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.

Objective::To build a reference fetal growth chart for the Chinese population based on fetal ultrasound measurements.Methods::This was a multicenter, population-based retrospective cohort study. Longitudinal ultrasound measurement data were collected from 24 hospitals in 18 provinces of China from 1 st September through 31 st October of 2019. The estimated fetal weight (EFW) was calculated based on head circumference, abdominal circumference, and femur length using Hadlock formula 3. Fetal growth curves were estimated using a two-level linear regression model with cubic splines. All participants were divided into two groups: the northern group ( n = 5829) and the southern group ( n = 3246) based on the geographical division of China and male fetus group ( n = 4775) and female fetus group ( n = 4300) based on fetal gender. The EFW was compared by fetal gender and geographical group. All statistical models were adjusted for maternal sociodemographic characteristics. Results::A total of 9075 participants with 31,700 ultrasound measurement records were included in this study. Male fetuses demonstrated significantly larger EFW compared to female ones starting at 16 weeks of gestation and extending to delivery (global test P < 0.01). The overall geographic difference in EFW was significant (global test P = 0.03), and week-specific comparisons showed that the northern group had a greater EFW starting at 15 weeks of gestation and extending to 29 weeks of gestation, although this difference did not extend to the time of delivery. The Z-score of EFW confirmed that our Chinese fetal growth charts differed from previously published standards. Conclusion::This study provides EFW and ultrasound biometric reference measurements for Chinese fetuses and reveals differences from other fetal growth charts. The chart is worth promoting in more regions of China but should be tested prudently before use.

Objective::To build a reference fetal growth chart for the Chinese population based on fetal ultrasound measurements.Methods::This was a multicenter, population-based retrospective cohort study. Longitudinal ultrasound measurement data were collected from 24 hospitals in 18 provinces of China from 1 st September through 31 st October of 2019. The estimated fetal weight (EFW) was calculated based on head circumference, abdominal circumference, and femur length using Hadlock formula 3. Fetal growth curves were estimated using a two-level linear regression model with cubic splines. All participants were divided into two groups: the northern group ( n = 5829) and the southern group ( n = 3246) based on the geographical division of China and male fetus group ( n = 4775) and female fetus group ( n = 4300) based on fetal gender. The EFW was compared by fetal gender and geographical group. All statistical models were adjusted for maternal sociodemographic characteristics. Results::A total of 9075 participants with 31,700 ultrasound measurement records were included in this study. Male fetuses demonstrated significantly larger EFW compared to female ones starting at 16 weeks of gestation and extending to delivery (global test P < 0.01). The overall geographic difference in EFW was significant (global test P = 0.03), and week-specific comparisons showed that the northern group had a greater EFW starting at 15 weeks of gestation and extending to 29 weeks of gestation, although this difference did not extend to the time of delivery. The Z-score of EFW confirmed that our Chinese fetal growth charts differed from previously published standards. Conclusion::This study provides EFW and ultrasound biometric reference measurements for Chinese fetuses and reveals differences from other fetal growth charts. The chart is worth promoting in more regions of China but should be tested prudently before use.

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

Copper bearing intrauterine device (Cu-IUD) is a widely used contraceptive method for women of childbearing age in China. It plays an important role in family planning and population control in China. In recent years, Cu-IUD is still used by hundreds of millions of women in China, and such devices still attract more attention in the field of women's health. This paper collects the information of all the 31 Cu-IUD products with valid registration certificate in China, including product name, manufacturer name, IUD structure and composition, schematic diagram, etc. From the perspective of safety and effectiveness evaluation of IUD, this paper reviewed and evaluated the relevant properties of Cu-IUD implanted in uterine cavity, including physical properties, chemical properties, biocompatibility evaluation, and clinical application related performance studies.

Copper bearing intrauterine device (Cu-IUD) is a widely used contraceptive method for women of childbearing age in China. It plays an important role in family planning and population control in China. In recent years, Cu-IUD is still used by hundreds of millions of women in China, and such devices still attract more attention in the field of women's health. This paper collects the information of all the 31 Cu-IUD products with valid registration certificate in China, including product name, manufacturer name, IUD structure and composition, schematic diagram, etc. From the perspective of safety and effectiveness evaluation of IUD, this paper reviewed and evaluated the relevant properties of Cu-IUD implanted in uterine cavity, including physical properties, chemical properties, biocompatibility evaluation, and clinical application related performance studies.

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 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 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.

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.