Direct acting antiviral agent for Chinese patients with chronic hepatitis C genotype 1b infection——a real world experience / 中华传染病杂志

Objective To evaluate the effectiveness and safety of direct-acting antiviral agents (DAA) treatment in Chinese chronic hepatitis C (CHC) patients with genotype (GT) 1b HCV infection in a real world setting .Methods The consecutive GT1b CHC Chinese patients treated with sofosbuvir (SOF) plus daclatasvir (DCV) (n＝62) or SOF plus ledipasvir (LDV) (n＝171) were enrolled from July 2014 to December 2016 at 302 Military Hospital of China .The treatment duration for all the patients was 12 weeks .All the clinical parameters were measured at baseline and then 4-weekly till 12 weeks after the end-of-treatment (EOT ).Baseline clinical characteristics ,treatment efficacy ,safety and tolerance were compared .Serum HCV RNA concentration was detected by means of COBAS TaqMan assay with a lower detection limit of 15 IU/mL ,and liver stiffness was measured using FibroScan?.Sustained virologic response (SVR) was defined as HCV RNA under the lower limit of quantification 12 weeks after EOT (SVR12).Students′t-test ,pearson χ2 test ,Spearman rank correlation analysis and Fisher exact test were used for comparison between groups when appropriate .Results Among 233 patients ,173 cases had baseline HCV RNA level ≥ 6 .0 lg IU/mL and 97 cases hade liver stiffness measurement (LSM )≥17.5 kPa.The baseline liver inflamation ,liver fibrosis ,and HCV RNA load of patients in the two groups were not significantly different (all P＞0 .05).The HCV RNA of all the 233 patients was undetectable at the end of 12-week treatment ,while 2 patients relapsed after 12 weeks of EOT with the overall SVR12 of 99.1% .HCV RNA decline was significantly faster in patients with lower LSM than those with higher LSM (ρ＝0 .233 ,P＝0 .001) ,and SVR12 was higher in those with lower LSM .In terms of other clinical characteristics of SOF+DCV and SOF+LVD groups ,alanine transaminase declined from (68 .0 ± 60 .1) and (70 .1 ± 56 .1) U/L to (21 .1 ± 10 .9) U/L and (15 .3 ± 9 .5) U/L ,respectively ,total bilirubin declined from (21 .3 ± 17 .3) and (18 .2 ± 14 .0) μmol/L to (13 .2 ± 6 .7) and (10 .2 ± 4 .6) μmol/L , respectively ,AFP declined from 19 .6 (10 .6 ,62 .3) and 15 .0 (12 .0 ,25 .0) μg/L to 6 .5(4 .5 ,18 .7) and 7 .8(5 .3 ,15 .4) μg/L ,respectively ,LSM declined from 17 .6 (8 .9 ,25 .4) and 15 .7 (7 .8 ,23 .9) kPa to 13.9(6 .5 ,21 .4) and 9 .1(5 .6 ,19 .9) kPa ,respectively ,serum album elevated form (37 .5 ± 5 .8) and (38 .7 ± 5 .5) g/L to (41 .3 ± 4 .7) and (42 .8 ± 5 .1) g/L ,respectively ,platelet elevated from (120.9 ± 78 . 2)×109/L and (136 .6 ± 65 .8 )× 109/L to (139 .5 ± 71.8 )× 109/L and (149 .7 ± 71.4 )× 109/L , respectively .Reports of adverse events were low in both groups .Conclusions Both SOF + DCV and SOF/LDV therapy are highly effective with ＞ 98% of SVR12 and reduce LSM value significantly with good safety for CHC GT1b Chinese patients .

Analysis of SLC25A13 gene mutations and prenatal diagnosis for 20 families affected with citrin deficiency / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To detect mutations of SLC25A13 gene in 20 families affected with citrin deficiency and provide prenatal diagnosis for them.</p><p><b>METHODS</b>The 20 probands and their parents were subjected to high-frequency mutation screening combined with Sanger sequencing. After confirming the genotype of each pedigree, genetic counseling and prenatal diagnosis were performed for their subsequent pregnancies.</p><p><b>RESULTS</b>Biallelic pathogenic mutations of the SLC25A13 gene were identified in all probands. These included three deletions (c.851del4, c.1092_1095delT, and c.495delA), two splice-site mutations (IVS6+5G to A and IVS11+1G to A), two nonsense mutations (c.775C to T (p.Q259X) and c.72T to A (p.Y24X)), one duplication mutation (c.1638_1660dup), one insertion (IVSl6ins3kb), and one missense mutation (c.1775A to C (p.Q592P)). Among 24 fetuses undergoing prenatal diagnosis, 8 had normal genotypes, 11 were mutation carriers, while 5 harbored biallelic mutations. Those with wild type alleles or heterozygous SLC25A13 mutations were delivered. Two fetuses harboring homozygous c.851del4 mutations were also delivered. Three fetuses harboring biallelic mutations were terminated.</p><p><b>CONCLUSION</b>Analysis of SLC25A13 gene mutations in families affected by citrin deficiency can provide evidence for molecular diagnosis and facilitate genetic counseling and prenatal diagnosis for the subsequent pregnancy, which can effectively reduce the risk of birth of further affected children.</p>

Genotype and phenotype analysis of a child with partial 18q deletion syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the genotype-phenotype correlation of a child with chromosome 18q deletion syndrome.</p><p><b>METHODS</b>G-banded karyotyping, single nucleotide polymorphism array (SNP array) and fluorescence in situ hybridization (FISH) were performed on the child with abnormal phenotypes. Genotype-phenotype correlation was explored following accurate mapping of the breakpoints on chromosome 18q. SNP array was also performed on the genome DNA derived from peripheral venous blood samples from both parents.</p><p><b>RESULTS</b>Chromosomal analysis revealed that the child has a karyotype of 46, XY, del(18) (q23). SNP array analysis detected a 9.855 Mb deletion (chr18: 68 158 880-78 014 123) at 18q22.2q23. Mapping of the breakpoints suggested that the deletion has overlapped with that of distal chromosome 18q deletion syndrome and encompassed several critical regions for this syndrome. SNP array performed on parental samples suggested that the 18q22.2q23 deletion was de novo in origin. FISH analysis of peripheral blood sample from the child confirmed the presence of 18qter deletion.</p><p><b>CONCLUSION</b>The phenotype of this child may be attributed to the deletion of distal 18q22.2q23, which has encompassed several critical regions for the 18q deletion syndrome.</p>

Improved identification for 5p deletion syndrome and partial trisomy 11q presented in a fetus by SNP array / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the prenatal application of single nucleotide polymorphism array (SNP array) in the identification of 5p deletion syndrome with partial trisomy 11q.</p><p><b>METHODS</b>G-banded karyotyping and SNP array were performed using amniocytes on a fetus with multiple malformations for the identification of chromosome abnormality. Furthermore, karyotyping was carried out on the parental peripheral blood specimens to ascertain the origin of chromosome abnormalities and then fluorescence in situ hybridization (FISH) was also utilized to confirm the results.</p><p><b>RESULTS</b>Karyotype of amniocyte showed 46, XY, der(5) (?::p15 → qter). SNP array revealed a 13.907 Mb deletion at 5p15.33p15.2 (chr5: 113576-14020561), overlapping the region of 5p deletion syndrome, and a 18.254 Mb duplication at 11q23.3 q25 (chr11: 116684627-134938470), overlapping no known syndrome. Karyotype of the parents showed a normal 46,XX in mother and 46,XY,t(5;11)(p15;q23) in father. Three-color metaphase FISH analysis on paternal peripheral blood specimens also confirmed the paternal karyotyping result.</p><p><b>CONCLUSION</b>SNP array could uncover 5p deletion syndrome with partial trisomy 11q unidentified by G-banded karyotyping and accurately locate the genomic breakpoints, facilitating the mapping of pathogenic critical regions and the identification of candidate genes, also accumulating research data for genotype-phenotype study.</p>

Ultrasound soft markers and fetal cardiac structural assessment at 11-14 weeks / 中华妇产科杂志

Objective To evaluate the detection rate of congenital heart defect (CHD) during the first trimester screening for chromosomal abnormalities,the role of ultrasound soft markers including increased nuchal translucency (NT),tricuspid regurgitation (TR) and abnormal ductus venosus (DV) flow in the screening for cardiac anomalies was also investigated.Methods From January 2009 to January 2012,4 673 fetuses were scanned at 11-14 weeks at Department of Fetal Medicine,the First Affiliated Hospital of Jinan University.The ultrasound findings and follow up outcomes were recorded,False-positive rate of different first-trimester ultrasound markers for the detection of CHD was calculated,sensitivity of the markers for all major CHD was calculated as well.Results There was a significant association between major CHD and first trimester ultrasound markers.(1) Overall findings:among the 4 673 fetuses,31 fetuses were diagnosed CHD prenatally,17,12 and 2 of which were detected in the first,second and third trimester,respectively.In 22 of the 31 CHD cases,invasive procedure was performed,fetal karyotype was abnormal in 12 cases,including triosmy 21 (5 cases),trisomy 18 (2 cases),trisomy 13 (2 cases),Turner syndrome (2 cases) and pericentric inversion of chromosome 9 (1 cases).(2) NT measurement and prenatal detected CHD:in 4 673 cases,NT measurement between 95th-99th percentile were present in 206 (4.41％),5 cases were diagnosed CHD prenatally,in 4 of 5 cases were detected in first trimester; NT measurement ＜ 95th percentile were present in 4 430(94.80％),16 cases were diagnosed CHD prenatally,in 5 of 16 cases were detected in first trimester; NT measurement ＞ 99th percentile (＞ 3.5 mm) were present in 37 (0.79％,37/4 673),10 cases were diagnosed CHD prenatally,in 8 of 10 cases were detected in first trimester.(3) TR and inverted a-wave at the DV and prenatal detected CHD:among 4 673 cases,TR or inverted a-wave at the DV were present in 51 (1.09％),98 (2.10％) respectively.TR was present in 8 of 31 CHD cases,inverted a-wave at the DV was present in 7 of 31 CHD cases.(4)Sensitivity of different first trimester ultrasound markers for detection of major CHD cases:in 31 CHD cases diagnosed prenatally,23 eased were defined as major CHD.Sensitivity of at least one of the ultrasound narkers,NT measurement between 95th-99th percentile,＞ 99th percentile(＞ 3.5 mm),TR or inverted a-wave at the DV for detection of major CHD eases was 74％ (17/23),22％ (5/23),39％ (9/23),35％ (8/23),30％ (7/23),respectively.(5) Specificity of different first trimester ultrasound markers for detection of CHD cases:specificity of NT measurement between 95th-99th percentile,＞ 99th percentile(＞ 3.5 mm),TR or inverted a-wave at the DV for detection of major CHD cases was 4.30％ (201/4 673),0.58％ (27/4 673),0.92％ (43/4 673),1.94％ (91/4 673).Conclusions Routine first trimester soft markers for chromosomal abnormalities screening combined with cardiac assessment can detect quite a number of major heart defects.Increased NT,TR and abnormal DV flow can be important indicators for echocardiography,which is favorable to early prenatal diagnosis of CHD.

Study on mode of delivery and singleton newborns term birth weight in 3 hospitals / 中华妇产科杂志

Objective To study newborns weight in singleton term births and the associationbetween newborns birth weight and mode of delivery in 3 hospitals.Methods From Jan.2005 to Dec.2009,13 963 singleton term live neonates born in the Department of Obstetrics and Gynecology of Peking University First Hospital(PU group),6519 neonates in Affiliated Hospital of Binzhou Medical College (BMC group,)and 8725 neonates in Miyun Hospital Affiliated to Capital Medical University,Yanjing Medical College(MYC group)were enrolled in this retrospective study.The newborns weight and the rate of macrosomia was calculated and compared.Those newborns from PU group and MYC group were divided into 2288 neonates at macrosomia group and 20 400 neonates at non-macrosomia group,their mode of deliveries were analyzed.Results(1)The mean neonatal birth weight were(3386 ± 414)g at PU group,(3389 ± 446)g at BMC group and(3445 ± 449)g at MYC group.Neonates born weight in MYC was significantly higher than those from in PU group and BMC group(P =0.000).Neonates born weight in BMC showed higher than those in PU group,which did.not reached statistical difference(P =0.638).(2)The incidence of macrosomia were 7.935％(1108/13 963)in PU group,9.802％(639/6519)in BMU group and 13.524％(1180/8725)in MYU group.The incidence of macrosomia in MYC group was higher than those in PU and BMC group,the incidence of macrosomia in BMC group was higher than that in PU group,which reached statistically difference(P =0.000).(3)The proportion of cesarean delivery were 75.306％(1723/ 2288)at macrosomia group,50.765％(10 356/20 400)at non-macrosomia group,which showed statistical difference(P =0.000).Conclusions(1)The difference of newborns birth weight existed in different administrative level hospital.(2)The risk of cesarean delivery due to macrosomia is higher than that of nonmacrosomia.(3)Obstetricians should pay more attention to nutrition in gestation period to lessen the incidence of macrosomia and cesarean section.

Investigation into the clinical suitability of Institute of Medicine 2009 guidelines regarding weight gain during pregnancy for women with full term singleton fetus in China / 中华妇产科杂志

ObjectiveTo study whether the current Institute of Medicine (IOM) pregnancy weight gain recommendationsvarybypre-pregnancybodymassindex(BMI)wassuitabletoChinese people.MethodsA study was conducted on 4736 term singleton live birth gravidas,who were diagnosed normal glucose metabolism and delivered in Peking University First Hospital in 2005 and 2009,by reviewing the medical records.Based on the pre-pregnant BMI,the selected cases were divided into 3 groups:low body mass group ( BMI ＜ 18.5 kg/m2,n =465 ),normal body mass group ( BMI 18.5 - 24.9 kg/m2,n =3549),over body mass group ( BMI ≥ 25 kg/m2,n =722).All the cases were divided into 3 subgroups based on pregnancy weight gain as below,within,and above the IOM recommendations in each pre-pregnant BMI group.Totally 4736 newborns were divided by birth weight into 3 groups:normal birth weight group ( weight 2500 - 4000 g,n =4339 ),macrosomia group ( weight ≥ 4000 g,n =359 ) and low birth weight group (weight ＜ 2500 g,n =38).The difference of age,gestational age,pre-pregnant weight,pre-pregnant BMI and history of delivery of cases between 2005 and 2009 were analyzed.The difference of pregnancy outcome of women whose gestational weight gain was below,within,and above the IOM recommendations was analyzed.Results (1) Compared to mothers with pregnancy weight gain within IOM recommendations in low body mass group,risk of low birth weight in offspring was elevated tendency with pregnancy weight gain below IOM recommendations ( OR =3.71,95％ CI:0.97 - 14.12,P =0.055 ).(2) In normal body mass group, compared to women with pregnancy weight gain within IOM recommendations, risk of macrosomia in offspring was elevated with pregnancy weight gain above IOM recommendations ( OR =2.14,95％ CI:1.62 - 2.83,P ＜ 0.01 ).( 3 ) In over body mass group,compared to women with pregnancy weight gain within IOM recommendations,risk of macrosomia in offspring was elevated ( OR =3.25,95％ CI:1.65 -6.39,P =0.001 ) and risk of hypertensive disorders complicating pregnancy was high ( OR =1.79,95％ CI:1.04 -3.09,P =0.037 ) in women with pregnancy weight gain above IOM recommendations.ConclusionThe current IOM pregnancy weight gain recommendations vary by pre-pregnancy BMI may be suitable to Chinese people.

Factors relevant to newborn birth weight in pregnancy complicated with abnormal glucose Metabolism / 中华妇产科杂志

Objective To investigate the influencing factors of neonatal birth body mass in women with abnormal glucose metabolism during pregnancy. Methods A study was conducted on 1157 singleton gravidas, who were diagnosed and treated for abnormal glucose metabolism and delivered in the Department of Obstetrics and Gynecology, First Hospital, Peking University from January 2005 to December 2009, by reviewing the medical records. Based on the pre-pregnant body mass index, the selected cases were divided into 4 groups: low body mass group [ body mass index (BMI) ＜ 18.5 kg/m2, n =53], ideal body mass group ( BMI 18.5 - 23.9 kg/m2, n = 647 ), over body mass group ( BMI 24.0 - 27.9 kg/m2, n = 323 ),and obese group (BMI≥28.0 kg/m2, n = 134). 1157 newborns were divided by birth body mass into 3 groups: normal birth body mass group (body mass 2500 -4000 g, n =987), of which 545 cases of birth body mass 3000 -3500 g for the appropriate newborns, macrosomia group (body mass≥4000 g, n = 112);low birth body mass group (body mass ＜ 2500 g, n = 58 ). The following information was collected,including pre-pregnancy body mass, height, gestational age of diagnosis and body mass gain after diagnosis,maternal serum level of cholesterol, history of adverse pregnancy, and family history of diabetes, gestational age, delivering body mass, neonatal birth body mass. The influence of pre-pregnant BMI, body mass gain during pregnancy, gestational age of diagnosis, body mass gain after diagnosis, maternal serum level of cholesterol, family history of diabetes on the newborns' birth body mass was analyzed. The appropriate ranges of gestational body mass gain were calculated in women with abnormal glucose metabolism. Results ( 1 )The average neonatal birth body mass for each group respectively were (3142 ±333) g for low body mass group, (3339 ±476) g for the ideal body mass group, (3381 ±581) g for over body mass group, and (3368 ± 644) g for obese group. The neonatal birth body mass was increasing with maternal pre-pregnant BMI, and average birth body mass of the newborns in low body mass group was lower than other 3 groups,respectively, the difference was statistically significant ( P ＜ 0.05 ). The difference was not statistically significant ( P ＞ 0.05 ), when it was compared among the obese group, ideal weight group and over body mass group. (2)The body mass gain during pregnancy in women delivered normal birth weight newborn and delivered macrosomia for each group respectively were ( 13.5 ±4.5 ) and ( 17.1±5.4) kg for the ideal body mass group, ( 11.6 ± 4.9 ) and ( 15.3 ± 6.4 ) kg for the over body mass group, ( 10.3 ± 5.0) and ( 14.7 ±7.4) kg for the obese group. The difference was statistically significant in 3 groups (P ＜ 0.05 ). The difference of body mass gain during pregnancy in women delivered normal birth weight newborn and delivered macrosomia for low body mass group could not be compared statistically, because of only 1 case delivered macrosomia. (3)The gestational age of diagnosis in women who delivered normal birth weight newborn and macrosomia for the ideal body mass group respectively were ( 27.8 ± 5.8) and ( 29.8 ± 5.3 ) weeks, the difference was statistically significant ( P ＜0.05 ). The gestational age of diagnosis in gravidas who delivered normal birth weight newborn and macrosomia for the over body mass group respectively were ( 26.7 ± 6.8)and (30.2 ± 4.1 ) weeks, the difference was statistically significant ( P ＜ 0.05 ). The gestational age of diagnosis in women who delivered normal birth weight newborn for obese group was (26.2 ± 7.5 )weeks, less than that of pregnant women who delivered macrosomia [ ( 25.7 ± 9.3 ) weeks ], but the difference was not statistically significant (P ＞ 0.05 ). The difference of the diagnosed gestational age for low body mass group could not be compared statistically, because of only 1 case delivered macrosomia. (4)Tbe serum triglyceride (TG) levels of pregnant women who delivered macrosomia was (3.1 ± 1.5) mmol/L, higher than that of pregnant women who delivered normal birth weight newborn [ (2.7 ± 1.2) mmol/L], and the difference was statistically significant (P ＜ 0.01 ). The serum high density lipoprotein cholesterol (HDL-C) levels of pregnant women who delivered macrosomia was ( 1.4 ± 0.3 ) mmol/L, lower than that of pregnant women who delivered normal birth weight newborn [( 1.7 ±0.9) mmol/L], and the difference was statistically significant (P＜0.01). The serum low-density lipoprotein cholesterol (LDL-C) and cholesterol level of pregnant women who delivered macrosomia respectively was ( 2.8 ± 0.8 ) and ( 5.4 ± 1.1 ) mmol/L, less than those of pregnant women who delivered normal birth weight newborn [ (3.0 ±0.9) mmol/L and (5.6 ±1.1) mmol/L], but the difference was not statistically significant (P ＞0.05). (5)The final regression model of variables into the top three were pre-pregnant BMI, body mass gain during pregnancy and maternal serum level of HDL-C, when analyzing the related factors of affecting neonatal birth body mass with multiple logistic regression analysis such as age, history of adverse pregnancy, family history of diabetes, prepregnancy BMI, body mass gain during pregnancy and after diagnosis of abnormal glucose metabolism,maternal serum level of cholesterol, abnormal glucose metabolism categories, gestational age and other factors ( P ＜ 0.01 ). Conclusion Pre-pregnant BMI, body mass gain during pregnancy and maternal serum level of HDL-C may affect the neonatal birth body mass whose mothers were complicated with abnormal glucose metabolism during pregnancy.