Benchmarking algorithms for single-cell multi-omics prediction and integration.

The development of single-cell multi-omics technology has greatly enhanced our understanding of biology, and in parallel, numerous algorithms have been proposed to predict the protein abundance and/or chromatin accessibility of cells from single-cell transcriptomic information and to integrate various types of single-cell multi-omics data. However, few studies have systematically compared and evaluated the performance of these algorithms. Here, we present a benchmark study of 14 protein abundance/chromatin accessibility prediction algorithms and 18 single-cell multi-omics integration algorithms using 47 single-cell multi-omics datasets. Our benchmark study showed overall totalVI and scArches outperformed the other algorithms for predicting protein abundance, and LS_Lab was the top-performing algorithm for the prediction of chromatin accessibility in most cases. Seurat, MOJITOO and scAI emerge as leading algorithms for vertical integration, whereas totalVI and UINMF excel beyond their counterparts in both horizontal and mosaic integration scenarios. Additionally, we provide a pipeline to assist researchers in selecting the optimal multi-omics prediction and integration algorithm.

Plasma alpha-trypsin inhibitor heavy chain 4 as an age-specific biomarker in the diagnosis and treatment of major depressive disorder.

Background: The diagnosis of major depressive disorder (MDD) mainly depends on subjective clinical symptoms, without an acceptable objective biomarker for the clinical application of MDD. Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) showed a high specificity as biomarker for the diagnosis and treatment of MDD. The present study aimed to investigate differences in plasma ITIH4 in two different aged MDD patients and underlying pathological mechanisms of plasma ITIH4 in the occurrence and development of MDD. Methods: Sixty-five adult MDD patients, 51 adolescent MDD patients, and 64 healthy controls (HCs) were included in the present study. A 14-days' antidepressive treatment was conducted in all MDD patients. Psychological assessments were performed and plasma ITIH4 and astrocyte-related markers were detected for all participants. Results: (1) Plasma levels of ITIH4 in adult MDD patients were significantly higher than adolescent MDD patients and HCs, and significantly increased plasma ITIH4 levels was observed in adolescent MDD patients compared with HCs (2). There were positive correlations between plasma ITIH4 levels and 24-item Hamilton Depression Scale (HAMD-24) scores and plasma glial fibrillary acidic protein (GFAP) levels in MDD patients, however, plasma ITIH4 levels were significantly correlated with age just in adult MDD patients (3). Plasma ITIH4 showed area under the curve values of 0.824 and 0.729 to differentiate adult MDD patients and adolescent MDD patients from HCs, respectively (4). There was significant decrease in plasma levels of ITIH4 between before and after antidepressive treatment in adult MDD patients, but not in adolescent MDD patients (5). Changed value of ITIH4 levels were correlated with the changed value of GFAP levels and changed rate of HAMD-24 scores in adult MDD patients following antidepressive treatment. Conclusion: Plasma ITIH4 may be potential plasma biomarkers of MDD with age-related specificity, which was associated with depressive symptoms astrocyte-related pathologic changes, and antidepressive treatment efficacy.

A Peptide-Drug Conjugate-Based Nanoplatform for Immunometabolic Activation and In Situ Nerve Regeneration in Advanced-Stage Alzheimer's Disease.

The formidable protection of physiological barriers and unclear pathogenic mechanisms impede drug development for Alzheimer's disease (AD). As defenders of the central nervous system, immune-metabolism function, and stemness of glial cells remain dormant during degeneration, representing a significant challenge for simultaneously targeting and modulating. Here, a modular nanoplatform is presented composed of peptide-drug conjugates and an inflammation-responsive core. The nanoplatform is transported through the blood-brain barrier via transcytosis and disassembles in the oxidative stress microenvironment upon intravenous administration. The released drug-conjugated modules can specifically target and deliver hydroxychloroquine (HCQ) and all-trans retinoic acid (ATRA) to microglia and astrocytes, respectively. The immune function of chronic tolerant microglia is activated by metabolic modulation, and reactive astrocytes trans-differentiate into functional neurons. In a transgenic mouse model, nanoplatform reduces levels of toxic proteins and inflammation while increasing neuronal density. This results in the amelioration of learning and memory decline. The modular nanoplatform provides design principles for multi-cellular targeting and combination nano-therapy for inflammation-related diseases.

Remote Functionalization of Inert C(sp3)-H Bonds via Dual Catalysis Driven by Alkene Hydrofluoroalkylation Using Industrial Feedstocks.

We have developed a dual-catalytic system capable of site-selective azidation of inert C(sp3)-H bonds with concomitant and modular anti-Markovnikov alkene fluoroalkylation. The protocol leverages the synergetic cooperation of both the photocatalyst and earth-abundant iron catalyst to deliver two radical species in succession to minimally functionalized alkenes. This powerful catalyst system exhibits broad scope, mild conditions, and excellent regioselectivity for a variety of substrates and fluoroalkyl fragments. The key to this C-centered radical relay is the matched rate of both photocatalytic and iron catalytic cycles, ensuring selective azidofluoroalkylation with a broad array of fluoroalkyl sources from trivial reagents.

Chronic environmental level exposure to perfluorooctane sulfonate overshadows graphene oxide to induce apoptosis through activation of the ROS-p53-caspase pathway in marine medaka Oryzias melastigma.

The widespread occurrence of perfluorooctane sulfonate (PFOS) and the mass production and application of graphene oxide (GO) lead to their inevitable release and interaction in the environment, which may enhance associated toxic impacts on aquatic organisms. This study elucidates the induction of apoptosis by 60-day chronic single and mixture exposures to environmentally relevant levels of PFOS (0.5 µg/L and 5 µg/L) and GO (1 mg/L) in adult marine medaka Oryzias melastigma. Results showed a significant increase (p < 0.05) in reactive oxygen species (ROS) levels, the apoptotic positive rate in livers, and activities of caspases 3, 8, and 9 in all treated groups compared to the control. PFOS individual and PFOS-GO combined exposures significantly impacted fish growth, upregulated expressions of six apoptosis-related genes including p53, apaf1, il1b, tnfa, bcl2l1, bax, as well as enriched cell cycle and p53 signaling pathways (transcriptomic analysis) related to apoptosis compared to control group. Besides higher ROS production, GO also had a higher binding affinity to proteins than PFOS, especially to caspase 8 as revealed by molecular docking. Overall, PFOS induced ROS-p53-caspase apoptosis pathway through multi-gene regulation during single or mixture exposure, while GO single exposure induced apoptosis through tissue damage and ROS-caspase pathway activation and direct docking with caspase 8 to activate the caspase cascade. Under co-exposure, the PFOS-induced apoptotic pathway overshadowed the GO-induced pathway, due to competition for limited active sites on caspases. These findings will contribute to a better understanding of the apoptosis mechanism and ecological risks of nanomaterials and per- and polyfluoroalkyl substances in marine ecosystems.

Prognostic significance of a 3-gene ferroptosis-related signature in lung cancer via LASSO analysis and cellular functions of UBE2Z.

Ferroptosis is a newly identified form of non-apoptotic programmed cell death resulting from iron-dependent lipid peroxidation. It is controlled by integrated oxidation and antioxidant systems. Ferroptosis exerts a crucial effect on the carcinogenesis of several cancers, including pulmonary cancer. Herein, a ferroptosis-associated gene signature for lung cancer prognosis and diagnosis was identified using integrative bioinformatics analyses. From the FerrDB database, 256 ferroptotic regulators and markers were identified. Of these, 25 exhibited differential expression between lung cancer and non-cancerous samples, as evidenced by the GSE19804 and GSE7670 datasets from the GEO database. Utilizing LASSO Cox regression analysis on TCGA-LUAD data, a potent 3-gene risk signature comprising CAV1, RRM2, and EGFR was established. This signature adeptly differentiates various survival outcomes in lung cancer patients, including overall survival and disease-specific intervals. Based on the 3-gene risk signature, lung cancer patients were categorized into high-risk and low-risk groups. Comparative analysis revealed 69 differentially expressed genes between these groups, with UBE2Z significantly associated with overall survival in TCGA-LUAD. UBE2Z was found to be upregulated in LUAD tissues and cells compared to normal controls. Functionally, the knockdown of UBE2Z curtailed aggressive behaviors in LUAD cells, including viability, migration, and invasion. Moreover, this knockdown led to a decrease in the mesenchymal marker vimentin while elevating the epithelial marker E-cadherin within LUAD cell lines. In conclusion, the ferroptosis-associated 3-gene risk signature effectively differentiates prognosis and clinical features in patients with lung cancer. UBE2Z was identified through this model, and it is upregulated in LUAD samples. Its knockdown inhibits aggressive cellular behaviors, suggesting UBE2Z's potential as a therapeutic target for lung cancer treatment.

Omega-3 Polyunsaturated Fatty Acids as a Protective Factor for Myopia.

PURPOSE: Animal models suggest omega-3 polyunsaturated fatty acids (PUFAs) may protect against myopia by modulating choroidal blood perfusion, but clinical evidence is scarce and mixed. We aimed to determine the causality between omega-3 PUFAs and myopia using Mendelian randomization (MR) analysis. DESIGN: Two-sample MR analysis. METHODS: Exposures are genetically predicted 18 fatty acids (FAs) related traits. Spherical equivalent refraction (SER) and axial length were used as measurements of myopia. Genome-wide association study summary data on blood levels of 18 FAs related traits (n=115,006), refractive spherical equivalent (n=351,091), axial length (n=69,945) and choroidal thickness (n=44,823) were sourced from the UK Biobank, the Genetic Epidemiology Research on Adult Health and Aging cohort, and the Consortium for Refractive Error and Myopia Study. We used five MR models and considered results statistically significant if the Bonferroni-corrected P-value was ≤2.78 × 10-3 in at least 3 MR models. The beta represents the change in outcomes (SER in diopter; axial length in mm; choroidal thickness in standard deviation) per standard deviation unit increase in FAs levels. RESULTS: At a Bonferroni-corrected significance, higher levels of omega-3 (Beta, 0.32-0.34), omega-3/total FAs ratio (Beta, 0.31-0.44), docosahexaenoic acid (DHA) (Beta, 0.36-0.46), DHA/total FAs ratio (Beta, 0.37-0.53), PUFAs/total FAs ratio (Beta, 0.07-1.003), and degree of unsaturation (Beta, 0.28-0.44) were associated with a more positive SER, suggesting a lower risk of myopia. Similar trends were observed for axial length albeit with borderline significance (P≤0.035 in ≥2 models). Higher levels of omega-3, DHA, DHA/total FAs ratio, PUFAs/total FAs ratio, PUFAs/monounsaturated FAs ratio, and degree of unsaturation were nominally associated with thicker choroidal thickness (Beta, 0.05-0.13; P≤0.045 in ≥2 models). CONCLUSION: Our multiple MR models suggest a protective effect of omega-3 and DHA on myopia, potentially through modulation of choroidal blood perfusion. Further randomized clinical trials are needed to confirm the effectiveness and determine the optimal dose and duration.

SIKVAV promotion proliferation of vascular endothelial cells and related mechanisms.

BACKGROUND: Vascular endothelial injury, a key factor in diabetic foot ulcers (DFUs) pathogenesis, is linked to the impaired proliferation and migration of vascular endothelial cells, modulated by hypoxia-inducible factor, growth factors, and inflammatory elements. OBJECTIVE: The present study assesses the role of SIKVAV (Ser-Ile-Lys-Val-Ala-Val), a peptide shown to enhance cell proliferation and migration, on mouse aortic endothelial cell (MAEC) and the corresponding molecular mechanisms. METHODS: MAEC were treated with SIKVAV at 0, 100, 200, 400, and 600 µg/mL for 0, 24, 48, and 72 h. Cell viability was tested using the CCK-8 assay. Proliferating cell nuclear antigen (PCNA), extracellular signal-regulated kinase 1/2 (ERK1/2), and protein kinase B (Akt) levels were measured by qRT-PCR and western blot. RESULTS: SIKVAV augmented PCNA mRNA expression and stimulated vascular endothelial cell proliferation in a concentration and time-dependent fashion. Furthermore, it amplified the expression of p-ERK1/2 and p-Akt, pivotal components of the mitogen-activated protein kinase (MAPK)/ERK1/2 and phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathways. The inhibition of these pathways suppressed PCNA mRNA expression, cell proliferation rate, and decreased p-ERK1/2 and p-Akt levels, highlighting SIKVAV's role in promoting vascular endothelial cell proliferation via these pathways. CONCLUSION: The results of this study confirmed that SIKVAV grafted onto scaffolds can accelerate the proliferation of vascular endothelial cells for the therapy of skin wounds, and provide a theoretical basis for its application in ischemic disease as synthesized biomaterials scaffolds of tissue engineering.

Magnetic tuning with minimal thermal drift in high-Q microspheres coated with magnetorheological polydimethylsiloxane.

Integration of whispering-gallery-mode (WGM) resonators with high-quality factors (Q) into advanced timing, oscillator, and sensing systems demands a platform that enables precise resonance frequency modulation. This study investigates the tuning characteristics of magnetorheological polydimethylsiloxane (MR-PDMS) coated microspheres (µ-spheres) employed as magnetic microresonators, achieving a Q value of 107 at the 1550 nm wavelength. Magnetic WGM resonators not only endow the device with magnetic adjustability but also markedly improve thermal resistance. Experimental findings reveal that the magnetic µ-sphere demonstrates a sensitivity of -32.53 MHz/mT, outperforming conventional magnetic WGM resonators. Furthermore, analysis of the temperature dependence shows a reduction in fluctuation to -2.85 MHz/K, thereby greatly enhancing the sensor's practical detection limit.

Schisandrol B inhibits calcification of aortic valve by targeting p53 related inflammatory and senescence.

Calcific aortic valve disease (CAVD) primarily involves osteogenic differentiation in human aortic valve interstitial cells (hVICs). Schisandrol B (SolB), a natural bioactive constituent, has known therapeutic effects on inflammatory and fibrotic disorders. However, its impact on valve calcification has not been reported. We investigated the effect of SolB on osteogenic differentiation of hVICs. Transcriptome sequencing was used to analyze potential molecular pathways affected by SolB treatment. The study also included an in vivo murine model using aortic valve wire injury surgery to observe SolB's effect on valve calcification. SolB inhibited the osteogenic differentiation of hVICs, reversing the increase in calcified nodule formation and osteogenic proteins. In the murine model, SolB significantly decreased the peak velocity of the aortic valve post-injury and reduced valve fibrosis and calcification. Transcriptome sequencing identified the p53 signaling pathway as a key molecular target of SolB, demonstrating its role as a molecular glue in the mouse double minute 2 (MDM2)-p53 interaction, thereby promoting p53 ubiquitination and degradation, which further inhibited p53-related inflammatory and senescence response. These results highlighted therapeutic potential of SolB for CAVD via inhibiting p53 signaling pathway and revealed a new molecular mechanism of SolB which provided a new insight of theraputic mechanism for CAVD.

Clinical value of complete blood count ratio in benign and malignant thyroid diseases.

OBJECTIVE: To investigate the clinical value of blood routine derivative biomarkers and thyroid function biomarkers in differentiating different thyroid diseases. METHODS: The differences of blood routine derived indexes neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), platelet-large cell rate (P-LCR) and thyroid function indexes between benign and malignant thyroid diseases were compared, and the differences of each index between different benign thyroid diseases were further compared. Univariate regression analysis model was used to analyze the clinical value of various indexes. Receiver operating characteristic curve (ROC) was used to calculate the area under the curve (AUC). RESULTS: There were statistically significant differences in PLR, NLR and P-LCR between patients with benign and malignant thyroid diseases (P < 0.05 for each). The results of univariate logistic regression analysis showed that P < 0.05 for all indicators except LMR, when PLR and NLR value increased by 1, the risk of thyroid malignancy decreased by 1 % and 21 %, when P-LCR value increased by 1, the risk of thyroid malignancy increased by 4 %. CONCLUSIONS: PLR, NLR and P-LCR are helpful to distinguish different benign thyroid diseases and to diagnose benign and malignant thyroid diseases.

Regulation of seawater dissolved carbon pools by environmental changes in Ulva prolifera originating sites: A new perspective on the contribution of U. prolifera to the seawater carbon sink function.

The Ulva prolifera bloom is considered one of the most serious ecological disasters in the Yellow Sea in the past decade, forming a carbon sink in its source area within a short period but becoming a carbon source at its destination. To explore the effects of different environmental changes on seawater dissolved carbon pools faced by living U. prolifera in its originating area, U. prolifera were cultured in three sets with different light intensity (54, 108, and 162 µmol m-2 s-1), temperature (12, 20, and 28 °C) and nitrate concentration gradients (25, 50, and 100 µmol L-1). The results showed that moderate light (108 µmol m-2 s-1), temperature (20 °C), and continuous addition of exogenous nitrate significantly enhanced the absorption of dissolved inorganic carbon (DIC) in seawater by U. prolifera and most promoted its growth. Under the most suitable environment, the changes in the seawater carbonate system were mainly dominated by biological production and denitrification, with less influence from aerobic respiration. Facing different environmental changes, U. prolifera continuously changed its carbon fixation mode according to tissue δ13C results, with the changes in the concentrations of various components of DIC in seawater, especially the fluctuation of HCO3- and CO2 concentrations. Enhanced light intensity of 108 µmol m-2 s-1 could shift the carbon fixation pathway of U. prolifera towards the C4 pathway compared to temperature and nitrate stimulation. Environmental conditions at the origin determined the amount of dissolved carbon fixed by U. prolifera. Therefore, more attention should be paid to the changes in marine environmental conditions at the origin of U. prolifera, providing a basis for scientific management of U. prolifera.

Transcranial ultrafast ultrasound Doppler imaging: A phantom study.

Ultrafast ultrasound Doppler imaging facilitates the assessment of cerebral hemodynamics with high spatio-temporal resolution. However, the significant acoustic impedance mismatch between the skull and soft tissue results in phase aberrations, which can compromise the quality of transcranial imaging and introduce biases in velocity and direction quantification of blood flow. This paper proposed an aberration correction method that combines deep learning-based skull sound speed modelling with ray theory to realize transcranial plane-wave imaging and ultrafast Doppler imaging. The method was validated through phantom experiments using a linear array with a center frequency of 6.25 MHz, 128 elements, and a pitch of 0.3 mm. The results demonstrated an improvement in the imaging quality of intracranial targets when using the proposed method. After aberration correction, the average locating deviation decreased from 1.40 mm to 0.27 mm in the axial direction, from 0.50 mm to 0.20 mm in the lateral direction, and the average full-width-at-half-maximum (FWHM) decreased from 1.37 mm to 0.97 mm for point scatterers. For circular inclusions, the average contrast-to-noise ratio (CNR) improved from 8.1 dB to 11.0 dB, and the average eccentricity decreased from 0.36 to 0.26. Furthermore, the proposed method was applied to transcranial ultrafast Doppler flow imaging. The results showed a significant improvement in accuracy and quality for blood Doppler flow imaging. The results in the absence of the skull were considered as the reference, and the average normalized root-mean-square errors of the axial velocity component on the five selected axial profiles were reduced from 17.67% to 8.02% after the correction.

TTYH3 Promotes Cervical Cancer Progression by Activating the Wnt/ß-Catenin Signaling Pathway.

The role of tweety homolog 3 (TTYH3) has been studied in several cancers, including hepatocellular carcinoma, cholangiocarcinoma, and gastric cancer. The results showed that TTYH3 is highly expression in cervical cancer tissues and cells and high TTYH3 expression correlates with poor prognosis in patients with cervical cancer. TTYH3 markedly reduced the apoptosis rate and promoted proliferation, migration, and invasion. Silencing of TTYH3 has been shown to have an inhibitory effect on cervical cancer progression. Moreover, TTYH3 enhanced EMT and activated Wnt/ß-catenin signaling. Furthermore, TTYH3 knockdown inhibited the tumor growth in vivo. In conclusion, TTYH3 promoted cervical cancer progression by activating the Wnt/ß-catenin signaling.

TTYH3 is upregulated in cervical cancer tissue and cells.TTYH3 promotes cervical cancer cell proliferation.TTYH3 inhibits cervical cancer cell apoptosis.TTYH3 induces cervical cancer cell migration and invasion.TTYH3 activates the Wnt signaling in cervical cancer cell.

Efficacy and safety of oncoplastic breast-conserving surgery versus conventional breast-conserving surgery: An updated meta-analysis.

INTRODUCTION: Breast cancer is the most common cancer among women. The surgical treatment of breast cancer has transitioned progressively from radical mastectomy to breast-conserving surgery. In this meta-analysis, we are aiming to compare oncoplastic breast-conserving surgery (OS) with conventional breast-conserving surgery (BCS) in terms of efficacy and safety. METHODS: We searched Medline, Web of Science, Embase, Cochrane databases, Clinicaltrial.gov, and CNKI until April 30, 2024. Data from cohort studies and randomized controlled trials (RCTs) were included. Outcomes included primary outcomes (re-excision, local recurrence, positive surgical margin, mastectomy), secondary outcomes and safety outcomes. The Cochrane Risk of Bias Assessment Tool and Newcastle-Ottawa Scale were used to evaluate the quality of outcomes. RESULTS: Our study included 52 studies containing 46,835 patients. Primary outcomes comprise re-excision, local recurrence, positive surgical margin, and mastectomy, there were significant differences favoring OS over BCS (RR 0.68 [0.56, 0.82], RR 0.62 [0.47, 0.82], RR 0.76 [0.59, 0.98], RR 0.66 [0.44, 0.98] respectively), indicating superior efficacy of OS. Additionally, OS demonstrated significant aesthetic benefits (RR 1.17 [1.03, 1.33] and RR 1.34 [1.18, 1.52]). While total complications were significantly fewer in the OS group (RR 0.70 [0.53, 0.94]), the differences in specific complications were not significant. Furthermore, subgroup analyses were conducted based on nationality, sample size, quality, and type. CONCLUSION: OS demonstrates either superior or at least comparable outcomes across various aspects when compared to BCS.

Neural Signals Associated with Orienting Response and Arousal Inhibition in Concealed Information Test.

Recent theory suggests that both the orienting response and arousal inhibition play roles in the effect of the concealed information test (CIT). However, the neural signatures associated with these two processes remain unclear. To address this issue, participants were motivated to either conceal or reveal crime-related stimulus during CIT while EEG was recorded. By using a temporal principal component analysis, we found that crime-related stimuli produced a larger early P3 than crime-irrelevant stimuli in both the conceal condition and reveal condition. This result suggests that this early P3 reflects an orienting response. In addition, we found that crime-related stimuli elicited a larger frontal negative slow wave than crime-irrelevant stimuli in the conceal condition but not the reveal condition, which suggests that the frontal negative slow wave reflects the arousal inhibition process. These results provide crucial evidence for understanding the neural basis underlying CIT.

Progesterone (P4) ameliorates cigarette smoke-induced chronic obstructive pulmonary disease (COPD).

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease associated with high morbidity and mortality worldwide. Oxidative injury and mitochondrial dysfunction in the airway epithelium are major events in COPD progression. METHODS AND RESULTS: The therapeutic effects of Progesterone (P4) were investigated in vivo and in vitro in this study. In vivo, in a cigarette smoke (CS) exposure-induced COPD mouse model, P4 treatment significantly ameliorated CS exposure-induced physiological and pathological characteristics, including inflammatory cell infiltration and oxidative injury, in a dose-dependent manner. The c-MYC/SIRT1/PGC-1α pathway is involved in the protective function of P4 against CS-induced COPD. In vitro, P4 co-treatment significantly ameliorated H2O2-induced oxidative injury and mitochondrial dysfunctions by promoting cell proliferation, increasing mitochondrial membrane potential, decreasing ROS levels and apoptosis, and increasing ATP content. Moreover, P4 co-treatment partially attenuated H2O2-caused inhibition in Nrf1, Tfam, Mfn1, PGR-B, c-MYC, SIRT1, and PGC-1α levels. In BEAS-2B and ASM cells, the c-MYC/SIRT1 axis regulated P4's protective effects against H2O2-induced oxidative injury and mitochondrial dysfunctions. CONCLUSION: P4 activates the c-MYC/SIRT1 axis, ameliorating CS-induced COPD and protecting both airway epithelial cells and smooth muscle cells against H2O2-induced oxidative damage. PGC-1α and downstream mitochondrial signaling pathways might be involved.

Clinical value of prenatal screening markers in early pregnancy combined with perinatal characteristics to predict fetal growth restriction.

Background: Due to the incomplete standardization of the etiology and diagnostic criteria for fetal growth restriction (FGR), there has been uncertainty in the early prediction of FGR. The comprehensive estimation of FGR was mainly based on various factors, such as maternal characteristics and medical history, nuchal translucency (NT), and serum biochemical markers [pregnancy-associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotropin (free ß-hCG)]. Herein, we performed a retrospective cohort study to investigate the correlation and diagnostic value of maternal markers such as PAPP-A, free ß-hCG, and NT in the first trimester with maternal characteristics, so as to provide theoretical basis for perinatal care and the application of low-dose aspirin. Methods: A retrospective cohort study was conducted to analyze the data of an FGR group and a non-FGR group. Chi-square test and Mann-Whitney U test were used for univariate analysis of qualitative or quantitative data, respectively. Modified Poisson regression calculated the relative risk (RR) and 95% confidence interval (CI) of perinatal variables; P<0.05 was considered statistically significant. Results: The multiple of median (MoM) of PAPP-A level and NT in the FGR group were lower than those of the non-FGR group [0.63 (0.12-2.08) vs. 1.01 (0.28-2.41) MoM, 1.30 (0.80-2.07) vs. 1.40 (0.80-2.20) cm, P<0.05]. The weight, score, and length of newborns in the FGR group were lower than those in the non-FGR group (all P<0.001). Modified Poisson regression analysis showed that gestational hypertension (GH) [RR =1.836 (95% CI: 1.188-2.836)], oligohydramnios [1.420 (95% CI: 1.022-1.973)], premature rupture of membranes (PROM) [0.641 (95% CI: 0.425-0.969)], female infant [1.539 (95% CI: 1.098-2.157)], low infant length [5.700 (95% CI: 3.416-9.509)], low birth weight [1.609 (95% CI: 1.012-2.559), and increased PAPP-A MoM [0.533 (95% CI: 0.369-0.769)] were associated with FGR. The cut-off value of PAPP-A + free ß-hCG + NT for predicting FGR was 0.190, with a sensitivity of 0.547 and a specificity of 0.778. Conclusions: Early screening markers combined with perinatal characteristics have better diagnostic value in predicting FGR and provide a scientific basis for the clinical use of low-dose aspirin to prevent FGR.

Representation of obesity in contemporary atrial fibrillation ablation randomized controlled trials.

BACKGROUND: The prevalence and impact of obesity on outcomes of atrial fibrillation (AF) ablation randomized controlled trials (RCTs) have not been well studied. OBJECTIVE: To examine the proportion of participants with obesity enrolled in RCTs of AF ablation and outcomes of ablation when subgroup analysis of participants with obesity were available. METHODS: We systematically searched PubMed and EMBASE for AF ablation RCTs published between January 1, 2015 to May 31, 2022. When body mass index (BMI) data were available, normal distribution was assumed and a z score was used to estimate the proportion of obesity. Results categorized by BMI or body weight status were reviewed. Authors were contacted for additional information. RESULTS: Of 148 eligible RCTs with 30174 participants, 144 (97.30%) RCTs did not report the proportion of participants with obesity, while published information regarding BMI was available in 63.51%. Three trials excluded patients based on BMI. Using reported BMI, we estimated the proportion of participants with obesity varied greatly across these trials, ranging from 5.82%-71.9% (median 38.02%, interquartile 29.64%, 49.10%). Patients with obesity were represented in a greater proportion among trials conducted in North America (50.23%) and Asia (44.72%), compared to others (32.16%), p < .001. Subgroup analysis or analysis adjusting for BMI was reported in only 13 (8.78%) RCTs; four (30.77%) of these suggested that BMI or body weight might negatively affect primary outcomes. CONCLUSION: Obesity is a common comorbidity among AF patients. However, most AF ablation RCTs underreported the proportion of participants with obesity and its impact on the primary outcomes.