Serum vitamin D status in a cohort of infants with food protein­induced gastrointestinal disease.

Increases in the prevalence of food allergy and vitamin D deficiency have been observed in recent years. The association between vitamin D levels and food allergy remains to be fully elucidated, and research focused on the prevalence of vitamin D insufficiency in infants with food protein-induced gastrointestinal disease in Chengdu, Sichuan is lacking. Thus, the present study aimed to determine the prevalence and clinical characteristics of serum 25 hydroxyvitamin D [25-(OH)D] insufficiency and sufficiency in infants with food protein-induced gastrointestinal disease. The present study also aimed to identify the potential predisposing factors of 25-(OH)D insufficiency. The present retrospective study analyzed data obtained from Chengdu Women's and Children's Central Hospital spanning between June 2021 and February 2022. Children with a confirmed diagnosis of food protein-induced gastrointestinal disease were enrolled in the present study. Blood indicators, including serum 25-(OH)D, serum total immunoglobulin E (IgE), specific IgE against allergens, and hemoglobin were measured during the course of the disease. Clinical characteristics of patients and blood examination results were obtained from the hospital electronic database. A total of 361 patients were included in the study group and 45 healthy individuals were included in the control group. The results of the present study demonstrated that serum 25-(OH)D levels of infants with protein-induced gastrointestinal disease were significantly lower compared with the control group. Notably, female participants with higher serum total IgE levels exhibited insufficient serum 25-(OH)D levels. However, the results of the logistic regression analysis revealed no predisposing factors associated with serum 25-(OH)D insufficiency. In conclusion, infants with food protein-induced gastrointestinal disease may exhibit a higher risk of low serum 25-(OH)D levels and this risk may be greater in females with higher total IgE.

[Selection of enteral nutrition regimens for children with abdominal Henoch-Schönlein purpura].

OBJECTIVE: To explore the reasonable and effective enteral nutrition regimen for children with abdominal Henoch-Schönlein purpura (HSP). METHODS: A retrospective analysis was performed on the medical data of children with abdominal HSP who were hospitalized from August 2013 to August 2018. According to the starting time of enteral nutrition after abdominal pain relief, the children were divided into three groups: < 24 hours (n=68), 24-48 hours (n=64), and 48-72 hours (n=60). According to the type of enteral nutrition, they were divided into another three groups:amino acid-based formula (n=53), extensively hydrolyzed lactoprotein formula (n=67), and normal diet (n=72). The recurrence rate of clinical symptoms and degree of satisfaction among family members were compared between groups. Based on the retrospective analysis, 166 children with abdominal HSP were enrolled in a prospective study. They were given extensively hydrolyzed lactoprotein formula after abdominal pain relief. According to the feeding time after abdominal pain relief, they were divided into three groups: < 24 hours (n=52), 24-48 hours (n=59), and 48-72 hours (n=55). The three groups were compared in terms of the recurrence rates of abdominal pain, rash, and hematochezia, the rate of use of parenteral nutrition and intravenous steroids, and the incidence rate of weight loss at discharge. RESULTS: The retrospective analysis showed that the children who were given extensively hydrolyzed lactoprotein formula for enteral nutrition at 24-48 hours after abdominal pain relief had a lower recurrence rate of clinical symptoms and the highest degree of satisfaction among their family members (P < 0.0167). The prospective study showed that the children who were given extensively hydrolyzed lactoprotein formula for enteral nutrition at 24-48 hours after abdominal pain relief had lower recurrence rates of rash and abdominal pain, a lower rate of use of parenteral nutrition, and a lower incidence rate of weight loss at discharge (P < 0.05). CONCLUSIONS: It is reasonable and effective to start the feeding with extensively hydrolyzed lactoprotein formula at 24-48 hours after abdominal pain relief in children with abdominal HSP.

Current status of fecal calprotectin as a diagnostic or monitoring biomarker for cow's milk protein allergy in children: a scoping review.

BACKGROUND: There are few approved biomarkers for diagnosis and monitoring of cow's milk protein allergy (CMPA), thus the oral food challenge remains to be the golden diagnostic standard. A potential biomarker is fecal calprotectin, a cytosolic protein, elevating in the presence of intestinal mucosal inflammation. We aimed to undertake a scoping review of the evidence pertaining to the current status of fecal calprotectin used for diagnosis and monitoring CMPA in children, and tried to indicate the aspects needed to be concerned in the future investigations and researches. METHODS: A scoping review was performed using the literature searched from PUBMED, EMBASE, and Web of Science Databases until July 2019 on the studies about the application of fecal calprotectin as a biomarker of CMPA in children. Studies were examined according to the inclusion and exclusion criteria. Data were extracted, and a narrative synthesis was conducted to summarize and analyze. RESULTS: Thirteen studies with different study design embracing 1238 children were included. The age range was from infants to adolescents. Most children with CMPA presented gastrointestinal symptoms, among which hematochezia was most common. Amount of data suggested that infants with CMPA represented elevated levels of fecal calprotectin, particularly with distinct significance in non-IgE-mediated CMPA groups. Decreases of fecal calprotectin after elimination diet were demonstrated in enrolled studies. However, no matter in the CMPA positive or negative groups, the changes of fecal calprotectin before or after challenge showed no significance. Contradictory results were generated from studies on the role of fecal calprotectin in predicting allergic disease. CONCLUSIONS: Available evidence is not sufficient to confirm the utilization of fecal calprotectin both in diagnosis and monitoring of CMPA and predicting for allergic disease. More clinical and bench researches with elaborate design should be conducted and the exact cut-off values of fecal calprotectin in different groups remain to be determined.

Fanconi-Bickel syndrome in an infant with cytomegalovirus infection: A case report and review of the literature.

BACKGROUND: Fanconi-Bickel syndrome (FBS) is a rare autosomal recessive disorder caused by mutation of the SLC2A2 gene, which encodes glucose transporter protein 2 (GLUT2). CASE SUMMARY: We report a 7-mo-old girl with cytomegalovirus infection presenting hepatomegaly, jaundice, liver transaminase elevation, fasting hypoglycemia, hyperglycosuria, proteinuria, hypophosphatemia, rickets, and growth retardation. After prescription of ganciclovir, the levels of bilirubin and alanine aminotransferase decreased to normal, while she still had aggravating hepatomegaly and severe hyperglycosuria. Then, whole exome sequencing was conducted and revealed a homozygous c.416delC mutation in exon 4 of SLC2A2 inherited from her parents, which was predicted to change alanine 139 to valine (p.A139Vfs*3), indicating a diagnosis of FBS. During the follow-up, the entire laboratory test returned to normal with extra supplement of vitamin D and corn starch. Her weight increased to normal range at 3 years old without hepatomegaly. However, she still had short stature. Although there was heterogeneity between phenotype and genotype, Chinese children had typical clinical manifestations. No hot spot mutation or association between severity and mutations was found, but nonsense and missense mutations were more common. Data of long-term follow-up were rare, leading to insufficient assessment of the prognosis in Chinese children. CONCLUSION: FBS is a rare genetic metabolic disease causing impaired glucose liver homeostasis and proximal renal tubular dysfunction. Results of urine and blood testing suggesting abnormal glucose metabolism could be the clues for FBS in neonates and infants. Genetic sequencing is indispensable for diagnosis. Since the diversity of disease severity, early identification and long-term follow-up could help improve patients' quality of life and decrease mortality.

The Role of Human Coronavirus Infection in Pediatric Acute Gastroenteritis.

Since human coronavirus (HCoV)-like particles were detected in the stool specimens of acute gastroenteritis and necrotizing enterocolitis children with electron microscopy, the relationship between HCoV and the pediatric gastrointestinal illness had been recognized. In recent years, the overall detection rates have been low and have varied by region. HCoVs have not been considered as the major pathogens in pediatric acute gastroenteritis. HCoVs detected in children with acute gastroenteritis have included 229E, OC43, HKU1, NL63, and severe acute respiratory syndrome coronavirus, Middle East Respiratory Syndrome Coronavirus and severe acute respiratory syndrome coronavirus-2 have also been associated with gastrointestinal symptoms in children. Although digestive tract has been recognized as an infection route, it has not been possible to fully investigate the association between HCoVs infection and the gastrointestinal symptoms because of the limited number of pediatric cases. Furthermore, pathologic features have not been clear. Till now, our knowledge of severe acute respiratory syndrome coronavirus-2 is limited. However, diarrhea and vomiting have been seen in pediatric cases, particularly in newborns and infants. It has been necessary to pay more attention on gastrointestinal transmission to identify the infected children early and avoid the children without apparent or mild symptoms becoming the sources of infection.

From SARS to COVID-19: What we have learned about children infected with COVID-19.

INTRODUCTION: Coronaviruses, both SARS-CoV and SARS-CoV-2, first appeared in China. They have certain biological, epidemiological and pathological similarities. To date, research has shown that their genes exhibit 79% of identical sequences and the receptor-binding domain structure is also very similar. There has been extensive research performed on SARS; however, the understanding of the pathophysiological impact of coronavirus disease 2019 (COVID-19) is still limited. METHODS: This review drew upon the lessons learnt from SARS, in terms of epidemiology, clinical characteristics and pathogenesis, to further understand the features of COVID-19. RESULTS: By comparing these two diseases, it found that COVID-19 has quicker and wider transmission, obvious family agglomeration, and higher morbidity and mortality. Newborns, asymptomatic children and normal chest imaging cases emerged in COVID-19 literature. Children starting with gastrointestinal symptoms may progress to severe conditions and newborns whose mothers are infected with COVID-19 could have severe complications. The laboratory test data showed that the percentage of neutrophils and the level of LDH is higher, and the number of CD4+ and CD8+T-cells is decreased in children's COVID-19 cases. CONCLUSION: Based on these early observations, as pediatricians, this review put forward some thoughts on children's COVID-19 and gave some recommendations to contain the disease.

[Clinical effect of alanyl-glutamine-enriched nutritional support in the treatment of children with abdominal Henoch-Schönlein purpura].

OBJECTIVE: To study the clinical effect of alanyl-glutamine-enriched nutritional support in the treatment of children with abdominal Henoch-Schönlein purpura. METHODS: Children with abdominal Henoch-Schönlein purpura who needed nutritional support were enrolled and stratified according to age, sex and the severity of disease, and were randomly divided into a control group (n=118) and an enriched nutritional support group (n=107). The control group was given nutritional support without using alanyl-glutamine, while the enriched nutritional support group was given alanyl-glutamine-enriched nutritional support. Intravenous steroids were used according to the severity of disease in both groups. Other therapies were the same in the two groups. The two groups were compared in terms of the length of hospital stay, the rate and duration of use of intravenous steroids, the recurrence rate of symptoms during hospitalization, the rate of total parenteral nutrition (TPN), the rate of weight loss and the rate of fasting for more than 5 days. All patients were followed up for 3 months after discharge to monitor the recurrence of symptoms. RESULTS: There were no significant differences in the length of hospital stay, the rate of TPN and the rate of fasting for more than 5 days between the two groups (P>0.05). Compared with the enriched nutritional support group, the control group showed significant increases in the rate and duration of use of intravenous steroids, the recurrence rate of symptoms and the rate of weight loss (P<0.05). After the 3-month follow-up, all the children resumed normal diet, and the recurrence rate of digestive symptoms was less than 20% in each group. Abdominal pain was the most common symptom (83.33%, 30/36), followed by vomiting and abdominal distention. No digestive hemorrhage was observed. All the symptoms were relieved after symptomatic treatment. No significant difference was found between the two groups in the recurrence rate of digestive symptoms (P=0.693). CONCLUSIONS: Alanyl-glutamine-enriched nutritional support in the treatment of children with abdominal Henoch-Schönlein purpura can reduce the use of intravenous steroids and weight loss, but without impact on the length of hospital stay and post-discharge recurrence.

[Epidemiological and clinical features of calicivirus-associated diarrhea in hospitalized children in Chengdu, China from 2012 to 2014].

OBJECTIVE: To investigate the epidemiological and clinical features of calicivirus-associated diarrhea in hospitalized children in Chengdu, China in recent years. METHODS: The clinical data of 267 children with calicivirus-associated diarrhea aged <5 years who were hospitalized in Chengdu Women and Children's Central Hospital (the only sentinel hospital for sample collection of pediatric viral diarrhea in Chengdu, Sichuan) between January 2012 and December 2014 were retrospectively studied. RESULTS: Among the 267 children, 200 (74.9%) were aged less than 1 year. The infection rate of calicivirus was 28.4%, 21.6%, and 27.1% in 2012, 2013, and 2014, respectively. Calicivirus was prevalent in summer and autumn (August to October). The detection rate of Norovirus II was 85.8% (229/267), and 244 children (91.4%) experienced an acute clinical course. Watery stool was the most common change in stool properties (82.0%, 219 children), and some specimens showed mucus and/or blood. Most children had moderate to severe fever. One hundred and thirty-eight children (53.9%) experienced a reduced serum prealbumin level. One hundred and fifty-nine children (59.6%) experienced flora imbalance. CONCLUSIONS: Calicivirus has become one of the major pathogens for diarrhea in children aged <5 years in Chengdu, with Norovirus II as the dominant strain. Calicivirus is prevalent in summer and autumn. Infants aged <1 year are the main population affected by calicivirus-associated diarrhea, with watery stool as the most common manifestation.

Current views of the relationship between Helicobacter pylori and Henoch-Schonlein purpura in children.

Helicobacter pylori (H. pylori) is one of the factors involved in the pathogenesis of various gastrointestinal diseases and may play a potential role in certain extra-intestinal diseases. H. pylori infection are mainly acquired during childhood, and it has been reported that in endemic areas of China the infection rates are extraordinarily higher in HSP children, particular those with abdominal manifestations. Furthermore, eradication therapy may ameliorate Henoch-Schonlein purpura (HSP) manifestations and decrease the recurrence of HSP. Therefore, results suggested that detection of H. pylori infection by appropriate method ought to be applied in HSP children. Current evidences indicate that local injury of gastric mucosa and immunological events induced by H. pylori infection are involved in the development of HSP. Increased serum IgA, cryoglobulins, C3 levels, autoimmunity, proinflammatory substances and molecular mimicry inducing immune complex and cross-reactive antibodies caused by H. pylori infection might play their roles in the course of HSP. However, there are no investigations confirming the causality between H. pylori infection and HSP, and the pathogenesis mechanism is still unclear. More bench and clinical studies need to be executed to elaborate the complex association between H. pylori and HSP.

Neuroprotective effect of brain-derived neurotrophic factor mediated by autophagy through the PI3K/Akt/mTOR pathway.

Brain­derived neurotrophic factor (BDNF) has been demonstrated to be a potent growth factor that is beneficial in neuronal functions following hypoxia­ischemia (HI). Mature BDNF triggers three enzymes, mitogen­activated protein kinase (MAPK), phosphatidylinositol 3­kinase (PI3K) and phosphoinositide phospholipase C-γ (PLCγ), which are its predominant downstream regulators. The PI3K­Akt signaling pathway is upstream of the mammalian target of rapamycin (mTOR), which is important in the induction of autophagy. However, whether the neuroprotective effect of BDNF is mediated by autophagy through the PI3K/Akt/mTOR pathway remains to be elucidated. Cortical neurons were cultured following isolation from pregnant rats (gestational days 16­18). The induction of autophagy following BDNF treatment was analyzed by microtubule­associated protein light chain 3 (LC3) conversion and autophagosome formation. The phosphorylation of Akt, mTOR and ribosomal protein S6 kinase (p70S6K) was analyzed in cultured cells with or without BDNF treatment. Cell viability was determined by a Cell Counting Kit­8 for estimating the protective effect of BDNF. Results demonstrated that autophagy was induced in cells with oxygen deprivation. BDNF promoted cell viability via the upregulation of autophagy. Moreover, LC3 upregulation was related to Akt/mTOR/p70S6K inhibition by BDNF. In conclusion, the results suggested that the neuroprotective effect of BDNF was mediated by autophagy through the PI3K/Akt/mTOR pathway.

Detection of clarithromycin-resistant Helicobacter pylori by stool PCR in children: a comprehensive review of literature.

BACKGROUND: Helicobacter pylori infection is acquired mainly during childhood. To eradicate H. pylori, clarithromycin-based triple therapy has been recommended in children and adults by the latest Maastricht Consensus. However, the prevalence of clarithromycin-resistant H. pylori was higher in children than that in adults. Therefore, rapid, reliable and noninvasive methods for detecting clarithromycin-resistant H. pylori strains should be developed for children. MATERIALS AND METHODS: Studies on evaluating stool PCR in detecting clarithromycin-resistant H. pylori and epidemiological surveys of the prevalence of clarithromycin-resistant H. pylori in children were searched in PubMed (from 1966 to December, 2011) for reviewing. RESULTS: The average rates of primary clarithromycin-resistant H. pylori ranged from less than 10% to more than 40% in different regions. The rates of secondary resistance to clarithromycin were higher than primary resistance in the same population. In H. pylori isolated from children, the frequent point mutations that are responsible for the clarithromycin resistance included A2143G, A2142G, A2142C and A2144G, and they varied geographically. Comparing with culture-based susceptibility tests, stool PCR performed excellently for their rapidity, independence of bacterial growth, reproducibility and easy standardization. However, stool PCR showed lower sensitivity but perfect specificity in detection of clarithromycin-resistant H. pylori in children. Methodology and mixed infections of resistant H. pylori strains might contribute to the considerable discrepancies of stool PCR results. CONCLUSION: Detection of clarithromycin-resistant H. pylori by stool PCR for children are reliable, rapid, noninvasive methods that are worthy of further clinical promotion. However, more evaluations of stool PCR in detection of clarithromycin-resistant H. pylori in children need to be conducted.

The neuroprotective roles of BDNF in hypoxic ischemic brain injury.

Hypoxia-ischemia (H/I) brain injury results in various degrees of damage to the body, and the immature brain is particularly fragile to oxygen deprivation. Hypothermia and erythropoietin (EPO) have long been known to be neuroprotective in ischemic brain injury. Brain-derived neurotrophic factor (BDNF) has recently been recognized as a potent modulator capable of regulating a wide repertoire of neuronal functions. This review was based on studies concerning the involvement of BDNF in the protection of H/I brain injury following a search in PubMed between 1995 and December, 2011. We initially examined the background of BDNF, and then focused on its neuroprotective mechanisms against ischemic brain injury, including its involvement in promoting neural regeneration/cognition/memory rehabilitation, angiogenesis within ischemic penumbra and the inhibition of the inflammatory process, neurotoxicity, epilepsy and apoptosis. We also provided a literature overview of experimental studies, discussing the safety and the potential clinical application of BDNF as a neuroprotective agent in the ischemic brain injury.

Is Helicobacter pylori infection associated with Henoch-Schonlein purpura in Chinese children? a meta-analysis.

BACKGROUND: The prevalence of Helicobacter pylori (H. pylori) infection is high in China. It not only causes the damage of gastric epithelium, but also plays a potential pathogenic role in several extraintestinal diseases. Henoch-Schonlein purpura (HSP) is one of the most common vasculitis syndromes affecting children. Although its cause is unclear, HSP is often considered to be associated with infectious agents. This metaanalysis of previously published studies was conducted using a predefined protocol to evaluate the underlying association between H. pylori infection and HSP in Chinese children. METHODS: Predefined search strategy and inclusion criteria were set up to select studies reporting the prevalence of H. pylori infection among HSP children and control groups. Included studies were subjected to quality assessment and data extraction by two independent reviewers. The pooled odds ratio (OR) was calculated as the effect size via both traditional and cumulative meta-analysis. Heterogeneity was investigated by subgroup analysis, and the nonparametric "trim and fill" method was performed to adjust the overall estimate for the existence of publication bias. RESULTS: Ten eligible studies covering 749 HSP children and 560 controls were included for metaanalysis. Observational epidemiology studies clearly aimed at detecting the potential association between H. pylori infection and HSP with retrospective data collection from the children enrolled consecutively. Overall, 49.27% (369/749) of HSP children had evidence of H. pylori infection compared with 23.39% (131/560) of children in the control group. The pooled OR of H. pylori infection in HSP children (10 studies with 749 HSP children) was 3.80 [95% confidence interval (CI): 2.54-5.68, P<0.001], and the overall estimate from the cumulative meta-analysis confirmed the association with more narrow confidence interval (OR=3.35, 95% CI: 2.95-3.81). In HSP children mainly with abdominal manifestations (8 studies with 337 HSP children), the pooled OR was 4.62 (95% CI: 2.66-8.01, P<0.001). The adjusted pooled OR was 2.04 (95% CI: 1.48-2.82, P<0.001), determined by the nonparametric "trim-andfill" method for eliminating the effect of publication bias. H. pylori eradication therapy (4 studies with 266 HSP children) was capable of reducing the recurrence of HSP (RR=0.38, 95% CI: 0.25-0.58, P<0.001). Although the subgroup analysis for heterogeneity suggested that diagnostic methods and geographical diversity might be account for the heterogeneity, statistical analysis of differences revealed no differences between subgroups, indicating their limited impact on the overall estimates. CONCLUSIONS: These results suggest the necessity of screening H. pylori infection in HSP children, particularly in those with gastrointestinal manifestations in China. Eradication therapy may reduce the recurrence of HSP in children with H. pylori infection. However, further mechanistic and more clinical studies in different populations and regions are needed to confirm this association and the effect of eradication of H. pylori in HSP children.