Clinical research of fibroscan ‒ TE-CAP at noninvasive diagnosis of hepatic steatosis in children.

BACKGROUND & AIMS: The authors assess the diagnostic accuracy of the Transient Elastography-Controlled Attenuation Parameter (TE-CAP) in children of Southern China. METHODS: 105 obese or overweight children and adolescents were enrolled in the diagnostic test of TE-CAP assessment of hepatic steatosis using MRI-PDFF. Hepatic steatosis grades S0-S3 were classified. Statistical correlation, agreement and consistency between methods were evaluated. The diagnostic efficiency of TE-CAP was evaluated. The authors used the cutoff value of TE-CAP to detect hepatic steatosis in another 356 children. RESULTS: The Area Under Curve (AUC) of TE-CAP for grade ≥ S1, ≥ S2, and ≥ S3 steatosis were 0.975, 0.984, and 0.997, respectively. For detecting ≥ S1 steatosis, TE-CAP had a sensitivity of 96 % and a specificity of 97 %. For detecting ≥ S2 steatosis, TE-CAP had a sensitivity of 97 % and a specificity of 93 %. For detecting ≥ S3 steatosis, TE-CAP had a sensitivity of 1 and a specificity of 94 %. TE-CAP and MRI-PDFF had a linear correlation (r = 0. 0.87, p < 0.001). The hepatic steatosis was identified in 40.2 % (143/356) of children in which the obesity and overweight were 69.8 % (113/162) and 40.0 % (18/45). CONCLUSION: TE-CAP showed excellent diagnostic accuracy in pediatric hepatic steatosis.

Radix Bupleuri aqueous extract attenuates MK801-induced schizophrenia-like symptoms in mice: Participation of intestinal flora.

Schizophrenia (SCZ) is a psychotic mental disorder characterized by cognitive, behavioral, and social impairments. However, current pharmacological treatment regimens are subpar in terms of effectiveness. This study aimed to investigate the function of Radix Bupleuri aqueous extract in SCZ in mouse models. The SCZ mouse model was established by MK-801 injection and feeding of Radix Bupleuri aqueous extract or combined antibiotics. Radix Bupleuri aqueous extract significantly improved the aberrant behaviors and neuronal damage in SCZ mice, upregulated SYP and PSD-95 expression and BDNF levels in hippocampal homogenates, down-regulated DA and 5-HT levels, and suppressed microglial activation in SCZ mice. Moreover, Radix Bupleuri aqueous extract improved the integrity of the intestinal tract barrier. The 16 S rRNA sequencing of feces showed that Radix Bupleuri extract modulated the composition of gut flora. Lactobacillus abundance was decreased in SCZ mice and reversed by Radix Bupleuri aqueous extract administration which exhibited a significant negative correlation with IL-6, IL-1ß, DA, and 5-HT, and a significant positive correlation with BDNF levels in hippocampal tissues. The abundance of Parabacteroides and Alloprevotella was increased in SCZ mice. It was reversed by Radix Bupleuri aqueous extract administration, which exhibited a positive correlation with IL-6, IL-1ß, and 5-HT and a negative correlation with BDNF. In conclusion, Radix Bupleuri aqueous extract attenuates the inflammatory response in hippocampal tissues and modulates neurotransmitter levels, exerting its neuroprotective effect in SCZ. Meanwhile, the alteration of intestinal flora may be involved in this process, which is expected to be an underlying therapeutic option in treating SCZ.

Gut microbiota in children with split-dose bowel preparations revealed by metagenomics.

Objective: Split-dose polyethylene glycol (PEG) is routinely used for bowel preparation before colonoscopy. This study aimed to investigate the composition of gut microbiota and its functions in pediatric patients undergoing split-dose PEG bowel preparation for colonoscopy to understand the stability and resilience of gut microbiota. Material and methods: From September to December 2021, 19 pediatric patients were enrolled at Shenzhen Children's Hospital and 76 samples (4 time points) were analyzed using metagenomics. Time points included Time_1 (one day before bowel preparation), Time_2 (one day after colonoscopy), Time_3 (two weeks after bowel preparation), and Time_4 (four weeks after bowel preparation). Result: Alpha diversity comparison at both the species and gene levels showed a decrease in community richness after colonoscopy, with little statistical significance. However, the Shannon diversity index significantly decreased (P<0.05) and gradually returned to pre-preparation levels at two weeks after bowel preparation. The genus level analysis showed six genera (Eubacterium, Escherichia, Intertinibacter, Veillonella, Ruminococcaceae unclassified, and Coprobacillus) significantly different across the four time periods. Additionally, at the species level, the abundance of Escherichia coli, Bacteroides fragilis, and Veillonella parvula significantly increased at one day after colonoscopy before gradually decreasing at two weeks after bowel preparation. In contrast, the abundance of Intertinibacter bartlettii decreased at one day after colonoscopy but then recovered at two weeks after bowel preparation, reaching the preoperative level at four weeks after bowel preparation. Furthermore, five functional pathways (base excision repair, biosynthesis of ansamycins, biosynthesis of siderophore group nonribosomal peptide, flavonoid biosynthesis, and biosynthesis of type II polyketide products) were significantly different across the four time periods, with recovery at two weeks after bowel preparation and reaching preoperative levels at four weeks after bowel preparation. Conclusions: Gut microbiota at the genus level, species level, and functional pathways are impacted in pediatric patients undergoing split-dose PEG bowel preparation and colonoscopy, with recovery two weeks following bowel preparation. However, the phylum level was not impacted. Modifications in gut microbiota composition and function may be investigated in future studies of bowel preparation. This study highlights the stability and resilience of gut microbiota among pediatric patients during bowel preparation.

Gut microbiome biomarkers in adolescent obesity: a regional study.

Purpose: This study aimed to characterize the gut microbiota in obese adolescents from Shenzhen (China), and evaluate influence of gender on BMI-related differences in the gut microbiome. Methods: Evaluation of physical examination, blood pressure measurement, serological assay and body composition were conducted in 205 adolescent subjects at Shenzhen. Fecal microbiome composition was profiled via high-throughput sequencing of the V3-V4 regions of the 16S rRNA gene. A Random Forest (RF) classifier model was built to distinguish the BMI categories based on the gut bacterial composition. Results: Fifty-six taxa consisting mainly of Firmicutes were identified that having significant associations with BMI; 2 OTUs belonging to Ruminococcaceae and 1 belonging to Lachnospiraceae had relatively strong positive correlations with body fate rate, waistline and most of serum biochemical properties. Based on the 56 BMI-associated OTUs, the RF model showed a robust classification accuracy (AUC 0.96) for predicting the obese phenotype. Gender-specific differences in the gut microbiome composition was obtained, and a lower relative abundance of Odoribacter genus was particularly found in obese boys. Functional analysis revealed a deficiency in bacterial gene contents related to peroxisome and PPAR signaling pathway in the obese subjects for both genders. Conclusions: This study reveals unique features of gut microbiome in terms of microbial composition and metabolic functions in obese adolescents, and provides a baseline for reference and comparison studies. Supplementary Information: The online version contains supplementary material available at 10.1007/s13755-023-00236-9.

The regulatory role of alternative splicing in inflammatory bowel disease.

Inflammatory bowel disease (IBD) mainly includes Crohn's disease and ulcerative colitis. These diseases have a progressive course of chronic relapse and remission and affect a large number of children and adults worldwide. The burden of IBD is rising worldwide, with levels and trends varying greatly in countries and regions. Like most chronic diseases, the costs associated with IBD are high, including hospitalizations, outpatient and emergency visits, surgeries, and pharmacotherapies. However, there is no radical cure for it yet, and its therapeutic targets still need further study. Currently, the pathogenesis of IBD remains unclear. It is generally assumed that the occurrence and development of IBD are related to the environmental factors, gut microbiota, immune imbalance, and genetic susceptibility. Alternative splicing contributes to a various diseases, such as spinal muscular atrophy, liver diseases, and cancers. In the past, it has been reported that alternative splicing events, splicing factors, and splicing mutations were associated with IBD, but there were no reports on the practical application for clinical diagnosis and treatment of IBD using splicing-related methods. Therefore, this article reviews research progress on alternative splicing events, splicing factors, and splicing mutations associated with IBD.

The relationship of Megamonas species with nonalcoholic fatty liver disease in children and adolescents revealed by metagenomics of gut microbiota.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children and adolescents. The gut microbiota plays an important role in the pathophysiology of NAFLD through the gut-liver axis. Therefore, we aimed to investigate the genus and species of gut microbiota and their functions in children and adolescents with NAFLD. From May 2017 to July 2018, a total of 58 children and adolescents, including 27 abnormal weight (AW) (obese) NAFLD patients, 16 AW non-NAFLD children, and 15 healthy children, were enrolled in this study at Shenzhen Children's Hospital. All of them underwent magnetic resonance spectroscopy (MRS) to quantify the liver fat fraction. Stool samples were collected and analysed with metagenomics. According to body mass index (BMI) and MRS proton density fat fraction (MRS-PDFF), we divided the participants into BMI groups, including the AW group (n = 43) and the Lean group (n = 15); MRS groups, including the NAFLD group (n = 27) and the Control group (n = 31); and BMI-MRS 3 groups, including NAFLD_AW (AW children with NAFLD) (n = 27), Ctrl_AW (n = 16) (AW children without NAFLD) and Ctrl_Lean (n = 15). There was no difference in sex or age among those groups (p > 0.05). In the BMI groups, at the genus level, Dialister, Akkermansia, Odoribacter, and Alistipes exhibited a significant decrease in AW children compared with the Lean group. At the species level, Megamonas hypermegale was increased in the AW group, while Akkermansia muciniphila, Dialister invisus, Alistipes putredinis, Bacteroides massiliensis, Odoribacter splanchnicus, and Bacteroides thetaiotaomicron were decreased in AW children, compared to the Lean group. Compared with the Control group, the genus Megamonas, the species of Megamonas hypermegale and Megamonas rupellensis, increased in the NAFLD group. Furthermore, the genus Megamonas was enriched in the NAFLD_AW group, while Odoribacter, Alistipes, Dialister, and Akkermansia were depleted compared with the Ctrl_Lean or Ctrl_AW group at the genus level. Megamonas hypermegale and Megamonas rupellensis exhibited a significant increase in NAFLD_AW children compared with the Ctrl_Lean or Ctrl_AW group at the species level. Compared with healthy children, the pathways of P461-PWY contributed by the genus Megamonas were significantly increased in NAFLD_AW. We found that compared to healthy children, the genus Megamonas was enriched, while Megamonas hypermegale and Megamonas rupellensis were enriched at the species level in children and adolescents with NAFLD. This indicates that the NAFLD status and/or diet associated with NAFLD patients might lead to the enrichment of the genus Megamonas or Megamonas species.

Study of Mental Health Status of the Resident Physicians in China During the COVID-19 Pandemic.

Objective: Investigating the mental health status of Chinese resident physicians during the 2019 new coronavirus outbreak. Methods: A cluster sampling method was adopted to collect all China-wide resident physicians during the epidemic period as the research subjects. The Symptom Checklist-90 self-rating scale was used to assess mental health using WeChat electronic questionnaires. Results: In total, 511 electronic questionnaires were recovered, all of which were valid. The negative psychological detection rate was 93.9% (480/511). Among the symptoms on the self-rating scale, more than half of the Chinese resident physicians had mild to moderate symptoms of mental unhealthiness, and a few had asymptomatic or severe unhealthy mental states. In particular, the detection rate of abnormality was 88.3% (451/511), obsessive-compulsive symptoms was 90.4% (462/511), the sensitive interpersonal relationship was 90.6% (463/511), depression abnormality was 90.8% (464)/511), anxiety abnormality was 88.3% (451/511), hostility abnormality was 85.3% (436/511), terror abnormality was 84.9% (434/511), paranoia abnormality was 86.9% (444/511), psychotic abnormalities was 89.0% (455/511), and abnormal sleeping and eating status was 90.8% (464/511). The scores of various psychological symptoms of pediatric resident physicians were significantly lower than those of non-pediatrics (p < 0.05). Conclusion: The new coronavirus epidemic has a greater impact on the mental health of Chinese resident physicians.

Early Diagnosis of Wilson's Disease in Children in Southern China by Using Common Parameters.

Objective: The aim of the study was to develop the early diagnostic criteria for Wilson's disease (WD) in young children in southern China by using alanine aminotransferase (ALT) elevation as the first manifestation. Methods: A cross-sectional retrospective analysis of the clinical data and genetic test results of children with WD in southern China in the past 4 years and the follow-up of their short-term prognosis were performed in this study. Results: A total of 30 children (5.08 ± 2.06 years old) with elevated ALT as the first manifestation of WD in southern China were enrolled in this study, including 14 females and 16 males. Specifically, in all of the 30 cases (100%), the serum ceruloplasmin (CP) level was decreased, whereas the 24-h urinary copper level was increased. The genetic mutation test of the ATP7B gene was used to confirm the diagnosis. In particular, the two mutation sites, including p.R778L and p.I1148T, had the highest mutation frequencies, approximately 23.0 and 10.7%, respectively. Through follow-up, most of the children had good recovery. Conclusion: Early diagnosis and treatment of WD would substantially increase the survival rate and have a better prognosis. In addition, in 5-year-old children from southern China, early diagnosis could be performed quickly by referring to the following three parameters: elevated ALT, decreased ceruloplasmin level, and increased 24-h urinary copper level. It lays a foundation for further studies with a larger sample size.

Level of IGF1 in follicular fluid associated with IVF pregnancy outcome in the application of growth hormone.

OBJECTIVES: The combination of growth hormone (GH) with gonadotropin was a prevalent method to improve clinical reproduction in adjuvant for assisted reproduction treatment (ART). However, the contradictory results from previous studies failed to confirm the benefits. The present study is focused on the mechanism analysis of GH-IGF1-gonadal axis in ART and the changes of IGF1 in follicular fluid among different types of patients. MATERIAL AND METHODS: We recruited 136 patients and divided them into eight groups according to their ages and ovarian reserves. The baseline characteristics of the study population were summarized. The therapeutic outcomes in the study population were observed. In the meantime, concentrations of IGF1 in follicular fluids from different types of patients who underwent GH strategy were measured by Western blot. The functional mechanism of GH-IGF1-gonadal axis in ART was also analyzed. RESULTS: We analyzed the baseline characteristics of the study population, the therapeutic outcome of GH-IGF-1-gonadal axis, as well as the relative protein level of IGF1 and IGFBP1 in follicular fluid from different groups. The chemical pregnancy rate was significantly increased in different degrees for groups with GH co-treatment compared to groups without GH co-treatment. The IGF1 in follicular fluid of patients under 35 years' old showed an upward trend compared with groups of poor, normal and high ovarian reserves. After GH induction, IGF1 in follicular fluid was significantly increased in patients over 35 years old. CONCLUSIONS: The study suggested that the application of GH might be beneficial to the pregnancy outcome in patients. GH application in patients older than 35 years might have a beneficial effect on pregnancy outcome via promoting the expression of IGF1. Our study indicates a different mechanism from GH application among younger and older patient in ART and provides a new clue for individual clinical treatment in infernity patients.

Two Novel Mutations in the SI Gene Associated With Congenital Sucrase-Isomaltase Deficiency: A Case Report in China.

Background: Congenital sucrase-isomaltase deficiency (CSID) is an autosomal recessive inherited disease that leads to the maldigestion of disaccharides and is associated with mutation of the sucrase-isomaltase (SI) gene. Cases of CSID are not very prevalent in China or worldwide but are gradually being identified and reported. Case Presentation: We report a case involving a 14-month-old male who presented with failure to thrive that had begun after food diversification and was admitted for chronic diarrhea. We used a whole-exome sequencing (WES) approach to identify mutations in this patient's genome. WES revealed two novel heterozygous mutations in the SI gene, c.2626C > T (p.Q876*) and c.2872C > T (p.R958C), which were confirmed by Sanger DNA sequencing. With a strict sucrose- and starch-restricted diet, the patient's diarrhea was resolved, and he began to gain weight. Conclusions: We report a case of novel variants in the SI gene that caused CSID. This report provides valuable information for the clinical field, especially in China.

Case Report: Novel Compound-Heterozygous Variants of SKIV2L Gene that Cause Trichohepatoenteric Syndrome 2.

Background: Trichohepatoenteric syndrome (THES) is a rare disease that mainly causes intractable diarrhea. It is classified into THES1 and THES2, which are associated with the tetratricopeptide repeat domain 37 (TTC37) gene and Ski2-like RNA helicase (SKIV2L) gene, respectively. THES is not very prevalent in China or worldwide, but new cases have increasingly been reported. Methods and Results: Here, we report the clinical and genetic information of a 1.5-month-old girl who was admitted to our hospital due to diarrhea and failure to thrive. Whole-exome sequencing (WES) revealed novel compound-heterozygous variants of the SKIV2L gene, c.3602_3609delAGCGCCTG (p.Q1201Rfs*2), and c.1990A > G (p.T664A) as the causative factors, which were confirmed via Sanger sequencing. Upon continuous feeding with an amino-acid formula through a gastric tube and parenteral nutrition, the patient resumed thriving and her stool frequency decreased. Conclusion: We report a girl carrying novel variants of the SKIV2L gene that cause THES2, thereby providing valuable information on the diagnosis of THES2 and expanding the spectrum of disease-causing SKIV2L mutations.

RNA Splicing: A Versatile Regulatory Mechanism in Pediatric Liver Diseases.

With the development of high-throughput sequencing technology, the posttranscriptional mechanism of alternative splicing is becoming better understood. From decades of studies, alternative splicing has been shown to occur in multiple tissues, including the brain, heart, testis, skeletal muscle, and liver. This regulatory mechanism plays an important role in physiological functions in most liver diseases. Currently, due to the absence of symptoms, chronic pediatric liver diseases have a significant impact on public health. Furthermore, the progression of the disease is accelerated in children, leading to severe damage to their liver tissue if no precautions are taken. To this end, this review article summarizes the current knowledge of alternative splicing in pediatric liver diseases, paying special attention to liver damage in the child stage. The discussion of the regulatory role of splicing in liver diseases and its potential as a new therapeutic target is also included.

Phylogenetic Comparison and Splicing Analysis of the U1 snRNP-specific Protein U1C in Eukaryotes.

As a pivotal regulator of 5' splice site recognition, U1 small nuclear ribonucleoprotein (U1 snRNP)-specific protein C (U1C) regulates pre-mRNA splicing by interacting with other components of the U1 snRNP complex. Previous studies have shown that U1 snRNP and its components are linked to a variety of diseases, including cancer. However, the phylogenetic relationships and expression profiles of U1C have not been studied systematically. To this end, we identified a total of 110 animal U1C genes and compared them to homologues from yeast and plants. Bioinformatics analysis shows that the structure and function of U1C proteins is relatively conserved and is found in multiple copies in a few members of the U1C gene family. Furthermore, the expression patterns reveal that U1Cs have potential roles in cancer progression and human development. In summary, our study presents a comprehensive overview of the animal U1C gene family, which can provide fundamental data and potential cues for further research in deciphering the molecular function of this splicing regulator.

Clinical significance of S100B protein in pregnant woman with early- onset severe preeclampsia.

OBJECTIVES: Preeclampsia is one of the most feared complications of pregnancy, which can progress rapidly to serious complications such as death of both mother and fetus. To present, the leading cause of preeclampsia is still debated. The purpose of this article was to explore the clinical significance of S100B protein, a kind of Ca2+ -sensor protein, in the early-onset severe preeclampsia. MATERIAL AND METHODS: Nine pregnant women with early-onset severe preeclampsia (the study group) and 13 healthy pregnant women (the control group) were included in this study. The level of S100B in the amniotic fluid, maternal blood, and umbilical cord blood were detected by enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance imaging (SPRi) methods. Diagnostic values of S100B for early-onset severe preeclampsia were assessed by Receiver Operating Characteristic (ROC) curve analysis. RESULTS: The levels of S100B in maternal blood and amniotic fluid in the study group were higher than those in the control group (p < 0.05). ROC curve analysis showed that S100B detected by SPRi method (SPRi-S100B) showed a cut-off level of 181 ng/mL with sensitivity of 100%, a specificity of 84.6%, and a Youden index of 0.846 in the maternal blood, which had better clinical significance and diagnostic value (at than that detected by ELISA (ELISA-S100B). CONCLUSIONS: The levels of S100B detected by SPRi in maternal blood can indicate early-onset severe preeclampsia and perinatal brain injury.

Phylogenetic comparison and splice site conservation of eukaryotic U1 snRNP-specific U1-70K gene family.

Eukaryotic cells can expand their coding ability by using their splicing machinery, spliceosome, to process precursor mRNA (pre-mRNA) into mature messenger RNA. The mega-macromolecular spliceosome contains multiple subcomplexes, referred to as small nuclear ribonucleoproteins (snRNPs). Among these, U1 snRNP and its central component, U1-70K, are crucial for splice site recognition during early spliceosome assembly. The human U1-70K has been linked to several types of human autoimmune and neurodegenerative diseases. However, its phylogenetic relationship has been seldom reported. To this end, we carried out a systemic analysis of 95 animal U1-70K genes and compare these proteins to their yeast and plant counterparts. Analysis of their gene and protein structures, expression patterns and splicing conservation suggest that animal U1-70Ks are conserved in their molecular function, and may play essential role in cancers and juvenile development. In particular, animal U1-70Ks display unique characteristics of single copy number and a splicing isoform with truncated C-terminal, suggesting the specific role of these U1-70Ks in animal kingdom. In summary, our results provide phylogenetic overview of U1-70K gene family in vertebrates. In silico analyses conducted in this work will act as a reference for future functional studies of this crucial U1 splicing factor in animal kingdom.

The diagnostic and treatment values of double-balloon enteroscopy in children's Meckel's diverticular bleeding.

ABSTRACT: The diagnostic and treatment values and safety of preoperative double-balloon enteroscopy (DBE) for Meckel's diverticula (MD) bleeding in children by retrospective review and analyses.The clinical data were collected and analyzed from 10 cases of children with MD receiving preoperative DBE examination and postoperative pathological confirmation. The diagnostic and treatment values and safety were assessed through the comparison of the DBE results and intra-operative observations and subsequently postoperative pathological results.Total cases are 10, 7 males and 3 females. The male to female ratio is 2.3 to 1. The youngest patient is 3.3 years old and oldest 12.1, the average age is 7.4 ±â€Š3.0. The lowest body weight is 12.6 kg and the average is 32.5 ±â€Š18.9 kg. The hematochezia was the main clinical manifestation in all patients with anemia and moderate to severe anemia were common (9/10, 90%). All patients had and tolerated the DBE procedures via anal route with 100% success rate. There were no observable complications during the examinations and post operations. All patients were diagnosed with MD by DBE. Exploratory laparoscopy and surgical operations were subsequently performed. All surgical samples were confirmed by pathology as bleeding MD. The postoperative follow-ups up to April 2019 (from 3 to 12 months) do not show any bleeding sign. Pathological examinations found ectopic gastric mucosa in 9 patients (90%) and one case had both ectopic gastric mucosa pancreatic tissue (10%). The distance of MD to ileocecal valve was from 60 to 100 cm (average 81.0 ±â€Š16.0 cm) by DBE examinations. Surgery showed similar findings from 30 to 100 cm (average 71.0 ±â€Š18.5) consistently to DBE. There is no statistical significance between 2 methods (Ζ = 1.715, Ρ = .086).DBE examination proves to be a safe method for diagnosing children's MD disease and can reliably determine the bleeding lesions in children's MD, providing valuable guidance for surgical treatment of children's MD bleeding.

Magnetic Resonance Imaging-Proton Density Fat Fraction vs. Transient Elastography-Controlled Attenuation Parameter in Diagnosing Non-alcoholic Fatty Liver Disease in Children and Adolescents: A Meta-Analysis of Diagnostic Accuracy.

Background and Aim: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children and adolescents, and its prevalence increases with obesity. Magnetic resonance imaging (MRI) and transient elastography (TE) have been widely used to non-invasively evaluate NAFLD in adults. This study aimed to determine the efficacy and accuracy of MRI-proton density fat fraction (MRI-PDFF) and TE-controlled attenuation parameter (TE-CAP) in distinguishing hepatic steatosis in children and adolescents. Materials and Methods: In this meta-analysis, the PubMed, Cochrane Library, Embase, Medline, and Web of Science databases were searched for articles that reported studies on the accuracy of MRI-PDFF or TE-CAP in grading the steatosis in children and adolescents with NAFLD. This study compared the sensitivity, specificity, and hierarchical summary receiver operating characteristic curves (HSROCs) of MRI-PDFF and TE-CAP in distinguishing between steatosis grades S0 and S1-3. Results: A total of eight articles involving 874 children and adolescents with NAFLD were included in this study. The proportions of steatosis grades were 5 and 95% for S0 and S1-3, respectively. MRI-PDFF accurately diagnosed S1-3 steatosis, with a summary sensitivity of 0.95 (95% CI, 0.92-0.97), specificity of 0.92 (95% CI, 0.77-0.98), and HSROC of 0.96 (95% CI, 0.94-0.98). Likewise, TE-CAP accurately diagnosed S1-3 steatosis, with a summary sensitivity of 0.86 (95% CI, 0.70-0.94), specificity of 0.88 (95% CI, 0.71-0.96), and HSROC of 0.94 (95% CI, 0.91-0.95). Following a "positive" measurement (over the threshold value) for S1-3, the corresponding post-test probabilities of MRI-PDFF and TE-CAP for the presence of steatosis reached 92 and 88%, respectively, at the pretest probability of 50%. When the values were below the mentioned threshold values ("negative" results), the post-test probabilities of MRI-PDFF and TE-CAP became 5 and 13%, respectively. Conclusion: Both MRI-PDFF and TE-CAP are highly accurate non-invasive methods to grade the hepatic steatosis in children and adolescents with NAFLD. Furthermore, MRI-PDFF is significantly more accurate in assessing steatosis grade than TE-CAP. Systematic Review Registration: PROSPERO, identifier: CRD42021220422.

The Twists and Turns of Diagnosis and Treatment of Pediatric Neuro-Behcet's Disease: A Case Report and Literature Review.

Background: The neurological manifestation of Behcet's disease (BD) is known as Neuro-Behcet's disease (NBD). The lack of a specific diagnostic method for NBD renders the diagnosis and treatment of NBD challenging. Methods and Results: We report a boy aged 11 years and 11 months who underwent right-eye intraocular lens implantation, appendectomy, perianal abscess removal, thalidomide therapy, and infliximab infusions for his Crohn disease. Magnetic resonance venography (MRV) and magnetic resonance imaging (MRI) were performed to address the onset of headache during the course of his treatment, and cerebral venous sinus thrombosis was detected. After the diagnosis of NBD, the patient was treated with anticoagulation therapy (nadroparin calcium), low-dose corticosteroids, and an immunosuppressant (cyclophosphamide), and consequently, he recovered. Conclusion: This case report shows that NBD is prone to misdiagnosis and missed diagnosis and should be diagnosed based on clinical manifestations and results from colonoscopy, pathological examination, and MRI or MRV.

Knee Joint Swelling at Presentation: A Case of Pediatric Crohn Disease With a TNFAIP3 Mutation.

Crohn disease (CD) is a chronic inflammatory disease, and its incidence in children is rising. Despite extensive reports and investigations, the pathogenesis of CD has not been clearly elucidated, particularly in regard to triggering factors. A genetic predisposition is considered important when investigating the mechanism leading to CD, and the discovery of new CD-associated genes has increased our understanding of its immunopathogenesis and improved the efficacy of its treatment of CD. Early detection and treatment (eg, as children) with gene-based precision therapy can effectively prevent complications related to CD. In this case, a Chinese Han boy with CD associated with a mutation of tumor necrosis factor α-induced protein 3 was treated with recombinant human tumor necrosis factor-a receptor II:IgG Fc fusion protein. We suspected the boy had CD because of chronic abdominal pain, aphthous stomatitis, moderate anemia, a high erythrocyte sedimentation rate (36-79 mm/h), multiple intestinal ulcers, knee joint swelling, and a tumor necrosis factor α-induced protein 3 mutation. After total enteral nutrition and hormone therapy for 5 months, his abdominal pain and joint symptoms did not improve, so we started gene-based precision therapy with recombinant human tumor necrosis factor-a receptor II: IgG Fc fusion protein, which may play an important role in restricting TNF-α-induced NF-κB signaling. After 3 weeks, inflammation indicators were within the normal range, and multiple ulcers and joint symptoms were relieved. The present case demonstrates a safe therapeutic schedule that leads to rapid improvements in the clinical and biochemical status of patients with CD.

The role of microRNA in cisplatin resistance or sensitivity.

INTRODUCTION: Cisplatin is a chemotherapy drug that has been used to treat a number of cancers for decades, and is still one of the most commonly used anti-cancer agents. However, some patients do not respond to cisplatin while other patients who were originally sensitive to cisplatin eventually develop chemoresistance, leading to treatment failure or/and tumor recurrence. AREAS COVERED: Different mechanisms contribute to cisplatin resistance or sensitivity, involving multiple pathways or/and processes such as DNA repair, DNA damage response, drug transport, and apoptosis. Among the various mechanisms, it appears that microRNAs play an important role in determining the resistance or sensitivity. In this article, we analyzed and summarized recent findings in this area, with the aim that these data can aid further research and understanding, leading to the eventual reduction of cisplatin resistance. EXPERT COMMENTARY: microRNAs can positively or negatively regulate cisplatin resistance by acting on molecules or/and pathways related to apoptosis, autophagy, hypoxia, cancer stem cells, NF-κB, and Notch1. It appears that the modulation of relevant microRNAs can effectively re-sensitize cancer cells to cisplatin regimen in certain types of cancers including breast, colorectal, gastric, liver, lung, ovarian, prostate, testicular, and thyroid cancers.