A Preliminary Finding: N-butyl-phthalide Plays a Neuroprotective Role by Blocking the TLR4/HMGB1 Pathway and Improves Mild Cognitive Impairment Induced by Acute Cerebral Infarction.

BACKGROUND: Most acute cerebral infarctions (ACI) may develop vascular dementia (VD), which involves almost all types of cognitive impairment. Unfortunately, there is currently no effective treatment for VD. Most patients exhibit mild cognitive impairment (MCI) before the development of VD. N-butyl-phthalide (NBP) is used to treat ACI and improve cognitive function. The oxygen and glucose deprivation (OGD) model of neurons is an in vitro model of ischemia, hypoxia, and cognitive dysfunction. METHODS: We conducted clinical studies and in vitro experiments to investigate the clinical efficacy and mechanism of action of NBP for treating ACI-induced MCI. Patients with ACI-induced MCI were randomly divided into control (Ctrl) and NBP groups. We assessed various indicators, such as clinical efficacy, montreal cognitive assessment scale (MOCA), activities of daily living (ADL), and cerebral infarct size in both groups before and after treatment. We observed the morphology of neurons and detected the survival rate, action potentials (APs), expression of high mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), and the interaction between TLR4 and HMGB1. RESULTS: The MOCA and ADL scores increased significantly after treatment in the NBP group. A OGD model of neurons was established, and the neurons were divided into Ctrl and NBP groups. We observed that the survival rate and APs amplitude of the neurons were significantly increased in the NBP group, whereas TNF-α expression was decreased. Furthermore, the interaction between TLR4 and HMGB1 decreased in the NBP group. CONCLUSION: NBP plays a neuroprotective role by inhibiting the TLR4/HMGB1 pathway and ameliorating ACI-induced MCI.

High false-positive non-invasive prenatal screening results for sex chromosome abnormalities: Are maternal factors the culprit?

OBJECTIVE: To explore the impact of maternal sex chromosome aneuploidies (SCAs) and copy number variation (CNV) on false-positive results of non-invasive prenatal screening (NIPS) for predicting foetal SCAs. METHODS: In total, 22 844 pregnant women were recruited to undergo NIPS. Pregnant women with high-risk of SCAs underwent prenatal diagnosis and maternal copy number variation sequencing (CNV-seq). RESULTS: Among 117 women with high-risk of SCAs, 72 accepted prenatal diagnosis, 86 accepted maternal CNV-seq, and 21 had maternal sex chromosome abnormalities. The abnormality rate was significantly higher than women at low-risk of SCAs (24.42% vs 3.51%). Using a novel parameter cffDNA (ChrX)/cffDNA, when the ratio was greater than 2, all foetuses had normal karyotype, and 75.0% (6/8) had abnormal maternal chromosome X. If the ratio was less than or equal to 2, only 10% (4/40) of the mothers had chromosome X CNV alterations, while 33.3% (13/40) of their foetuses had sex chromosomes CNV abnormalities. CONCLUSIONS: Approximately 25% of pregnant women with SCAs predicted by NIPS had sex chromosome abnormalities as determined by CNV-seq. The ratio of cffDNA (ChrX)/cffDNA can tentatively distinguish the maternal or foetal origin of abnormal cell-free DNA. In a reanalysis of previous NIPS data, false-positive results caused by maternal CNV might be elucidated.

[Performance of prenatal screening by non-invasive cell-free fetal DNA testing for women with various indications].

OBJECTIVE To assess the performance of non-invasive prenatal testing (NIPT) based on massive parallel sequencing. METHODS A total of 10 275 maternal blood samples were collected. Fetal chromosomal aneuploides were subjected to low coverage whole genome sequencing. Patients with high risks received further prenatal diagnosis. The outcome of all patients were followed up. RESULTS High-throughput sequencing detected 72 pregnancies with fetal autosomal chromosomal aneuploidy, including 57 cases of trisomy 21, 14 cases of trisomy 18, and 1 case of trisomy 13. The positive predictive value for trisomies 21 and 18 were 98.25% and 91.67%, respectively. Comparing its performance in intermediate or high risk pregnancies, advanced maternal age pregnancies and volunteering to test pregnancies, the positive predictive value were 100%, 95%, 90% and 50%, respectively. The follow up result was only 1 case of 21 trisomy false negative with high risk. For the 56 cases of trisomy 21, the high risk group accounted for 55%, advanced maternal age accounted for 29%, the intermediate risk referred to 14%, the volunteering to test group accounted for 2%. CONCLUSION The performance of NIPT for trisomies 21, 18 and 13 was satisfactory. The method can be used for women with advanced gestational age. NIPT has offered an ideal secondary screening method for those with an intermediate or high risk, and can reduce the rate of birth defects.

Noninvasive prenatal testing for the detection of fetal chromosome 17 microduplication: clinical implications and findings.

BACKGROUND:  Noninvasive prenatal testing (NIPT) is widely used to screen for fetal aneuploidies. However, there are few reports of using NIPT for screening chromosomal microduplications and microdeletions. This study aimed to investigate the application efficiency of NIPT for detecting chromosomal microduplications. METHODS: Four cases of copy number gains on the long arm of chromosome 17 (17q12) were detected using NIPT and further confirmed using copy number variation (CNV) analysis based on chromosome microarray analysis (CMA). RESULTS: The prenatal diagnosis CMA results of the three cases showed that the microduplications in 17q12 (ranging from 1.5 to 1.9 Mb) were consistent with the NIPT results. The karyotypic analysis excluded other possible unbalanced rearrangements. The positive predictive value of NIPT for detecting chromosomal 17q12 microduplication was 75.0%. CONCLUSIONS:  NIPT has a good screening effect on 17q12 syndrome through prenatal diagnosis, therefore it could be considered for screening fetal CNV during the second trimester. With the clinical application of NIPT, invasive prenatal diagnoses could be effectively reduced while also improving the detection rate of fetal CNV.

Safety, immunogenicity and immune-persistence of heterologous prime-boost immunization with BBIBP-CorV and ZF2001 against SARS-CoV-2 in healthy adults aged 18 years or older.

BACKGROUND: Because SARS-CoV-2 mutations and immunity wane over time, a third dose of heterologous COVID-19 vaccine is proposed for individuals primed with inactivated COVID-19 vaccine. RESEARCH DESIGN AND METHODS: We conducted a single-center, open-label trial to assess the safety, immunogenicity, and immune-persistence of a heterologous BBIBP-CorV/ZF2001 prime-boost vaccination in Chinese adults. 480 participants who had been primed with two doses of BBIBP-CorV, received a third dose of ZF2001 after an interval of 3-4, 5-6, or 7-9 months. RESULTS: The overall incidence of adverse reactions within 30 days after vaccination was 5.83%. No serious adverse reactions were reported. The respective geometric mean titers (GMTs) of neutralizing antibodies for 3-4, 5-6, and 7-9 months groups at baseline were 2.06, 2.02, and 2.10; which increased to 55.42, 63.45, and 62.06 on day 14; then decreased to 17.53, 23.79, and 26.73 on day 30; before finally waning to 8.29, 9.24, and 9.51 on day 180. After the booster, the three groups showed no significant differences in GMTs. GMTs were lower in older participants than younger participants. CONCLUSIONS: A heterologous BBIBP-CorV/ZF2001 prime-boost vaccination was safe and immunogenic. Prime-boost intervals did not affect the immune response. The immune response was weaker in older adults than younger adults. CLINICAL TRIAL IDENTIFIER: NCT05205083.

Individualized Implementation of Youth Quality of Life Instrument-Research Version (YQOL-R) Among Chinese Adolescents with Different Weight Status.

Purpose: This study implemented the individualized Youth Quality of Life Instrument-Research Version (YQOL-R) to estimate the quality of life (QoL) among Chinese adolescents with three different Body Mass Index (BMI) levels. The study aims to explore and provide a reference for developing individualized QoL (IQoL) measurements in China. Methods: The sample consisted of 822 aged 11-18 from nine schools. The data collection included all participants' primary characters (age, sex, annual household income, parental education, and recruitment community) and their self-report QoL. Precisely, based on the generic measurement of YQOL-R, we developed IQoL measurements by asking adolescents' perceived five most important things to them (IQOLimportance) and the aspects they most want to change (IQOLchange) from 19 facets, respectively. The one-way analysis of variance (ANOVA) was applied to compare total and subscale scores of IQOLimportance, IQOLchange, and YQOL-R among adolescents with three different weight status. Also, the data analysis used multivariable linear regression modeling to test the effects on scores of IQOLimportance and IQOLchange. Results: Overall, the obese adolescents identified "Having good physical health" as the most important (54.03%) and most like-to-change (42.65%); in contrast, the normal-weight group ranked "Being myself" as the top facet of IQOLimportance (52.42%) and "Having good friends" as the top facet of IQOLchange (43.12%). The obese adolescents' reported IQOLimportance scores are significantly lower than those of the normal-weight group (P=0.039). However, there is no significant difference in IQOLchange score among the three weight-status groups. The multivariable linear regression models indicated that adolescents who are girls (P=0.035), have higher educated fathers (P=0.049), and are overweight/obese (P=0.041) self-reported worse IQOLimportance score; yet, the girls (P=0.023) and older adolescents (P=0.004) answered lower IQOLchange scores. In addition, adolescents who had higher educated mothers (P=0.047; 0.023) and responded with higher total YQOL-R scores (P<0.001; <0.001) reported higher IQOLimportance and IQOLchange scores. Conclusion: In the current study, although the self-reported YQOL-R scores from different weight status did not present a significant difference, the obese group reported a statistical trend towards lower IQOLimportance scores than the normal-weight and overweight adolescents. These findings emphasize that IQOLimportance and IQOLchange could capture adolescents' perspectives with different weight statuses about their lives, which are unique as complementary health outcomes accompanying YQOL-R in health surveys and interventions among Chinese adolescents.

Clinical evaluation of non-invasive prenatal screening for the detection of fetal genome-wide copy number variants.

OBJECTIVE: This study explores and discusses the possible factors affecting the positive predictive value (PPV) of non-invasive prenatal screening (NIPS) for the detection of fetal copy number variants (CNVs) in pregnant women. METHODS: NIPS was performed for 50,972 pregnant women and 212 cases were suspected as fetal CNVs. Post additional genetic counseling for these women, 96 underwent invasive prenatal diagnosis (amniocentesis), following which they received chromosomal microarray analysis (CMA). We analyzed the PPV of NIPS for the detection of fetal CNVs and the possible interference factors that could affect the PPV. RESULTS: Among the 96 pregnant women that received prenatal diagnosis by CMA, 37 cases were confirmed to be true positive for fetal CNVs with a PPV of 38.5%. There was no significant difference between the women with different NIPS indications. Five cases were reported as the false positive and false negative of fetal CNVs and the differences were mainly reflected in the inconsistency of chromosome fragments. Depending on the sizes of the CNVs, the PPVs were 48.7% for CNVs < 3 Mb, 41.4% for CNVs falling within 3 ~ 5 Mb, 42.9% for the CNVs falling within 5 ~ 10 Mb, and 14.3% for CNVs > 10 Mb. Based on the chromosomal locations of CNVs, the PPV(4.8%) of the chromosomes of group C(including chromosomes 6 ~ 12), was lower than that of the other groups (41.2% ~ 66.7%) (p = 0.021). However, there were no significant differences in the CNV characteristics, fetal fractions, unique reads, and the Z-scores between these groups. CONCLUSION: NIPS with a low-coverage sequencing depth has a certain effect on detection of fetal CNVs with the PPV of 38.5%. Chromosomal locations of CNVs may be the main factor that influences its effect. This study can contribute to an increased accuracy in genetic counseling and in predicting NIPS results that are positive for fetal CNVs.

Safety and immunogenicity of heterologous recombinant protein subunit vaccine (ZF2001) booster against COVID-19 at 3-9-month intervals following two-dose inactivated vaccine (CoronaVac).

Background: In response to SARS-CoV-2 mutations and waning antibody levels after two-dose inactivated vaccines, we assessed whether a third dose of recombinant protein subunit vaccine (ZF2001) boosts immune responses. Methods: An open-label single-center non-random trial was conducted on people aged 18 years and above at five sites in China. All participants received a two-dose inactivated vaccine (CoronaVac) as their prime doses within 3-9 months of the trial. Primary outcomes were safety and immunogenicity, primarily the geometric mean titers (GMTs) of neutralizing antibodies to live wildtype SARS-CoV-2. Results: A total of 480 participants (median age, 51; range 21-84 years) previously vaccinated with two-dose CoronaVac received a third booster dose of ZF2001 3-4, 5-6, or 7-9-months later. The overall incidence of adverse reactions within 30 days after vaccination was 5.83% (28/480). No serious adverse reactions were reported after the third dose of ZF2001. GMTs in the 3-4-, 5-6-, and 7-9-month groups before vaccination were 3.96, 4.60, and 3.78, respectively. On Day 14, GMTs increased to 33.06, 47.51, and 44.12, respectively. After the booster, GMTs showed no significant difference among the three prime-boost interval groups (all P>0.05). Additionally, GMTs in older adults were lower than those in younger adults on Day 14 for the three groups (P=0.0005, P<0.0001, and P<0.0001). Conclusion: Heterologous boosting with ZF2001 was safe and immunogenic, and prime-boost intervals did not affect the immune response. The immune response was weaker in older than younger adults.

Immunogenicity and safety of the 9-valent human papillomavirus vaccine in Chinese females 9-45 years of age: A phase 3 open-label study.

BACKGROUND: The 9-valent human papillomavirus (9vHPV; HPV6/11/16/18/31/33/45/52/58) vaccine was approved for use in Chinese women aged 16-26 years in 2018. This phase 3, open-label study (NCT03903562) compared 9vHPV vaccine immunogenicity and safety in Chinese females aged 9-19 years and 27-45 years with Chinese females aged 20-26 years; we report results from day 1 through 1 month post-Dose 3. The study will continue through 54 months post-Dose 3 to assess antibody persistence in Chinese girls aged 9-19 years. METHODS: Participants aged 9-45 years received three doses of the 9vHPV vaccine. Geometric mean titers (GMTs) and seroconversion percentages for anti-HPV6/11/16/18/31/33/45/52/58 antibodies were determined by competitive Luminex immunoassay in serum samples obtained at day 1 and 1 month post-Dose 3. Adverse events (AEs) within 30 days post-vaccination and serious AEs (SAEs) occurring at any time were recorded. RESULTS: In total, 1990 participants (690 aged 9-19 years; 650 aged 20-26 years; 650 aged 27-45 years) were enrolled. At 1 month post-Dose 3, >99% of participants in the per-protocol immunogenicity population seroconverted to each vaccine HPV type. Anti-HPV6/11/16/18/31/33/45/52/58 antibody GMTs in the 9-19-year age group were non-inferior to those in participants aged 20-26 years. Anti-HPV6/11/16/18/31/33/45/52/58 seroconversion percentages in the 27-45-year age group were non-inferior to those in participants aged 20-26 years. Injection-site and systemic AEs were reported by 43.3% and 50.9%, 50.5% and 57.1%, and 43.8% and 43.4% of participants aged 9-19, 20-26, and 27-45 years, respectively. There were no vaccine-related SAEs, discontinuations due to AEs, and deaths. CONCLUSION: Antibody responses induced by 9vHPV vaccination in Chinese females aged 9-19 years and 27-45 years were non-inferior to those in Chinese females aged 20-26 years. The vaccine was generally well tolerated. CLINICALTRIALS: gov Identifier: NCT03903562.

Efficacy, safety and immunogenicity of hexavalent rotavirus vaccine in Chinese infants.

A randomized, double-blind, placebo-controlled multicenter trial was conducted in healthy Chinese infants to assess the efficacy and safety of a hexavalent live human-bovine reassortant rotavirus vaccine (HRV) against rotavirus gastroenteritis (RVGE). A total of 6400 participants aged 6-12 weeks were enrolled and randomly assigned to either HRV (n â€‹= â€‹3200) or placebo (n â€‹= â€‹3200) group. All the subjects received three oral doses of vaccine four weeks apart. The vaccine efficacy (VE) against RVGE caused by rotavirus serotypes contained in HRV was evaluated from 14 days after three doses of administration up until the end of the second rotavirus season. VE against severe RVGE, VE against RVGE hospitalization caused by serotypes contained in HRV, and VE against RVGE, severe RVGE, and RVGE hospitalization caused by natural infection of any serotype of rotavirus were also investigated. All adverse events (AEs) were collected for 30 days after each dose. Serious AEs (SAEs) and intussusception cases were collected during the entire study. Our data showed that VE against RVGE caused by serotypes contained in HRV was 69.21% (95%CI: 53.31-79.69). VE against severe RVGE and RVGE hospitalization caused by serotypes contained in HRV were 91.36% (95%CI: 78.45-96.53) and 89.21% (95%CI: 64.51-96.72) respectively. VE against RVGE, severe RVGE, and RVGE hospitalization caused by natural infection of any serotype of rotavirus were 62.88% (95%CI: 49.11-72.92), 85.51% (95%CI: 72.74-92.30) and 83.68% (95%CI: 61.34-93.11). Incidences of AEs from the first dose to one month post the third dose in HRV and placebo groups were comparable. There was no significant difference in incidences of SAEs in HRV and placebo groups. This study shows that this hexavalent reassortant rotavirus vaccine is an effective, well-tolerated, and safe vaccine for Chinese infants.

Comprehensive Evaluation of Non-invasive Prenatal Screening to Detect Fetal Copy Number Variations.

OBJECTIVE: To evaluate the effectiveness of non-invasive prenatal screening (NIPS) in prenatal screening of fetal pathogenic copy number variants (CNVs). MATERIALS AND METHODS: We evaluated the prenatal screening capacity using traditional and retrospective approaches. For the traditional method, we evaluated 24,613 pregnant women who underwent NIPS; cases which fetal CNVs were suggested underwent prenatal diagnosis with chromosomal microarray analysis (CMA). For the retrospective method, we retrospectively evaluated 47 cases with fetal pathogenic CNVs by NIPS. A systematic literature search was performed to compare the evaluation efficiency. RESULTS: Among the 24,613 pregnant women who received NIPS, 124 (0.50%) were suspected to have fetal CNVs. Of these, 66 women underwent prenatal diagnosis with CMA and 13 had true-positive results. The positive predictive value (PPV) of NIPS for fetal CNVs was 19.7%. Among 1,161 women who did not receive NIPS and underwent prenatal diagnosis by CMA, 47 were confirmed to have fetal pathogenic CNVs. Retesting with NIPS indicated that 24 of these 47 cases could also be detected by NIPS, representing a detection rate (DR) of 51.1%. In total, 10 publications, namely, six retrospective studies and four prospective studies, met our criteria and were selected for a detailed full-text review. The reported DRs were 61.10-97.70% and the PPVs were 36.11-80.56%. The sizes of CNVs were closely related to the accuracy of NIPS detection. The DR was 41.9% (13/31) in fetuses with CNVs ≤ 3 Mb, but was 55.0% (11/20) in fetuses with CNVs > 3 Mb. Finally, to intuitively show the CNVs accurately detected by NIPS, we mapped all CNVs to chromosomes according to their location, size, and characteristics. NIPS detected fetal CNVs in 2q13 and 4q35. CONCLUSION: The DR and PPV of NIPS for fetal CNVs were approximately 51.1% and 19.7%, respectively. Follow-up molecular prenatal diagnosis is recommended in cases where NIPS suggests fetal CNVs.

Sensibility of linkage information and effectiveness of estimated distributions.

The probabilistic model building performed by estimation of distribution algorithms (EDAs) enables these methods to use advanced techniques of statistics and machine learning for automatic discovery of problem structures. However, in some situations, it may not be possible to completely and accurately identify the whole problem structure by probabilistic modeling due to certain inherent properties of the given problem. In this work, we illustrate one possible cause of such situations with problems consisting of structures with unequal fitness contributions. Based on the illustrative example, we introduce a notion that the estimated probabilistic models should be inspected to reveal the effective search directions and further propose a general approach which utilizes a reserved set of solutions to examine the built model for likely inaccurate fragments. Furthermore, the proposed approach is implemented on the extended compact genetic algorithm (ECGA) and experiments are performed on several sets of additively separable problems with different scaling setups. The results indicate that the proposed method can significantly assist ECGA to handle problems comprising structures of disparate fitness contributions and therefore may potentially help EDAs in general to overcome those situations in which the entire problem structure cannot be recognized properly due to the temporal delay of emergence of some promising partial solutions.

Enabling the extended compact genetic algorithm for real-parameter optimization by using adaptive discretization.

An adaptive discretization method, called split-on-demand (SoD), enables estimation of distribution algorithms (EDAs) for discrete variables to solve continuous optimization problems. SoD randomly splits a continuous interval if the number of search points within the interval exceeds a threshold, which is decreased at every iteration. After the split operation, the nonempty intervals are assigned integer codes, and the search points are discretized accordingly. As an example of using SoD with EDAs, the integration of SoD and the extended compact genetic algorithm (ECGA) is presented and numerically examined. In this integration, we adopt a local search mechanism as an optional component of our back end optimization engine. As a result, the proposed framework can be considered as a memetic algorithm, and SoD can potentially be applied to other memetic algorithms. The numerical experiments consist of two parts: (1) a set of benchmark functions on which ECGA with SoD and ECGA with two well-known discretization methods: the fixed-height histogram (FHH) and the fixed-width histogram (FWH) are compared; (2) a real-world application, the economic dispatch problem, on which ECGA with SoD is compared to other methods. The experimental results indicate that SoD is a better discretization method to work with ECGA. Moreover, ECGA with SoD works quite well on the economic dispatch problem and delivers solutions better than the best known results obtained by other methods in existence.

Short-term dynamic changes in neutralizing antibodies against enterovirus 71 after vaccination.

BACKGROUND: Short-term dynamic changes in neutralizing antibodies against EV71 and EV71-IgM after inactivated EV71 vaccine injection are unknown. METHODS: This study was designed as a randomized, open-label study and was registered at ClinicalTrials.gov (NCT03278132). In total, 120 healthy infants aged 6-35 months were randomized 1:1:1 to provide a second blood sample on day 10, day 20, or day 30 after the first vaccine dose, respectively. RESULTS: According to the per-protocol set, a rapid immune response against EV71 was observed 10 days after the first EV71 vaccine dose, with antibody titers ≥1:8 in 89.19% of participants (95% CI: 74.58-96.97%) on day 10, in 80.65% (95% CI: 62.53-92.55%) on day 20, in 66.67% (95% CI: 49.03-81.44%) on day 30, and in 100% (95% CI: 96.52%-.) on day 60. Based on an ELISA, the percentages of participants positive for EV71-IgM on day 0 and day 60 were 1.71% (2 out of 117) and 82.86% (87 out of 105), respectively. CONCLUSIONS: The EV71 vaccine could be used for contingency vaccination to further control EV71-associated disease outbreaks. Caution should be taken in using the EV71-IgM test for rapid EV71 infection diagnosis after EV71 vaccine administration. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03278132.

Efficacy and safety of a live attenuated influenza vaccine in Chinese healthy children aged 3-17 years in one study center of a randomized, double-blind, placebo-controlled phase 3 clinical trial, 2016/17 season.

BACKGROUND: No data on the safety and efficacy of a live attenuated influenza vaccine in China have ever been reported. METHODS: At a site of a phase 3 randomized, double-blind, placebo-controlled clinical trial in eastern China, eligible healthy children aged 3-17 years underwent randomization to receive live attenuated vaccine or placebo at a ratio of 1:1. The primary objective of the study was the prevention of laboratory-confirmed influenza illness during the surveillance period, starting on day 15 after vaccination. RESULTS: A total of 2000 participants were enrolled, with 998 receiving the vaccine and 1001 receiving placebo. Sixty-four cases of influenza-like illness were observed, of which, 44 were laboratory-confirmed (12 in vaccine group versus 32 in placebo group). Vaccine efficacy was 62.5% (95%CI: 27.6-80.6) against all types of influenza and 63.3% (95%CI: 27.5-81.5) against influenza H3N2 illness. 11 severe adverse events reported (7 in LAIV group versus 4 in placebo group) were all deemed to be non-vaccine-related. Adverse events occurred in 412 (41.3%) participants in the vaccine group versus 389 (38.9%; p = 0.274) participants in the placebo group. Significant increase incidence of fever was observed in participants in the vaccine group, especially in those aged 3-9 years. CONCLUSIONS: The live attenuated influenza vaccine showed good efficacy and safety among 3- to 17-year-olds children during the 2016-2017 season at a site in eastern China. Clinical Trial Registry Number: NCT02964065.

Clinical evaluation of NIPS for women at advanced maternal age: a multicenter retrospective study.

Objective: To explore the clinical effect of noninvasive prenatal screening (NIPS) for the women at advanced maternal age (AMA) and discuss the relationship between women's age and NIPS effect.Methods: Fourteen thousand thirty-five women at AMA who accepted NIPS from two prenatal diagnosis centers were recruited for this study. NIPS were checked by Illumina Next CN 500. All the AMA women received prenatal genetic counseling, selected prenatal diagnosis and different clinical treatments according to the results of NIPS.Results: A total of 114 cases (0.81%) got the NIPS-positive results of T21/T18/T13. One hundred four cases of them accepted prenatal diagnosis and 87 cases were proved as true positive. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 100, 99.88, 92.55 and 100%, respectively. Seventy-four women (0.53%) showed NIPS-positive results of sex chromosomal aneuploidies (SCAs). After informed consent, 46 women (62.2%) accepted fetus karyotype analysis. Nineteen cases were identified as true positive results, while 27 cases were false positive results. The PPV for SCAs in AMA women was 41.3%. The PPV of T21/T18/T13 in AMA women over 40 was 100%, while it was 81.91% for the women whose age was 35 ∼ 40 years old. There was also rising trend in PPV of fetal sex chromosome with the increased age (62.50 versus 36.84%).Conclusions: NIPS is a good choice for AMA pregnant women. It can not only achieve satisfactory clinical effect, but also greatly reduce invasive prenatal diagnosis. We will get better effect of NIPS by further managing AMA women stratified by their age.

Not all chromosome aberrations can be detected by NIPT in women at advanced maternal age: A multicenter retrospective study.

OBJECTIVE: To discuss the detectability of NIPT for pregnant women at advanced maternal age (AMA), and mainly focused on how many fetal abnormalities will be missed by NIPT. METHODS: A total of 4194 women at AMA who accepted cytogenetic prenatal diagnosis were recruited in this study. All the AMA women received amniocentesis at 18-23 weeks. Combined with our detection level of NIPT and literature reports, we evaluated the detectability of NIPT. RESULTS: After cell karyotype analysis, a total of 233 (5.56%) fetuses were confirmed to have chromosomal abnormalities, including 91.0% were abnormal chromosome number and 9.0% were abnormal chromosome structure. According to the detectability of NIPT we calculated, 87.6% abnormal results could also be detected by NIPT. However, NIPT would miss 12.4% abnormal results which could be originally found by the karyotype analysis of amniotic fluid cells. The major types of missed fetal abnormalities include structural rearrangement, mosaic and triploidy. Meanwhile, there were no relationship between the detectability of NIPT and the age of AMA pregnant women. CONCLUSIONS: About 12.4% of fetal chromosomal abnormalities will be missed if NIPT completely replaces invasive prenatal diagnosis in AMA women. Fortunately, these types of fetal abnormalities missed by NIPT did not increase with the age elevating of pregnant women.

Second-trimester Maternal Serum Screening Biomarkers in the Risk Assessment for Preeclampsia.

To evaluate the predictive value of second-trimester maternal serum screening biomarkers for preeclampsia, we analyzed the second-trimester serum prenatal screening data of pregnant women, and identified preeclampsia diagnosis by hospitalization records. 198 cases who developed preeclampsia and 1171 healthy controls were included in this study. In 15~20 gestational weeks, the cases who developed into preeclampsia had lower serum levels of uE3, uE3 MoM, but higher AFP MoM than controls, while no difference on AFP, fß-hCG, and fß-hCG MoM were found. A higher level of uE3 MoM was associated with a lower risk of preeclampsia (OR=0.35, 95% CI:0.19-0.65, P=0.0009). In addition, threshold effect was observed between preeclampsia and the MoM value of AFP and fß-hCG, the risk of preeclampsia increased when the AFP MoM≥1.43(OR=1.93, 95% CI:1.20-3.11, P=0.0064), or fß-hCG MoM≥2.31(OR=2.59, 95% CI:1.46-4.59, P=0.0012).

Particle swarm optimization with recombination and dynamic linkage discovery.

In this paper, we try to improve the performance of the particle swarm optimizer by incorporating the linkage concept, which is an essential mechanism in genetic algorithms, and design a new linkage identification technique called dynamic linkage discovery to address the linkage problem in real-parameter optimization problems. Dynamic linkage discovery is a costless and effective linkage recognition technique that adapts the linkage configuration by employing only the selection operator without extra judging criteria irrelevant to the objective function. Moreover, a recombination operator that utilizes the discovered linkage configuration to promote the cooperation of particle swarm optimizer and dynamic linkage discovery is accordingly developed. By integrating the particle swarm optimizer, dynamic linkage discovery, and recombination operator, we propose a new hybridization of optimization methodologies called particle swarm optimization with recombination and dynamic linkage discovery (PSO-RDL). In order to study the capability of PSO-RDL, numerical experiments were conducted on a set of benchmark functions as well as on an important real-world application. The benchmark functions used in this paper were proposed in the 2005 Institute of Electrical and Electronics Engineers Congress on Evolutionary Computation. The experimental results on the benchmark functions indicate that PSO-RDL can provide a level of performance comparable to that given by other advanced optimization techniques. In addition to the benchmark, PSO-RDL was also used to solve the economic dispatch (ED) problem for power systems, which is a real-world problem and highly constrained. The results indicate that PSO-RDL can successfully solve the ED problem for the three-unit power system and obtain the currently known best solution for the 40-unit system.

Noninvasive prenatal screening for fetal common sex chromosome aneuploidies from maternal blood.

Objective To explore the feasibility of high-throughput massively parallel genomic DNA sequencing technology for the noninvasive prenatal detection of fetal sex chromosome aneuploidies (SCAs). Methods The study enrolled pregnant women who were prepared to undergo noninvasive prenatal testing (NIPT) in the second trimester. Cell-free fetal DNA (cffDNA) was extracted from the mother's peripheral venous blood and a high-throughput sequencing procedure was undertaken. Patients identified as having pregnancies associated with SCAs were offered prenatal fetal chromosomal karyotyping. Results The study enrolled 10 275 pregnant women who were prepared to undergo NIPT. Of these, 57 pregnant women (0.55%) showed fetal SCA, including 27 with Turner syndrome (45,X), eight with Triple X syndrome (47,XXX), 12 with Klinefelter syndrome (47,XXY) and three with 47,XYY. Thirty-three pregnant women agreed to undergo fetal karyotyping and 18 had results consistent with NIPT, while 15 patients received a normal karyotype result. The overall positive predictive value of NIPT for detecting SCAs was 54.54% (18/33) and for detecting Turner syndrome (45,X) was 29.41% (5/17). Conclusion NIPT can be used to identify fetal SCAs by analysing cffDNA using massively parallel genomic sequencing, although the accuracy needs to be improved particularly for Turner syndrome (45,X).