and healthy growth in early childhood. This article aims to clarify the concepts of prebiotics and postbiotics，discuss their mechanisms of action，and evaluate their clinical application in pediatrics，which will contribute to the in-depth research and application of prebiotics and postbiotics in pediatrics in the future.

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Gastroscopic characteristics of pediatric eosinophilic gastrointestinal diseases：An analysis of 121 cases  LI Jing, YU Fei-hong, QIN Xiu-min, et al 2024, 39(1): 51-55.  DOI: 10.19538/j.ek2024010610 Abstract ( )   Objective    To summarize the gastroscopic findings of pediatric eosinophilic gastrointestinal diseases（EGIDs）with upper gastrointestinal tract involvement. Methods    Collect and analyze the results of gastroscopy in children with EGIDs with upper gastrointestinal tract involvement admitted to the Gastroenterology Department，Beijing Children's Hospital，Capital Medical University from January 1，2016 to December 31，2022. Results    A total of 121 children with EGIDs were included in the study（89 males and 32 females）. There were 31 cases（25.62%） of esophageal involvement，39 cases（32.23%）of gastric involvement，and 85 cases（70.25%） of duodenum involvement.Common abnormalities in patients with esophageal involvement were mucosal roughness（32.26%），hyperemia and edema（25.81%），rings（9.68%），erosion（9.68%），and erythema（9.68%），and gastroscopy was normal in 45.16% of patients.Gastric mucosal hyperemia and edema（100%），mottling（71.79%），erythema（25.64%），mucous lake turbidity or bile dyed（23.08%），hemorrhage（20.51%），erosion（15.38%），mucosal roughness（15.38%），and ulcers（12.82%） were observed in gastric involvement  patients. Gastroscopy was normal in 28.24% of patients with duodenal involvement，the common abnormalities of whom were mucosal hyperemia and edema（58.82%），ulcer（31.76%），white exudates（23.53%），erythema（22.35%），roughness（22.35%），and erosion（15.29%），etc. The incidence of ulcers in children with duodenal involvement was higher than that in children with gastric involvement（χ2=5.011，P<0.05），while hemorrhage was more common in the stomach（χ2=5.940，P<0.05）. Conclusion    The gastroscopic manifestations of pediatric EGIDs are non-specific.Mucosal roughness，hyperemia and edema and rings are observed in patients with esophageal involvement. There is mucosal hyperemia and edema，mottling and erythema in patients with gastric involvement. In children with duodenal involvement，the common abnormalities are mucosal hyperemia and edema，ulcers，white exudates and erythema.About half of children with esophageal involvement and a quarter of children with duodenal involvement have normal gastroscopic findings.

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Correlation between pathological biopsy of gastric antrum and Helicobacter pylori（Hp） infection in 13C breath test of children with peptic ulcer：An analysis of 111 cases ZHAO Lan-lan, WU Wen-hong, ZHANG Wei-bo, et al 2024, 39(1): 56-60.  DOI: 10.19538/j.ek2024010611 Abstract ( )   Objective    To explore the correlation between the severity of gastric antrum inflammation by pathological biopsy and positive Helicobacter pylori（Hp）in children with peptic ulcer under electronic gastroscopy，and provide certain evidence-based basis for clinical diagnosis and treatment. Methods    A total of 111 children who had peptic ulcers confirmed by gastroscopy at the Pediatric Department of the First Affiliated Hospital of Xiamen University from October 2019 to July 2021 were included as the observation subjects. General data were collected and various related indicators were analyzed at the same time，including as 13C breath test，pathological biopsy of gastric antrum，immunohistochemistry，etc.，in order to study the correlation between the severity of gastric antrum inflammation and positive Hp in children with peptic ulcer. Results    Among 111 children with peptic ulcer，there was 1 gastric ulcer，108 duodenal ulcer，and 2 compound ulcers；among them 96 cases received 13C breath test，94 cases received gastric antrum biopsy and immunohistochemistry. All the 13 cases with Hp-positive in gastroscopy pathological biopsy had moderate to severe antral inflammation， and the difference between positive group and negative group was statistically significant （rank sum=931.5，P<0.05）. The same results were also found in 19 patients with positive 13C breath test （H=10.280，P<0.05）. The antral inflammation in patients with negative Hp in 13C breath test and gastroscopy biopsy was more mild， and the difference between positive and negative groups was statistically significant （rank sum=888.5，P<0.001）. Conclusion    Hp infection is the main cause of maderate to severe inflammation in the gastric antrum of peptic ulcer；a positive Hp biopsy is more likely to reflect the severity of gastric antrum inflammation than a positive 13C breath test. Electronic gastroscopy is extremely necessary for children with a positive 13C breath test，which can give a stronger evidence-based proof for performing anti-Hp treatment.

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Research progress of NLRC4-associated autoinflammatory disorders WANG Li, TANG Xue-mei 2024, 39(1): 61-64.  DOI: 10.19538/j.ek2024010612 Abstract ( )   NOD-like receptor family caspase activation and recruitment domain（CARD）- containing 4 protein associated autoinflammatory disorders（NLRC4-AIDs）are a kind of early-onset auto-inflammatory disease with NLRC4 gene gain-of -mutation. NLRC4 is a main component of cytoplasmic NLRC4 inflammasome.Because of NLRC4 mutaion，over activation of NLRC4 inflammasome leads to active caspase-1，causes the increase of IL-1 and IL-18， and induces systemic inflamatory. NLRC4-AIDs have various clinical phenotypes，with a spectrum of clinical manifestations ranging from familial cold-induced urticaria to neonatal-onset multisystem infammatory disease（NOMID），life-threatening macrophage activation syndrome（MAS）and autoinflammation with infantile enterocolitis（AIFEC）.NLRC4-AIDs are characterized by high levels of free IL-18 in the serum of patients and invasion of lymphocytes in skin biopsy. Early and rapid identification of diseases by specific biomarkers，timely clinical and genetic diagnosis，and early intervention with targeted immunomodulatory therapy are the key strategies to improve the prognosis of NLRC4-AIDs patients. The aim of this article is to review the research progress of NLRC4-AIDS.

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Analysis of electroencephalogram in 2 cases of infancy pertussis encephalopathy burst suppression ZHANG Dong-mei, DU Lan, CHENG Xing-feng, et al 2024, 39(1): 65-67.  DOI: 10.19538/j.ek2024010613 Abstract ( )   The data of 2 children with pertussis encephalopathy admitted to Wuhan Children's Hospital，Tongji Medical College，Huazhong University of Science and Technology from September 2022 to October 2022 were retrospectively analyzed，and their clinical characteristics，diagnosis and treatment methods were summarized. It is found that the onset age of the 2 children with pertussis encephalopathy was within 3 months，and 1 of them had a history of contact with patients with cough，and no infection lesions were found in brain MRI.The convulsive seizures of the 2 children occurred at 2-3 weeks in the course of the disease，and the outbreak inhibition of EEG was present at 5-7 weeks in the course of the disease.In case 1，the EEG condition could be improved after the use of topax + levetiracetam. In case 2，the electroencephalogram was finally improved by the combination of topac and valproic acid. The literature analysis shows that pertussis encephalopathy is more common in infants of small months who have not received pertussis vaccine，most of which are caused by contact with coughing family members，and convulsive seizures are not correlated with EEG changes. This paper shows that topathy can effectively control seizures，and at the same time，by combination with other anti-seizure drugs EEG improvement is achieved.

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Clinical characteristics and differential diagnosis of Pitt-Hopkins syndrome: A report of cases SHENG Qian-qian, ZHAO Peng, CHEN Shu-juan, et al 2024, 39(1): 68-72.  DOI: 10.19538/j.ek2024010614 Abstract ( )   Analyze the clinical characteristics of 3 patients with Pitt -Hopkins syndrome（PTHS）due to TCF4 gene mutation ，who were hospitalized in Tianjin Children’s Hospital from May to July 2019. All the 3 children underwent whole exon sequencing，and the positive results were verified by first-generation sequencing.Summarize its clinical features and differentiate it with other Rett- like syndromes. The results showed that all 3 proband had heterozygous variation of TCF4 gene，and their parents were wild-type.All the 3 children presented with global developmental delay，special facial features and autism spectrum disorder.Among them，1 patient had epilepsy and obvious autonomic nerve symptoms.In the differential diagnosis with other Rett - like syndromes，the facial features of children had high specificity.The clinical features of PTHS caused by TCF4 gene mutation and other Rett - like syndromes are mostly overlapped.Facial features are key to differential diagnosis.

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STX1B gene-related epilepsy：A family report and literature review LAN Ming-ping, CHEN Jia-lei, LIU Ping, et al 2024, 39(1): 73-76.  DOI: 10.19538/j.ek2024010615 Abstract ( )   Clinical data of a family with STX1B gene mutation were collected from the Department of Neurology， Chengdu Women and Children's Central Hospital in January 2020. "STX1B" or "syntaxin 1B"both in Chinese and English were used as keywords to search in PUBMED， VIP， CNKI， and Wanfang databases (up to May 31， 2021). The results showed that the child was a 2-year-old boy who started with frequent seizures， which could be induced by fever. His mother and his brother had history of febrile seizures when they were young. The treatment with sodium valproate and oxcarbazepine was not effective at the beginning， and then oxcarbazepine was tapered off and topiramate was added and no seizures recurred. Whole exome sequencing of the fanily revealed a heterozygous missense mutation， c.697G > A (p.Glu233Lys)， in the STX1B gene， which was inherited from his mother， while his brother had no mutation at this site，and this variant had not been reported in the literature before. One Chinese article and 12 English articles were retrieved. There were various seizure types reported in the literature， including generalized tonic-clonic seizures， focal seizures， atonic seizures， and myoclonic atonic seizures. A total of 27 mutations and 3 cases of whole gene deletion were reported in the literature， including 13 missense mutations， 8 frameshift mutations， 5 nonsense mutations， and 1 small fragment insertion. It is concluded that STX1B genes are mainly missense mutations and frameshift mutations， and the clinical phenotype is heterogeneous. We describe a mutation that has not been reported before and it may respond well to topiramate.

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Analysis of SKIV2L gene variants in a child with tricho-hepato-enteric syndrome ZHENG Yu-can, LIU Zhi-feng, JIN Yu, et al 2024, 39(1): 77-80.  DOI: 10.19538/j.ek2024010616 Abstract ( )   To explore the clinical features and genetic variants of a patient with tricho-hepato-enteric syndrome（THES） admitted to the Department of Gastroenterology in the Chidren’s Hospital of Nanjing Medical University on Jan.24， 2021. Genomic DNA was extracted from the peripheral blood of the child and his parents.Genetic variants were detected by next-generation sequencing.Candidate variants were verified by Sanger sequencing followed by bioinformatic analysis. The child presents with clinical symptoms of liver damage，diarrhea，woolly and brittle hair and growth retardation.The microscopic hair examination showed trichorrhexis nodosa. Novel compound heterozygous SKIV2L gene variants（c.29C>T/c.321C>G）were detected in the child. The two variants have not been reported before，the sites are conserative， and many kinds of bioinformatics predict them as harmful. It is concluded that compound heterozygous variants（c.29C>T/c.321C>G）of SKIV2L gene is the etiology of the patient.The two novel variants expand the spectrum of SKIV2L gene variant and provid the basis for genetic counseling of the family.