Incidence of extrauterine growth retardation and its risk factors in very preterm infants during hospitalization: a multicenter prospective study. / ä½é™¢æžæ—©äº§å„¿å®«å¤–ç”Ÿé•¿è¿Ÿç¼“åŠç›¸å ³å› ç´ çš„å¤šä¸­å¿ƒå‰çž»æ€§ç ”ç©¶.

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS: It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.

A Novel NR0B1 Gene Mutation Causes Different Phenotypes in Two Male Patients with Congenital Adrenal Hypoplasia.

X-linked congenital adrenal hypoplasia is characterised by the acute onset of primary adrenal insufficiency in infancy or early childhood and hypogonadotropic hypogonadism (HH) at puberty, arising from mutations of the nuclear receptor subfamily 0 group B member 1 (NR0B1) gene. This study investigated an extended family with two affected males (patient A: 23 years and patient B: 2 months old) and three carrier females. Sequencing analysis of the NR0B1 gene coding region from the family revealed a novel hemizygous deletion [c.604delT; p.(C202Afs*62)] in the two male patients. Furthermore, the patients' respective mothers and their common grandmother had this heterozygous mutation, but it was not present in the Human Gene Mutation Database. The two male patients showed inconsistent clinical features at onset, particularly in early childhood; however, it is possible that the younger patient will eventually show a delay of puberty, feminisation, and nonspermatogenesis in adulthood, similar to that in the older patient. Identification of a novel NR0B1 mutation in this family is important for the diagnosis and genetic counselling of children with primary adrenal insufficiency and HH, and will be helpful for predicting long-term clinical symptoms.

[Effect of glutaryl-CoA dehydrogenase gene silencing and high-concentration lysine on the viability of BRL hepatocytes].

OBJECTIVE: To investigate the effect of glutaryl-CoA dehydrogenase (GCDH) gene silencing and accumulation of lysine metabolites on the viability of hepatocytes. METHODS: BRL cells were divided into normal control group, negative control group, and GCDH silencing group. The shRNA lentiviral vector for silencing GCDH gene was constructed, and the BRL hepatocytes in the GCDH silencing group and the negative control group were infected with this lentivirus and negative control virus respectively, and then cultured in a medium containing 5 mmol/L lysine. Immunofluorescence assay was used to measure the infection efficiency of lentivirus. Western blot was used to measure the expression of GCDH protein. MTT assay was used to evaluate cell viability. Hoechest33342 staining was used to measure cell apoptosis. Western blot was used to measure the expression of Caspase-3, an index of cell apoptosis. RESULTS: The lentivirus constructed effectively silenced the GCDH gene in hepatocytes (P<0.01). MTT assay and Hoechest 33342 staining showed no significant differences in cell viability and apoptosis between groups (P>0.05). There was also no significant difference in the expression of Caspase-3 protein between groups (P>0.05). CONCLUSIONS: GCDH gene silencing and accumulation of lysine metabolites may not cause marked hepatocyte injury.

Effects of SOCS 1/3 gene silencing on the expression of C/EBPα and PPARγ during differentiation and maturation of rat preadipocytes.

BACKGROUND: Suppressor of cytokine signaling-1 and -3 (SOCS-1 and SOCS-3) are two important negative regulators in the insulin-signaling pathway, and their overexpression may aggravate insulin resistance. Subjects with insulin resistance are often obese and have increased expressions of SOCS-1 and SOCS-3. We speculated that SOCS-1 and SOCS-3 may be involved in abnormal deposition of adipose tissues during insulin resistance. METHODS: A catch-up growth intrauterine growth retardation (CG-IUGR) rat model with insulin resistance was established; mRNA and protein expression of SOCS-1, SOCS-3, the CCAAT/enhancer binding protein (C/EBPα), and peroxisome proliferator-activated receptor (PPARγ) in adipose tissue were measured by real-time PCR and western blot; plasmids carrying small hairpin RNAs (shRNAs) targeting the SOCS-1 and SOCS-3 genes were constructed and transfected into preadipocytes, which were then induced to mature. At 72 h after differentiation was induced, the expressions of C/EBPα and PPARγ, two important molecules promoting the differentiation of preadipocytes, were detected. RESULTS: Expressions of SOCS-1, SOCS-3, C/EBPα, and PPARγ were markedly increased in adipose tissues of CG-IUGR rats, whereas the expressions of C/EBPα and PPARγ were significantly reduced after gene silencing of SOCS-1 or SOCS-3 in adipocytes. CONCLUSION: Overexpression of SOCS-1 and SOCS-3 may enhance the expression of C/EBPα and PPARγ, resulting in abnormal deposition of adipose tissues during insulin resistance.

[Effects of PI3K inhibitor LY294002 on the differentiation of mouse preadipocytes and the expression of C/EBPα and PPARγ].

OBJECTIVE: This study examined the effects of PI3K inhibitor LY294002 on the differentiation of mouse preadipocytes and the expression of CCAAT enhancer binding protein α (C/EBPα) and peroxisome proliferation activated receptor γ (PPARγ), in order to study the possible roles of insulin receptor substrate (IRSs)/PI3K signal pathway in the differentiation of preadipocytes. METHODS: The mouse 3T3-L1 cells were cultured normally and divided into experimental and control groups. 3T3-L1 cells in the experimental group were treated with PI3K inhibitor LY294002 (25 µmol/L) and those in the control group were treated with DMSO culture medium. 3-isobutyl-1-methylxanthine (IBMX) (0.5 mmol/L), dexamethasone (10-6 mol/L) and insulin (5 µg/mL) were used to induce the differentiation of 3T3-L1 preadipocytes in both groups. Before culture, and 2, 4 and 8 days after culture, the cells were collected to detect the expression of C/EBPα and PPARγ by real-time PCR and Western blot assays. The lipid droplets of 3T3-L1 preadipocytes were observed by oil-red O staining. RESULTS: PI3K inhibitor LY294002 did not affect the expression of C/EBPα and PPARγ in un-induced 3T3-L1 preadipocytes (P>0.05), but decreased the expression of C/EBPα and PPARγ during the in vitro induced differentiation of 3T3-L1 preadipocytes compared with the control group (P<0.05 or 0.01). The lipid droplets count was greatly reduced by LY294002. CONCLUSIONS: PI3K inhibitor LY294002 can inhibit the differentiation of mouse 3T3-LI preadipocytes and the expression of C/EBPα and PPARγ in the differentiation of 3T3-LI preadipoeytes, suggesting that IRSs/PI3K signal pathway may play an important role in the differentiation of 3T3-L1 preadipocytes by regulating the expression of C/EBPα and PPARγ.