Puerarin Affects 1HMR Spectroscopy Quantified Hepatic Fat Signal Fraction in Intrauterine Growth Restricted Rats.

OBJECTIVE: This study aimed to investigate the impact of puerarin early intervention on growth parameters and Hepatic Fat Signal Fraction (HFF) quantification in Intrauterine Growth Restricted(IUGR)rats through Proton Magnetic resonance spectroscopy (1H-MRS). METHODS: Pregnant rats were divided into three groups: control, IUGR with puerarin treatment, and IUGR without treatment. The treatment and nontreatment groups were received a low-protein diet during pregnancy, while the control group received a normal diet. After birth, pups in the treatment group received a unilateral intraperitoneal injection of 50 mg/kg/d puerarin. Male rats were evaluated at 3,8 and 12 weeks, including measurements of weight, body length and waist circumference and body mass index (BMI). Conventional magnetic resonance imaging and 1HMRS were conducted using a 3.0 T whole-body MR scanner. RESULTS: Newborn pups in the treatment and non-treatment groups showed significantly lower body weight, BMI, and body length at 3 weeks compared to the control group. However, there were no significant differences in HFF and waist circumference between the three groups at 3 weeks. At 8 and 12 weeks post-delivery, significant differences in body weight, BMI, waist circumference were observed in newborn pups of IUGR non-treatment rats compared to the control group. In contrast, there were no significant differences in body weight, BMI, waist circumference between the treatment group and the control group at 8 and 12 weeks. Moreover, the treatment group exhibited notably higher HFF compared to the control group at both time points. At 12 weeks post-birth, a significant difference in HFF was observed between the IUGR non-treatment and treatment groups, although no significant difference was found at 8 weeks. CONCLUSION: Early intervention with puerarin following birth has a significant impact on liver fat content and may potentially reduce adult obesity among IUGR rats.

[Functional MRI assessment of microstructural and perfusion changes in the kidneys of rats with intrauterine growth restriction]. / åŠŸèƒ½ç£å ±æŒ¯è¯„ä¼°å®«å† å‘è‚²è¿Ÿç¼“ä»”é¼ è‚¾è„å¾®è§‚ç»“æž„åŠçŒæ³¨æ”¹å˜.

OBJECTIVES: To explore the value of functional magnetic resonance imaging (MRI) techniques, including intravoxel incoherent motion (IVIM), T1 mapping, and T2 mapping, in assessing the microstructural and perfusion changes in the kidneys of rats with intrauterine growth restriction (IUGR). METHODS: An IUGR rat model was established through a low-protein diet during pregnancy. Offspring from pregnant rats on a low-protein diet were randomly divided into an IUGR 8-week group and an IUGR 12-week group, while offspring from pregnant rats on a normal diet were divided into a normal 8-week group and a normal 12-week group (n=8 for each group). The apparent diffusion coefficient (ADC), true diffusion coefficient (Dt), pseudo-diffusion coefficient (D*), perfusion fraction (f), T1 value, and T2 value of the renal cortex and medulla were compared, along with serum creatinine and blood urea nitrogen levels among the groups. RESULTS: The Dt value in the renal medulla was higher in the IUGR 12-week group than in the IUGR 8-week group, and the D* value in the renal medulla was lower in the IUGR 12-week group than in both the normal 12-week group and the IUGR 8-week group (P<0.05). The T1 value in the renal medulla was higher than in the cortex in the IUGR 8-week group, and the T1 value in the renal medulla was higher in the IUGR 12-week group than in both the IUGR 8-week group and the normal 12-week group, with the cortical T1 value in the IUGR 12-week group also being higher than that in the normal 12-week group (P<0.05). The T2 values in the renal medulla were higher than those in the cortex across all groups (P<0.05). There were no significant differences in the T2 values of either the cortex or medulla among the groups (P>0.05). There were no significant differences in serum creatinine and blood urea nitrogen levels among the groups (P>0.05). Glomerular hyperplasia and hypertrophy without significant fibrotic changes were observed in the IUGR 8-week group, whereas glomerular atrophy, cystic stenosis, and interstitial inflammatory infiltration and fibrosis were seen in the IUGR 12-week group. CONCLUSIONS: IVIM MRI can be used to assess and dynamically observe the microstructural and perfusion damage in the kidneys of IUGR rats. MRI T1 mapping can be used to evaluate kidney damage in IUGR rats, and the combination of MRI T1 mapping and T2 mapping can further differentiate renal fibrosis in IUGR rats.

Docosahexaenoic acid improves cognition and hippocampal pyroptosis in rats with intrauterine growth restriction.

Background and Objective: Intrauterine growth restriction (IUGR) is defined as the failure of a fetus to reach its genetic growth potential in utero resulted by maternal, placental, fetal, and genetic factors. Previous studies have reported that IUGR is associated with a high incidence of neurological damage, although the precise causes of such damage remain unclear. We aimed to investigate whether cognitive impairment in rats with IUGR is related to pyroptosis of hippocampal neurons and determine the effect of early intervention with docosahexaenoic acid (DHA). Methods: Learning and memory function was assessed using the Morris water maze test. The morphological structure and ultrastructure of the hippocampus was examined via hematoxylin and eosin staining and electron microscopy respectively. The pyroptosis of hippocampal neuron was detected by gasdermin-D (GSDMD) immunofluorescence staining, mRNA and protein expression of nuclear localization leucine-rich-repeat protein 1 (NLRP1), caspase-1, GSDMD, and quantification of inflammatory cytokines interleukin (IL)-1ß and IL-18 in the hippocampus. Results: IUGR rats exhibited decreased learning and memory function, morphological structure and ultrastructural changes in hippocampus compared to controls. IUGR rats also exhibited increased hippocampal quantification of GSDMD immunofluorescence staining, increased mRNA and protein expression of NLRP1, caspase-1, and GSDMD, and increased quantification of IL-1ß and IL-18 in the hippocampus. Intervention with DHA attenuated these effects. Conclusion: Cognitive impairment in rats with IUGR may be related to pyroptosis of hippocampal neurons. Early intervention with DHA may attenuate cognitive impairment and reduce hippocampal pyroptosis in rats with IUGR.

Clinical characteristics of bronchopulmonary dysplasia in very preterm infants. / 极早早产儿支气管肺发育不良的临床特征.

OBJECTIVES: With the development of perinatal and neonatal intensive care medicine, the survival rate of very premature infants increases year by year. However, the incidence of bronchopulmonary dysplasia (BPD) increases year by year, which seriously affects the survival prognosis of very premature infants. How to prevent and treat BPD effectively has become the focus of neonatologists. This study aims to provide ideas for the prevention and treatment of BPD in very preterm infants via analyzing the clinical characteristics of BPD. METHODS: A total of 472 cases of very premature infants admitted to the Divison of Neonatology, Department of Pediatrics at the Second Xiangya Hospital of Central South University were retrospectively selected and assigned into a BPD group (n=147) and a non-BPD group (n=325) according to the diagnosis of BPD. Clinical data of each group were collected to find out the clinical characteristics of BPD in very preterm infants. Basic information, maternal pregnancy data, laboratory findings, nutritional support, respiratory support patterns and duration, and systemic complications were included. RESULTS: Compared with the non-BPD group, gestational age, birth weight, head circumference and body length in the BPD group were lower, the Apgar score in 1st min and 5th min and average body weight growth rate were lower (all P<0.05); the ratios of male, very low birth weight (VLBW), and extremely low birth weight (ELBW) in the BPD group were higher than those in the non-BPD group (all P<0.5); the incidence of maternal cervical insufficiency and the rate of using embryo transfer technology in the BPD group were higher than those in the non-BPD group, and the rate of using prenatal hormone in the BPD group was lower than that in the non-BPD group (all P<0.05). The positive rate of sputum culture in the BPD group was higher than that in the non-BPD group (P<0.05), and the white blood cell count, neutrophil ratio, and procalcitonin in the BPD group were higher than those in the non-BPD group (all P<0.05). The period of fasting, minimal feeding, total parenteral nutrition (TPN), and partial parenteral nutrition (PPN) in the BPD group were longer than those in the non-BPD group (all P<0.05). The duration of nasal catheter oxygen inhalation and mechanical ventilation in the BPD group was longer than that in the non-BPD group, and the rates of mechanical ventilation at Day 1, 3, 7, 14, 21 and 28 after birth were higher than those in the non-BPD group (all P<0.05). The incidence of respiratory distress syndrome, apnea of prematurity, respiratory failure, pneumonia, pulmonary hemorrhage, pleural effusion, persistent pulmonary hypertension, hemodynamic patent ductus arteriosus, cytomegalovirus infection, neonatal necrotic enterocolitis, cholestasis, anemia, abnormal blood system, hypothyroidism, retinopathy of prematurity, and internal environment disorders in the BPD group were significantly higher than those in non-BPD group (all P<0.05). CONCLUSIONS: There are significant differences between very premature infants with BPD and those without BPD in general information, maternal history, inflammatory indicators, nutritional support, respiratory support, comorbidities and complication rates. To ensure normal fetal development, reducing the inflammatory reaction of very premature infants, establishing enteral nutrition as early as possible, shortening the time of mechanical ventilation, and reducing the occurrence of complications are beneficial to decrease the incidence of BPD in very premature infants and improve the long-term prognosis of BPD.

Etiology and clinical characteristics of neonatal sepsis in different medical setting models: A retrospective multi-center study.

Objective: General hospitals admit lower gestational age neonates than maternal and child health care centers, therefore associated with a higher morbidity and mortality. This study aimed to assess the etiology and clinical characteristics of neonatal sepsis in different medical setting models. Methods: Neonates admitted to 5 tertiary medical centers, including one national general hospital, two maternal and child health care hospitals and two regional general hospitals, in central-south China with culture-proven sepsis between January 2010 and December 2019 were included in the study. We compared maternal and neonatal characteristics, pathogen distribution, treatment and neonatal outcomes among 3 different medical setting models in this retrospective cohort. Results: We identified 757 episodes of culture-proven sepsis in 757 neonates. The predominant pathogens were coagulase-negative staphylococci, Klebsiella pneumoniae, Escherichia coli and Group B streptococci. A total of 683 neonates with detailed information were involved in further comparison; 54.6% were from the national general hospital, 35.9% were from the maternal and child health care hospital, and 9.5% were from the regional general hospital. Neonates in national and regional general hospitals had significantly lower gestational age and birthweight (P < 0.001). Patterns of pathogen distribution were different among these medical setting models. Early-onset sepsis was more common in maternal and child health care hospitals (61.4% vs. 42.1% vs. 46.7%, P < 0.001), while hospital-acquired late-onset sepsis was more common in national and regional general hospitals (32.7% vs. 33.3% vs. 11.4%, P < 0.001). The proportion of complications or comorbidities of neonates in maternal and child health care hospitals were significantly lower than neonates in national and regional general hospitals (P < 0.001). The case fatality rate was significantly higher in regional general hospitals (10.8% vs. 3.2% vs. 0.8%, P = 0.001). Conclusion: We report distinct patterns of clinical characteristics, pathogens and outcomes in patient subgroups with neonatal sepsis from national general hospital, maternal and child health care hospital and regional general hospital. It might have some implications for improvement of prevention, management and empirical antibiotic use in neonatal sepsis in different setting models, especially in resource-limited settings from middle and low-income countries.

[A 10-year retrospective study of pathogens and antimicrobial resistance in neonatal sepsis]. / æ–°ç”Ÿå„¿è´¥è¡€ç—‡ç— åŽŸèŒåŠè€è¯æ€§10年回顾性分析.

OBJECTIVES: To investigate the changes in the pathogen spectrum and antimicrobial resistance over time in neonatal sepsis. METHODS: The medical data were collected from the neonates who were diagnosed with sepsis in the Second Xiangya Hospital of Central South University from January 2010 to December 2019. The incidence rate of sepsis, the pathogen spectrum, and the characteristics of antimicrobial resistance were analyzed. RESULTS: The incidence rate of neonatal sepsis was 4.02% (447/11 111). The top four pathogens detected were coagulase-negative staphylococci (CoNS), Klebsiella pneumoniae, Escherichia coli, and Candida. The incidence rate of sepsis and the pathogen spectrum showed no significant changes over time. Klebsiella pneumoniae was the most frequent pathogen in preterm infants, very low birth weight infants, and small-for-gestational-age infants, accounting for 33.9%, 29.5%, and 42.5%, respectively. CoNS, Klebsiella pneumoniae, and Escherichia coli had a high resistance rate to penicillins and third-generation cephalosporins. CONCLUSIONS: The incidence of neonatal sepsis is high, and the main pathogen is CoNS. The pathogens of neonatal sepsis have a high resistance rate to penicillins and third-generation cephalosporins. It is recommended to enhance the prevention and control of neonatal infection, strengthen the surveillance of pathogens, and further standardize the rational use of antibiotics.

[Correlation of Lipin gene expression with hepatic fat content in rats with intrauterine growth retardation]. / LipinåŸºå› è¡¨è¾¾ä¸Žå®«å† å‘è‚²è¿Ÿç¼“å¤§é¼ è‚è„è„‚è‚ªå«é‡çš„ç›¸å ³æ€§ç ”ç©¶.

OBJECTIVES: To study the correlation of the expression of Lipin1 in visceral adipose tissue and Lipin2 in liver tissue with hepatic fat content in rats with intrauterine growth retardation (IUGR). METHODS: Pregnant rats were given a low-protein (10% protein) diet during pregnancy to establish a model of IUGR in neonatal rats. The pregnant rats in the control group were given a normal-protein (21% protein) diet during pregnancy. The neonatal rats were weighed and liver tissue was collected on day 1 and at weeks 3, 8, and 12 after birth, and visceral adipose tissue was collected at weeks 3, 8, and 12 after birth. The 3.0T 1H-magnetic resonance spectroscopy was used to measure hepatic fat content at weeks 3, 8, and 12 after birth. Real-time PCR was used to measure mRNA expression levels of Lipin2 in liver tissue and Lipin1 in visceral adipose tissue. Western blot was used to measure protein levels of Lipin2 in liver tissue and Lipin1 in visceral adipose tissue. A Pearson correlation analysis was performed to investigate the correlation of mRNA and protein expression of Lipin with hepatic fat content. RESULTS: The IUGR group had significantly higher mRNA and protein expression levels of Lipin1 in visceral adipose tissue than the control group at weeks 3, 8, and 12 after birth (P<0.05). Compared with the control group, the IUGR group had significantly lower mRNA and protein expression levels of Lipin2 in liver tissue on day 1 after birth and significantly higher mRNA and protein expression levels of Lipin2 at weeks 1, 3, 8, and 12 after birth (P<0.05). At week 3 after birth, there was no significant difference in hepatic fat content between the IUGR and control groups (P>0.05), while at weeks 8 and 12 after birth, the IUGR group had a significantly higher hepatic fat content than the control group (P<0.05). The protein and mRNA expression levels of Lipin1 were positively correlated with hepatic fat content (r=0.628 and 0.521 respectively; P<0.05), and the protein and mRNA expression levels of Lipin2 were also positively correlated with hepatic fat content (r=0.601 and 0.524 respectively; P<0.05). CONCLUSIONS: Upregulation of the mRNA and protein expression levels of Lipin1 in visceral adipose tissue and Lipin2 in liver tissue can increase hepatic fat content in rats with IUGR and may be associated with obesity in adulthood.

Therapeutic advances in overcoming intrauterine growth restriction induced metabolic syndrome.

Intrauterine growth restriction (IUGR) remains a great public health challenge as it affects neonatal survival and influences their normal biological development and metabolism. Several clinical researches have revealed the occurrence of metabolic syndrome, such as insulin resistance, obesity, type 2 diabetes mellitus, oxidative stress, dyslipidemia, as direct results of IUGR. Therefore, it is essential to understand its underlying mechanism, impact and develop effective therapies. The purpose of this work is to review the current knowledge on IUGR induced metabolic syndrome and relevant therapies. Here in, we elaborate on the characteristics and causes of IUGR by pointing out recent research findings. Furthermore, we discuss the impact of IUGR on different organs of the body, followed by preclinical studies on IUGR using suitable animal models. Additionally, various metabolic disorders with their genetic implications, such as insulin resistance, type 2 diabetes mellitus, dyslipidemia, obesity are detailed. Finally, the current therapeutic options used in the treatment of IUGR are summarized with some prospective therapies highlighted.

Etiology, antimicrobial resistance, and risk factors of neonatal sepsis in China: a systematic review and meta-analysis from data of 30 years.

OBJECTIVE: To evaluate the regional etiology, antimicrobial resistance (AMR) pattern, and risk factors in neonates with sepsis in China. METHODS: We performed a systematic review and meta-analysis by searching Medline, Embase, Scopus, and Web of Science in December 2020. Studies of neonatal sepsis from China published between 2011 and 2020 were included. We pooled the proportion of pathogens and calculated the odds ratios of risk factors with 95% CIs using a random-effects model. RESULTS: We included 29 studies of 164,750 neonates with sepsis. The studies comprise data from 1990 to 2019. Coagulase-negative staphylococci (CoNS), Escherichia coli and Klebsiella spp accounted for 33% (95% CI 24-43), 17% (13-20), and 14% (11-17), respectively. Group B streptococcus (GBS) was the predominant isolate in early-onset sepsis (EOS) (21%, 95% CI 10-31), while the proportion of CoNS was the largest in late-onset sepsis (LOS) (32%, 95% CI 22-43). Resistance of CoNS to penicillin was found in 95% (95% CI 92-98) of 511 cases and Klebsiella spp to ampicillin in 95% (95% CI 90-99) of 364 cases. Maternal underlying diseases (2.61, 95% CI 1.48-4.61), mechanical ventilation (2.41, 1.37-4.23), central venous catheter placement (2.74, 1.77-4.26), peripherally inserted central catheter (PICC) placement (4.26, 2.80-6.49), multiple antibiotic uses (5.35, 1.85-15.43) and total parenteral nutrition (7.96, 2.04-31.02) were risk factors of neonatal sepsis. CONCLUSION: CoNS, E. coli, and Klebsiella spp were the predominant pathogens in neonatal sepsis in China. AMR was still a significant issue in NICUs. Total parenteral nutrition, multiple antibiotic uses, and PICC placement were the most relevant risk factors.

Application of Electrocardiogram Localization during Peripherally Inserted Central Catheter Line Insertion into the Persistent Left Superior Vena Cava of Neonates.

BACKGROUND: Most neonates with persistent left superior vena cava (PLSVC) have no clinical symptoms or hemodynamic changes, and this anomaly is only found during cardiac catheterization, pacemaker implantation, or central venous catheterization. Electrocardiogram (ECG) localization is helpful for the application of the peripherally inserted central catheter (PICC) technique in neonates with PLSVC. OBJECTIVE: To explore the characteristic waveforms of the P wave when a PICC under ECG localization is applied in neonates with PLSVC. STUDY DESIGN: The observation and management strategies for the P wave changes during catheter insertion (CI) of two neonates with PLSVC admitted to our institution between January and July 2020, who underwent PICC line insertion, were summarized. RESULTS: The characteristic P wave changes in two children with a PICC line inserted via the PLSVC were observed. When a wide inverted P wave appeared on ECG, the catheter was immediately withdrawn by 0.5 cm, a bidirectional P wave gradually appeared and then disappeared. After that, the catheter was further withdrawn by 0.5 cm. After catheterization, the optimal position of the PICC was confirmed by X-ray photography and bedside B-ultrasound. The PICC line was removed as scheduled after indwelling for 18 and 29 days, respectively, in the two cases, and no PICC-related complications occurred during indwelling. CONCLUSION: The characteristic P wave changes on ECG during CI provide important clinical reference values for the application of the PICC technique under ECG localization in neonates with PLSVC. KEY POINTS: · Electrocardiogram localization.. · Peripherally inserted central catheter.. · Persistent left superior vena cava..

The timing of withdrawal from caffeine citrate in very preterm infants. / æžæ—©æ—©äº§å„¿æž¸æ©¼é ¸å’–å•¡å› åœç”¨æ—¶æœºçš„ä¸´åºŠç ”ç©¶.

OBJECTIVES: To study the clinical features and outcome of very preterm infants withdrawn from caffeine citrate at different time points. METHODS: A retrospective analysis was performed on the medical data of the preterm infants with a gestational age of <32 weeks, who were hospitalized in the Division of Neonatology, the Second Xiangya Hospital of Central South University, from January 1, 2016 to November 30, 2020. According to the time of withdrawal from caffeine citrate, the infants who met the study criteria were divided into the group with withdrawal before the last week of hospitalization and the group with withdrawal within the last week of hospitalization. The two groups were compared in terms of clinical features, features of citric caffeine use, length of hospital stay and hospital costs, change in the intensity of respiratory support, and preterm complications. RESULTS: A total of 403 preterm infants were enrolled, with 285 infants in the group with withdrawal before the last week of hospitalization and 118 infants in the group with withdrawal within the last week of hospitalization. There were no significant differences in clinical features between the two groups (P>0.05). Compared with the group with withdrawal before the last week of hospitalization, the group with withdrawal within the last week of hospitalization had a significantly longer duration of the use of caffeine citrate, a significantly shorter length of hospital stay, a significantly lower rate of increased intensity of respiratory support after withdrawal, and a significantly lower incidence rate of moderate or severe bronchopulmonary dysplasia (P<0.05). CONCLUSIONS: A relatively long course of caffeine citrate treatment is more beneficial to the short-term clinical outcome of very preterm infants.

Plasma levels of amino acids and derivatives in retinopathy of prematurity.

Background: Retinopathy of prematurity (ROP) is a retinal disease that causes blindness in premature infants. This study aimed to reveal the changes in amino acids and derivatives in the plasma of ROP patients compared with premature infants without ROP. Methods: Metabolomics targeting amino acids and their derivatives was conducted to assess their plasma levels in ROP patients (n=58) and premature infants without ROP (n=25), and KEGG pathway analysis was used to identify the involved pathways. Results: Among the 31 assessed metabolites, the levels of 4 amino acids were significantly altered in the ROP group. Creatinine was downregulated in the plasma of the ROP patients, while the levels of citrulline, arginine, and aminoadipic acid were upregulated in the ROP group. Significant correlations were identified between the ROP stage and plasma levels of citrulline, creatinine, and aminoadipic acid. The involved pathways included biosynthesis of amino acids, arginine and proline metabolism, and arginine biosynthesis. Conclusion: The plasma levels of citrulline, creatinine, arginine, and aminoadipic acid were significantly changed in ROP patients. These metabolites could be considered potential biomarkers of ROP, and their related metabolic pathways might be involved in ROP pathogenesis.

[Risk factors for metabolic bone disease of prematurity in very/extremely low birth weight infants: a multicenter investigation in China].

OBJECTIVE: To investigate the incidence rate and risk factors for metabolic bone disease of prematurity (MBDP) in very low birth weight/extremely low birth weight (VLBW/ELBW) infants. METHODS: The medical data of 61 786 neonates from multiple centers of China between September 1, 2013 and August 31, 2016 were retrospectively investigated, including 504 VLBW/ELBW preterm infants who met the inclusion criteria. Among the 504 infants, 108 infants diagnosed with MBDP were enrolled as the MBDP group and the remaining 396 infants were enrolled as the non-MBDP group. The two groups were compared in terms of general information of mothers and preterm infants, major diseases during hospitalization, nutritional support strategies, and other treatment conditions. The multivariate logistic regression analysis was used to investigate the risk factors for MBDP. RESULTS: The incidence rate of MBDP was 19.4% (88/452) in VLBW preterm infants and 38.5% (20/52) in ELBW preterm infants. The incidence rate of MBDP was 21.7% in preterm infants with a gestational age of < 32 weeks and 45.5% in those with a gestational age of < 28 weeks. The univariate analysis showed that compared with the non-MBDP group, the MBDP group had significantly lower gestational age and birth weight, a significantly longer length of hospital stay, and a significantly higher incidence rate of extrauterine growth retardation (P < 0.05). Compared with the non-MBDP group, the MBDP group had significantly higher incidence rates of neonatal sepsis, anemia, hypocalcemia, and retinopathy of prematurity (P < 0.05). The MBDP group had a significantly lower mean feeding speed, a significantly higher age when reaching total enteral feeding, and a significantly longer duration of parenteral nutrition (P < 0.05). The use rate of caffeine citrate in the MBDP group was significantly higher, but the use rate of erythropoietin was significantly lower than that in the non-MBDP group (P < 0.05). The multivariate logistic regression analysis showed that gestational age < 32 weeks, hypocalcemia, extrauterine growth retardation at discharge, and neonatal sepsis were risk factors for MBDP (P < 0.05). CONCLUSIONS: A lower gestational age, hypocalcemia, extrauterine growth retardation at discharge, and neonatal sepsis may be associated an increased risk of MBDP in VLBW/ELBW preterm infants. It is necessary to strengthen perinatal healthcare, avoid premature delivery, improve the awareness of the prevention and treatment of MBDP among neonatal pediatricians, and adopt positive and reasonable nutrition strategies and comprehensive management measures for preterm infants.

Association of vitamin D status at birth with pulmonary disease morbidity in very preterm infants.

OBJECTIVE: We aimed to assess whether serum 25-hydroxyvitamin D (25(OH)D) levels at birth are associated with pulmonary disease morbidities in very preterm infants. METHODS: This prospective cohort analysis included 93 infants born before 32 weeks of gestation in the Second Xiangya Hospital of Central South University between March 2016 and February 2017. Participants were classified into three groups according to their 25(OH)D levels at birth. The groups were compared in terms of demographic variables and pulmonary disease morbidities. RESULTS: The mean serum 25(OH)D level at birth was 35.7 ± 19.1 nmol/L, and 38 (40.9%), 31 (33.3%), and 24 (25.8%) infants had 25(OH)D levels of less than 25 nmol/L, 25-50 nmol/L, and more than or equal to 50 nmol/L, respectively. There was a statistically significant difference in neonatal respiratory distress syndrome (RDS) rates among the three groups (43.6% vs. 35.9% vs. 20.5%, p = .029). The rates of bronchopulmonary dysplasia, apnea, respiratory failure, persistent pulmonary hypertension, and pulmonary hemorrhage did not differ significantly among the groups. Logistic analysis, adjusted for gestational age and birth weight, showed that a low serum 25(OH)D level (<50 nmol/L) was a risk factor for RDS (odds ratio, 0.195; p = .017). CONCLUSION: There was a high prevalence of low 25(OH)D levels (<50 nmol/L) and an association between vitamin D status and RDS in very preterm infants. However, more research on this association is required.

Effect of Folic Acid Supplementation on Renal Phenotype and Epigenotype in Early Weanling Intrauterine Growth Retarded Rats.

BACKGROUND/AIMS: The objective of this study was to examine the responses of p53 promoter methylation involved in kidney structure and function of early weaning intrauterine growth retarded (IUGR) rats to dietary folic acid supplementation. METHOD: Sprague-Dawley rats were fed isocaloric diets containing either 21% protein diet (normal feed) or 10% protein diet throughout pregnancy and normal feed during lactation. After weaning, Offspring were then fed onto normal feed and normal feed supplemented with 5 mg folic acid / kg feed for a month, this produced 4 dietary groups (maternal diet/ weanling diet): Con, Folic, IUGR and IUGR+Folic. Renal function, renal structure, p53 promoter methylation and protein expression of offspring rats were measured at postnatal 2 months and 3 months. RESULTS: Glomerular volume, blood urea nitrogen, 24 hours urine protein were significantly elevated in IUGR rats compared with Con rats but were decreased by dietary folic acid supplementation. p53 protein expression in IUGR rats were significantly higher than that in Con rats, and p53 promoter methylation status in IUGR rats was reduced significantly compared with Con rats. However, the changes in p53 gene expression and DNA methylation status of IUGR rats were reversed by dietary folic acid supplementation. CONCLUSIONS: Our study showed for the first time that folic acid supplementation during early period of life could reverse the abnormality in renal p53 methylation status and protein expression, glomerular volume and renal function of IUGR rats offspring.

Dynamic p53 protein expression and phosphorylation in the kidneys of rats that experienced intrauterine growth restriction.

AIM: This study investigated the mechanisms involved in intrauterine growth restriction (IUGR). METHODS: The IUGR model was established by feeding pregnant SD rats a low-protein diet. Protein expression and phosphorylation were detected using Western blot and/or immunohistochemistry. Cell apoptosis was detected by TUNEL staining. The MDM2 mRNA expression was measured by real-time PCR. RESULTS: Pups from the IUGR group had significantly lower body (7th day, 2 months) and kidney weights (1st day, 7th day, 2 months) compared to pups from the control group (p < 0.01). The glomeruli number in IUGR pups was significantly less than that in the control pups at 2 and 3 months after birth (p < 0.01). p53 protein level and p53 phosphorylation at Ser(15) were time-dependently decreased in the kidney at 1st day, 7th day, 21st day, 2 months and 3 months, but their levels in the kidney of the IUGR pups was significantly higher than that in control pups at each time point (p < 0.05, p < 0.01, or p < 0.001). Significantly more positive p21 staining was observed in IUGR pups than in control pups at each time point. Real-time PCR of MDM2 mRNA expression showed no significant difference between IUGR and control pups (p > 0.05). Significant apoptosis was observed in the kidneys of IUGR pups compared to control pups. CONCLUSION: Malnutrition-induced IUGR may be associated with the activation of p53-p21 signaling in the kidney.

Apoptosis in the kidneys of rats that experienced intrauterine growth restriction.

AIM: Intrauterine growth retardation (IUGR) can affect kidney development, leading to reduction in glomerular number. However, the associated cellular and molecular mechanisms have not been fully elucidated. This study investigated cell apoptosis and Bcl-2 and Bax expression in the kidney of IUGR pups. METHODS: The IUGR model was established in pregnant rats with 10% low-protein diet. Renal cell apoptosis was detected using TUNEL staining. Ki67 protein expression was measured by immunohistochemistry. Bcl-2 and Bax mRNA expression was measured by real-time polymerase chain reaction (PCR). RESULTS: Significant decreases in the number of glomeruli was observed in the kidney of IUGR pups 2 and 3 months after birth (P < 0.01). Obvious apoptosis was observed in the kidney in both groups 1 d, 7 d, and 21 d after birth with a peak at 7 d. Significantly higher apoptosis index was observed in the kidney of IUGR pups compared to control pups (P < 0.01). No significant difference in proliferation was observed between the two groups. Significantly lower Bcl-2 mRNA expression, Bcl-2/Bax ratio, and higher Bax mRNA expression were observed in IUGR pups compared to control pups after birth (P < 0.01). CONCLUSION: The reduction in glomerular number in IUGR pups is associated with increase in renal cell apoptosis. The reduction in Bcl-2/Bax ratio may play a crucial role in renal cell apoptosis in IUGR pups.

[Ganciclovir therapy for congenital cytomegalovirus infection in newborn infants: a meta analysis].

OBJECTIVE: To evaluate the efficacy and safety of ganciclovir therapy for congenital cytomegalovirus (CMV) infection in newborn infants. METHODS: The randomized controlled trials (RCTs) and quasi-RCTs on ganciclovir therapy for congenital CMV were reviewed in the following electronic databases: PubMed (January 1988 to January 2009), EMbase (January 1988 to January 2009), the Cochrane library (Issue 3, 2003 and Issue 1, 2009), the Chinese Journals Full-text Database (January 1994 to January 2009), the Chinese Biological Medical Disc (January 1994 to January 2009) and the Chinese Medical Current Contents (January 1994 to January 2009). Quality assessment, data extraction, and meta analysis were performed. RESULTS: Ten papers were included. Meta analysis showed that the ganciclovir therapy increased the improvement rate (91.4% vs 34.0%; p<0.01) and led CMV infection indexes to become negative in more patients (87.6% vs 15.3%; p<0.01) and decreased incidence of hearing disturbance (4.7% vs 37.2%; p<0.01) as compared with the non-ganciclovir therapy control group. The incidence of the ganciclovir-therapy-related side effects was low. CONCLUSIONS: Ganciclovir treatment may increase the improvement rate and the rate of CMV infection indexes becoming negative, and decrease incidence of hearing disturbance, with few side effects, in newborn infants with CMV infection. However the supporting evidence is not strong due to few trials and more high-quality research is needed.

[Comparison of therapeutic effect of different doses of ganciclovir for neonatal congenital cytomegalovirus infection].

OBJECTIVE: Ganciclovir is a first-line drug for treatment of cytomegalovirus (CMV) infection. However, some ganciclovir treatment-related side-effects can be found. This study aimed to compare the efficacy and side effects of relatively low and high doses of ganciclovir in the treatment of neonatal congenital CMV infection. METHODS: One hundred and sixty-seven neonates with congenital CMV infection were randomly assigned to high-dose (n=79) and low-dose ganciclovir groups (n=88). The high-dose ganciclovir group was injected with ganciclovir of 7.5 mg/kg in the inducement phase and of 10 mg/kg in the maintaining phase. The low-dose ganciclovir group was injected with ganciclovir of 5 mg/kg in the inducement and the maintaining phases. The efficacy and side effects were observed in the two groups. RESULTS: After treatment the clinical symptoms and signs were obviously improved in both groups. CMV-IgM became negative in 93.8% of neonates in the high-dose ganciclovir group and 93.1% of neonates in the low-dose ganciclovir group (P>0.05). CMV-DNA became negative in 80.8% of neonates in the high-dose ganciclovir group and in 86.7% in the low-dose ganciclovir group (P>0.05). The low-dose ganciclovir group had lower incidence of side effects than the high-dose ganciclovir group: vomiting 2.3% vs 11.4%; anemia 8.0% vs 20.3%; reduction of neutrophilic granulocytes 5.7% vs 16.5%; increase in platelet count 8.0% vs 18.9% (P<0.05). CONCLUSIONS: Low-dose ganciclovir has the same clinical efficacy to high-dose ganciclovir for treatment of neonatal congenital CMV infection, but fewer side effects occur in the low-dose group.