Optimizing parenteral nutrition to achieve an adequate weight gain according to the current guidelines in preterm infants with birth weight less than 1500 g: a prospective observational study.

AIM: European Society for Clinical Nutrition and Metabolism released the guidelines on pediatric parenteral nutrition in 2018. We aimed to compare the parenteral nutrition (PN) regimen with the current guidelines, evaluate weight gain and explore the correlation of parenteral macronutrient and energy intakes with weight gain outcome in preterm infants with birth weight less than 1500 g. METHODS: A prospective observational study was conducted. Parenteral macronutrients and energy intakes were described. Weight gain during PN was assessed. Nutritional factors associated with weight gain outcome after PN were identified using a cox proportional hazards model. RESULTS: A total of 163 infants were included in this study, in which 41 were extremely low birth weight (ELBW) infants and 122 were very low birth weight (VLBW) infants. Average glucose, amino acid, lipid, and energy during the first postnatal week were 7.5 g/kg/d, 2.4 g/kg/d, 0.8 g/kg/d, 48 kcal/kg/d. Median maximum glucose, amino acid, lipid, and energy were 11.1 g/kg/d, 3.5 g/kg/d, 3 g/kg/d, 78 kcal/kg/d. Median days to maximum glucose, amino acid, lipid, and energy were 10, 9, 12, 11 days. The proportion of appropriate for gestational age (AGA) infants was 76.9%. The ratio of infants without poor weight gain outcome after PN was 38%. With every 0.1 g/kg/d decrease of maximum amino acid and average lipid during the first postnatal week, the probability of appropriate weight gain outcome decreased by 77.6 and 74.4% respectively. With each additional day to maximum glucose and energy, the probability of appropriate weight gain outcome decreased by 5.6 and 6.1% respectively. CONCLUSIONS: Most preterm infants with birth weight less than 1500 g remain below the latest recommended nutrition goals. The poor weight gain outcome of these infants after PN is related to insufficient parenteral macronutrient and energy intakes. PN strategies should be improved according to the latest evidence-based recommendations.

Long Non-coding RNA MEG3 Alleviated Ulcerative Colitis Through Upregulating miR-98-5p-Sponged IL-10.

Ulcerative colitis (UC) is a refractory chronic colitis disease with the particularly complex cause. Recently, long noncoding RNAs (lncRNAs) have been reported to be related to the development of UC. LncRNA MEG3 has been proved to play an anti-inflammatory role in a variety of inflammatory diseases, which share similar pathogenesis with UC, indicating the potential involvement of lncRNA MEG3 in UC. This study aims to investigate the functional role and underlying mechanism of lncRNA MEG3 in UC. Gradient concentration of H2O2 (0, 20, 50, 100, and 200 µM) was used to induce Caco-2 damage models in vitro. Cell viability was detected by cell counting kit-8 (CCK-8) assay. LncRNA MEG3, miR-98-5p, and IL-10 levels in H2O2-treated Caco-2 cells were assessed by performing real-time quantitative polymerase chain reaction (RT-qPCR). Moreover, the binding relationship between lncRNA MEG3 and miR-98-5p, as well as the binding relationship between miR-98-5p and IL-10, was validated using dual-luciferase reporter assay. 2, 4, 6-Trinitrobenzenesulfonic acid solution (TNBS) was applied to induce ulcerative colitis in young rats. The body weight, disease activity index (DAI), length and weight of the colons, pathological scores of UC rats, reactive oxygen species (ROS), and inflammatory cytokines were determined to evaluate the effects of lncRNA MEG3 on the progression of UC. Besides, hematoxylin-eosin (HE) staining was exploited to observe histological changes of UC rat colons. In addition, western blotting analysis was also performed to evaluate the apoptosis and pyroptosis-related protein levels. Moreover, lncRNA MEG3, miR-98-5p, and IL-10 levels in UC rat colons were further assessed by RT-qPCR. Meanwhile, IL-10 expression was determined using immunohistochemistry. LncRNA MEG3 and IL-10 levels were distinctly decreased while miR-98-5p was increased in Caco-2 damage models and UC rats. Bioinformatics analysis predicted the binding sites of lncRNA MEG3 to miR-98-5p and miR-98-5p to IL-10. Besides, dual-luciferase reporter assay validated the negative correlation between lncRNA MEG3 and miR-98-5p, miR-98-5p, and IL-10. Overexpressed lncRNA MEG3 reduced. DAI scores and colon weight/length ratio improved UC ulceration. In addition, upregulation of lncRNA MEG3 relieved oxidative stress, inflammatory response, apoptosis, and pyroptosis of UC rat colons. LncRNA MEG3 overexpression alleviates the serve ulceration of UC rat colons by upregulating IL-10 expression via sponging miR-98-5p. To sum up, this study reveals the protective role of lncRNA MEG3 in the development of UC and may provide potential therapeutic targets for UC.

"Gilbert's-like" syndrome as part of a spectrum of persistent unconjugated hyperbilirubinemia in post-chronic hepatitis patients.

Gilbert's syndrome (GS) patients present with remittent unconjugated hyperbilirubinemia. In this study, we investigated the correlation between polymorphisms in the gene encoding UDP-glucuronosyltransferase, UGT1A1, and the development of unconjugated hyperbilirubinemia in clinical GS and post-hepatitis hyperbilirubinemia. Blood samples were collected from 285 patients, including 85 patients who were clinically diagnosed with GS, 70 patients who had indirect hyperbilirubinemia during the recovery period of chronic liver diseases, 109 patients with normal hepatic function and 21 chronic active hepatitis patients. All samples were tested for the presence of the *28/*6 UGT1A1 genotype by pyrosequencing. Compared with the GS-control group, a significant difference in variations of the UGT1A1*28/*6 allele gene was found in GS patients. The post-hepatitis group showed a significant difference in the UGT1A1*28/*6 allele gene frequency distribution relative to that in the hepatitis control group. There were no significant differences between the GS group and post-hepatitis group in the distribution of the UGT1A1*28/*6 allele gene frequency and UGT1A1 diplotypes. UGT1A1*28/*6 gene polymorphisms in patients who had indirect hyperbilirubinemia while recovering from chronic liver diseases presented similar patterns as those seen for GS patients. These findings suggest that a "Gilbert's-like" syndrome might be part of the spectrum of persistent unconjugated hyperbilirubinemia in post-chronic hepatitis patients.

Efficacy of Mesenchymal Stromal Cells for Fistula Treatment of Crohn's Disease: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIM: The introduction of mesenchymal stromal cells (MSCs) has changed the management of Crohn's fistula, while it remains controversial. The aim of this study was to provide an overview of efficacy and optimum state of MSCs treatment on Crohn's fistula. METHODS: Studies reporting MSCs treatment on Crohn's fistula were searched and included. A fixed-effects model was used to assess the efficacy of MSCs, and outcomes of healing and recurrence were used to evaluate the best states of MSCs intervention. RESULTS: Fourteen articles were enrolled (n = 477). Pooled analysis showed MSCs had a significant efficacy compared to other treatments [risk difference: 0.21 (0.09, 0.32), P = 0.000]. Notably, after MSCs treatment, the group of Crohn's disease activity index (CDAI) baseline >150 group had a higher healing rate (HR) and a clinical response (a change in CDAI of >50 points) (79.17 ± 8.78 vs. 47.54 ± 15.90, P = 0.011) compared to CDAI baseline of <150. The duration time of CD and fistulas had a negative correlation with HR accompanied by MSC therapy (r = -0.900, -0.925). Then, a moderate dose MSCs (2-4 × 107 cells/ml) had a higher HR (80.07%) and lower recurrence rate (RR 13.98%) compared to other dosages. Moreover, adipose-derived MSCs therapy had an advantage over bone marrow-derived MSCs in terms of low RR (7.4 ± 4.28 vs. 13.39 ± 0.89). CONCLUSIONS: The evidence supported the effect of MSCs at a more appropriate time of Crohn's fistula. And CDAI baseline (the points >150) has been a candidate for evaluating effectiveness of MSCs application on Crohn's fistula.