OBJECTIVETo explore the value of next-generation sequencing for the non-invasive prenatal testing of fetal chromosomal aneuploidies.

METHODSPlasma from 4004 women with singleton pregnancy at a gestational age between 12-35(+5) weeks was collected prior to amniocentesis between April 19th 2011 and December 31st 2013. The samples were divided into three groups: (1) High risk for Down syndrome by biochemical screening; (2) Advanced maternal age; (3) Abnormalities by ultrasound or other methods. Plasma DNA extracted from above samples was sequenced at low coverage. Positive results were verified against the karyotypes of the fetuses. For those with negative results, the fetuses were followed up by telephone call for at least six months after birth.

RESULTSAmong 4003 samples subjected to non-invasive prenatal diagnosis, 66 (1.65%) had a positive result. In group 1, 22 cases of trisomy 21 (T21), 3 cases of trisomy 18 (T18), 1 case of 13 trisomy (T13), 8 cases of 45,X and 2 cases of other chromosomal abnormality were detected. In group 2, 13 cases of T21, 2 cases of T18, 1 case of T13, 5 cases of 45,X, 2 cases of 47,XXN and 1 case of other chromosomal abnormality were detected. In group 3, 1 case of T21, 1 case of T18, 1 case of T13, and 3 cases of 47,XXN were detected. For 55 samples underwent prenatal diagnosis, 30 cases of T21 and 4 cases of T18 were discovered, which was consistent with the results of non-invasive prenatal diagnosis. For the 13 cases indicated as 45,X, 3 were verified by karyotype analysis, 2 were verified as mosaicism (45,X/46,XN), 8 were 46,XN (false positives). For the 5 cases indicated as 47,XXN, 2 were verified by karyotype analysis, the other 3 were 46,XN (false positives). Karyotypes of 3 cases suspected for other chromosomal abnormalities were all verified as 46,XN (false positive). Until May 1st 2014, telephone follow-up for those with negative screening results only identified a boy with facial abnormalities and developmental delay, which was similar to his older sister, combined karyotyping and fluorescence in situ hybridization analysis has verified the karyotype of the boy as 46,XY,rec(14)dup(14q)inv(14)(p12q14)pat.

CONCLUSIONOur results indicated that sequencing of plasma free DNA can rapidly detect fetal chromosomal aneuploidies. The method is non-invasive, and the results are highly consistent with karyotype analysis in terms of accuracy and specificity. Non-invasive testing can be used as an effective adjunct to conventional prenatal diagnostic methods, which can greatly reduce unnecessary invasive prenatal diagnosis. However, the sensitivity and accuracy for aneuploidy detection other than chromosome 13/18/21 still need to be improved.

Adult ; Aneuploidy ; Asian Continental Ancestry Group ; genetics ; China ; Chromosomes, Human, Pair 18 ; genetics ; Chromosomes, Human, Pair 21 ; genetics ; Chromosomes, Human, Pair 8 ; genetics ; Down Syndrome ; diagnosis ; embryology ; genetics ; Female ; Fetal Diseases ; diagnosis ; genetics ; High-Throughput Nucleotide Sequencing ; methods ; Humans ; Infant ; Male ; Pedigree ; Pregnancy ; Prenatal Diagnosis ; methods

OBJECTIVETo investigate the surgical technique of skeletonization of the great saphenous vein (GSV) at the saphenofemoral junction (SFJ) in surgical intervention of primary varicosity and evaluate the outcomes one year after the operation.

METHODSA total of 624 cases (774 limbs) of primary varicosity of the GSV were prospectively divided into skeletonization group (265 cases, 325 limbs) and control group (359 cases, 449 limbs). In the skeletonization group, skeletonization of the GSV at the SFJ, its branches and other aberrantly joined superficial veins was performed, and in the control group, routine high ligation of the GSV was performed, after which laser-ablation of the GSV, GSV stripping, Muller's operation, mutilation of the perforators and ulcer-related operations were performed in both groups.

RESULTSTwenty cases in the skeletonization group were found to have superficial veins directly joining into the femoral vein or into the GSV in different tissue layers. In 14 cases in the control group, the superficial veins of the internal femoris or lateral femoris were mistaken for the GSV. No difference was found in the operating time between the two groups (t=0.68, P>0.05), but the skeletonization group had a significantly less bleeding volume (t=1.75, P<0.05). Statistical differences were found between the two groups in intraoperative bleeding rate in the inguinal regions, venous clinical severity scores (2.1∓0.5 vs 4.6∓0.9, t=1.96, P<0.05), and residual varicosity and recurrences (3/325 vs 13/449, V=1.25, P<0.05) at the one year follow-up.

CONCLUSIONSkeletonization of the GSV and its branches and other aberrantly joined superficial veins at the SFJ can decrease the postoperative residual varicosity and recurrence due to blood reflux.

Adult ; Aged ; Aged, 80 and over ; Female ; Groin ; blood supply ; surgery ; Humans ; Male ; Middle Aged ; Prospective Studies ; Saphenous Vein ; pathology ; surgery ; Treatment Outcome ; Varicose Veins ; pathology ; surgery