Generally, small for gestational age(SGA) infants will catch up with growth after birth, but some SGAs fail to show enough catch-up growth, leading to physical growth backwardness, and the risk of metabolic diseases in adult offspring increases. The application of exogenous growth hormone replacement therapy can ensure and promote the occurrence of SGA catching up with growth. However, as growth hormone exerts therapeutic effects in related clinical diseases, clinical attention is gradually being paid to whether growth hormone may bring long-term risks. This article aims to review the efficacy and potential risks of growth hormone treatment for SGA.

Bacterial endotoxin is considered as one of the critical risk factors in medical devices, especially implanted devices that directly or indirectly contact with blood circulating system. In that case, endotoxin limits for implanted medical devices is important in determine the safety of medical devices. According to GB/T 14233.2-2005, the requirements of endotoxin index for intrathoracic medical devices is 2.15 EU per device. However, the definition of "intrathoracic medical devices" is vague. Specifically, "for cardiovascular system application" instead of "intrathoracic application" is more reasonable. With the deeper understanding of the risk of endotoxin in medical devices and considering the internationally accepted standards, the limits of endotoxin in medical devices for cardiovascular system application is acceptable at 20 EU per device.
Endotoxins

OBJECTIVETo assess the value of pre-gestational deafness-related mutation screening for the prevention and intervention of congenital deafness.

METHODSIn this study, 2168 couples with normal hearing were screened for common mutations associated with congenital deafness using real-time fluorescence quantitative PCR. The mutations have included GJB2 c.235delC and c.299_300delAT, SLC26A4 c.2168A>G and c.IVS7-2A>G, and mtDNA 12SrRNA c.1494C>T and c.1555A>G. For couples who have both carried heterozygous mutations of the same gene, genetic counseling and prenatal diagnosis were provided.

RESULTSAmong of the 4 336 individuals, 178 (4.06%) were found to carry a mutation. Mutation rate for c.235delC and c.299_300delAT of GJB2 gene, c.IVS7-2 A>G and c.2168 A>G of SLC26A4 gene, c.1555 A>G and c.1494 C>T of DNA 12S rRNA gene were 0.91%, 0.20%, 0.68%, 0.11%, 0.1% and 0.01%, respectively. For six couples who have both carried mutations of the same gene, all fetuses showed a normal karyotype, while DNA sequencing indicated that two fetuses have carried homozygous c.235delC mutation of the GJB2 gene, one carried a heterozygous c.235delC mutation of the GJB2 gene, one carried heterozygous mutation of GJB2 gene (c.299_300delAT), and two have carried a heterozygous mutation of c.IVS7-2A>G of the SLC26A4 gene.

CONCLUSIONPre-gestational screening for deafness gene mutation can facilitate avoidance the birth of affected children and has a great clinical value for the prevention and intervention of birth defect.

Connexins ; genetics ; Deafness ; congenital ; genetics ; prevention & control ; Female ; Humans ; Mutation ; Pregnancy ; Prenatal Diagnosis

OBJECTIVE:To study the in vitro antioxidant activity of chitosan(CTS)degradation derivatives and its preventive effects on drug-induced liver injury fibosis. METHODS:Acid hydrolysis method was used to prepare the CTS degradation deriva-tives CTS-3,CTS-6,CTS-8,CTS-10 for different hydrolysis time(3,6,8,10 h). The viscosity-average relative molecular mass and deacetylation degree of CTS and its degradation derivatives were determined,and its antioxidant activity was evaluated by de-tecting its in vitro scavenging ability on 1,1-diphenyl-2-trinitrophenylhydrazine (DPPH) and superoxide anion (O2-) radicals. Us-ing CTS-10 for in vivo liver injury fibosis prevention test,mice were randomly divided into normal control group(water),model group(water),CTS-10 high-dose,medium-dose,low-dose groups(100,50,25 mg/mL),8 in each group. Mice were intragastri-cally administrated 0.2 mL,then withdrawal after continuous 24 d. Then levofloxacin hydrochloride was intragastrically given for 7 d to establish drug-induced liver injury model(except for normal control group). Western blot method was used to detect the expres-sions of tumor necrosis factor α(TNF-α),transforming growth factor β1(TGF-β1)and Decorin protein in liver tissue of mice. RE-SULTS:The viscosity-average relative molecular mass of CTS,CTS-3,CTS-6,CTS-8,CTS-10 were 21.70×104,6.70×104,6.30× 104,5.01×104,4.87×104;and deacetylation degree were 83.44％,74.62％,67.28％,64.83％,54.23％,respectively. All of them had certain scavenging ability on DPPH and O2-,in which,CTS-10 was the strongest(25.47％ and 56.31％). Compared with nor-mal control group,expressions of TNF-α,TGF-β1 and Decorin protein in liver tissue in model group were enhanced (P<0.05). Compared with model group,expressions of TNF-α,TGF-β1 and Decorin protein in liver tissue in CTS-10 medium-dose and high-dose groups were weakened(P<0.01). CONCLUSIONS:The viscosity-average relative molecular mass and deacetylation de-gree of CTS-10 in CTS degradation derivatives are lower with stronger antioxidant activity,and show certain preventive effects on drug-induced liver injury fibosis in mice.

Objective To investigate the roles of phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway and its regulatory protein peroxisome proliferator-activated receptor γ (PPAR γ) and phosphatase and tension homologue deleted on chromosome 10 (PTEN) in regulating insulin sensitivity in rats with fetal growth restriction (FGR).Methods Sixteen pregnant rats were randomly divided into two groups including FGR and control groups on the 12th day of pregnancy (eight in each group).The FGR group was given low protein diet (8％ of casein) and restriction diet to establish the neonatal rat model of FGR.All maternal rats after delivery and newborn rats after weaning on 21 days after born were fed with normal diet.Each time blood samples were collected from eight newborn rats of each group to measure levels of fasting plasma glucose (FPG) and fasting insulin(FINS) at the time points of 21 days,two and four months after birth.Then insulin resistance index (IRI) and insulin sensitivity index (ISI) were calculated to evaluate insulin sensitivity.Expression of PI3K,AKT,PPAR γγ,PTEN and glucose transporters 4 (GLUT4) in skeletal muscle at mRNA and protein levels were measured at 21 days,two and four months after birth with real time fluorescence polymerase chain reaction and Western blot,respectively.Relationships between the expression of key molecules of PI3K/AKT signaling pathway and insulin sensitivity were analyzed.T-test,and Pearson's correlation analysis were used for statistical analysis.Results (1) The average birth weight of newborn rats in the FGR group was lower than that of the control group [(4.37± 0.69) vs (7.03±0.55) g,t=-20.75,P＜0.05].The incidence of FGR in the FGR group was 93.33％ (70/75).(2) Compared with normal offspring,those in the FGR group showed significantly increased FPG [two months after birth:(5.53± 0.58) vs (7.49 ± 0.38) mmol/L,t=8.08;four months afterbirth:(6.35±0.66) vs (8.94±0.90) mmol/L,t=6.58],FINS [two months afterbirth:(9.18±0.66) vs (14.67± 1.90) mU/L,t=7.71;four months after birth:(33.08±2.76) vs (56.33±2.81) mU/L,t=16.71] and IR1 (two months after birth:2.25±0.31 vs 4.90±0.81,t=8.63;four months after birth:9.30±0.90 vs 22.44±3.10,t=1 1.51),but decreased ISI (two months after birth:0.020 ± 0.002 vs 0.009± 0.001,t=-10.1 4;four months after birth:0.005±0.000 vs 0.002 ±0.000,t=-14.91) at two and four months after birth (all P＜0.05).(3) Compared with normal offspring,those in the FGR group showed decreased expression of PI3K (21 days after birth:0.082±0.028 vs 0.019±0.004,t=-6.29;two months after birth:0.020±0.003 vs 0.010±0.005,t=-4.78;four months after birth:0.014±0.004 vs 0.003±0.001,t=-7.87) and GLUT4 (21 days after birth:0.132±0.057 vs 0.041 ±0.019,t=-4.32;two months after birth:0.183±0.084 vs 0.069±0.017,t=-3.74;four months after birth:0.248±0.069 vs 0.113±0.040,t=-4.74) at mRNA level at 21 days,two and four months after birth (all P＜0.05).Compared with normal offspring,decreased expression of PPAR γ (two months after birth:0.028±0.002 vs 0.012±0.005,t=-3.70;four months after birth:0.030±0.008 vs 0.012±0.005,t=-3.80) and increased expression of PTEN (two months after birth:0.020±0.004 vs 0.045±0.014,t=5.09;four months after birth:0.023±0.007 vs 0.034±0.009,t=2.57) at mRNA level were observed in offspring of the FGR group at two and four months after birth (all P＜0.05).(4) Compared with normal offspring,expression of PI3K protein (21 days after birth:0.22±0.01 vs 0.17±0.02,t=-6.62;two months after birth:0.27±0.03 vs 0.16±0.02,t=-7.25;four months after birth:0.18±0.01 vs 0.09±0.02,t=-9.79) and GLUT4 protein (21 days after birth:0.21 ±0.01 vs 0.03±0.01,t=-27.29;two months after birth:0.10±0.01 vs 0.06t±0.01,t=-3.90;four months after birth:0.13 ±0.01 vs 0.08± 0.02,t=-8.10) decreased in offspring in the FGR group at 21 days,two and four months after birth (all P＜0.05).Compared with normal offspring,those in the FGR group showed decreased expression of PPAR γ protein (two months after birth:0.10 ± 0.01 vs 0.07± 0.01,t =-7.29;four months after birth:0.09±0.01 vs 0.08±0.01,t=-2.83),but increased expression of PTEN at protein level (two months after birth:0.10±0.01 vs 0.15±0.02,t=6.01;four months after birth:0.09±±0.01 vs 0.13±0.02,t=5.51) at two and four months after birth (all P＜0.05).(5) The IRI levels in offsprings in the FGR group were negatively correlated with the expression of PI3K,GLUT4 and PPAR γ at protein level (two months after birth:r=-0.90,-0.92 and-0.79;four months after birth:r=-0.92,-0.75 and-0.73,all P＜0.05),but positively correlated with the expression of PTEN at protein level (r=0.87 and 0.86,both P＜0.05) at two and four months after birth.Conclusions The abnormal expression of the key molecules of PI3K/AKT signaling pathway precedes the decrease of insulin sensitivity in newborn rats with FGR and the expression regulatory protein PPAR γ and PTEN are also changed,suggesting that these molecules may induce the impairment of insulin sensitivity in rats with FGR and be involved in the development of insulin resistance.

Objective To investigate the relationship between the expression of imprinted gene CDKN1C in placenta and the birth weight of neonates.Methods Twenty-nine term small for gestational age (SGA) neonates admitted to Peking University Third Hospital from January 1,2014 to December 31,2014 were recruited,and 29 appropriate for gestational age (AGA) neonates with a difference of not more than one week in gestational age served as controls.Fresh placental tissue was collected and the expression of imprinted gene CDKN1C mRNA in the placenta were detected by real-time fluorescence quantitative-polymerase chain reaction,and its protein expression was estimated by Western-blot.Chi-square test,independent-sample t test,Pearson's correlation analysis were used for statistical analysis.Results The CDKN1C mRNA expression level in SGA was significantly higher than that in AGA (0.133± 0.059 vs 0.100±0.046,t=2.401,P=0.020),so was the CDKN1C protein expression (0.280±0.043 vs 0.190±0.041,t=8.410,P=0.000).The CDKN1C mRNA expression levels were negatively correlated with birth weight in both groups (SGA group,r=-0.587,P=0.001;AGA group,r=-0.569,P=0.001),and the correlation was slightly stronger in SGA (r2=0.344) than in AGA (r2=0.324).The CDKN1C protein expression levels of the two groups were negatively correlated with birth weight (SGA group,r=-0.579,P=0.001;AGA group,r=-0.497,P=0.006),the correlation being stronger in SGA group (r2=0.335) than in AGA group (r2=0.247).The CDKN1C mRNA and protein expression levels of the two groups were negatively correlated with birth weight for gender,especially in males [mRNA:r2=0.293(male)vs r2=0.185(female);protein:r2=0.730 (male) vs r2=0.601(female)].Neither CDKN1C mRNA nor protein expression level was correlated to the placenta weight (mRNA:SGA group,r=0.119,P=0.540;AGA group,r=-0.069,P=0.722;protein:SGA group,r=0.126,P=0.515;AGA group,r=-0.247,P=0.196).Conclusions The expressions of CDKN1C mRNA and protein may be related to birth weight of term SGA neonates,especially in male infants.

ObjectiveTo investigate the effects of the asphyxia as a Second Hit on renal function during early stage after birth in small for gestational age (SGA) infants.MethodsThe infants who were hospitalized within 24 hours after birth in Peking University Third Hospital between January 2013 and March 2015 were retrospectively enrolled, and divided into different groups depending on gestational age and asphyxia history. There were 40 preterm non-asphyxia SGA infants and 80 controls who were preterm non-asphyxia appropriate for gestational age (AGA) infants; 11 preterm asphyxia SGA infants and an equal number of preterm asphyxia AGA infants as controls; 33 term non-asphyxia SGA infants and 33 term non-asphyxia AGA infants as controls; and four term asphyxia SGA infants and 13 term asphyxia AGA infants as controls. Blood urea nitrogen (BUN), serum creatinine (SCr), and estimate glomerular filtration rate (eGFR) were tested within 48 h after admission and the incidence of abnormal indexes was compared between groups byt-test and Fisher exact test.Results(1) Compared with preterm non-asphyxia AGA group, BUN level significantly decreased in preterm non-asphyxia SGA group [(3.99±1.69) vs (5.11±2.08) mmol/L,t=2.948, P=0.004]. Compared with term non-asphyxia AGA group, term non-asphyxia SGA group had higher SCr level [(72.03±10.29) vs (62.58±12.27)μmol/L,t=3.390,P=0.001] and lower eGFR level [(25.19±4.07) vs (33.99±8.75) ml/(min·1.73 m2),t=5.238,P=0.000]. (2) Compared with preterm non-asphyxia AGA infants, preterm asphyxia AGA infants had higher BUN [(6.96±3.09) vs (5.11±2.08) mmol/L,t=2.602,P=0.011] and SCr [(76.45±10.11) vs (66.70±13.18)μmol/L,t=2.357,P=0.021] and lower eGFR level [(15.86±2.31) vs (19.54±5.08) ml/(min·1.73 m2),t=2.361,P=0.020]. Compared with preterm non-asphyxia SGA group, there was a significant increase in BUN level [(6.70±3.37) vs (3.99±1.69) mmol/L,t=2.581,P=0.025] and decrease in eGFR level [(14.80±4.67) vs (18.66±5.03) ml/(min·1.73 m2),t=2.285,P=0.027] in preterm asphyxia SGA group. Changes in term infants were similar to preterm infants. (3) Compared with asphyxia AGA group, asphyxia SGA group showed a higher frequency of abnormal eGFR in term infants (4/4 vs 4/13, Fisher exact test,P=0.029). ConclusionsAsphyxia as a probable Second Hit can influence the renal function during early stage in both preterm and term infants, especially in SGA infants.

OBJECTIVETo evaluate the efficacy of combined newborn hearing screening and deafness-related mutation screening.

METHODSEleven thousand and forty-six newborn babies were screened with otoacoustic emission, automatic auditory brainstem response and genetic testing using a standard protocol. Common mutations of three deafness-related genes have included GJB2 (c.235delC, c.299-300delAT), mtDNA 12srRNA (c.1494C>T, c.1555A>G) and SLC26A4 (c.2168A>G, c.IVS7-2A>G).

RESULTSThe detection rate for hearing loss in the first-step screening was 0.81% (90/11,046). 513 individuals were found to carry one or two mutant alleles, which gave a carrier rate of 4.64% (513/11,046). Five hundred and eighty-four newborns were positive for hearing screening and genetic screening. Among these, 19 have failed both tests, 71 have failed hearing screening, and 494 have failed genetic screening. The combined hearing and genetic screening has given a positive rate of 5.29%.

CONCLUSIONNeither hearing screening nor genetic screening is sufficient to identify individuals susceptible to auditory disorders. Combined used of these methods can improve the rate of detection.

Asian Continental Ancestry Group ; genetics ; China ; Connexin 26 ; Connexins ; genetics ; DNA Mutational Analysis ; DNA, Mitochondrial ; chemistry ; genetics ; Deafness ; diagnosis ; ethnology ; genetics ; Gene Frequency ; Genetic Predisposition to Disease ; ethnology ; genetics ; Genetic Testing ; methods ; Genotype ; Hearing ; genetics ; Hearing Tests ; Humans ; Infant, Newborn ; Membrane Transport Proteins ; genetics ; Mutation ; Neonatal Screening ; methods ; Polymerase Chain Reaction ; RNA, Ribosomal ; genetics ; Reproducibility of Results ; Sensitivity and Specificity

Objective To explore the effects of folic acid and vitamin B12 supplement in maternal lactation on insulin resistance in fetal growth restriction (FGR) in rat offspring.Methods Eighteen Sprague-Dawley female rats and male rats were used.Pregnant rats were randomly divided into two groups at 12 days:normal-protein group (NP,n=6) and low-protein group (LP,n=12).The were 84 FGR newborn pups in LP group (93.3％,84/90).Forty-eight FGR newborn pups were randomly selected and divided into two groups (24 in each group):intervention group and non-intervention group.The intervention group was fed with high folate and vitamin B12 in the diet;and non-intervention group and NP group were fed normal diet.All of the newborn pups were weaned at 21 days after birth and then fed with normal diet.At days 21,60 and 120 d after birth,eight pups were randomly selected from each group and fasting plasma glucose (FPG),fasting insulin (FINS),blood diglyceride (TG) and cholesterol (TC) were measured.The insulin resistance index (IRI) and insulin sensitivity index (ISI) were calculated to evaluate insulin sensitivity.Variance and Student-Newman-Keuls tests were used for statistical analysis.Results (1) The incidence of FGR:Birth weight of LP offspring [(4.44±0.58) g] was significantly lower than that of NP ones [(7.03±0.56) g] (t=15.75,P ＜ 0.05).(2) FPG and FINS:at day 21 after birth,FPG of the non-intervention group,intervention group and NP group was (4.8±0.3),(4.8±0.4) and (4.6±0.3) mmol/L (F=0.57),respectively;FINS was (4.2± 0.2),(4.5 ±0.4) and (4.3 ±0.1) mU/L (F=0.31),respectively;and there was no significant difference among the three groups (both P ＞ 0.05).At day 60,FPG of the three groups was (7.5±0.4),(6.9± 1.0) and (5.5±0.6) mmol/L (F=17.14);FINS was (14.7± 1.9),(10.7± 1.0) and (9.2± 0.7) mU/L (F=38.34),respectively.At day 120,FPG was (8.9±0.9),(8.0±0.8) and (6.4±0.7) mmol/L (F=21.60);FINS was (56.3±2.8),(38.2±2.5) and (33.1 ±2.8) mU/L (F=164.46).FPG and FINS were highest in the non-intervention group,and lowest in NP group,with significant differences among the three groups of pups (all P ＜ 0.05).(3) IRI and ISI:at day 21,IRI of the non-intervention group,intervention group and the control group was 0.9±0.1,0.9±0.1 and 0.9±0.2 (F=0.49);ISI was-(3.0±0.7),-(3.0±0.1) and-(3.0±0.3) (F=0.69);and there was no significant difference among the three groups (both P ＞ 0.05).At day 60,IRI of the three groups was 4.9±0.8,3.3±0.3 and 2.2±0.3 (F=49.48);ISI was-(4.7±0.2),-(4.3±0.1) and-(3.9±0.1) (F=63.47).At day 120,IRI of the three groups was 22.4±3.1,13.6±2.0 and 9.3±0.9 (F=75.15);ISI was -(6.2 ± 0.1),-(5.7 ± 0.1) and-(5.3 ± 0.1) (F=104.42);and there were significant differences among the three groups (all P ＜ 0.05).(4) TC and TG:at day 21,TC of the non-intervention group,intervention group and the control group was (2.0±0.1),(2.0±0.1) and (2.0±0.1) mmol/L (F=0.10);TG was (0.75±0.1),(0.77±0.1) and (0.74±0.1) mmol/L (F=0.33);and there was no significant difference among the three groups (both P ＞ 0.05).At day 60,TC of the three groups was (2.3 ± 0.1),(2.2 ± 0.1) and (2.0± 0.2) mmol/L (F=8.34);TG was (1.5 ± 0.2),(1.2±0.1) and (1.0±0.2) mmol/L (F=17.93).At day 120,TC was (2.4±0.2),(2.2±0.1) and (2.1 ±0.1) mmol/L (F=6.12);TG was (1.7±0.5),(1.2±0.3) and (l.0±0.1) mmol/L (F=9.80).The TC and TG were highest in the non-intervention group and the lowest in the control group;and there were significant differences among the three groups (all P ＜ 0.05).Conclusion Supplementing folic acid and vitamin B12 in maternal lactation can improve in some extent insulin resistance in FGR rats,but not sufficient enough to completely repair glucose and lipid metabolism.

Objective:To explore the hepatocyte insulin sensitivity of intrauterine growth retardation ( IUGR) rats and establish an insulin resistance cell model in vitro.Methods: An IUGR animal model was established by protein malnutrition during the mother pregnancy .On 60 d and 90 d after birth , the offspring rats were fasted for 12 hours and then their angular vein blood was collected to measure the fasting plasma glucose and fasting serum insulin level , then the insulin resistance index ( HOMA-IR) and insulin sensitivity index ( ISI) were calculated .The insulin sensitivity was evaluated by HOMA-IR and ISI.Primary hepatocytes from each group were respectively isolated by two-step perfusion with collage-nase and were defined as normal hepatocytes group and IUGR hepatocytes group .The normal hepatocyte group was divided into two groups: control group and insulin induction group .Insulin induction group was established by primary cultures of normal hepatocyte incubated with varying dilutions of insulin . CCK-8 was used to detect the viability of the cultured hepatocytes .Glucose oxidase-peroxidase method kit was used to measure glucose consumption of the hepatocytes .Results:HOMA-IR was significantly higher in IUGR rats than in the normal rats at the age of 60 days ( t=-17 .02 , P<0 .05 ) and 90 days ( t=-12.52, P<0.05).ISI was significantly lower than in the normal rats aged 60 days (t=5.61, P<0.05) and 90 days (t=12.42, P<0.05).There were no significant differences in hepatocyte viability among the control group , IUGR group and insulin induction group after incubation of 48 h on day 60 (F=1.34, P=0.29) and day 90 (F=0.22, P=0.81).The glucose consumption of the IUGR group and insulin induction group were significantly decreased compared with the control group on day 60 ( F=9.28, P=0.002) and day 90 (F=56.60, P<0.001), while there was no significant difference be-tween the IUGR group and insulin induction group (P=0.08, P=0.10).Conclusion:The insulin sen-sitivity of hepatocytes of IUGR rats decreased from adolescence to adulthood .High-dilution insulin may induce insulin resistance cell model in vitro.