Evaluation of chromosomal abnormalities from preimplantation genetic testing to the reproductive outcomes: a comparison between three different structural rearrangements based on next-generation sequencing.

PURPOSE: The aim of this study was to determine factors affecting the chromosome imbalance in blastocysts and reproductive outcomes by a comparison between the reciprocal translocation (REC), inversion (INV), and Robertsonian translocation (ROB) carriers. METHODS: Couples with one partner carrying translocation or inversion underwent preimplantation genetic testing for chromosomal structural rearrangement (PGT-SR) cycles, including 215 PGT-SR cycles performed in subsequent 164 frozen-thawed embryo transfer cycles and 61 prenatal diagnoses of fetuses and 59 normal live birth babies. A total of 899 samples were processed by whole-genome amplification followed by next-generation sequencing (NGS). Karyotype and chromosome microarray analyses were used to confirm the PGT results from the amniotic fluid samples. RESULTS: A total of 843 blastocysts from 124 REC, 21 INV, and 35 ROB carriers were diagnosed by PGT-SR. The percentage of unbalanced blastocysts was significantly higher in REC than in INV and ROB carriers (64.31% vs. 28.05% vs. 37.02%). Stratification analysis of female carrier age and gonadotropin doses showed no significant increase in unbalanced chromosomal abnormalities in the three groups. Also, the different breakpoints in chromosomal arms did not affect the rate of unbalanced chromosomes in the embryos. Logistic regression indicated blastocyst quality as a statistically significant risk factor associated with unbalanced chromosomal abnormalities from translocation carriers (P < 0.001). The source of abnormalities in the three groups showed significant differences such that the abnormalities in REC mostly originated from parental translocation but the abnormalities in INV were mainly de novo variations. 164 blastocysts were transferred, and there were no significant differences in the clinical pregnancy rate and miscarriage rate. A total of 59 healthy babies were born, and there were no significant differences in the gender ratio and birth height, except the birth weight of boys between INV and ROB groups (P = 0.02). The results of amniocentesis revealed that more fetuses have normal chromosomal karyotypes than balanced carriers, particularly in the REC group. CONCLUSIONS: Reciprocal translocation carriers have more risk of unbalanced rearrangement, but embryonic chromosome abnormalities of inversion carriers come mainly from de novo variations. This is the first study specifically comparing three different PGT-SRs using the NGS method and evaluating their reproductive outcomes. Our findings will provide the reciprocal translocation, inversion, and Robertsonian translocation carrier couples with more accurate genetic counseling on the reproductive risk of chromosomal imbalance.

Epidemiological characteristics and phylogenic analysis of human respiratory syncytial virus in patients with respiratory infections during 2011-2016 in southern China.

BACKGROUND: Human respiratory syncytial virus (RSV) is one of the most important pathogens that cause acute respiratory infections in children and immunocompromised adults. This work was conducted to understand the epidemiological and phylogenetic features of RSV in southern China during 2011-2016. METHODS: A total of 16 024 nasopharyngeal swabs were collected from patients with respiratory infections in 14 hospitals, and screened for RSV and seven other respiratory viruses using real-time PCR. Six hundred and twenty-three RSV-positive samples from 13 hospitals were further analyzed for subtypes. G gene sequencing and phylogenetic analysis were performed based on 46 RSV-A and 15 RSV-B strains. RESULTS: RSV was detected in 9.5% of the 16 024 specimens, the highest among the eight respiratory viruses screened. Most of these specimens came from inpatients and children under 3 years of age. The incidence of RSV-A (9.4%) was higher than that of RSV-B (4.4%) in children (<15 years), but not in adults (0.64% vs. 0.58%). A 2-year RSV-A dominance followed by a 1-year RSV-B dominance pattern was found. The co-detection rate of RSV was 25.1%. The main prevalent genotypes were NA1, ON1, and BA9. The prevalent RSV-A genotype in 2011-2012 was NA1, close to Chongqing and Brazil, but a new Hong Kong ON1 genotype was introduced and became the prevalent genotype in Guangzhou in 2014-2015. Deduced amino acid sequence analysis confirmed the ongoing evolution and a high selection pressure of RSV-A and B strains, especially in RSV-A ON1 and NA1 genotypes. CONCLUSIONS: This study demonstrated the molecular epidemiological characteristics of RSV in patients with respiratory infections in southern China.

Epidemiology characteristics of human coronaviruses in patients with respiratory infection symptoms and phylogenetic analysis of HCoV-OC43 during 2010-2015 in Guangzhou.

Human coronavirus (HCoV) is one of the most common causes of respiratory tract infection throughout the world. To investigate the epidemiological and genetic variation of HCoV in Guangzhou, south China, we collected totally 13048 throat and nasal swab specimens from adults and children with fever and acute upper respiratory infection symptoms in Gunazhou, south China between July 2010 and June 2015, and the epidemiological features of HCoV and its species were studied. Specimens were screened for HCoV by real-time RT-PCR, and 7 other common respiratory viruses were tested simultaneously by PCR or real-time PCR. HCoV was detected in 294 cases (2.25%) of the 13048 samples, with most of them inpatients (251 cases, 85.4% of HCoV positive cases) and young children not in nursery (53.06%, 156 out of 294 HCoV positive cases). Four HCoVs, as OC43, 229E, NL63 and HKU1 were detected prevalent during 2010-2015 in Guangzhou, and among the HCoV positive cases, 60.20% were OC43, 16.67% were 229E, 14.97% were NL63 and 7.82% were HKU1. The month distribution showed that totally HCoV was prevalent in winter, but differences existed in different species. The 5 year distribution of HCoV showed a peak-valley distribution trend, with the detection rate higher in 2011 and 2013 whereas lower in 2010, 2012 and 2014. The age distribution revealed that children (especially those <3 years old) and old people (>50 years) were both high risk groups to be infected by HCoV. Of the 294 HCoV positive patients, 34.69% (101 cases) were co-infected by other common respiratory viruses, and influenza virus was the most common co-infecting virus (30/101, 29.70%). Fifteen HCoV-OC43 positive samples of 2013-2014 were selected for S gene sequencing and phylogenetic analysis, and the results showed that the 15 strains could be divided into 2 clusters in the phylogenetic tree, 12 strains of which formed a separate cluster that was closer to genotype G found in Malaysia. It was revealed for the first time that genotype B and genotype G of HCoV-OC43 co-circulated and the newly defined genotype G was epidemic as a dominant genotype during 2013-2014 in Guanzhou, south China.

Bax-interacting factor-1 inhibits cell proliferation and promotes apoptosis in prostate cancer cells.

Prostate cancer (PCa) is one of the most common malignant tumors and the second leading cause of cancer-related death among males. Bax-interacting factor-1 (Bif-1) is a member of Endophilin family, which binds to and activates the BAX protein in response to the apoptosis signaling pathway. Loss of Bif-1 may suppress the intrinsic pathway of apoptosis and promote tumorigenesis, but there is also converse evidence that Bif-1 could in part be responsible for the tumorigenesis and the role of Bif-1 in PCa development is not clear. In the present study, we aimed to understand the relationships between Bif-1 expression and PCa development. The mRNA and protein expression levels of Bif-1 in PCa cell lines, benign prostatic hyperplasia (BPH) (n=100) and PCa tissues (n=100, including low Gleason-scored PCa n=43 and high Gleason-scored PCa n=57) were detected and the effects of Bif-1 overexpression on the apoptosis, proliferation and migration in LNCaP cells were explored. Bif-1 mRNA levels of PCa cell lines were analyzed by real-time PCR and the protein levels were detected by western blotting. Bif-1 expression in BPH and PCa samples was detected by immunohistochemistry. To build Bif-1 overexpression PCa cells, Bif-1 gene was transfected into LNCaP cells by pcDNA3.1(+)­Bif-1 vector. Cell apoptosis was detected by flow cytometric analysis, cell proliferation measured by 3­(4,5­dimethylthiazol­2­yl)­2,5­diphenyltetrazolium bromide (MTT) assay and cell migration was analyzed by wound­healing assay. The results proved that Bif-1 is downregulated in both PCa cell lines (P<0.01) and clinical samples (P<0.05), and Bif-1 expression is suppressed with the cancer progression (BPH vs. PCa P<0.01, and low Gleason-scored PCa vs. high Gleason-scored PCa P<0.05). Overexpression of Bif-1 could significantly inhibit cell proliferation (P<0.05) and enhancing PCa cell apoptosis (P<0.05), but it did not affect the migration ability (P>0.05). Our findings give strong evidence that Bif-1 is involved in PCa tumorigenesis and acts as a suppressor in PCa progression, and may have significance in understanding the process of PCa development.