Effects of the timing of the initiation of dietary intake on pediatric type 1 diabetes for diabetic ketoacidosis.

BACKGROUND: Precision treatment of pediatric diabetic ketoacidosis (DKA) has been the focus of research for decades. Whether the timing of the initiation of dietary intake contributes to DKA correction is ignored. METHODS: We conducted a retrospective study to investigate the effects of the timing of the initiation of dietary intake on DKA correction in Children's Hospital of Nanjing Medical University, a tertiary children's hospital, from June 2017 to December 2020. Individual basic characteristic and clinical information of all DKA cases (n = 183) were collected. Multiple linear regression, logistic regression model and random forest (RF) model were used to assess the effect of the timing of the initiation of dietary intake on DKA correction. RESULTS: The mean age of the children diagnosed with DKA was 6.95 (SD 3.82) years. The median DKA correction time and the timing of the initiation of dietary intake was 41.72 h and 3.13 h, respectively. There were 62.3% (n = 114) patients corrected DKA at the end of the 48-h rehydration therapy. For each hour delay in starting dietary intake, child's DKA correction was prolonged by 0.5 (95% CI 1.05, 1.11, P < 0.001) hours and the adjusted odds of DKA over 48 h was increased by 8% (OR = 1.08, 95% CI: 1.05, 1.11, P < 0.001) after adjustment for potential confounders. The RF model based on the timing of the initiation of dietary intake and child's weight and systolic pressure achieved the highest AUC of 0.789. CONCLUSION: Pediatricians should pay attention to the effect of the timing of the initiation of dietary intake, a controllable factor, on DKA correction.

A clinical study of acute kidney injury in children with type 1 diabetes and diabetic ketoacidosis. / 1åž‹ç³–å°¿ç— ä¼´ç³–å°¿ç— é ®ç—‡é ¸ä¸­æ¯’æ‚£å„¿å‘ç”Ÿæ€¥æ€§è‚¾æŸä¼¤çš„ä¸´åºŠç ”ç©¶.

OBJECTIVES: To investigate the incidence rate of acute kidney injury (AKI) in children with type 1 diabetes and diabetic ketoacidosis (DKA) and the risk factors for AKI in children with DKA. METHODS: A retrospective analysis was performed on 45 children with type 1 diabetes and DKA who attended Children's Hospital of Nanjing Medical University from 2018 to 2020. According to the presence or absence of AKI on admission, they were divided into two groups: non-AKI (n=37) and AKI (n=8). Socio-demographic data and physical examination data on admission were collected, including height, weight, blood pressure, and heart rate. Chemiluminescence particle immunoassay was used to determine the levels of serum creatinine and blood urea nitrogen on admission and at discharge. The multivariate logistic regression model was used to assess the risk factors for AKI in children with type 1 diabetes and DKA. RESULTS: The 45 children had a median age of 9.2 years at diagnosis. Among the 8 children (18%) with AKI on admission, 6 had stage 1 AKI and 2 had stage 3 AKI. An increase in corrected serum sodium level was an independent risk factor for AKI in children with type 1 diabetes and DKA (P<0.05), and a relatively high insulin level on admission was an independent protective factor against AKI (P<0.05). CONCLUSIONS: There is a high incidence rate of AKI in children with type 1 diabetes and DKA. It is important to correct DKA actively, control blood glucose in time, and perform renal function tests and follow-up regularly in such children.

Trends and Hospital Variations in Surgical Outcomes for Cholangiocarcinoma in New York State.

BACKGROUND: This population-based study examined surgical outcomes and hospital and post-acute care resource use after operations of cholangiocarcinoma during 2005-2012. STUDY DESIGN: Using New York State hospital claims, we identified subjects with intrahepatic tumor who underwent hepatectomy only (n = 2089), subjects with perihilar tumor who underwent hepatectomy and biliary-enteric anastomosis (BEA; n = 389) or BEA only (n = 3721), and subjects with distal cholangiocarcinoma undergoing pancreatectomy or pancreaticoduodenectomy (n = 228). We performed trend analyses for each group and calculated overall risk-adjusted mortality, complication, and 30-day readmission rates for hospitals using multivariable logistic regressions. RESULTS: Mortality rate was roughly 12 % over years for perihilar cases undergoing hepatectomy and BEA, significantly higher than the rates of other 3 groups (p = 0.000). The overall complication rate was 40 % for subjects undergoing both hepatectomy and BEA, more than doubling the rate for subjects undergoing hepatectomy or BEA alone (p = 0.000). Average LOS declined markedly for perihilar cases undergoing hepatectomy and BEA (from 21 days in 2005 to 16 days in 2012) and subjects with distal cholangiocarcinoma (from 22 days in 2005 to 16 days in 2012), but other outcomes did not change dramatically. Risk-adjusted hospital outcome rates varied substantially. CONCLUSIONS: Surgical patients with cholangiocarcinoma incur considerable mortality, postoperative complications, and resource uses, especially among those undergoing hepatectomy and BEA for perihilar tumors.

Insights from lncRNAs Profiling of MIN6 Beta Cells Undergoing Inflammation.

Type 1 diabetes mellitus (T1DM) is an organ-specific autoimmune disease characterized by chronic and progressive apoptotic destruction of pancreatic beta cells. During the initial phases of T1DM, cytokines and other inflammatory mediators released by immune cells progressively infiltrate islet cells, induce alterations in gene expression, provoke functional impairment, and ultimately lead to apoptosis. Long noncoding RNAs (lncRNAs) are a new important class of pervasive genes that have a variety of biological functions and play key roles in many diseases. However, whether they have a function in cytokine-induced beta cell apoptosis is still uncertain. In this study, lncRNA microarray technology was used to identify the differently expressed lncRNAs and mRNAs in MIN6 cells exposed to proinflammatory cytokines. Four hundred forty-four upregulated and 279 downregulated lncRNAs were detected with a set filter fold-change ≧2.0. To elucidate the potential functions of these lncRNAs, Gene Ontology (GO) and pathway analyses were used to evaluate the potential functions of differentially expressed lncRNAs. Additionally, a lncRNA-mRNA coexpression network was constructed to predict the interactions between the most strikingly regulated lncRNAs and mRNAs. This study may be utilized as a background or reference resource for future functional studies on lncRNAs related to the diagnosis and development of new therapies for T1DM.

Clinical and Functional Characterization of Novel INSR Variants in Two Families With Severe Insulin Resistance Syndrome.

Objective: Defects in the insulin receptor (INSR) gene cause various severe insulin resistance conditions, including Donohue syndrome (DS), Rabson-Mendenhall syndrome (RMS) and type A insulin resistance (type A-IR). This study aimed to investigate the clinical characterization and molecular defects in three Chinese children with INSR-related insulin resistance syndrome. Methods: We reviewed the clinical data of three Chinese children with INSR-related insulin resistance syndrome from two unrelated kindreds. Genetic analysis was performed using whole-exome sequencing and the effects of the novel variants were further assessed by in vitro functional assays. Results: The proband with type A-IR presented with acanthosis nigricans, hypertrichosis, and euglycemia with mild insulin resistance in early childhood. His sister presented with features typical of type A-IR and was diagnosed with diabetes mellitus with severe insulin resistance at the age of 9.8 years. The proband with DS showed typical dysmorphic characteristics, severe intrauterine growth retardation, extreme insulin resistance, fasting hypoglycemia and postprandial hyperglycemia from birth. The heterozygote variants c.[3670G>A]; c.[3614C>T] were identified in both siblings with type A-IR; and c.[749_751del]; c.[3355C>T] in the patient with DS. In vitro studies showed that the novel variant c.749_751del [p.(Thr250del)] in the α-subunit, reduced expression of the mature INSR protein and severely impaired INSR function. In contrast, the novel variant c.3670G>A [p.(Val1224Met)] in the ß-subunit had no effect on total protein expression and phosphorylation of INSR and Akt, suggesting that the variant p.Val1224Met appeared to be tolerated and was not responsible for the severe insulin resistance. Conclusion: Our study detailed the clinical features of three patients with type A-IR and DS, and identified two novel variants in the INSR gene. Functional assays indicated the novel variant p.Thr250del was pathogenic. In contrast, the novel variant p.Val1224Met was suggested to be tolerated by our experimental data, even though bioinformatics analyses predicted the variant as deleterious.

Turner syndrome with rapidly progressive puberty: a case report and literature review.

This report describes a clinically rare and atypical case of 46,X,idic(X)(q21.32)/45,X-type Turner syndrome with rapidly progressive puberty development. After 11 months of treatment with recombinant human growth hormone (rhGH), the child's height increased. After 18 months of treatment with rhGH, the child showed secondary sex characteristics. The child was followed up for 1 year after the appearance of the secondary sex characteristics, and regular menses were still present. This case indicates that modern molecular biology techniques should be used rationally to further investigate the existence of X-chromosome translocations and occult chimeras to prevent misdiagnosis.

Research and prospect of peptides for use in obesity treatment (Review).

Obesity and its related diseases, such as type 2 diabetes, hypertension and cardiovascular disease, are steadily increasing worldwide. Over the past few decades, numerous studies have focused on the differentiation and function of brown and beige fat, providing evidence for their therapeutic potential in treating obesity. However, no specific novel drug has been developed to treat obesity in this way. Peptides are a class of chemically active substances, which are linked together by amino acids using peptide bonds. They have specific physiological activities, including browning of white fat. As signal molecules regulated by the neuroendocrine system, the role of polypeptides, such as neuropeptide Y, brain-gut peptide and glucagon-like peptide in obesity and its related complications has been revealed. Notably, with the rapid development of peptidomics, peptide drugs have been widely used in the prevention and treatment of metabolic diseases, due to their short half-life, small apparent distribution volume, low toxicity and low side effects. The present review summarizes the progress and the new trend of peptide research, which may provide novel targets for the prevention and treatment of obesity.

Differential Profile of Plasma Circular RNAs in Type 1 Diabetes Mellitus.

BACKGROUND: No currently available biomarkers or treatment regimens fully meet therapeutic needs of type 1 diabetes mellitus (T1DM). Circular RNA (circRNA) is a recently identified class of stable noncoding RNA that have been documented as potential biomarkers for various diseases. Our objective was to identify and analyze plasma circRNAs altered in T1DM. METHODS: We used microarray to screen differentially expressed plasma circRNAs in patients with new onset T1DM (n=3) and age-/gender-matched healthy controls (n=3). Then, we selected six candidates with highest fold-change and validated them by quantitative real-time polymerase chain reaction in independent human cohort samples (n=12). Bioinformatic tools were adopted to predict putative microRNAs (miRNAs) sponged by these validated circRNAs and their downstream messenger RNAs (mRNAs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to gain further insights into T1DM pathogenesis. RESULTS: We identified 68 differentially expressed circRNAs, with 61 and seven being up- and downregulated respectively. Four of the six selected candidates were successfully validated. Curations of their predicted interacting miRNAs revealed critical roles in inflammation and pathogenesis of autoimmune disorders. Functional relations were visualized by a circRNA-miRNA-mRNA network. GO and KEGG analyses identified multiple inflammation-related processes that could be potentially associated with T1DM pathogenesis, including cytokine-cytokine receptor interaction, inflammatory mediator regulation of transient receptor potential channels and leukocyte activation involved in immune response. CONCLUSION: Our study report, for the first time, a profile of differentially expressed plasma circRNAs in new onset T1DM. Further in silico annotations and bioinformatics analyses supported future application of circRNAs as novel biomarkers of T1DM.

Stereoselective interactions of lactic acid enantiomers with HSA: Spectroscopy and docking application.

Lactic acid enantiomers, normally found in fermented food, are absorbed into the blood and interact with plasma carrier protein human serum albumin (HSA). Unveiling the effect on the function and structure of HSA during chiral interaction can give a better understanding of the different distribution activities of the two enantiomers. Multi-spectroscopic methods and molecular modelling techniques are used to study the interactions between lactic acid enantiomers and HSA. Time-resolved and steady-state fluorescence spectra manifest that the fluorescence quenching mechanism is mainly static in type, due to complex formation. Binding interactions, deduced by thermodynamic calculation, agree with the docking prediction. Docking results and kinetic constants represent chiral-recognizing discriminations consistently. The bindings of lactic acid enantiomers lead to some microenvironmental and slight conformational changes of HSA as shown by circular dichroism (CD), synchronous and three-dimensional fluorescence spectra. This investigation may yield useful information about the possible toxicity risk of lactic acid enantiomers to human health.