Association of risk factors for high blood pressure across 46 low- and middle-income countries: A multi-country cross-sectional analysis.

Background: Despite acknowledging the influence of various lifestyle and metabolic risk factors on hypertension, it remains uncertain to identify the primary contributors and differentiate which modifiable risk factors mediate the causal effects of hypertension. We aimed to examine the hierarchical association of eight prominent lifestyle and metabolic risk factors, along with demographic variables, with hypertension in adults and to explore the mediating effects of modifiable metabolic risk factors on hypertension. Methods: A cross-sectional study was conducted in 46 low- and middle-income countries using the World Health Organization (WHO) STEPwise approach to noncommunicable disease risk factor surveillance from 2002 to 2020. In a sample of 179 535 non-pregnant adults, we assessed the weighted population-attributable risk percentages (PAR%) for hypertension associated with eight risk factors. Additionally, we investigated the mediating role of metabolic risk factors on the effects of lifestyle risk factors on hypertension. Results: After adjusting for the sample weight in each country, 26.7% of participants had hypertension. The prevalence of hypertension was highest in those aged ≥65 years, with obesity-associated hypertension (45.7%) exceeding the rates for overweight (32.2%) and non-overweight individuals (18.2%). These eight risk factors collectively explain 83.7% of the PAR% associated with hypertension adjusted for the communal variance. Among the modifiable factors, obesity contributed to a weighted PAR% of 38.2%, while sedentary behaviour and low physical activity combined accounted for a weighted PAR% of 3.1%. Overweight/obesity played a predominant mediating role in the correlation between lifestyle risk factors and systolic and diastolic blood pressure, with the indirect effect accounting for approximately 25-64% and 13-80% of the total effect, respectively. Conclusions: These findings offer new insights into the modified risk factors associated with hypertension in adults in low- and middle-income countries, highlighting the crucial role of maintaining a normal body weight for the effective prevention and management of hypertension.

Establishment and application of a reverse dot blot assay for 13 mutations of hearing-loss genes in primary hospitals in China.

Background: Hearing loss is a common sensorineural dysfunction with a high incidence in China. Although genetic factors are important causes of hearing loss, hearing-related gene detection has not been widely adopted in China. Objective: Establishing a rapid and efficient method to simultaneously detect hotspot hearing loss gene mutations. Methods: A reverse dot blot assay combined with a flow-through hybridization technique was developed for the simultaneous detection of 13 hotspot mutations of 4 hearing loss-related genes including GJB2, GJB3, SLC26A4, and the mitochondrial gene MT-RNR1. This method involved PCR amplification systems and a hybridization platform. Results: The technique can detect 13 hotspot mutations of 4 hearing loss-related genes. And a total of 213 blood samples were used to evaluate the availability of this method. Discussion: Our reverse dot blot assay was a simple, rapid, accurate, and cost-effective method to identify hotspot mutations of 4 hearing loss-related genes in a Chinese population.

Deep metagenomic characterization of the gut virome in pregnant women with preeclampsia.

Preeclampsia (PE), a pregnancy-specific syndrome, has been associated with the gut bacteriome. Here, to investigate the impact of the gut virome on the development of PE, we identified over 8,000 nonredundant viruses from the fecal metagenomes of 40 early-onset PE and 37 healthy pregnant women and profiled their abundances. Comparison and correlation analysis showed that PE-enriched viruses frequently connected to Blautia species enriched in PE. By contrast, bacteria linked to PE-depleted viruses were often the Bacteroidaceae members such as Bacteroides spp., Phocaeicola spp., Parabacteroides spp., and Alistipes shahii. In terms of viral function, PE-depleted viruses had auxiliary metabolic genes that participated in the metabolism of simple and complex polysaccharides, sulfur metabolism, lipopolysaccharide biosynthesis, and peptidoglycan biosynthesis, while PE-enriched viruses had a gene encoding cyclic pyranopterin monophosphate synthase, which seemed to be special, that participates in the biosynthesis of the molybdenum cofactor. Furthermore, the classification model based on gut viral signatures was developed to discriminate PE patients from healthy controls and showed an area under the receiver operating characteristic curve of 0.922 that was better than that of the bacterium-based model. This study opens up new avenues for further research, providing valuable insights into the PE gut virome and offering potential directions for future mechanistic and therapeutic investigations, with the ultimate goal of improving the diagnosis and management of PE.IMPORTANCEThe importance of this study lies in its exploration of the previously overlooked but potentially critical role of the gut virome in preeclampsia (PE). While the association between PE and the gut bacteriome has been recognized, this research takes a pioneering step into understanding how the gut virome, represented by over 8,000 nonredundant viruses, contributes to this condition. The findings reveal intriguing connections between PE-enriched viruses and specific gut bacteria, such as the prevalence of Blautia species in individuals with PE, contrasting with bacteria linked to PE-depleted viruses, including members of the Bacteroidaceae family. These viral interactions and associations provide a deeper understanding of the complex dynamics at play in PE.

Electrically tunable dual polarization states of light using lithium niobate-based nanograting.

Tuning polarization states of light electrically has unique advantages in the integration of optoelectronic devices. Here, a lithium niobate-based nanograting is proposed to dynamically tune the polarization state of both the reflected and transmitted lights simultaneously in the near-infrared range. By judiciously designing the nanograting, a quasi-bound state in the continuum (qBIC) is excited under the excitation of an obliquely incident plane wave. The excited mode with a high quality-factor and enhanced local electric field can respond to a refractive index change in nanograting structures as small as 10-4 level, which can be generated with a low external voltage via the electro-optic effect. As a result, both the polarization states of reflected and transmitted lights can be dynamically tuned from a right circular polarization to a linear polarization state. The proposed lithium niobate-based nanograting for tuning dual polarization states of light with a qBIC mode suggests a promising electrical scheme for achieving high speed optoelectronic devices.

Incidence, process of care, and outcomes of out-of-hospital cardiac arrest in China: a prospective study of the BASIC-OHCA registry.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is an important global public health issue, but its epidemiology and outcomes in low-income and middle-income countries remain largely unknown. We aim to comprehensively describe the incidence, process of care, and outcomes of OHCA in China. METHODS: In the prospective, multicentre, population-based Baseline Investigation of Out-of-hospital Cardiac Arrest (BASIC-OHCA) registry study, participating sites were selected from both urban and rural areas in all seven geographical regions across China. All patients with OHCA assessed by emergency medical service (EMS) staff were consecutively enrolled from Aug 1, 2019, to Dec 31, 2020. Patients with suspected cardiac arrest assessed by bystanders whose return of spontaneous circulation was achieved without the need for defibrillation or EMS personnel cardiopulmonary resuscitation were excluded. Patients with all key variables missing were excluded, including resuscitation attempt, age, sex, witnessed status, cause, all process of care indicators, and all outcome measures. In this analysis, we included data for EMS agencies serving 25 monitoring sites (20 urban and five rural) that included the entire serving population, data for the whole of 2020, and at least 50 OHCA patients in 2020. Data were collected and reported using the Utstein template. We calculated the crude incidence of EMS-assessed OHCA in 2020. We also report data on baseline characteristics (including sex, cause, location of OHCA, and presence of shockable rhythm), process of care (including EMS response time, cardiopulmonary resuscitation, defibrillation, and advanced life support), and outcomes of non-traumatic OHCA between Aug 1, 2019, and Dec 31, 2020, including survival and survival with favourable neurological outcomes at discharge or 30 days, and at 6 and 12 months. FINDINGS: Of 115·1 million people served by the 25 participating sites, 132 262 EMS-assessed patients with OHCA were enrolled, and resuscitation was attempted for 42 054 (31·8%) patients between Aug 1, 2019, and Dec 31, 2020. The crude incidence of EMS-assessed OHCA was 95·7 per 100 000 population (95% CI 95·6-95·8) in 2020. Among 38 227 individuals with non-traumatic OHCA, 25 958 (67·9%) were male, 30 282 (79·2%) had a cardiac arrest at home, 32 523 (85·1%) had a presumed cardiac cause, and 2297 (6·0%) presented with an initial shockable rhythm. 4049 (11·5%) of 35 090 patients with an unwitnessed or bystander-witnessed OHCA received dispatcher-assisted cardiopulmonary resuscitation and 7121 (20·3%) received bystander cardiopulmonary resuscitation; only 14 (<0·1%) patients were assessed by bystanders with an automated external defibrillator. The median EMS response time was 12 min (IQR 9-16). At hospital discharge or 30 days, 441 (1·2%) of 38 227 survived, 304 (0·8%) survived up to 6 months, and 269 (0·7%) up to 12 months. At hospital discharge or 30 days, 309 (0·8%) survived with favourable neurological outcomes, 257 (0·7%) had favourable neurological outcomes at 6 months, and 236 (0·6%) at 12 months. INTERPRETATION: Our findings revealed a high burden of EMS-assessed OHCA with a low proportion of resuscitation attempts. The suboptimal implementation of chain of survival and unsatisfactory prognosis call for national efforts to improve the care and outcomes of patients with OHCA in China. FUNDING: The National Science & Technology Fundamental Resources Investigation Program of China, the State Key Program of the National Natural Science Foundation of China, Taishan Pandeng Scholar Program of Shandong Province, the Key Research & Development Program of Shandong Province, the Interdisciplinary Young Researcher Groups Program of Shandong University, the Clinical Research Center of Shandong University, the ECCM Program of Clinical Research Center of Shandong University, and the Natural Science Foundation of Shandong Province.

Effect of arteriosclerotic intracranial arterial vessel wall enhancement on downstream collateral flow.

BACKGROUND: The effect of arteriosclerotic intracranial arterial vessel wall enhancement (IAVWE) on downstream collateral flow found in vessel wall imaging (VWI) is not clear. Regardless of the mechanism underlying IAVWE on VWI, damage to the patient's nervous system caused by IAVWE is likely achieved by affecting downstream cerebral blood flow. The present study aimed to investigate the effect of arteriosclerotic IAVWE on downstream collateral flow. METHODS: The present study recruited 63 consecutive patients at the Second Hospital of Hebei Medical University from January 2021 to November 2021 with underlying atherosclerotic diseases and unilateral middle cerebral artery (MCA) M1-segment stenosis who underwent an magnetic resonance scan within 3 days of symptom onset. The patients were divided into 4 groups according to IAVWE and the stenosis ratio (Group 1, n = 17; Group 2, n = 19; Group 3, n = 13; Group 4, n = 14), and downstream collateral flow was analyzed using three-dimensional pseudocontinuous arterial spin labeling (3D-pCASL) and RAPID software. The National Institutes of Health Stroke Scale (NIHSS) scores of the patients were also recorded. Two-factor multivariate analysis of variance using Pillai's trace was used as the main statistical method. RESULTS: No statistically significant difference was found in baseline demographic characteristics among the groups. IAVWE, but not the stenosis ratio, had a statistically significant significance on the late-arriving retrograde flow proportion (LARFP), hypoperfusion intensity ratio (HIR), and NIHSS scores ( F = 20.941, P <0.001, Pillai's trace statistic = 0.567). The between-subject effects test showed that IAVWE had a significant effect on the three dependent variables: LARFP ( R2 = 0.088, F = 10.899, P = 0.002), HIR ( R2 = 0.234, F = 29.354, P <0.001), and NIHSS ( R2 = 114.339, F = 33.338, P <0.001). CONCLUSIONS: Arteriosclerotic IAVWE significantly reduced downstream collateral flow and affected relevant neurological deficits. It was an independent factor affecting downstream collateral flow and NIHSS scores, which should be a focus of future studies. TRIAL REGISTRATION: ChiCTR.org.cn, ChiCTR2100053661.

Shortened fetal long bones: A notable intrauterine phenotypic feature in SHOX-associated skeletal dysplasia.

OBJECTIVE: To explore the intrauterine phenotypic spectrum of short stature homeobox-containing (SHOX) gene-associated skeletal dysplasia and provide genetic counseling at-risk pregnancies. METHOD: We analyzed the fetuses with SHOX-microdeletions identified by single nucleotide polymorphism (SNP)-array. The intrauterine phenotypes and outcomes were further elaborated. RESULTS: Nine fetuses carrying a single SHOX-microdeletion were reported, with deletion sizes ranging from 0.134 to 1.35 Mb. Shortened long bones were observed in all fetuses, varying from -2.0 standard deviation (SD) to -5.3 SD. Moreover, all cases had a femur length/foot ratio less than 0.87 and a femur/abdominal circumference ratio greater than 0.16, suggesting that non-lethal skeletal dysplasia may be involved. Two fetuses showed intrauterine growth restriction, and two had nasal bone hypoplasia. Prenatal ultrasonography did not reveal other obvious anomalies, including the Madelung deformity. Five microdeletions were inherited and one was de novo. Five terminations and four newborns were recorded. Two newborns had normal stature, and two were short-statured (height <3rd percentile), with one having inflexible wrists. CONCLUSIONS: SHOX haploinsufficiency may manifest with shortened fetal long bones. The combination of history taking, prenatal ultrasonography, and SNP-array can prompt early prenatal diagnosis and timely postnatal treatment of SHOX-associated skeletal dysplasia.

The impact of non-optimum temperatures, heatwaves and cold spells on out-of-hospital cardiac arrest onset in a changing climate in China: a multi-center, time-stratified, case-crossover study.

Background: Out-of-hospital cardiac arrest (OHCA) is a time-critical and fatal medical emergency that has been linked to non-optimal temperatures. However, the future burden of OHCA due to non-optimal temperatures, heatwaves, and cold spells under climate change has not been well evaluated. Methods: We conducted a time-stratified case-crossover study in 15 Northern Chinese cities throughout 2020 to estimate the exposure-response relationships of non-optimal temperatures, heatwaves, and cold spells with hourly OHCA onset in hot and cold seasons. We obtained future daily average temperatures by using 20 general circulation models under two greenhouse gas emission scenarios: one with certain emission control and the other with relaxed control. Lastly, we projected the change of OHCA burden under these two climate scenarios. Findings: We analyzed a total of 29,671 OHCA patients and found that high temperatures and heatwaves as well as low temperatures and cold spells were all significantly associated with an increased risk of OHCA onset. Under the scenario of uncontrolled emissions, the attributable fraction (AF) of OHCA due to high temperatures and heatwaves would increase by 4.94% and 6.99% from the 2010s to 2090s, respectively. The AF due to low temperatures would decrease by 1.27% by the 2090s and the effects of cold spells were projected to be marginal after the 2050s. Under a medium emission control scenario, the upward trend of heat-related OHCA burden would become flat, and the decline in cold-related OHCA burden would also slow down. Interpretation: Our study provides evidence of significant morbidity risk and burden of OHCA associated with global warming across Northern China. Our findings indicate that the increase in OHCA burden attributable to heat could not be offset by the decrements attributable to cold, emphasizing the importance of mitigation policies for limiting global warming and reducing the associated risks of OHCA onset. Funding: National Science & Technology Fundamental Resources Investigation Project (2018FY100600, 2018FY100602), National Key R&D Program of China (2020YFC1512700, 2020YFC1512705, 2020YFC1512703), Key R&D Program of Shandong Province (2021ZLGX02, 2021SFGC0503), Natural Science Foundation of Shandong Province (ZR2021MH231), Taishan Pandeng Scholar Program of Shandong Province (tspd20181220), the Interdisciplinary Young Researcher Groups Program of Shandong University (2020QNQT004), ECCM Program of Clinical Research Center of Shandong University (2021SDUCRCA001, 2021SDUCRCA002), foundation from Clinical Research Center of Shandong University (2020SDUCRCB003), National Natural Science Foundation of China (82272240).

Performance of noninvasive prenatal testing for twin pregnancies in South China.

OBJECTIVE: The purpose of this study was to evaluate the performance of noninvasive prenatal testing (NIPT) for the detection of chromosomal aneuploidies and copy number variations (CNVs) in twin pregnancies. METHOD: A cohort of 2010 women with twin pregnancies was recruited. 1331 patients opted for NIPT, and 679 patients opted for expanded NIPT (NIPT-plus). All high-risk patients were advised to undergo invasive prenatal diagnosis. All participants were followed up until 6 months after birth. RESULTS: Twenty-two cases were predicted to have a high risk of chromosome abnormalities by NIPT, of which 14 pregnant women underwent invasive prenatal diagnosis. The 14 cases included 3 cases of trisomy 21, 1 case of trisomy 18, 1 case of trisomy 7, 2 cases of sex chromosome aneuploidies (SCAs), and 7 cases of CNVs, of which the confirmed cases numbered 2, 1, 0, 1, and 0, respectively. Twenty cases were predicted to have a high risk of chromosome abnormalities by NIPT-plus, of which 16 pregnant women underwent invasive prenatal diagnosis. The 16 cases included 1 case of trisomy 21, 1 case of trisomy 7, 7 cases of SCAs, and 7 cases of CNVs, of which were confirmed in 1, 0, 3, and 2, respectively. No false-negative result was reported during the follow-up period. CONCLUSION: The NIPT/NIPT-plus has excellent performance in the detection of chromosome aneuploidies in twin pregnancies. But for CNVs, the effectiveness of NIPT is poor, and the NIPT-plus have a certain detection efficiency. It is worth noting that pre- and post-genetic counseling is especially important, and the chorionicity, mode of conception, clinical indications, and fetal fraction should be considered as influencing factors.

Association between cell-free DNA fetal fraction and pregnant character: a retrospective cohort study of 27,793 maternal plasmas.

To determine the association between cell-free DNA fetal fraction (cffDNA) and various prenatal characters to better guide the clinical application of noninvasive prenatal screening (NIPS), a retrospective cohort study of 27,793 women with singleton pregnancies was conducted. Results indicated that no significant difference on cffDNA between trisomy/sex chromosome aneuploidy (SCA) and non-trisomy groups was found. However, the fetal fraction (FF) in the T18 and T13 subgroups were significantly lower than that in the non-trisomy group, while the FF in the T21 group was significantly higher than the non-trisomy group. Pearson's correlation analysis revealed a positive correlation between √FF and gestational week in the T21, SCA, and non-trisomy groups. A negative correlation between maternal age and √FF in T21 and non-trisomy cases was found, but a positive correlation in SCA group. Compared to the decreasing trend in FF in the T21 group, no significant difference was observed in the SCA group. The √FF level was negatively correlated to maternal BMI in T21 and non-trisomy group, while a positive correlation in SCA group. FF was close related to the result of NIPS and related maternal factors. Though NIPS has increased accuracy, the complexity still should be recognized especially in clinical practice.

Fine and coarse particulate air pollution and out-of-hospital cardiac arrest onset: a nationwide case-crossover study in China.

Out-of-hospital cardiac arrest (OHCA) is a global public health concern. Nationwide studies on the effects of short-term exposure to particulate matter (PM) on OHCA risk are rare in regions with high PM levels, and evidence for coarse PM (PM2.5-10) is limited and inconsistent. To evaluate the associations between fine PM (PM2.5) and PM2.5-10 and OHCA onset, a time-stratified case-crossover study was conducted on 77,261 patients with cardiac OHCA in 26 cities across China in 2020. Daily PM2.5 and PM2.5-10 concentrations were assessed with high-resolution and full-coverage PM estimations. Conditional logistic regression models were applied in analyses. Each interquartile range of PM increase in 3-day moving average was associated with an increased risk of cardiac OHCA onset of 2.37% (95% CI, 1.20-3.56%) for PM2.5 and 2.12% (95% CI, 0.70-3.56%) for PM2.5-10. Stratified analyses showed higher susceptibility in patients over 75 years for PM2.5 exposure and with diabetes for PM2.5-10. This first nationwide study in region with high PM levels and great PM variability found not only PM2.5 but also PM2.5-10 were associated with a higher risk of OHCA onset, which could add powerful epidemiological evidence to this field and provide new evidence for the formulation of air quality guidelines.

Distinct Lipids Profiles and Associations With Clinical Indicators and Gut Microbiota in Children With Prader-Willi Syndrome.

Lipid metabolism is closely linked to adiposity. Prader-Willi syndrome (PWS) is a typical genetic disorder causing obesity; however, the distinct lipidomic profiles in PWS children have not been thoroughly investigated. Herein, serum lipidomics analyses were simultaneously explored in PWS, simple obesity (SO), and normal children (Normal). Results indicated that the total concentration of phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) in the PWS group were significantly deceased compared with both the SO and the Normal group. In contrast, compared with the Normal group, there was an overall significant increase in triacylglycerol (TAG) levels in both the PWS and the SO groups, with the highest found in SO group. Thirty-nine and 50 differential lipid species were screened among 3 groups: between obesity (PWS and SO) and the Normal group. Correlation analysis revealed distinct profiles in PWS that was different from other 2 groups. Notably, PC (P16:0/18:1), PE (P18:0-20:3), PE (P18:0-20:4)) showed significant negative correlation with body mass index (BMI) only in the PWS group. PE (P16:0-18:2) showed a negative association with BMI and weight in the PWS group, but significant positive correlation in the SO group; no statistically significant association was found in the Normal group. We also found a significant negative correlation between Blautia genus abundance and several significantly changed lipids, including LPC (14:0), LPC (16:0), TAG (C50:2/C51:9), TAG (C52:2/C53:9), TAG (C52:3/C53:10), and TAG (C52:4/C53:11), but no significant correlation in the Normal group and the SO group. Similarly, in the PWS group, the Neisseria genus was significantly negatively associated with acylcarnitine (CAR) (14:1), CAR (18:0), PE (P18:0/20:3), and PE (P18:0/20:4), and extremely positively associated with TAG (C52:2/C53:9); no obvious correlations were observed in the Normal group and the SO group.

Combined fetal fraction to analyze the Z-score accuracy of noninvasive prenatal testing for fetal trisomies 13, 18, and 21.

OBJECTIVE: This study aims to evaluate the correlation combined fetal fraction and Z-score for fetal trisomies 13, 18, and 21 of NIPT by the semiconductor sequencing platform and further analyze the differences of different sequencing depths. METHODS: A cohort of 61,581 pregnancies were recruited for NIPT. Invasive prenatal diagnostic confirmation is recommended in all high-risk NIPT cases. Logistic regression and rank correlation analysis were applied to analyze the relationship between different parameters. ROC curve analysis was adopted to analyze the cutoff values of Z-score and fetal fraction. RESULTS: A total of 278 common trisomy pregnancies were verified in 377 NIPT-positive results. The fitted logistic regression models revealed that Z-scores of NIPT-positive results were significantly associated with PPVs (p < 0.05). The ROC curve analysis showed that the optimal cutoff value of Z-scores for T21, T18, and T13 was 7.597, 4.944, and 9.135 for NIPT and 9.489, 8.004, and 12.4 for NIPT-plus. If combing fetal fraction as another evaluation factor, the PPV of trisomy 21 gradually improved. We analyzed the correlation between the fetal fraction and the PPV, which revealed that the fetal fraction was significantly correlated with PPV. By analyzing the PPV of different groups divided by the associated criteria obtained from ROC curve, the PPV of high Z-score and high fetal fraction is higher in groups of Z-score > the optimal cutoff value. CONCLUSION: The results of this study show that the fetal fraction is significantly correlated with the PPV. Combining fetal fraction with Z-score is significantly better than in groups of Z-score-associated criteria; clinicians can give more accurate and efficient prenatal genetic counseling.

Phenotypic findings and pregnancy outcomes of fetal rare autosomal aneuploidies detected using chromosomal microarray analysis.

BACKGROUND: Aneuploidies are the most common chromosomal abnormality and the main genetic cause of adverse pregnancy outcomes. Since numerous studies have focused on common trisomies, relatively little is known about the association between phenotypic findings and rare autosomal aneuploidies (RAAs). We conducted a retrospective study of 48,904 cases for chromosomal microarray analysis in a large tertiary referral center and reported the overall frequencies, clinical manifestations, and outcomes of prenatal RAAs. RESULTS: A total of 90 RAAs were detected, of which 83 cases were mosaic trisomies and 7 were non-mosaic trisomies. Chromosomes 16, 22, and 9 were identified as the major chromosomes involving RAAs. The four predominant indications for prenatal diagnosis in our RAA cases were RAA-positive in noninvasive prenatal screening, advanced maternal age, ultrasound abnormalities, and high-risk for serum prenatal screening. Cardiovascular defects were the most frequently observed structural abnormalities, followed by musculoskeletal anomalies. Increased nuchal translucency and persistent left superior vena cava, the major soft marker abnormalities involved, were also observed in our RAA cases. Clinical outcomes were available for all RAAs, with 63 induced abortions and 27 live births recorded. CONCLUSIONS: Variable phenotypes and outcomes were observed, which were highly heterogeneous in cases of prenatal RAAs. Thus, a cautious and comprehensive strategy should be implemented during prenatal counseling for RAAs.

Non-Invasive Prenatal Diagnosis of Monogenic Disorders Through Bayesian- and Haplotype-Based Prediction of Fetal Genotype.

Background: Non-invasive prenatal diagnosis (NIPD) can identify monogenic diseases early during pregnancy with negligible risk to fetus or mother, but the haplotyping methods involved sometimes cannot infer parental inheritance at heterozygous maternal or paternal loci or at loci for which haplotype or genome phasing data are missing. This study was performed to establish a method that can effectively recover the whole fetal genome using maternal plasma cell-free DNA (cfDNA) and parental genomic DNA sequencing data, and validate the method's effectiveness in noninvasively detecting single nucleotide variations (SNVs), insertions and deletions (indels). Methods: A Bayesian model was developed to determine fetal genotypes using the plasma cfDNA and parental genomic DNA from five couples of healthy pregnancy. The Bayesian model was further integrated with a haplotype-based method to improve the inference accuracy of fetal genome and prediction outcomes of fetal genotypes. Five pregnancies with high risks of monogenic diseases were used to validate the effectiveness of this haplotype-assisted Bayesian approach for noninvasively detecting indels and pathogenic SNVs in fetus. Results: Analysis of healthy fetuses led to the following accuracies of prediction: maternal homozygous and paternal heterozygous loci, 96.2 ± 5.8%; maternal heterozygous and paternal homozygous loci, 96.2 ± 1.4%; and maternal heterozygous and paternal heterozygous loci, 87.2 ± 4.7%. The respective accuracies of predicting insertions and deletions at these types of loci were 94.6 ± 1.9%, 80.2 ± 4.3%, and 79.3 ± 3.3%. This approach detected pathogenic single nucleotide variations and deletions with an accuracy of 87.5% in five fetuses with monogenic diseases. Conclusions: This approach was more accurate than methods based only on Bayesian inference. Our method may pave the way to accurate and reliable NIPD.

Light modulation based on the enhanced Kerr effect in molybdenum disulfide nanostructures with curved features.

A novel type of molybdenum disulfide (MoS2) nanoparticles (NPs) was chemically synthesized, which possessed curved features with three-dimensional (3D) freedom compared with planar two-dimensional (2D) materials. Due to the introduction of curved features, the synthesized NPs exhibited a strongly enhanced nonlinear refractive index (n2 ∼ 10-5 cm-2 W-1) and third-order susceptibility (χ(3) ∼ 10-7 esu), which were experimentally verified by the spatial self-phase modulation effect in the visible wavelength range. Both the nonlinear parameters were two orders of magnitude higher than their planar MoS2 nanostructure counterparts. In addition, the relative change of the effective nonlinear refractive index Δn2/n2 was found to be distinctly dependent on the intensity of the applied electromagnetic field. Moreover, an all-optical modulation was experimentally realized based on the spatial cross-phase modulation effect. Our results demonstrate planar MoS2 materials with 3D features as potential candidates for next generation all-optical applications and open a substantial approach for the design of efficient nanomaterials with favorable optical nonlinearity.

Orthodontic Rubber Band-Assisted Endoscopic Submucosal Dissection: An Efficient Method for Treating Superficial Colorectal Tumors.

BACKGROUND: Colorectal endoscopic submucosal dissection (ESD) is a complex operation. Effective traction is crucial. We have successfully used an orthodontic rubber band (ORB) combined with the clip traction method to assist ESD (ORB-ESD). The aim of this retrospective study is to describe the method and to compare the efficacy and safety of ORB-ESD versus conventional ESD in the treatment of superficial colorectal tumors. METHODS: We retrospectively analyzed the data of patients with superficial colorectal tumor (with diameter ≥ 20 mm) who received either ORB-ESD (n = 34) or conventional ESD (n = 90) between January 2019 and September 2020. Propensity score matching (PSM) was used to match the clinical data of 31 pairs of patients in each group. RESULTS: Operation time was significantly shorter for ORB-ESD than for conventional ESD (34.5 minutes vs. 56 minutes, P ≤ 0.001). In the propensity-matched cohorts, the operation time remained significantly shorter in the ORB-ESD patients (35 minutes vs. 50 minutes, P = 0.001). Postoperative adverse events, en bloc resection rate, and R0 resection rate were comparable between the two groups (P > 0.05), both before and after propensity score matching. In the ORB subgroup analysis, the trainee and expert ESD operation times were similar (37 (26-53) vs. 33.5 (26-37) minutes, respectively; P = 0.274). CONCLUSION: ORB-ESD appears to be an effective technique for ESD of colorectal cancer. Our findings need to be confirmed in large prospective multicenter studies.

[Analysis of the results of chromosomal trisomies 21, 18 and 13 screening among 40 628 women by non-invasive prenatal testing].

OBJECTIVE: To assess the clinical value of non-invasive prenatal testing (NIPT) for the screening of trisomy and copy number variations (CNVs) of chromosomes 21, 18 and 13. METHODS: From January 2015 to December 2019, 40 628 pregnant women underwent NIPT testing using high-throughput sequencing and bioinformatics analysis to test the cell-free fetal DNA in maternal plasma. High-risk pregnant women underwent invasive prenatal diagnosis, while low-risk ones were followed up by telephone. RESULTS: The three most common indications included intermediate risk of serological screening, high risk of serological screening and advanced maternal age. Among all pregnant women, 257 cases were detected as trisomy 21, 18 and 13 (170, 49 and 38 cases, respectively). 227 cases chose invasive prenatal diagnosis, with respectively 122, 28 and 10 cases confirmed. The positive predictive value (PPV) was 81.33% (122/150), 65.12% (28/43), 29.41% (10/34), respectively. Two false negative cases of trisomy 18 were found during follow-up. Meanwhile, NIPT has detected 46 cases (15, 16 and 15 cases, respectively) CNVs on chromosomes 21, 18 and 13, among which 37 cases underwent invasive prenatal diagnosis. There were 5, 3 and 5 positive cases, which yielded a PPV of 41.67% (5/12), 25%(3/12) and 33.33%(5/15), respectively. Two other chromosome CNVs were accidentally discovered among the false positive samples. CONCLUSION: The incidence of chromosomal abnormalities in the serological screening high-risk group was 52.02%, which was significantly higher than other groups. NIPT has a high sensitivity and specificity for the screening of trisomies 21, 18 and 13, while its accuracy for detecting CNVs of chromosomes 21, 18 and 13 needs to be improved. As a screening method, NIPT has a great clinical value, though there are still limitations of false positive and false negative results.Comprehensive pre- and post-test genetic counseling should be provided to the patients.

Outcomes of pregnancies with trisomy 16 mosaicism detected by NIPT: a series of case reports.

BACKGROUND: Trisomy 16 (T16) is thought to be the most frequent chromosome abnormality at conception, which is often associated with a high risk of abnormal outcomes. METHODS: A retrospective analysis of 14 cases with high risk of T16 by noninvasive prenatal testing (NIPT) was conducted. All cases in the analysis involved prenatal diagnosis, karyotyping and chromosomal microarray analysis. CASE REPORTS: NIPT detected 12 cases of T16 and 2 cases of T16 mosaicism. Prenatal diagnosis confirmed 5 true positive cases and 9 false positive cases. Among the 5 true positive cases, 3 cases had ultrasound abnormalities. All of the 9 false positive cases continued their pregnancies. The newborns who were from these 9 false positive cases except 1 case (case 7) had low birth weights (< 2.5 kg) and there were also 2 premature deliveries. CONCLUSION: NIPT serves as a fast and early prenatal screening method, giving clues to chromosome abnormalities and providing guidance for managing pregnancy. Confined placental mosaicism in 16 pregnancies may be at higher risk for preterm delivery.

Performances of NIPT for copy number variations at different sequencing depths using the semiconductor sequencing platform.

OBJECTIVE: To evaluate the performance of noninvasive prenatal testing (NIPT) and NIPT-PLUS for the detection of genome-wide microdeletion and microduplication syndromes (MMSs) at different sequencing depths. The NIPT sequencing depth was 0.15X, and the data volume was 3 million reads; the NIPT-PLUS sequencing depth was 0.4X, and the data volume was 8 million reads. METHODS: A cohort of 50,679 pregnancies was recruited. A total of 42,969 patients opted for NIPT, and 7710 patients opted for NIPT-PLUS. All high-risk cases were advised to undergo invasive prenatal diagnosis and were followed up. RESULTS: A total of 373 cases had a high risk of a copy number variation (CNV) as predicted by NIPT and NIPT-PLUS: NIPT predicted 250 high-risk CNVs and NIPT-PLUS predicted 123. NIPT-PLUS increased the detection rate by 1.02% (0.58% vs 1.60%, p < 0.001). A total of 291 cases accepted noninvasive prenatal diagnosis, with 197 cases of NIPT and 94 cases of NIPT-PLUS. The PPV of CNV > 10 Mb for NIPT-PLUS was significantly higher than that for NIPT (p = 0.02). The total PPV of NIPT-PLUS was 12.56% higher than that of NIPT (43.61% vs 30.96%, p = 0.03). CONCLUSION: NIPT-PLUS had a better performance in detecting CNVs in terms of the total detection rate and total PPV. However, great care must be taken in presenting results and providing appropriate counseling to patients when deeper sequencing is performed in clinical practice.