Colonization of fecal microbiota from patients with neonatal necrotizing enterocolitis exacerbates intestinal injury in germfree mice subjected to necrotizing enterocolitis-induction protocol via alterations in butyrate and regulatory T cells.

BACKGROUND: Necrotizing enterocolitis (NEC) remains a life-threatening disease in neonates. Numerous studies have shown a correlation between the intestinal microbiota and NEC, but the causal link remains unclear. This study aimed to demonstrate the causal role of gut microbiota in NEC and explore potential mechanisms involved. METHODS: Eighty-one fecal samples from patients with NEC and eighty-one matched controls (matched to the NEC infants by gestational age, birth weight, date of birth, mode of delivery and feeding patterns) were collected. To explore if altered gut microbiota contributes to the pathogenesis of NEC, fecal microbiota transplantation (FMT) was carried out in germ-free (GF) mice prior to a NEC-induction protocol that included exposure to hypoxia and cold stress. Butyric acid was also administered to demonstrate its role in NEC. The fecal microbiota from patients and mice were analyzed by 16S rRNA gene sequencing analysis. Short chain fatty acid (SCFA) levels were measured by gas chromatography-mass spectrometry (GC-MS). The ontogeny of T cells and regulatory T cells (Tregs) in lamina propria mononuclear cells (LPMC) from the ileum of patients and mice were isolated and analyzed by flow cytometry.The transcription of inflammatory cytokines was quantified by qRT-PCR. RESULTS: NEC patients had increased Proteobacteria and decreased Firmicutes and Bacteroidetes compared to fecal control samples, and the level of butyric acid in the NEC group was lower than the control group. FMT in GF mice with samples from NEC patients achieved a higher histological injury scores when compared to mice that received FMT with control samples. Alterations in microbiota and butyrate levels were maintained in mice following FMT. The ratio of Treg/CD4+T (Thelper) cells was reduced in both NEC patients and mice modeling NEC following FMT. CONCLUSIONS: The microbiota was found to have NEC and the microbial butyrate-Treg axis was identified as a potential mechanism for the observed effects.

Domino Synthetic Strategy for Tetrahydrothiopyran Derivatives from Benzaldehydes, 2-Acetylfuran/2-Acetylthiophene, and Sodium Sulfide.

A novel domino reaction from benzaldehydes and 2-acetylfuran/2-acetylthiophene with sodium sulfide was developed to synthesize a series of tetrahydrothiopyran (THTP) derivatives. The reaction proceeded well to construct a tetrahydrothiopyran ring and five new bonds in one step. A mechanism is proposed, involving a stepwise Aldol/double Michael addition/Aldol (AMMA) reaction cascade. In this transformation, sodium sulfide acts as a nucleophile and base. This method is characterized by transition-metal-free, commercially available starting materials and mild reaction conditions.

Clinical features and partial proportional molecular genetics in neonatal diabetes mellitus: a retrospective analysis in southwestern China.

PURPOSE: To explore the relationship of phenotype and genotype of neonatal diabetes mellitus (NDM) in southwestern China. METHODS: Sixteen cases of NDM admitted to Children's Hospital of Chongqing Medical University from May 2009 to May 2019 were included in this study. The clinical features of the included infants were retrospectively analyzed. Peripheral blood samples of the patients and their parents were collected for mutation detection. RESULTS: Among the 16 cases of NDM, 8 cases were permanent neonatal diabetes mellitus (PNDM) (including 3 clinical syndromes), and 3 cases were transient neonatal diabetes mellitus (TNDM). Mutation detection was performed in six cases. The mutation genes and their loci were FOXP3 p.V408M, KCNJ11 p.C166Y, ABCC8 p.S830P, KCNJ11 p.I182T, KCNJ11 p.G334D, and ZFP57 p.R125X,412. ABCC8 p.S830P was the new found pathogenic site of gene mutation. According to the clinical features and follow-up results, one case was diagnosed as IPEX syndrome, two as DEND syndrome, two as simple PNDM, and one as TNDM. All the TNDM could spontaneously alleviate and then insulin was withdrawn. In PNDM, 75% of those with KATP channel gene mutation could be completely or partially converted to oral sulfonylureas treatment, however, the rest cases needed lifelong insulin replacement therapy. CONCLUSION: The clinical manifestations and treatment regimens of patients with NDM vary according to the type of gene mutation. Even the same mutant genotype has differences in phenotype and response to treatment.

Interleukin 35: A novel candidate biomarker to diagnose early onset sepsis in neonates.

BACKGROUND: Early onset sepsis (EOS) remains a major cause of morbidity and mortality in newborns; however, current diagnostic tools are inadequate. We evaluated the accuracy of a novel cytokine, interleukin (IL)-35, for the diagnosis of EOS in comparison with other infection markers. METHODS: One hundred fifty-seven neonates with suspected sepsis in the first 3days of life were enrolled in this perspective study. All enrolled patients were divided into infected group and unlikely infected group according to clinical data. IL-35, C-reactive protein (CRP), procalcitonin (PCT), white blood cell (WBC) count, and blood culture were measured once the suspected EOS was documented. RESULTS: Serum concentration of IL-35 was increased significantly in the infected group compared with the unlikely infected group (median 36.4 versus 27.1pg/ml, respectively, p<0.001). The area under receiver-operating characteristic (ROC) curve were 0.756 for IL-35, 0.713 for PCT (age-adjusted), 0.670 for CRP, and 0.619 for WBC. With a cut-off value of 31.7pg/ml, the diagnostic sensitivity and specificity of IL-35 were 78.48% and 66.67%, respectively. Moreover, unlike PCT concentration, IL-35 concentration did not fluctuate in neonates who were unlikely to be infected (p=0.885). CONCLUSION: The diagnostic performance of IL-35 was superior to that of PCT and other commonly used markers, suggesting that IL-35 may be a valuable tool for EOS diagnosis.