Supramolecular coordination platinum metallacycle-based multilevel wound dressing for bacteria sensing and wound healing.

The exploitation of novel wound healing methods with real-time infection sensing and high spatiotemporal precision is highly important for human health. Pt-based metal-organic cycles/cages (MOCs) have been employed as multifunctional antibacterial agents due to their superior Pt-related therapeutic efficiency, various functional subunits and specific geometries. However, how to rationally apply these nanoscale MOCs on the macroscale with controllable therapeutic output is still challenging. Here, a centimeter-scale Pt MOC film was constructed via multistage assembly and subsequently coated on a N,N'-dimethylated dipyridinium thiazolo[5,4-d]thiazole (MPT)-stained silk fabric to form a smart wound dressing for bacterial sensing and wound healing. The MPT on silk fabric could be used to monitor wound infection in real-time through the bacteria-mediated reduction of MPT to its radical form via a color change. The MPT radical also exhibited an excellent photothermal effect under 660 nm light irradiation, which could not only be applied for photothermal therapy but also induce the disassembly of the Pt MOC film suprastructure. The highly ordered Pt MOC film suprastructure exhibited high biosafety, while it also showed improved antibacterial efficiency after thermally induced disassembly. In vitro and in vivo studies revealed that the combination of the Pt MOC film and MPT-stained silk can provide real-time information on wound infection for timely treatment through noninvasive techniques. This study paves the way for bacterial sensing and wound healing with centimeter-scale metal-organic materials.

A narrative review on the role of genetics in children with acute recurrent pancreatitis and chronic pancreatitis.

The incidence of pancreatitis in children has increased over the past two decades. With advances in molecular biological techniques and clinical research, genetic variations have emerged as a pivotal etiological factor in pediatric pancreatitis. This review aims to summarize recent clinical research advancements in understanding pediatric pancreatitis caused by various gene mutations. As of the year 2020, researchers had identified 12 genes implicated in the pathogenesis of pancreatitis. These genes primarily contributed to the development of pancreatitis through three mechanisms. Pancreatitis resulting from these gene mutations exhibits several distinct characteristics, including early onset, a heightened risk of developing pancreatic duct stones, rapid disease progression, and a significantly increased risk of pancreatic endocrine and exocrine dysfunction, as well as pancreatic cancer in the future. Genetic sequencing is recommended for children with pancreatitis based on six indications. The sequencing not only assists in the clinical diagnosis but also enhances our understanding of the pathophysiology of pancreatitis.

Assessing the Understanding of Helicobacter pylori Infection Among Chinese Pediatricians.

Background: Helicobacter pylori (Hp) is a global public health concern, particularly among children. While the "detection and treatment" approach gains ground in adult patients, paediatricians have divergent opinions regarding the current clinical protocols for diagnosing and treating Hp infection. Some argue for its potential impact on children's growth, emphasizing the need for adequate attention. Additionally, there are uncertainties regarding the appropriate screening tests for children who require Hp testing or have functional dyspepsia. Objective: This study aims to investigate pediatricians' current perspectives and understanding of Hp infection to provide valuable insights for Hp treatment. Methods: This study employs a cross-sectional research design. A questionnaire was designed using the "Questionnaire Star" platform and distributed online to physicians participating in the 12th Shanghai Pediatric Gastroenterology Forum in September 2020. The questionnaire covered topics such as physician professional information, the status of Hp diagnosis in hospitals, Hp knowledge, and knowledge of Hp treatment. Categorical data from each group were analyzed using chi-square tests to understand the diagnostic and treatment practices of pediatricians regarding Hp infection. Results: Among the 218 participating physicians who completed the questionnaire, 49.5% specialized in gastroenterology and practiced in hospitals equipped with Hp testing capabilities. Additionally, 85.8% practiced in hospitals with electronic gastroscopes. Notably, 94% considered Hp an infectious disease. Pediatric gastroenterology specialists, in particular, favored endoscopy for Hp detection compared to non-pediatric gastroenterologists. The investigation revealed variations in Hp detection understanding and consensus among the enrolled physicians. Challenges included determining the age for initiating Hp treatment in children and implementing family-based strategies. Conclusions: Further research is essential to inform the development of comprehensive detection and treatment strategies for Hp infection in children. Currently, the primary approach may involve individualized and standardized diagnosis and treatment.

Plasminogen Activator Inhibitor-1 Potentiates Neutrophil Infiltration and Tissue Injury in Colitis.

The mechanism underlying inflammatory bowel disease (IBD) remains unclear. We aimed to identify early diagnostic biomarkers and understand their roles in the pathogenesis of IBD. Methods: We identified plasminogen activator inhibitor-1 (PAI-1) as a potential key gene that is upregulated in IBD based on published transcriptomic datasets. To further determine the role of PAI-1 in disease pathogenesis, we induced colitis in wild-type (WT) and PAI-1 knockout (KO) mice by administering dextran sulfate sodium (DSS). We used an RNA array of genes and 16S rRNA sequencing of the microbiome to analyze PAI-1 function. The colon and serum PAI-1 levels in humans were further evaluated for their diagnostic value. Results: PAI-1 expression was significantly increased in patients and DSS-induced WT mice but reduced in PAI-1 KO mice. These changes were associated with significantly decreased neutrophil infiltration in colonic tissues. The RNA array revealed that the CXC chemokines CXCL1 and CXCL5 and their common receptor CXCR2 were among the most significantly different genes between the PAI-1 KO mice with DSS-induced colitis and the WT mice. Mechanistically, PAI-1 deficiency led to blunted activation of the NF-κB pathway in the colon epithelium. The gut microbiome was altered in the PAI-1 KO mice, which showed enriched abundances of short-chain fatty acid-producing genera and diminished abundances of pathogenic genera. Receiver operating characteristic (ROC) curve analysis revealed the diagnostic value of PAI-1. Conclusions: Our data suggest a previously unknown function of PAI-1 inducing neutrophil-mediated chemokine expression by activating the NF-κB pathway and affecting the function of the gut microbiome. PAI-1 could be a potential diagnostic biomarker and a therapeutic target in IBD.

Multi-omics reveals the mechanisms of DEHP driven pulmonary toxicity in ovalbumin-sensitized mice.

The plasticizer di- (2-ethylhexyl) phthalate (DEHP) is considered a risk factor for allergic diseases and has attracted public attention for its adverse effects on health. However, respiratory adverse effects after DEHP exposure in food allergies have rarely been reported. MiRNAs are considered to be key regulators in the complex interrelationships between the host and microbiome and may be a potential factor involved in DEHP-induced pulmonary toxicity. To investigate the adverse effects of DEHP on the lung during sensitization, we established an ovalbumin (OVA)-sensitized mouse model exposed to DEHP and performed 16S rDNA gene sequencing, miRNA sequencing, and correlation analysis. Our results showed that DEHP aggravated the immune disorder in OVA-sensitized mice, which was mainly characterized by an increase in the proportion of Th2 lymphocytes, and further enhanced OVA-induced airway inflammation without promoting pulmonary fibrosis. Compared with the OVA group, DEHP interfered with the lung microbial community, making Proteobacteria the dominant phylum, while Bacteroidetes were significantly reduced. Differentially expressed miRNAs were enriched in the PI3K/AKT pathway, which was closely related to immune function and airway inflammation. The expression of miR-146b-5p was elevated in the DEHP group, which was positively correlated with the proportion of Th2 cells and significantly negatively correlated with the abundance of Bacteroidetes. The results indicate that DEHP may interfere with the expression of miR-146b-5p, affect the composition of the lung microbiota, induce an imbalance in T cells, and lead to immune disorders and airway inflammation. The current study uses multi-omics to reveal the potential link between the plasticizer DEHP and allergic diseases and provides new insights into the ecotoxicology of environmental exposures to DEHP.

[Association between drug trough concentration and disease outcome before infliximab maintenance treatment in children with Crohn's disease]. / å ‹ç½—æ©ç— æ‚£å„¿è‹±å¤«åˆ©è¥¿å•æŠ—ç»´æŒæ²»ç–—å‰è¡€è¯æµ“åº¦ä¸Žç–¾ç— è½¬å½’çš„å ³ç³».

OBJECTIVES: To study the association between infliximab trough level (IFX-TL) prior to maintenance treatment and disease outcome in children with Crohn's disease (CD). METHODS: A retrospective analysis was performed on 35 children with CD who received induction therapy with infliximab (IFX) and the measurement of IFX-TL before maintenance treatment from August 2018 to November 2021. Clinical data and laboratory markers at baseline and before maintenance treatment were collected, and the association between outcome and IFX-TL was analyzed. RESULTS: The clinical remission group, endoscopic remission group, and combined remission group had a significantly higher IFX-TL level than the corresponding non-remission groups (P<0.05), and there was no significant difference in the IFX-TL level between the biological remission and non-biological remission groups (P>0.05). The receiver operating characteristic (ROC) curve showed that IFX-TL had an area under the ROC curve of 0.959 (95%CI: 0.894-1) in predicting clinical remission, with a sensitivity of 90% and a specificity of 100% at the optimal cutoff value of 2.3 µg/mL (P<0.001). CONCLUSIONS: Among children with CD receiving infliximab induction therapy, the children achieving clinical and endoscopic remission before maintenance treatment tend to have a higher level of IFX-TL. IFX-TL has a certain predictive value for clinical remission.

Rapamycin regulates osteogenic differentiation through Parkin-mediated mitophagy in rheumatoid arthritis.

Varying degrees of bone destruction and bone loss occur in the development of rheumatoid arthritis (RA). Nevertheless, the mechanism underlying osteoporosis in the development of RA is not completely elucidated. Recent evidence indicates that mitophagy may play a vital role in regulating the differentiation and function of preosteoblast. Parkin is associated with mitophagy and various inflammatory diseases, but the precise role of Parkin in the treatment of osteoporosis in RA is unclear. In the present study, we found that the abnormal bone metabolism of RA is related to the activation of the mechanistic targets of mTORC1 pathway, and chronic inflammation which regulates the differentiation of preosteoblast through mitophagy. In this study, we found that Parkin was upregulated, and the mitochondrion was damaged in tumor necrosis factor alpha (TNF-α) stimulated preosteoblasts. Rapamycin (RAPA, an mTORC1 pathway blocker) upregulation of Parkin-mediated mitophagy tends to attenuate mitochondrial impairment caused by TNF-α in preosteoblasts. Theexperimentinvivo demonstrated that the combination therapy with TNF-α neutralizing antibody and RAPA significantly reduced osteoporosis in AIA mice. Drug inhibition of this pathway can be a potential treatment for osteoporosis in patients with RA.

An Assessment Framework for the Training of General Practitioners and Specialists Based on EPAs.

Purpose: The purpose of this study is to explore the practicality and feasibility of EPA (level 4 theory) for establishing medical training and service model in China. Method: We opted for a mixed qualitative and quantitative research method, considering both explanatory and exploratory sequential designs. The qualitative research comprehended focus groups and interviews conducted with two panels of experts. The quantitative research was conducted to collect data about the applicability of international entrustable professional activities (EPAs) pediatrics standards in the Chinese context by organizing a seminar with a sample of 60 pediatricians. A questionnaire was designed with EPAs and distributed within professional networks. Structural equation modeling and statistical analysis were used to process the data. Results: In this study, Medical Service-Groups Model (MSGM) with four levels was successfully established to measure the correlation between specialized and general EPAs. As expected, results showed that specialized EPAs were built on top of general EPAs. There may be a mediating mechanism that general EPAs contribute to the lower level of specialization EPAs. In addition, levels 1 and 2 were primarily needed to lay the groundwork for levels 3 and 4, and these higher levels of EPAs were still the most informative for specialized Gastroenterology EPAs. Conclusions: The diagnosis and treatment level of primary general practitioners, as the basis of the pediatric medical service chain, affected the clinical disposal ability of specialists. The establishment of MSGM provided a theoretical basis for the linkage training of general practitioners and specialist physicians. In future studies, scholars must explore China's EPAs based on unique national conditions.

Characteristics of Gut Microbiome and Its Metabolites, Short-Chain Fatty Acids, in Children With Idiopathic Short Stature.

Background: The gut microbiome is important for host nutrition and metabolism. Whether the gut microbiome under normal diet regulate human height remains to be addressed. Our study explored the possible relationship between gut microbiota, its metabolic products and the pathogenesis of idiopathic short stature disease (ISS) by comparing the gut microbiota between children with ISS and of normal height, and also the short-chain fatty acids (SCFAs) produced by the gut microbiota. Methods: The subjects of this study were 32 prepubescent children aged 4-8 years. The fecal microbial structure of the subjects was analyzed by 16S rRNA high-throughput sequencing technology. The concentrations of SCFAs in feces were determined by gas chromatography-mass spectrometry. Results: The richness of gut microbiota in ISS group was decreased, and the composition of gut microbiota was significantly different between ISS group and control group. The relative abundance of nine species including family Ruminococcaceae and genera Faecalibacterium and Eubacterium, in ISS group was significantly lower than that in control group (P<0.05). The relative abundance of 10 species, such as those belonging to genus Parabacteroides and genus Clostridium, in ISS group was significantly higher than that in control group (P<0.05). The concentration of total SCFAs and butyrate in ISS group was significantly lower than that in control group. The correlation analysis among different species, clinical indicators, and SCFAs showed that the relative abundance of family Ruminococcaceae and genera Faecalibacterium and Eubacterium was positively correlated with the standard deviation score of height. Furthermore, the concentrations of total SCFAs and butyrate were positively correlated with serum insulin-like growth factor 1 (IGF-1)-SDS. Disease prediction model constructed based on the bacteria who abundance differed between healthy children and ISS children exhibited high diagnostic value (AUC: 0.88). Conclusions: The composition of gut microbiota and the change in its metabolite levels may be related to ISS pathogenesis. Strains with increased or decreased specificity could be used as biomarkers to diagnose ISS.

Magnetically Guided Capsule Endoscopy and Magnetic Resonance Enterography in Children With Crohn's Disease: Manifestations and the Value of Assessing Disease Activity.

Objective: To investigate the value of magnetically guided capsule endoscopy (MGCE) and magnetic resonance enterography (MRE) in assessing the activity of pediatric Crohn's disease. Methods: Clinical data from 82 subjects with pediatric Crohn's disease, who underwent MGCE and MRE from October 2018 to March 2021 were analyzed retrospectively. Pairwise comparisons of several indexes, including MaRIA, CECDAI, PCDAI, and SES-CD, were performed by Spearman's rank correlation test and kappa consistency analysis. CECDAI and MaRIA values predicted whether patients were moderately or severely active (PCDAI ≥30) clinically by logistic regression analysis. The area under the receiver operating characteristic curve (AUC) quantified the evaluation value of moderate to severe activity of pediatric CD. Results: In judging the severity of CD in the small intestine, the correlation coefficient between CECDAI and MaRIA was 0.406 (p < 0.05), and the kappa value of the consistency analysis was 0.299 (p < 0.05). MaRIA was weakly correlated with PCDAI (r = 0.254, p < 0.05), and they were weakly consistent in assessing the activity of Crohn's disease (kappa = 0.135, p < 0.05). For predicting clinically moderate to severe activity, the fitted AUC based on CECDAI and MarRIA was 0.917, which was higher than applying a single parameter (CECDAI = 0.725, MarRIA = 0.899, respectively). MaRIA and serum albumin were significantly and negatively correlated (r = -1.064, p < 0.05). The consistency of the detection rate of gastric ulcers by MGCE and gastroscopy was moderate (kappa = 0.586, p < 0.05), and the detection rate of ulcers in the terminal ileum between MGCE and colonoscopy showed high consistency (kappa = 0.609, p < 0.05). Conclusions: MGCE and MRE are valuable, non-invasive methods for evaluating small bowel lesions in children with CD. The combined application of MGCE and MRE can better characterize the disease activity.

Autosomal recessive 333 base pair interleukin 10 receptor alpha subunit deletion in very early-onset inflammatory bowel disease.

BACKGROUND: Interleukin 10 receptor alpha subunit (IL10RA) dysfunction is the main cause of very early-onset inflammatory bowel disease (VEO-IBD) in East Asians. AIM: To identify disease-causing gene mutations in four patients with VEO-IBD and verify functional changes related to the disease-causing mutations. METHODS: From May 2016 to September 2020, four young patients with clinically diagnosed VEO-IBD were recruited. Before hospitalization, using targeted gene panel sequencing and trio-whole-exome sequencing (WES), three patients were found to harbor a IL10RA mutation (c.301C>T, p.R101W in one patient; c.537G>A, p.T179T in two patients), but WES results of the fourth patient were not conclusive. We performed whole-genome sequencing (WGS) on patients A and B and reanalyzed the data from patients C and D. Peripheral blood mononuclear cells (PBMCs) from patient D were isolated and stimulated with lipopolysaccharide (LPS), interleukin 10 (IL-10), and LPS + IL-10. Serum IL-10 levels in four patients and tumor necrosis factor-α (TNF-α) in the cell supernatant were determined by enzyme-linked immunosorbent assay. Phosphorylation of signal transducer and activator of transcription 3 (STAT3) at Tyr705 and Ser727 in PBMCs was determined by western blot analysis. RESULTS: The four children in our study consisted of two males and two females. The age at disease onset ranged from 18 d to 9 mo. After hospitalization, a novel 333-bp deletion encompassing exon 1 of IL10RA was found in patients A and B using WGS and was found in patients C and D after reanalysis of their WES data. Patient D was homozygous for the 333 bp deletion. All four patients had elevated serum IL-10 levels. In vitro, IL-10-stimulated PBMCs from patient D failed to induce STAT3 phosphorylation at Tyr705 and only minimally suppressed TNF-α production induced by LPS. Phosphorylation at Ser727 in PBMCs was not affected by LPS or LPS + IL-10 in both healthy subjects and in patient D. CONCLUSION: WGS revealed a novel 333-bp deletion of IL10RA in four patients with VEO-IBD, whereas the WES results were inconclusive.

Characteristics of Fecal Microbiota and Machine Learning Strategy for Fecal Invasive Biomarkers in Pediatric Inflammatory Bowel Disease.

Background: Early diagnosis and treatment of pediatric Inflammatory bowel disease (PIBD) is challenging due to the complexity of the disease and lack of disease specific biomarkers. The novel machine learning (ML) technique may be a useful tool to provide a new route for the identification of early biomarkers for the diagnosis of PIBD. Methods: In total, 66 treatment naive PIBD patients and 27 healthy controls were enrolled as an exploration cohort. Fecal microbiome profiling using 16S rRNA gene sequencing was performed. The correlation between microbiota and inflammatory and nutritional markers was evaluated using Spearman's correlation. A random forest model was used to set up an ML approach for the diagnosis of PIBD using 1902 markers. A validation cohort including 14 PIBD and 48 irritable bowel syndrome (IBS) was enrolled to further evaluate the sensitivity and accuracy of the model. Result: Compared with healthy subjects, PIBD patients showed a significantly lower diversity of the gut microbiome. The increased Escherichia-Shigella and Enterococcus were positively correlated with inflammatory markers and negatively correlated with nutrition markers, which indicated a more severe disease. A diagnostic ML model was successfully set up for differential diagnosis of PIBD integrating the top 11 OTUs. This diagnostic model showed outstanding performance at differentiating IBD from IBS in an independent validation cohort. Conclusion: The diagnosis penal based on the ML of the gut microbiome may be a favorable tool for the precise diagnosis and treatment of PIBD. A study of the relationship between disease status and the microbiome was an effective way to clarify the pathogenesis of PIBD.

ERp29 forms a feedback regulation loop with microRNA-135a-5p and promotes progression of colorectal cancer.

Expression of endoplasmic reticulum (ER) stress-associated genes is often dysregulated in cancer progression. ER protein 29 (ERp29) is abnormally expressed in many neoplasms and plays an important role in tumorigenesis. Here, we showed ERp29 is a novel target for microRNA-135a-5p (miR-135a-5p) to inhibit the progression of colorectal cancer (CRC); correspondingly, ERp29 acts as an oncoprotein in CRC by promoting proliferation and metastasis of CRC cells, and suppressing apoptosis of the cells. More importantly, we found that miR-135a-5p expression is reversely upregulated by ERp29 through suppressing IL-1ß-elicited methylation of miR-135a-5p promoter region, a process for enterocyte to maintain a balance between miR-135a-5p and ERp29 but dysregulated in CRC. Our study reveals a novel feedback regulation loop between miR-135a-5p and ERp29 that is critical for maintaining appropriate level of each of them, but partially imbalanced in CRC, resulting in abnormal expression of miR-135a-5p and ERp29, which further accelerates CRC progression. We provide supporting evidence for ERp29 and miR-135a-5p as potential biomarkers for diagnosis and treatment of CRC.

Crohn's disease with pulmonary granuloma in a child: a case report and review of the literature.

Crohn's disease (CD) is a chronic granulomatous disease that affects the gastrointestinal system. Additionally, CD has multiple extraintestinal manifestations, and bronchopulmonary manifestations are extremely rare. Pulmonary lesions can occur before the diagnosis of CD; thus, pulmonary manifestations are often overlooked, which leads to misdiagnoses. Herein, we present a case with pulmonary nodules being exhibited before the patient was diagnosed with CD. To the best of our knowledge, only a few cases concerning this phenomenon have been reported. We describe an 11-year-old boy with a two-year history of anemia and without any gastrointestinal symptoms. He did not receive any thorough inspection until arthralgia occurred. Multiple nodules were found in his bilateral lungs via computed tomography scan. Combined with the child's medical history, physical examinations, and all of the investigations, the final diagnosis was CD with pulmonary nodules and arthritis. After 2 months of treatment, the patient's symptoms had significantly improved. To summarize the clinical manifestations, auxiliary examination features, and treatments of CD in children with pulmonary involvement, we also review the relevant characteristics of pulmonary involvement in CD patients. This case indicates the importance of recognizing the pulmonary manifestations of CD. Clinicians should be aware of the possibility of CD when their patients have lung nodules, even in children with no typical manifestations of CD.

The Impact of Gut Microbiome on Metabolic Disorders During Catch-Up Growth in Small-for-Gestational-Age.

Objective: Catch-up growth (CUG) in small for gestational age (SGA) leads to increased risk of metabolic syndrome and cardiovascular diseases in adults. It remains unclear if microbiota could play an important role in CUG-SGA independent of genetic or nutritional factors. The present study explored the role of gut microbiota in, and its association with, metabolic disorders during CUG-SGA. Methods: An SGA rat model was established by restricting food intake during pregnancy, and the rats were divided into catch-up growth (CUG-SGA) and non-catch-up growth (NCUG-SGA) groups based on body weight and length at the fourth postnatal week. High-throughput sequencing of 16S rRNA was conducted to detect the diversity and composition of the gut microbiota. Fecal short-chain fatty acids (SCFAs) were detected by gas chromatography-mass spectrometry. Transcriptome sequencing of liver tissue was performed and verified using real-time PCR. Concentrations of insulin and total cholesterol were determined using enzyme-linked immunosorbent assay. Results: The composition of gut microbiota in CUG-SGA rats differed from that of NCUG-SGA rats, with reduced abundance of Lactobacillus in the CUG-SGA group. The decrease in Lactobacillus was significantly associated with increased body weight and upregulated insulin and total cholesterol levels. Five SCFAs and two branched chain fatty acids were significantly higher in the CUG-SGA group than in the NCUG-SGA group. Additionally, SCFAs were positively associated with clinical indices such as weight, body mass index, insulin, and total cholesterol. Transcriptomic data revealed that insulin-like growth factor-2 expression was significantly decreased in CUG-SGA rats and was associated with a decrease in Lactobacillus bacteria. Conclusion: Lactobacillus and SCFAs were associated with the metabolic disorders during CUG in SGA. Gut microbiome may play a certain role on metabolic disorders during catch-up growth in small-for-gestational-age.

Valuable clinical indicators for identifying infantile-onset inflammatory bowel disease patients with monogenic diseases.

BACKGROUND: Infantile-onset inflammatory bowel disease (IO-IBD) occurs in very young children and causes severe clinical manifestations, which has poor responses to traditional inflammatory bowel disease (IBD) treatments. At present, there are no simple and reliable laboratory indicators for early screening IO-IBD patients, especially those in whom the disease is caused by monogenic diseases. AIM: To search for valuable indicators for early identifying IO-IBD patients, especially those in whom the disease is caused by monogenic diseases. METHODS: A retrospective analysis was performed in 73 patients with IO-IBD admitted to our hospital in the past 5 years. Based on the next-generation sequencing results, they were divided into a monogenic IBD group (M-IBD) and a non-monogenic IBD group (NM-IBD). Forty age-matched patients with allergic proctocolitis (AP) were included in a control group. The clinical manifestations and the inflammatory factors in peripheral blood were evaluated. Logistic regression analysis and receiver operating characteristic (ROC) curve analysis were used to identify the screening factors and cut-off values of IO-IBD as well as monogenic IO-IBD, respectively. RESULTS: Among the 44 M-IBD patients, 35 carried IL-10RA mutations, and the most common mutations were c.301C>T (p.R101W, 30/70) and the c.537G>A (p.T179T, 17/70). Patients with higher serum tumor necrosis factor (TNF)-α value were more likely to have IBD [odds ratio (OR) = 1.25, 95% confidence interval (CI): 1.05-1.50, P = 0.013], while higher serum albumin level was associated with lower risk of IBD (OR = 0.86, 95%CI: 0.74-1.00, P = 0.048). The cut-off values of TNF-α and albumin were 17.40 pg/mL (sensitivity: 0.78; specificity: 0.88) and 36.50 g/L (sensitivity: 0.80; specificity: 0.90), respectively. The increased ferritin level was indicative of a genetic mutation in IO-IBD patients. Its cut-off value was 28.20 ng/mL (sensitivity: 0.93; specificity: 0.92). When interleukin (IL)-10 level was higher than 33.05 pg/mL (sensitivity: 1.00; specificity: 0.84), or the onset age was earlier than 0.21 mo (sensitivity: 0.82; specificity: 0.94), the presence of disease-causing mutations in IL-10RA in IO-IBD patients was strongly suggested. CONCLUSION: Serum TNF-α and albumin level could differentiate IO-IBD patients from allergic proctocolitis patients, and serum ferritin and IL-10 levels are useful indicators for early diagnosing monogenic IO-IBD.

Self-Assembly of Metallacages into Centimeter Films with Tunable Size and Emissions.

The coupling of material systems at different length scales enables new ways to take advantage of the unique properties of nano-/macroscale materials. Here, the self-organization of assembled metallacages generated ultralong nanowires, followed by the formation of nanowire-based soft films with diameters up to 6.5 cm. In contrast to previous reports that mainly focused on the preparation of metallacage assemblies with dimensions on the nano-/micrometer scale, the preparation of centimeter assemblies can serve as the bridge between nanostructures and the macroscopic world.

Disordered Gut Microbiota in Children Who Have Chronic Pancreatitis and Different Functional Gene Mutations.

OBJECTIVES: Chronic pancreatitis (CP) is a serious condition whose pathogenic mechanism is unclear. Interactions of host genetic factors with gut microbiota have a role, but little is known, especially in children with CP (CCP), in which the external factors are less important. Our objective was to identify the main gut microbiota genera in CCP and to characterize the functional mutations of these patients. METHODS: We used 16S rRNA sequencing to compare the gut microbiota of healthy controls with patients who had CCP and different functional gene mutations. RESULTS: CCP is characterized by gut microbiota with remarkably reduced alpha diversity. Receiver operating characteristic curve analyses indicated that the abundances of 6 genera-Faecalibacterium, Subdoligranulum, Phascolarctobacterium, Bifidobacterium, Eubacerium, and Collinsella-were significantly decreased in CCP, with an area under curve (AUC) of 0.92 when considering all 6 genera together. Functional analysis of gut microbiota in CCP indicated reduced ribosomal activity, porphyrin and chlorophyll metabolism, starch and sucrose metabolism, and aminoacyl-tRNA biosynthesis, but an enrichment of phosphotransferase system pathways. The abundance of Butyricicoccus was significantly decreased in CCP in the presence of CFTR mutations when combined with mutations in CASR, CTSB, SPINK1, and/or PRSS1. The abundance of Ruminococcaceae was significantly increased in CCP when there were mutations in CASR, CTSB, SPINK1, and/or PRSS1. Patients with CCP but no gene mutations had greater abundances of Veillonella and reduced abundances of Phascolarctobacterium. DISCUSSION: CCP is associated with a depletion of probiotic gut microbiota, and CCP patients with different functional gene mutations have different gut microbiota.

Study of disease phenotype and its association with prognosis of paediatric inflammatory bowel disease in China.

BACKGROUND: To investigate the unique features of inflammatory bowel disease (IBD) in children, we wanted to identify whether there might be a strong correlation between the disease phenotype and its prognosis at various ages in paediatric patients. METHODS: We collected data from patients diagnosed with IBD (ulcerative colitis (UC) or Crohn's disease (CD)) from 2002 to 2016. The diagnosis was made according to the Porto criteria and Paris Classification. Patient characteristics, clinical manifestations and treatments were collected. Risk factors for surgery, mortality and relapse were analysed by Cox proportional hazard models. RESULTS: Of the 143 patients, 113 had CD, and 30 had UC; there were 89 males and 54 females with a median age of 9 years (y). Thirteen patients in the 0-2 y group were identified as having mutations in IL-10 receptor A, and this mutation was significantly more common in this age group than in 3-9 and 10-16 y patients. The risk factor for surgery was the B3 phenotype; risk factors for death were age 0-2 y and B3 phenotype; 0-2 y, B3 phenotype and steroid dependency were risk factors for early relapse. CONCLUSIONS: Clinical manifestations of the onset of IBD in infants and toddlers were extensive and aggressive and were closely associated with early relapse and death. It is of particular interest that some of these patients developed IBD due to monogenic disorders; thus, introduction of genetic testing is essential for these patients.