Machine learning-causal inference based on multi-omics data reveals the association of altered gut bacteria and bile acid metabolism with neonatal jaundice.

Early identification of neonatal jaundice (NJ) appears to be essential to avoid bilirubin encephalopathy and neurological sequelae. The interaction between gut microbiota and metabolites plays an important role in early life. It is unclear whether the composition of the gut microbiota and metabolites can be used as an early indicator of NJ or to aid clinical decision-making. This study involved a total of 196 neonates and conducted two rounds of "discovery-validation" research on the gut microbiome-metabolome. It utilized methods of machine learning, causal inference, and clinical prediction model evaluation to assess the significance of gut microbiota and metabolites in classifying neonatal jaundice (NJ), as well as the potential causal relationships between corresponding clinical variables and NJ. In the discovery stage, NJ-associated gut microbiota, network modules, and metabolite composition were identified by gut microbiome-metabolome association analysis. The NJ-associated gut microbiota was closely related to bile acid metabolites. By Lasso machine learning assessment, we found that the gut bacteria were associated with abnormal bile acid metabolism. The machine learning-causal inference approach revealed that gut bacteria affected serum total bilirubin and NJ by influencing bile acid metabolism. NJ-associated gut bile acids are potential biomarkers of NJ, and clinical prediction models constructed based on these biomarkers have some clinical effects and the model may be used for disease risk prediction. In the validation stage, it was found that intestinal metabolites can predict NJ, and the machine learning-causal inference approach revealed that bile acid metabolites affected NJ itself by affecting the total bilirubin content. Intestinal bile acid metabolites are potential biomarkers of NJ. By applying machine learning-causal inference methods to gut microbiome-metabolome association studies, we found NJ-associated intestinal bacteria and their network modules and bile acid metabolite composition. The important role of intestinal bacteria and bile acid metabolites in NJ was determined, which can predict the risk of NJ.

Association analysis of the intestinal microbiome-metabolome found that neonatal jaundice (NJ)-related intestinal microbiota, network modules and metabolite composition, and the intestinal microbiota are closely related to bile acid metabolites.Gut bacteria were found to affect serum total bilirubin (TBIL) and NJ by influencing bile acid metabolism through a machine learning-causal inference approach, and bile acid metabolites affected NJ itself by affecting the TBIL content.NJ-associated gut bacteria and bile acids are potential biomarkers of NJ, and clinical decision-making models based on these biomarkers have some clinical effects for disease risk prediction.

Association between Ureaplasma urealyticum colonization and bronchopulmonary dysplasia in preterm infants: a systematic review and meta-analysis.

Background: Bronchopulmonary dysplasia (BPD) is the most prevalent chronic lung disease in preterm infants. Studies have shown that Ureaplasma urealyticum (UU) infection is linked to its pathogenesis. However, it remains controversial whether UU colonization in preterm infants increases the risk of developing BPD. Objective: This study aimed to conduct a systematic review and meta-analysis to summarize the correlation between UU and BPD. Methods: We searched PubMed, Embase, the Cochrane Library, Web of Science, Wanfang Database, Chinese National Knowledge Infrastructure Database, Chinese Science and Technique Journal Database, and the China Biology Medicine disc from their inception to March 15, 2024. We included cohort and case-control studies investigating the association between UU infections and BPD in preterm infants, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The Newcastle-Ottawa Scale was used for quality assessment. The outcome was defined as the continued need for oxygen or respiratory support at 28 days after birth (BPD28) or at 36 weeks postmenstrual age (BPD36). Considering the potential publication bias in observational studies, we used a random-effects meta-analysis model, assessed heterogeneity (I2), performed subgroup analyses, evaluated publication bias, and graded the quality of evidence. Results: The meta-analysis included 36 cohort studies encompassing 5,991 participants. Among these, 20 reported on BPD28, 13 on BPD36, and 3 on both. The results indicated a significant association between UU colonization and BPD28 (odds ratio (OR): 2.26, 95% confidence interval (CI): 1.78-2.85, P < 0.00001, 23 studies, very low certainty of evidence) and BPD36 (OR: 2.13, 95% CI: 1.47-3.07, P < 0.0001, 16 studies, very low certainty of evidence). Conclusion: There is a correlation between UU colonization and the development of BPD in preterm infants. Future research should prioritize well-designed, large-scale, high-quality randomized controlled trials (RCTs) to comprehensively assess the risk of BPD in neonates following UU infection and to provide stronger evidence for clinical screening and prevention strategies to improve the prognosis of affected newborns. Systematic Review Registration: https://www.crd.york.ac.uk/, identifier (CRD42024524846).

The Association of Neonatal Gut Microbiota Community State Types with Birth Weight.

BACKGROUND: while most gut microbiota research has focused on term infants, the health outcomes of preterm infants are equally important. Very-low-birth-weight (VLBW) or extremely-low-birth-weight (ELBW) preterm infants have a unique gut microbiota structure, and probiotics have been reported to somewhat accelerate the maturation of the gut microbiota and reduce intestinal inflammation in very-low preterm infants, thereby improving their long-term outcomes. The aim of this study was to investigate the structure of gut microbiota in ELBW neonates to facilitate the early identification of different types of low-birth-weight (LBW) preterm infants. METHODS: a total of 98 fecal samples from 39 low-birth-weight preterm infants were included in this study. Three groups were categorized according to different birth weights: ELBW (n = 39), VLBW (n = 39), and LBW (n = 20). The gut microbiota structure of neonates was obtained by 16S rRNA gene sequencing, and microbiome analysis was conducted. The community state type (CST) of the microbiota was predicted, and correlation analysis was conducted with clinical indicators. Differences in the gut microbiota composition among ELBW, VLBW, and LBW were compared. The value of gut microbiota composition in the diagnosis of extremely low birth weight was assessed via a random forest-machine learning approach. RESULTS: we briefly analyzed the structure of the gut microbiota of preterm infants with low birth weight and found that the ELBW, VLBW, and LBW groups exhibited gut microbiota with heterogeneous compositions. Low-birth-weight preterm infants showed five CSTs dominated by Enterococcus, Staphylococcus, Klebsiella, Streptococcus, Pseudescherichia, and Acinetobacter. The birth weight and clinical indicators related to prematurity were associated with the CST. We found the composition of the gut microbiota was specific to the different types of low-birth-weight premature infants, namely, ELBW, VLBW, and LBW. The ELBW group exhibited significantly more of the potentially harmful intestinal bacteria Acinetobacter relative to the VLBW and LBW groups, as well as a significantly lower abundance of the intestinal probiotic Bifidobacterium. Based on the gut microbiota's composition and its correlation with low weight, we constructed random forest model classifiers to distinguish ELBW and VLBW/LBW infants. The area under the curve of the classifiers constructed with Enterococcus, Klebsiella, and Acinetobacter was found to reach 0.836 by machine learning evaluation, suggesting that gut microbiota composition may be a potential biomarker for ELBW preterm infants. CONCLUSIONS: the gut bacteria of preterm infants showed a CST with Enterococcus, Klebsiella, and Acinetobacter as the dominant genera. ELBW preterm infants exhibit an increase in the abundance of potentially harmful bacteria in the gut and a decrease in beneficial bacteria. These potentially harmful bacteria may be potential biomarkers for ELBW preterm infants.

Clinical characteristics and correlation analysis of IVIG resistance in children with kawasaki disease complicated with hip synovitis: case-control study.

Objective: To investigate the clinical characteristics and risk factors of Kawasaki disease (KD) complicated with hip synovitis. Methods: Children with KD admitted from January 1, 2011, to December 31, 2020, in the KD database of Yuying Children's Hospital Affiliated with Wenzhou Medical University were retrospectively included. We selected KD children with hip synovitis as the case group and KD children without hip synovitis as the control group to analyze the possible risk factors of hip synovitis in KD children. Results: Among 2,871 KD children admitted to our center in recent years, 28 had hip synovitis. In this study 140 KD children were enrolled, including 28 KD children with hip synovitis and 112 children with general KD (within one month of admission). The onset age of KD patients with hip synovitis was 30.92 (23.23-49.99) months, and there were 17 cases of bilateral hip involvement. The course of synovitis (limited movement, joint pain, lameness, unwillingness to stand, etc.) ranged from 1 to 19 days, with an average of (8.8 ± 4.6) days. We treated all KD children with IVIG (Intravenous immunoglobulin) plus aspirin, among which five patients in the case group developed coronary artery damage, six acquired IVIG resistance, and synovial inflammation disappeared within two weeks. Age, weight, length of stay, and incidence of IVIG resistance significantly differed between the two groups (P = 0.001, 0.005, <0.001, and 0.035, respectively). Logistic regression analysis showed that KD combined with hip synovitis was an independent risk factor for developing propyl pellet resistance, with an OR value of 4.625 (95% CI: 1.095, 19.526). Conclusion: KD combined with hip synovitis mainly involves bilateral hip joints, and joint pain and limited movement are the main clinical features. The symptoms are mild and self-limiting. KD combined with hip synovitis is a risk factor for IVIG resistance. Hip synovitis is a good predictor of IVIG resistance.

Bovine colostrum to supplement the first feeding of very preterm infants: The PreColos randomized controlled trial.

BACKGROUND & AIMS: Gut immaturity leads to feeding difficulties in very preterm infants (<32 weeks gestation at birth). Maternal milk (MM) is the optimal diet but often absent or insufficient. We hypothesized that bovine colostrum (BC), rich in protein and bioactive components, improves enteral feeding progression, relative to preterm formula (PF), when supplemented to MM. Aim of the study is to determine whether BC supplementation to MM during the first 14 days of life shortens the time to full enteral feeding (120 mL/kg/d, TFF120). METHODS: This was a multicenter, randomized, controlled trial at seven hospitals in South China without access to human donor milk and with slow feeding progression. Infants were randomly assigned to receive BC or PF when MM was insufficient. Volume of BC was restricted by recommended protein intake (4-4.5 g/kg/d). Primary outcome was TFF120. Feeding intolerance, growth, morbidities and blood parameters were recorded to assess safety. RESULTS: A total of 350 infants were recruited. BC supplementation had no effect on TFF120 in intention-to-treat analysis [n (BC) = 171, n (PF) = 179; adjusted hazard ratio, aHR: 0.82 (95% CI: 0.64, 1.06); P = 0.13]. Body growth and morbidities did not differ, but more cases of periventricular leukomalacia were detected in the infants fed BC (5/155 vs. 0/181, P = 0.06). Blood chemistry and hematology data were similar between the intervention groups. CONCLUSIONS: BC supplementation during the first two weeks of life did not reduce TFF120 and had only marginal effects on clinical variables. Clinical effects of BC supplementation on very preterm infants in the first weeks of life may depend on feeding regimen and remaining milk diet. TRIAL REGISTRATION: http://www. CLINICALTRIALS: gov: NCT03085277.

Development of a novel forensic age estimation strategy for aged blood samples by combining piRNA and miRNA markers.

In forensic investigations, age estimation is vital for determining whether a suspect is under or over the legally defined adult age. With breakthroughs in RNA sequencing technology, small noncoding RNAs have provided new ways to solve problems related to the age estimation of trace or aged samples, owing to their small molecular weight and better stability. In our previous study, we had applied miRNAs for the age estimation of bloodstains; however, further improvement of the existing model is needed. PIWI-interacting RNAs (PiRNAs), which are 24-32 nt noncoding small RNA molecules involved in the PIWI-piRNA pathway, play an important role in the aging process. In this study, we explored the possibility of simultaneously analyzing piRNAs and miRNAs for better age estimation purpose. Through massively parallel sequencing, five age-related piRNAs were identified in blood samples that had been stored for eight years. Further real-time PCR analysis revealed that two piRNAs (piR-000753 and piR-020548) showed relatively higher efficiency in age estimation. Additionally, two age-related miRNAs (miR-324-3p and miR-330-5p) were used to build the estimation model. Among all algorithms tested, gradient boosting showed the lowest mean absolute error (MAE) and root mean square error (RMSE) values (3.171 and 4.403 years, respectively) for the validation dataset (n = 110). The errors of the model were less than 5 years and 10 years for 81.82% and 96.36% of the samples, respectively. The results suggest that the combined use of piRNA and miRNA markers may increase the accuracy of age estimation, and our new model has great potential for application in forensic casework.

CircRNA7632 down-regulation alleviates endothelial cell dysfunction in Kawasaki disease via regulating IL-33 expression.

Kawasaki disease (KD) is a form of idiopathic vasculitis frequently accompanied by coronary artery lesions, which involves endothelial dysfunction. Recent studies have demonstrated that circular RNAs (circRNAs) are implicated in many cardiovascular diseases. However, few studies have examined the role of circRNAs on endothelial dysfunction in KD. In this study, we investigated the role of circ7632 on endothelial-mesenchymal transition (EndoMT) in KD and then explored the underlying mechanism. Children diagnosed with KD and age-matched healthy controls (HC) were included. Sera samples were collected. Primary human umbilical vein endothelial cells (HUVECs) were obtained and incubated with 15% HC and KD serum for 48 h. The mRNA and protein expression of mesenchymal markers vimentin and α-smooth muscle actin (α-SMA) and endothelial marker zonula occludens-1 (ZO-1) in HUVECs transfected with plasmid-circ7632 and si-circ7632 were detected by RT-qPCR and Western blot analysis. CCK8, scratch test, and migration test were performed to examine the effect of circ7632 on the cell proliferation and migration. The circ7632 level was higher in HUVECs treated by KD serum than in HUVECs treated with HC serum. Overexpression of circ7632 significantly increased vimentin and α-SMA expression, decreased ZO-1 expression, and also decreased cell proliferation. Down-regulation of circ7632 expression got the opposite results. RNA-seq analysis, and confirmatory experiment displayed that down-regulation of circ7632 decreased IL-33 expression, and IL-33 silencing mitigated KD serum-mediated EndoMT. Our study revealed that circ7632 level was elevated in KD serum-treated HUVECs. Circ7632 down-regulation could alleviate EndoMT likely through decreasing IL-33 expression. The circ7632 may become a potential therapeutic target for KD.

Albumin level and progression of coronary artery lesions in Kawasaki disease: A retrospective cohort study.

Background: Albumin (ALB) level is closely associated with the occurrence of intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs) in Kawasaki disease (KD). The association between ALB level and CALs progression, is critical to the prognosis of KD patients. But little is known about it. This study aims to investigate the effect of the ALB level on CALs progression in KD patients. Methods: A total of 3,479 KD patients from 1 January 2005 to 30 November 2020, in Wenzhou, China were recruited. A total of 319 KD patients who had CALs and ALB data, and finish the follow-up as requested were enrolled in this study. They were classified into the low ALB group and the normal ALB group, divided by 30 g/L. CALs outcomes were classified into two categories according to the CALs changes from the time that CALs were detected within 48 h before or after IVIG treatment to 1 month after disease onset: progressed and no progressed. Multiple logistic regression models were used to assess the independent effect of ALB level on CALs progression among KD patients. Stratified analysis was performed to verify the ALB level on CALs progression among patients in different subgroups. Results: Higher proportion of IVIG resistance (P < 0.001), receiving non-standard therapy (P < 0.001), and receiving delayed IVIG treatment (P = 0.020) were detected in patients with lower ALB level. Patients with lower ALB level had higher C-reactive protein (CRP) level (P = 0.097) and white blood cell count (WBC) (P = 0.036). After adjustment for confounders, patients with lower ALB level had higher odds of CALs progression; the adjusted odds ratio (OR) was 3.89 (95% CI: 1.68, 9.02). Similar results were found using stratification analysis and sensitivity analysis. Male gender and age over 36 months, as covariates in multiple logistic regression models, were also associated with CALs progression. Conclusion: Low ALB level is identified as an independent risk factor for CALs progression in KD patients. Male gender and age over 36 months are also proved to be risk factors for CALs progression. Further investments are required to explore its mechanisms.

CircRNA-3302 promotes endothelial-to-mesenchymal transition via sponging miR-135b-5p to enhance KIT expression in Kawasaki disease.

Endothelial-to-mesenchymal transition (EndMT) is implicated in myofibroblast-like cell-mediated damage to coronary artery wall of Kawasaki disease (KD) patients, which subsequently increases the risk of coronary artery aneurysm. Many circular RNAs (circRNAs) have been reported to be associated with cardiovascular diseases. However, the roles and underlying molecular mechanism of circRNAs in KD-associated EndMT remains indefinite. In this research, we screened out circRNA-3302 from human umbilical vein endothelial cells (HUVECs) treated by sera from healthy controls (HCs) or KD patients via circRNA sequencing (circRNA-seq). In addition, circRNA-3302 upregulation was verified in endothelial cells stimulated by KD serum and pathological KD mice modeled with Candida albicans cell wall extracts (CAWS). Moreover, in vitro experiments demonstrated that overexpression of circRNA-3302 could markedly induce EndMT, and silencing of circRNA-3302 significantly alleviated KD serum-mediated EndMT. To further explore the molecular mechanisms of circRNA-3302 inducing EndMT, RNA sequencing (RNA-seq), a dual-luciferase reporter system, nuclear and extra-nuclear RNA isolation, RT-qPCR and Western blot analyses and so on, were utilized. Our data demonstrated that circRNA-3302 contributed to the KD-associated EndMT via sponging miR-135b-5p to enhance KIT expression. Collectively, our results imply that circRNA-3302 plays an important role in KD-associated EndMT, providing new insights into minimizing the risks of developing coronary artery aneurysms.

Identifying Rare Genetic Variants of Immune Mediators as Risk Factors for Autism Spectrum Disorder.

Autism spectrum disorder (ASD) affects more than 1% of children, and there is no viable pharmacotherapeutic agent to treat the core symptoms of ASD. Studies have shown that children with ASD show changes in their levels of immune response molecules. Our previous studies have shown that ASD is more common in children with folate receptor autoantibodies. We also found that children with ASD have abnormal gut immune function, which was characterized by a significant increase in the content of immunoglobulin A and an increase in gut-microbiota-associated epitope diversity. These studies suggest that the immune mechanism plays an important role in the occurrence of ASD. The present study aims to systematically assess gene mutations in immune mediators in patients with ASD. We collected genetic samples from 72 children with ASD (2−12 years old) and 107 healthy controls without ASD (20−78 years old). We used our previously-designed immune gene panel, which can capture cytokine and receptor genes, the coding regions of MHC genes, and genes of innate immunity. Target region sequencing (500×) and bioinformatics analytical methods were used to identify variants in immune response genes associated with patients with ASD. A total of 4 rare variants were found to be associated with ASD, including HLA-B: p.A93G, HLA-DQB1: p.S229N, LILRB2: p.R322H, and LILRB2: c.956-4C>T. These variants were present in 44.44% (32/72) of the ASD patients and were detected in 3.74% (4/107) of the healthy controls. We expect these genetic variants will serve as new targets for the clinical genetic assessment of ASD, and our findings suggest that immune abnormalities in children with ASD may have a genetic basis.

Machine learning approach identifies meconium metabolites as potential biomarkers of neonatal hyperbilirubinemia.

Background: The gut microbiota plays an important role in the early stages of human life. Our previous study showed that the abundance of intestinal flora involved in galactose metabolism was altered and correlated with increased serum bilirubin levels in children with jaundice. We conducted the present study to systematically evaluate alterations in the meconium metabolome of neonates with jaundice and search for metabolic markers associated with neonatal jaundice. Methods: We included 68 neonates with neonatal hyperbilirubinemia, also known as neonatal jaundice (NJ) and 68 matched healthy controls (HC), collected meconium samples from them at birth, and performed metabolomic analysis via liquid chromatography-mass spectrometry. Results: Gut metabolites enabled clearly distinguishing the neonatal jaundice (NJ) and healthy control (HC) groups. We also identified the compositions of the gut metabolites that differed significantly between the NJ and HC groups; these differentially significant metabolites were enriched in aminyl tRNA biosynthesis; pantothenic acid and coenzyme biosynthesis; and the valine, leucine and isoleucine biosynthesis pathways. Gut branched-chain amino acid (BCAA) levels were positively correlated with serum bilirubin levels, and the area under the receiver operating characteristic curve of the random forest classifier model based on BCAAs, proline, methionine, phenylalanine and total bilirubin reached 96.9%, showing good potential for diagnostic applications. Machine learning-based causal inference analysis revealed the causal effect of BCAAs on serum total bilirubin and NJ. Conclusions: Altered gut metabolites in neonates with jaundice showed that increased BCAAs and total serum bilirubin were positively correlated. BCAAs proline, methionine, phenylalanine are potential biomarkers of NJ.

The Significance of Symptoms in Predicting Coronary Artery Aneurysms of Kawasaki Disease, Especially in Female Patients.

Background: Kawasaki disease (KD) is an acute febrile systemic vasculitis of unknown etiology that occurs during early childhood, commonly involving the coronary artery, and can lead to coronary artery aneurysms (CAAs). Methods: The demographic, clinical, and laboratory data of KD patients without coronary artery lesions (N-CAL) and with CAA were collected during 2005-2020 at the Second Affiliated Hospital of Wenzhou Medical University. The patients were divided into the development cohort and the validation cohort. First, we compared the general information, symptoms, and laboratory data of N-CAL and CAA patients in the development cohort and the total cohort and screened out the different indices by logistic regression analysis. Then, we established three models and compared the area under the curve (AUC) values of the receiver operating characteristic (ROC) curves to identify meaningful models for CAA, which were further verified by decision curve analysis (DCA). Second, taking into account previous reports on the importance of gender to CAA, gender stratification was conducted. Results: The analysis of clinical and blood indices revealed the following novel features: (i) Many factors were found to be related to CAA, including IVIG resistance and the symptoms of rash, oral changes, and cervical lymphadenopathy. (ii) The development cohort was analyzed by logistic regression, and three models were established. The ROC curves showed that Model 2, composed of IVIG resistance, rash, oral changes, and cervical lymphadenopathy, had a better AUC value and easily to evaluate in the prediction of CAA. (iii) The selected model for predicting CAA in the development cohort was further confirmed in the validation cohort through DCAs. (iv)We further compared the items enrolled in the three models above between the N-CAL and CAA groups by sex, and the results indicated that female KD patients without rash, oral changes, and cervical lymphadenopathy were more likely to develop CAA. Conclusion: The absence of rash, oral changes, and cervical lymphadenopathy are risk factors for CAA, especially in female KD patients. Accurately recognizing symptoms, early diagnosis, and standard treatment for KD are key to reducing the incidence of CAA.

Clinical Manifestations of Neonatal Hyperbilirubinemia Are Related to Alterations in the Gut Microbiota.

BACKGROUND AND PURPOSE: Neonatal hyperbilirubinemia, also known as neonatal jaundice, is a common and frequent clinical condition with a complex etiology that can lead to brain damage in severe cases. Early recognition of hyperbilirubinemia and timely intervention and treatment can help reduce the occurrence of sequelae. This study was conducted to identify whether the gut microbiota composition can distinguish neonates with hyperbilirubinemia. METHODS: Meconium samples were collected from 69 neonates with neonatal jaundice (NJ) and 69 age- and sex-matched neonates without clinically significant jaundice (healthy controls; HCs) for 16S rRNA gene sequencing and microbiome analysis. RESULTS: Compared with HCs, the Chao 1 richness index of the gut microbiota was significantly decreased in the NJ group. The relative abundance of the probiotic gut bacterium, Lactobacillus, was significantly lower in the NJ group than in the HC group, whereas the abundances of potentially harmful gut bacteria, such as Escherichia coli and Staphylococcus, were significantly higher in the NJ group than in HCs. Correlation of the gut microbiota and clinical indicators revealed a positive correlation between Escherichia coli/Staphylococcus and serum total bilirubin levels. Finally, the results of a random forest machine-learning method to evaluate the possibility of using NJ-associated gut microbiota compositions as potential NJ biomarkers revealed an area under the curve of 96.88%. CONCLUSIONS: The abundances of Escherichia coli and Staphylococcus were positively correlated with serum total bilirubin levels. Hence, the gut microbiota composition is a potential biomarker of NJ.

Diversity of the T cell receptor ß chain complementarity-determining region 3 in peripheral blood of neonates with sepsis: an analysis based on immune repertoire sequencing. / å ç–«ç»„åº“æµ‹åºåˆ†æžæ–°ç”Ÿå„¿è„“æ¯’ç—‡æ‚£è€ å¤–å‘¨è¡€T细胞受体ß链CDR3çš„å¤šæ ·æ€§.

OBJECTIVES: To investigate the diversity of peripheral blood T cell receptor (TCR) ß chain complementarity-determining region 3 (CDR3) based on immune repertoire sequencing in neonates with sepsis and the possible pathogenesis of neonatal sepsis. METHODS: A total of 12 neonates with sepsis were enrolled as the case group, and 9 healthy full-term infants, matched for gestational age, birth weight, and age, were enrolled as the control group. Omega nucleic acid purification kit (SQ blood DNA Kit II) was used to extract DNA from peripheral blood samples, TCR ß chain CDR3 was amplified by multiplex PCR, and then high-throughput sequencing was performed for the products to analyze the diversity of TCR ß chain CDR3 and the difference in expression. RESULTS: The length and type of TCR ß chain CDR3 were similar between the case and control groups, and Gaussian distribution was observed in both groups. With D50 and Shannon-Wiener index as the evaluation indices for diversity, the case group had a significantly lower diversity of TCR ß chain CDR3 than the control group (P<0.05). The frequency of 48 genes in TCR ß chain V segment was compared, and the results showed that compared with the control group, the case group had significantly higher frequencies of TRBV10-3, TRBV2, and TRBV20-1 (P<0.05). The frequency of 13 genes in TCR ß chain J segment were compared, and the results showed that compared with the control group, the case group had significantly higher frequencies of TRBJ2-3, TRBJ2-5, and TRBJ2-7 (P<0.05). CONCLUSIONS: There is a significant change in the diversity of TCR ß chain CDR3 in the peripheral blood of neonates with sepsis, suggesting that it might be associated with the immune pathogenesis of neonatal sepsis.

Value of near-infrared spectroscopy in monitoring intestinal tissue oxygen saturation in preterm infants with hemodynamically significant patent ductus arteriosus: a prospective research. / è¿‘çº¢å¤–å ‰è°±æŠ€æœ¯å¯¹æœ‰è¡€æµåŠ¨åŠ›å­¦æ„ä¹‰çš„åŠ¨è„‰å¯¼ç®¡æœªé—­æ—©äº§å„¿è‚ é“ç»„ç»‡æ°§é¥±å’Œåº¦ç›‘æµ‹ä»·å€¼çš„å‰çž»æ€§ç ”ç©¶.

OBJECTIVES: To study the change in regional oxygen saturation (rSO2) of intestinal tissue in preterm infants with hemodynamically significant patent ductus arteriosus (hsPDA) by near-infrared spectroscopy, and the clinical significance of the change in intestinal oxygen level in preterm infants with hsPDA. METHODS: The preterm infants with patent ductus arteriosus (PDA) who had gestational age <32 weeks and/or birth weight <1 500 g were prospectively enrolled, who were admitted to the Department of Neonatology, Shenzhen Longgang Central Hospital from October 2017 to October 2020.According to the diagnostic criteria for hsPDA, the preterm infants with patent ductus arteriosus (PDA) were divided into two groups: hsPDA and non-hsPDA. According to closure of the ductus arteriosus after oral administration of ibuprofen, the preterm infants in the hsPDA group were subdivided into two groups: hsPDA closure and hsPDA non-closure. Hemodynamic parameters were measured at diagnosis of PDA and after treatment, and the level of intestinal tissue rSO2 was monitored continuously to analyze its change. RESULTS: A total of 241 preterm infants with PDA were enrolled, with 55 infants (22.8%) in the hsPDA group and 186 infants (77.2%) in the non-hsPDA group. There were 36 infants (65%) in the hsPDA closure group and 19 infants (35%) in the hsPDA non-closure group. Compared with the non-hsPDA group, the hsPDA group had a significantly higher left atrial diameter/aortic root diameter ratio and significantly lower left ventricular ejection fraction and fractional shortening (P<0.05). At each time point within 6 hours after diagnosis (1, 2, 4, and 6 hours), the hsPDA group had significantly lower intestinal tissue rSO2 than the non-hsPDA group (P<0.05), and intestinal tissue rSO2 gradually decreased over time in the hsPDA group (P<0.05), with the lowest level of 0.448±0.014 at 6 hours. Compared with the hsPDA non-closure group, the hsPDA closure group had a significantly lower left atrial diameter/aortic root diameter ratio and significantly higher left ventricular ejection fraction and fractional shortening (P<0.05). At each time point within 48-96 hours after treatment (48, 72, and 96 hours), the hsPDA closure group had significantly higher intestinal tissue rSO2 than the hsPDA non-closure group (P<0.05), and intestinal tissue rSO2 gradually increased since 24 hours after treatment in the hsPDA closure group (P<0.05), with the highest level of 0.578±0.031 at 96 hours. CONCLUSIONS: hsPDA has an impact on intestinal tissue oxygenation in preterm infants, and continuous monitoring of intestinal tissue rSO2 by near-infrared spectroscopy can help to guide the clinical management of hsPDA in preterm infants.

Clinical follow-up study of 166 cases of children with hypertension.

BACKGROUND: Childhood hypertension is a challenge for pediatricians to discover and diagnose. We sought to analyze its clinical characteristics and related risk factors in patients at a single center. METHODS: From 2009 to 2019, 166 children with hypertension were retrospectively analyzed, and their clinical manifestations and relevant laboratory data were collected for statistical analysis. RESULTS: A total of 120 males and 46 females were included in this study. Males were more common than females (P=0.012), and 86.7% were from rural areas. Hypertension appeared in all age groups, but most of them were puberty (52.4%). Most primary hypertension cases (57/91) had no obvious clinical symptoms, and BMI (OR 1.085, 95% CI: 1.004-1.173, P=0.038) and a family history of hypertension (OR 5.605, 95% CI: 2.229-14.092, P<0.001) were the risk factors. In the 75 secondary hypertension cases, renal hypertension (62.7%) was the main cause and headache and dizziness were the most common symptoms, and the serum urea is a risk factor (OR 1.524, 95% CI: 1.037-2.239, P=0.032). CONCLUSIONS: BMI and a family history of hypertension were associated with primary hypertension. The serum urea was related to secondary hypertension. Emphasis on family history, strengthening family health management and education and publicity of hypertension, were important for diagnosis and detection of children with hypertension.

Machine learning applied to serum and cerebrospinal fluid metabolomes revealed altered arginine metabolism in neonatal sepsis with meningoencephalitis.

BACKGROUND: Neonatal sepsis with meningoencephalitis is a common complication of sepsis, which is a leading cause of neonatal death and neurological dysfunction. Early identification of neonatal sepsis with meningoencephalitis is particularly important for reducing brain damage. We recruited 70 patients with neonatal sepsis, 42 of which were diagnosed as meningoencephalitis, and collected cerebrospinal fluid (CSF) and serum samples. The purpose of this study was to find neonatal sepsis with meningoencephalitis-related markers using unbiased metabolomics technology and artificial intelligence analysis based on machine learning methods. RESULTS: We found that the characteristics of neonatal sepsis with meningoencephalitis were manifested mainly as significant decreases in the concentrations of homo-l-arginine, creatinine, and other arginine metabolites in serum and CSF, suggesting possible changes in nitric oxide synthesis. The antioxidants taurine and proline in the serum of the neonatal sepsis with meningoencephalitis increased significantly, suggesting abnormal oxidative stress. Potentially harmful bile salts and aromatic compounds were significantly increased in the serum of the group with meningoencephalitis. We compared different machine learning methods and found that the lasso algorithm performed best. Combining the lasso and XGBoost algorithms was successful in predicting the concentration of homo-l-arginine in CSF per the concentrations of metabolite markers in the serum. CONCLUSIONS: On the basis of machine learning combined with analysis of the serum and CSF metabolomes, we found metabolite markers related to neonatal sepsis with meningoencephalitis. The characteristics of neonatal sepsis with meningoencephalitis were manifested mainly by changes in arginine metabolism and related changes in creatinine metabolism.

IL-37b alleviates endothelial cell apoptosis and inflammation in Kawasaki disease through IL-1R8 pathway.

Kawasaki disease (KD) is an acute vasculitis of pediatric populations that may develop coronary artery aneurysms if untreated. It has been regarded as the principal cause of acquired heart disease in children of the developed countries. Interleukin (IL)-37, as one of the IL-1 family members, is a natural suppressor of inflammation that is caused by activation of innate and adaptive immunity. However, detailed roles of IL-37 in KD are largely unclear. Sera from patients with KD displayed that IL-37 level was significantly decreased compared with healthy controls (HCs). QRT-PCR and western blot analyses showed that the expression level of IL-37 variant, IL-37b, was remarkably downregulated in human umbilical vein endothelial cells (HUVECs) exposed to KD sera-treated THP1 cells. Therefore, we researched the role of IL-37b in the context of KD and hypothesized that IL-37b may have a powerful protective effect in KD patients. We first observed and substantiated the protective role of IL-37b in a mouse model of KD induced by Candida albicans cell wall extracts (CAWS). In vitro experiments demonstrated that IL-37b alleviated endothelial cell apoptosis and inflammation via IL-1R8 receptor by inhibiting ERK and NFκB activation, which were also recapitulated in the KD mouse model. Together, our findings suggest that IL-37b play an effective protective role in coronary endothelial damage in KD, providing new evidence that IL-37b is a potential candidate drug to treat KD.

Overweight, obesity and coronary artery lesions among Kawasaki disease patients.

BACKGROUND AND AIMS: Overweight is associated with increased cardiovascular disease in general populations. However, a similar relationship among Kawasaki Disease (KD) patients was unclear. The study aimed to investigate the relation between weight-for-height and coronary artery lesions (CAL) among KD patients, and whether laboratory indices modified this relation. METHODS AND RESULTS: All consecutive KD patients from January 2009 to December 2014 in a city in China were reviewed, and classified into overweight/obese and control groups. All patients were followed to assess the occurrence of CAL by echocardiography for two months from disease onset. The independent effect of overweight/obesity on CAL was evaluated after adjustment for confounders. The interaction effect between overweight and laboratory indices was examined. The prevalence of overweight/obesity among KD patients was 18.5% (95%CI: 16.0%, 21.0%). The proportion of male patients and the proportion of non-standard IVIG treatment were significantly higher in overweight/obese children in comparison with their counterparts. Overweight/obesity was associated with increased odds of total CAL (aOR = 1.69, 95%CI: 1.16, 2.45) and also increased odds of CAL after treatment (aOR = 1.96, 95%CI: 1.09, 3.51); after adjustment for age, gender, KD type, change of medical departments, number of days before admission, treatment regimen and laboratory index. Similar results were found using stratification analysis. In addition, patients at risk of overweight were also associated with significantly increased risk of CAL. There was interaction between weight-for-height and platelet, WBC, and albumin. CONCLUSIONS: Overweight/obesity may be an independent risk factor for CAL among KD patients. Some laboratory indicators may modify this association.