Lymph node metastasis in early invasive lung adenocarcinoma: Prediction model establishment and validation based on genomic profiling and clinicopathologic characteristics.

BACKGROUND: The presence of lymph node (LN) metastasis directly affects the treatment strategy for lung adenocarcinoma (LUAD). Next-generation sequencing (NGS) has been widely used in patients with advanced LUAD to identify targeted genes, while early detection of pathologic LN metastasis using NGS has not been assessed. METHODS: Clinicopathologic features and molecular characteristics of 224 patients from Ruijin Hospital were analyzed to detect factors associated with LN metastases. Another 140 patients from Huashan Hospital were set as a test cohort. RESULTS: Twenty-four out of 224 patients were found to have lymph node metastases (10.7%). Pathologic LN-positive tumors showed higher mutant allele tumor heterogeneity (p < 0.05), higher tumor mutation burden (p < 0.001), as well as more frequent KEAP1 (p = 0.001), STK11 (p = 0.004), KRAS (p = 0.007), CTNNB1 (p = 0.017), TP53, and ARID2 mutations (both p = 0.02); whereas low frequency of EGFR mutation (p = 0.005). A predictive nomogram involving male sex, solid tumor morphology, higher T stage, EGFR wild-type, and TP53, STK11, CDKN2A, KEAP1, ARID2, KRAS, SDHA, SPEN, CTNNB1, DICER1 mutations showed outstanding efficiency in both the training cohort (AUC = 0.819) and the test cohort (AUC = 0.780). CONCLUSION: This study suggests that the integration of genomic profiling and clinical features identifies early-invasive LUAD patients at higher risk of LN metastasis. Improved identification of LN metastasis is beneficial for the optimization of the patient's therapy decisions.

Prenatal Exposure of PFAS in Cohorts of Pregnant Women: Identifying the Critical Windows of Vulnerability and Health Implications.

Cohorts of pregnant women in 2018 and 2020 were selected to explore prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances (PFAS). Maternal serum during the whole pregnancy (first to third trimesters) and matched cord serum were collected for the analysis of 50 PFAS. Perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), and 6:2 fluorotelomer sulfonic acid (6:2 FTS) were the dominant PFAS in both the maternal and cord serum. The median ∑PFAS concentration was 14.18 ng/mL, and the ∑PFAS concentration was observed to decline from the first trimester to the third trimester. The transplacental transfer efficiencies (TTE) of 29 PFAS were comprehensively assessed, and a "U"-shaped trend in TTE values with increasing molecular chain length of perfluoroalkyl carboxylic acid (PFCA) was observed in this study. Moreover, the maternal concentrations of 9-chlorohexadecafluoro-3-oxanonane-1-sulfonic acid (6:2 Cl-PFESA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUdA), perfluorododecanoic acid (PFDoA), PFOS, and hexafluoropropylene oxide dimer acid (HFPO-DA) in the 2020 cohort were significantly lower than those in the 2018 cohort, declining by about 23.85-43.2% from 2018 to 2020 (p < 0.05). Higher proportions of emerging PFAS were observed in fetuses born in 2020. This birth cohort was collected during the COVID-19 epidemic period. The change in the PFAS exposure scene might be in response to the different exposure profiles of the 2018 and 2020 cohorts, which are attributed to the impact of COVID-19 on the social activities and environment of pregnant women. Finally, by application of a multiple informant model, the third trimester was identified as the critical window of vulnerability to PFAS exposure that affects birth weight and birth length.

DL-Serine Hydrazide Hydrochloride Multiple-site Synergy Induced Effective and Stable Formamidine-Rich Perovskite Solar Cells.

The efficiency and stability of solar cells are two key indicators that determine for the commercial feasibility of photovoltaic devices. Formamidine-cesium perovskite has been extensively investigated since its excellent thermal stability and has great potential in achieving high power conversion efficiency. However, during the aging process, especially under light conditions, formamidine-rich perovskites are prone to produce iodine, and the escape of iodine is one of the important factors leading to device degradation. Here, DL-Serine Hydrazide Hydrochloride containing the reducing group is introduced into the precursor solution of formamidine-cesium perovskite, which achieves multiple-site passivation. Hydrazine reacts with iodine to reduce it to iodine ions, inhibiting the escape of iodine. In addition, carbonyl groups and uncoordinated lead ions form coordination bonds to reduce defects. In the end, the perovskite solar cell with DL-Serine Hydrazide Hydrochloride added achieves a champion efficiency of 22.22%, and maintains 85.88% of the initial efficiency after continuous exposure under 1 sun for 7000 s at a relative humidity of ≈40%. Additionally, DL-Serine Hydrazide Hydrochloride added device shows good stability in air environments with relative humidity of 50%-60%. DL-Serine Hydrazide Hydrochloride improves the stability of formamidine-rich perovskite solar cells and provides a low-cost strategy for commercial development.

Mitochondrial glycerol 3-phosphate dehydrogenase deficiency exacerbates lipotoxic cardiomyopathy.

Metabolic diseases such as obesity and diabetes induce lipotoxic cardiomyopathy, which is characterized by myocardial lipid accumulation, dysfunction, hypertrophy, fibrosis and mitochondrial dysfunction. Here, we identify that mitochondrial glycerol 3-phosphate dehydrogenase (mGPDH) is a pivotal regulator of cardiac fatty acid metabolism and function in the setting of lipotoxic cardiomyopathy. Cardiomyocyte-specific deletion of mGPDH promotes high-fat diet induced cardiac dysfunction, pathological hypertrophy, myocardial fibrosis, and lipid accumulation. Mechanically, mGPDH deficiency inhibits the expression of desuccinylase SIRT5, and in turn, the hypersuccinylates majority of enzymes in the fatty acid oxidation (FAO) cycle and promotes the degradation of these enzymes. Moreover, manipulating SIRT5 abolishes the effects of mGPDH ablation or overexpression on cardiac function. Finally, restoration of mGPDH improves lipid accumulation and cardiomyopathy in both diet-induced and genetic obese mouse models. Thus, our study indicates that targeting mGPDH could be a promising strategy for lipotoxic cardiomyopathy in the context of obesity and diabetes.

Disruption of maternal vascular remodeling by a fetal endoretrovirus-derived gene in preeclampsia.

BACKGROUND: Preeclampsia, one of the most lethal pregnancy-related diseases, is associated with the disruption of uterine spiral artery remodeling during placentation. However, the early molecular events leading to preeclampsia remain unknown. RESULTS: By analyzing placentas from preeclampsia, non-preeclampsia, and twin pregnancies with selective intrauterine growth restriction, we show that the pathogenesis of preeclampsia is attributed to immature trophoblast and maldeveloped endothelial cells. Delayed epigenetic reprogramming during early extraembryonic tissue development leads to generation of excessive immature trophoblast cells. We find reduction of de novo DNA methylation in these trophoblast cells results in selective overexpression of maternally imprinted genes, including the endoretrovirus-derived gene PEG10 (paternally expressed gene 10). PEG10 forms virus-like particles, which are transferred from the trophoblast to the closely proximate endothelial cells. In normal pregnancy, only a low amount of PEG10 is transferred to maternal cells; however, in preeclampsia, excessive PEG10 disrupts maternal vascular development by inhibiting TGF-beta signaling. CONCLUSIONS: Our study reveals the intricate epigenetic mechanisms that regulate trans-generational genetic conflict and ultimately ensure proper maternal-fetal interface formation.

Rapid electrodeposition of Cu nanoparticle film on Ni foam as an integrated 3D free-standing electrode for non-invasive and non-enzymatic creatinine sensing.

High cost, inherent destabilization, and intricate fixing of enzyme molecules are the main drawbacks of enzyme-based creatinine sensors. The design of a low-cost, stabilizable, and enzyme-free creatinine sensing probe is essential to address these limitations. In this work, an integrated three-dimensional (3D) free-standing electrode was designed to serve as a non-enzymatic creatinine sensing platform and was fabricated by rapid electrodeposition of a dense copper nanoparticle film on nickel foam (Cu NP film/NF). This low-cost, stable, easy-to-fabricate, and binder-free Cu NP film/NF electrode has abundant active sites and excellent electrochemical performance. Cyclic voltammetry measurements show a wide linear range (0.25-24 mM), low detection limit (0.17 mM), and high sensitivity (306 µA mM-1 cm-2). The developed sensor shows high recovery of creatinine concentration in real urine. Besides, it has better specificity, reproducibility, and robustness in detecting creatinine. These excellent results suggest that a non-enzymatic creatinine sensor based on an integrated 3D free-standing Cu NP film/NF electrode has good potential for non-invasive detection of urinary creatinine.

Genetic insights into the 'sandwich fusion' subtype of Klippel-Feil syndrome: novel FGFR2 mutations identified by 21 cases of whole-exome sequencing.

BACKGROUND: Klippel-Feil syndrome (KFS) is a rare congenital disorder characterized by the fusion of two or more cervical vertebrae during early prenatal development. This fusion results from a failure of segmentation during the first trimester. Although six genes have previously been associated with KFS, they account for only a small proportion of cases. Among the distinct subtypes of KFS, "sandwich fusion" involving concurrent fusion of C0-1 and C2-3 vertebrae is particularly noteworthy due to its heightened risk for atlantoaxial dislocation. In this study, we aimed to investigate novel candidate mutations in patients with "sandwich fusion." METHODS: We collected and analyzed clinical data from 21 patients diagnosed with "sandwich fusion." Whole-exome sequencing (WES) was performed, followed by rigorous bioinformatics analyses. Our focus was on the six known KFS-related genes (GDF3, GDF6, MEOX1, PAX1, RIPPLY2, and MYO18). Suspicious mutations were subsequently validated through in vitro experiments. RESULTS: Our investigation revealed two novel exonic mutations in the FGFR2 gene, which had not previously been associated with KFS. Notably, the c.1750A > G variant in Exon 13 of FGFR2 was situated within the tyrosine kinase domain of the protein, in close proximity to several established post-translational modification sites. In vitro experiments demonstrated that this certain mutation significantly impacted the function of FGFR2. Furthermore, we identified four heterozygous candidate variants in two genes (PAX1 and MYO18B) in two patients, with three of these variants predicted to have potential clinical significance directly linked to KFS. CONCLUSIONS: This study encompassed the largest cohort of patients with the unique "sandwich fusion" subtype of KFS and employed WES to explore candidate mutations associated with this condition. Our findings unveiled novel variants in PAX1, MYO18B, and FGFR2 as potential risk mutations specific to this subtype of KFS.

Longitudinal Cervical Length Measurements and Spontaneous Preterm Birth in Singleton and Twin Pregnancies.

Importance: Changes in cervical length in twin pregnancies exhibit various patterns, but it is unclear whether the mechanism underlying spontaneous preterm birth (sPTB) is consistent. The existence of detailed phenomena in singleton pregnancies is also unclear. Objectives: To explore the different patterns in cervical length trajectories in singleton and twin pregnancies and to analyze whether the immunological mechanisms of sPTB are consistent among these cervical length patterns. Design, Setting, and Participants: This cohort study recruited pregnant individuals who received antenatal care and delivered at Peking University Third Hospital in Beijing, China, between January 1, 2014, and December 31, 2022. Individuals with singleton and twin pregnancies were included. Exposures: Cervical length measurements and white blood cell (WBC) indicators. Main Outcomes and Measures: The primary outcome was sPTB. Longitudinal trajectory cluster analysis was used to identify patterns of changes in cervical length in singleton and twin pregnancies. A random-effects model with cubic spline was used to fit and compare the longitudinal trajectory of WBC indicators among early preterm birth, moderate to late preterm birth, and term birth. Results: A total of 43 559 pregnant individuals were included; of these, 41 706 had singleton pregnancies (mean [SD)] maternal age, 33.0 [4.0] years) and 1853 had twin pregnancies (mean [SD] maternal age, 33.3 [3.6] years). Two distinct patterns of cervical length changes were observed in both singleton and twin pregnancies: shortened (21 366 singletons and 546 twins) and stable (20 340 singletons and 1307 twins). In singleton pregnancies, WBC count was associated with early sPTB in individuals with both shortened cervix (odds ratio [OR], 1.35; 95% CI, 1.00-1.82) and stable cervix (OR, 1.64; 95% CI, 1.07-2.50). However, for twin pregnancies, the association of WBC count (OR, 3.13; 95% CI, 1.58-6.18) with the risk of early sPTB was observed only in individuals with a shortened cervix. Conclusions and Relevance: This study identified 2 distinct cervical length patterns: shortened and stable. These patterns revealed 2 preterm birth mechanisms in twin pregnancies, with the immunopathogenesis of sPTB found only in the shortened cervix pattern; in singleton pregnancies, maternal immune response was associated with a higher risk of sPTB regardless of a shortened or stable cervix.

Serum lipid reference values recommended during a twin pregnancy and evaluating its association with perinatal outcomes.

BACKGROUND: Maternal lipid metabolism fluctuations have been shown to increase the risk of adverse pregnancy outcomes. However, there is no consensus over what constitutes normal maternal lipid values during twin pregnancy. Therefore, the aim of this study was to establish a serum lipid reference range for a twin pregnancy. METHODS: A retrospective survey was conducted, from 2011 to 2021, at the Peking University Third Hospital. A total of 881 twin pregnancies, with lipid data from early and middle pregnancies, were included. After excluding those with adverse pregnancy outcomes, we performed a descriptive analysis of total cholesterol (TC), triglycerides (TG), high-density lipid cholesterol (HDL-C), and low-density lipid cholesterol (LDL-C) levels, using the mean and standard deviation to determine appropriate percentiles. We later determined the lipid reference range in early and middle pregnancy based on the initial results. We evaluated Inappropriate lipid levels associations with pregnancy outcomes, including gestational diabetes, pregnancy-induced hypertension, small for gestational age. RESULTS: (1) Serum levels of TC, TG, LDL-C, and HDL-C increased significantly from early to late pregnancy, where the greatest increase was observed in TG. (2) Based on the results, we recommend that TC, TG, and LDL-C serum reference values during early and middle pregnancy should be less than the 95th percentile. On the other hand, HDL-C should be greater than the 5th percentile. During early pregnancy, the values recommended are TC < 5.31 mmol/L, TG < 2.25 mmol/L, HDL > 1.02 mmol/L and LDL < 3.27 mmol/L, and those during middle pregnancy are TC < 8.74 mmol/L, TG < 4.89 mmol/L, HDL > 1.25 mmol/L and LDL < 5.49 mmol/L, while the values during late pregnancy are TC < 9.11 mmol/L, TG < 6.70 mmol/L, HDL > 1.10 mmol/L and LDL < 5.81 mmol/L. Higher levels of blood lipids were associated with GDM, PE, SGA. CONCLUSIONS: We suggested a reference ranges for blood lipids during the twin pregnancy in a Chinese population. The reference ranges recommended by this study can be used to identify women with twin pregnancies using unfavorable lipid values. Higher levels of blood lipids were associated with adverse pregnancy outcomes.

An MRI-Based Radiomics Nomogram for Differentiation of Benign and Malignant Vertebral Compression Fracture.

RATIONALE AND OBJECTIVES: This study aimed to develop and validate a magnetic resonance imaging (MRI)-based radiomics nomogram combining radiomics signatures and clinical factors to differentiate between benign and malignant vertebral compression fractures (VCFs). MATERIALS AND METHODS: A total of 189 patients with benign VCFs (n = 112) or malignant VCFs (n = 77) were divided into training (n = 133) and validation (n = 56) cohorts. Radiomics features were extracted from MRI T1-weighted images and short-TI inversion recovery images to develop the radiomics signature, and the Rad score was constructed using least absolute shrinkage and selection operator regression. Demographic and MRI morphological characteristics were assessed to build a clinical factor model using multivariate logistic regression analysis. A radiomics nomogram was constructed based on the Rad score and independent clinical factors. Finally, the diagnostic performance of the radiomics nomogram, clinical model, and radiomics signature was validated using receiver operating characteristic and decision curve analysis (DCA). RESULTS: Six features were used to build a combined radiomics model (combined-RS). Pedicle or posterior element involvement, paraspinal mass, and fluid sign were identified as the most important morphological factors for building the clinical factor model. The radiomics signature was superior to the clinical model in terms of the area under the curve (AUC), accuracy, and specificity. The radiomics nomogram integrating the combined-RS, pedicle or posterior element involvement, paraspinal mass, and fluid sign achieved favorable predictive efficacy, generating AUCs of 0.92 and 0.90 in the training and validation cohorts, respectively. The DCA indicated good clinical usefulness of the radiomics nomogram. CONCLUSION: The MRI-based radiomics nomogram, combining the radiomics signature and clinical factors, showed favorable predictive efficacy for differentiating benign from malignant VCFs.

Relationship between one-carbon metabolism and fetal growth in twins: A cohort study.

We investigated the associations of one-carbon metabolism (OCM)-related metabolites, including choline, betaine, dimethylglycine (DMG), and methionine with fetal growth of twins. This hospital-based cohort study included dichorionic twin gestations. Blood samples were collected at a median of 14.7 weeks of gestation. Blood plasma metabolite levels were measured using high-performance liquid chromatography-triple quadrupole mass spectrometry. Generalized estimating equations and mixed effects models were used to explore associations between plasma metabolite levels and fetal growth. In total, 115 women with dichorionic diamniotic pregnancies were included. The maternal plasma DMG level was negatively correlated with fetal birth weight (ß = -43.5, 95% confidence interval [CI] = -74.1 to -12.8, p < .05) and head circumference (ß = -0.23, 95% CI = -0.39 to -0.07, p < .05). Other metabolites were not significantly associated with birth weight, body length, head circumference (HC), or chest circumference. Analysis of the relationships between plasma metabolite levels and fetal biological parameters on ultrasound revealed that the maternal choline level was negatively correlated with fetal abdominal circumference (AC) (ß = -0.12, 95% CI = 0.24 to -0.004, p < .05); the maternal DMG level was negatively correlated with fetal AC (ß = -0.17, 95% CI = 0.28-0.07, p < .05), femur length (ß = 0.02, 95% CI = 0.04-0.003, p < .05), and estimated fetal weight (ß = 26.4, 95% CI = -41.6 to -11.2, p < .05), but not with HC. The maternal methionine level was negatively correlated with HC (ß = -0.08, 95% CI = -0.14 to -0.02, p < .05). The plasma level of the OCM-related metabolite DMG during the second trimester was negatively correlated with fetal intrauterine growth and birth weight. However, further studies with larger samples are needed.

Reduced-visit antenatal care model combined with telemedicine for low-risk pregnant women: protocol for a randomised controlled trial.

INTRODUCTION: Antenatal care (ANC) is a critical measure to reduce maternal and perinatal morbidity and mortality. However, there are issues of too many visits and cumbersome procedures of ANC in many maternity hospitals of China. In the past 2 years, reduced-visit ANC models combined with remote monitoring have been recommended and implemented at most hospitals in China during the COVID-19 pandemic. Nevertheless, due to limited evaluations of the cost-effectiveness, policy-makers remain confused on how to appropriately integrate online delivery strategies with routine models to improve ANC quality and efficiency sustainably at scale. This trial aims to evaluate the effectiveness, acceptability and cost of a reduced-visit ANC model combined with telemedicine. METHODS AND ANALYSIS: A single-blind, randomised controlled trial will be conducted among low-risk pregnant women at Peking University Third Hospital in Beijing. 1476 patients (738 in each group) would be required, and they will be randomly assigned in a 1:1 ratio to receive the reduced-visit ANC combined with telemedicine services or the routine ANC. The primary outcome is the composite rate of adverse maternal and perinatal outcomes which will be extracted from the medical records. Secondary outcomes include acceptability of ANC models, which is assessed by satisfaction with ANC, pregnancy-related stress and ANC costs measured from the perspectives of both service providers and demanders. Both intention-to-treat and per-protocol analyses will be performed. Non-inferiority tests will be used to compare the two ANC models for the primary outcome. A cost-effectiveness analysis comparing the two ANC models will be conducted by estimating the incremental cost-effectiveness ratios. ETHICS AND DISSEMINATION: This study was approved by the ethical review committee of the Peking University Third Hospital (Beijing, China). The results of this study will be published in peer-reviewed scientific journals and presented at relevant academic conferences. TRIAL REGISTRATION NUMBER: NCT05290467.

Numerical Simulation on Preparing Uniform and Stable Perovskite Wet Film in Slot-Die Coating Process.

Slot-die coating is regarded as a reliable and potential technology for preparing large-area perovskite solar cells with high efficiency and low cost. Therein, the formation of continuous and uniform wet film is of significance to obtain a high-quality solid perovskite film. In this work, the rheological properties of the perovskite precursor fluid are analyzed. Then, the ANSYS Fluent is introduced to establish an integrated model of internal and external flow fields during the coating process. The model is applicable to all perovskite precursor solutions with near-Newtonian fluids. Based on the theoretical simulation of finite element analysis, the preparation of 0.8 M-FAxCs1-xPbI3, one of the typical large-area perovskite precursor solutions, is explored. Accordingly, this work indicates that the coupling process parameters like the fluid supply velocity (Vin) and coating velocity (V) determine the uniformity that the solution flows out of the slit and is coated onto the substrates, and the coating windows for a uniform and stable perovskite wet film is obtained. For the upper boundary range of the coating windows, the maximum value of V and Vin follows V = 0.003 + 1.46Vin (Vin ≤ 0.1 m/s), while for its lower boundary range, the minimum value of V and Vin is V = 0.002 + 0.67Vin (Vin ≤ 0.1 m/s). When Vin is higher than 0.1 m/s, the film will break due to the excessive V. Finally, the real experiment verifies the accuracy of the numerical simulation. Hopefully, this work is of reference value for the development of the slot-die coating forming process on the perovskite precursor solution approximating Newtonian fluid.

Comparison of the 2009 Institute of Medicine and 2021 Chinese guidelines for gestational weight gain: A retrospective population-based cohort study.

OBJECTIVE: To analyze the associations between gestational weight gain (GWG) and perinatal outcomes based on the GWG guidelines of the Chinese Nutrition Society (CNS) and the Institute of Medicine (IOM). METHODS: This was a retrospective study with 9075 low-risk singleton pregnant women. Logistic regression model was used to analyze associations between GWG categories and perinatal outcomes. Sensitivity analyses were performed based on pre-pregnancy body mass index (calculated as weight in kilograms divided by the square of height in meters). RESULTS: Excessive GWG as defined by the two guidelines was associated with a higher risk of adverse perinatal outcomes. Inadequate GWG was associated with higher risks of small for gestational age (adjusted odds ratio [aOR] 1.34, 95% confidence interval [CI] 1.10-1.64) and preterm birth (aOR 1.70, 95% CI 1.22-2.36), but a lower risk of large for gestational age (LGA) (aOR 0.77, 95% CI 0.63-0.95) according to the IOM guidelines. When using the CNS guidelines, inadequate GWG was associated with only a lower risk of preterm birth (aOR 1.80, 95% CI 1.19-2.70). Sensitivity analyses suggested that excessive GWG was associated with a higher risk of LGA in underweight women. CONCLUSIONS: Both guidelines could demonstrate the relationship between GWG and adverse perinatal outcomes. The CNS guidelines were more suitable for the Chinese population with underweight or normal weight before pregnancy, whereas IOM was more suitable for pregnant women with inadequate GWG.

Gestational Vitamin E Status and Gestational Diabetes Mellitus: A Retrospective Cohort Study.

OBJECTIVES: To examine the association between vitamin E (VE) status and gestational diabetes mellitus (GDM). METHODS: A retrospective cohort study was conducted by using data of 52,791 women at 137 hospitals across 22 provinces of China. A fasting plasma glucose (FPG) level of ≥5.1 mmol/L between the 24th and 40th weeks of gestation was used as the criteria for the diagnosis of GDM. Mean FPG level and GDM rate were calculated within each combination of the first-trimester VE concentration categories and gestational change categories. The associations of the first-trimester VE concentrations and gestational VE change with FPG and GDM were examined by employing generalized additive models (GAMs). RESULTS: 7162 (13.57%) cases were diagnosed with GDM. The GDM rate was 22.44%, 11.50%, 13.41%, 12.87%, 13.17%, 13.44%, 12.64%, and 14.24% among women with the first-trimester VE concentrations of <7.2, 7.2-7.9, 8.0-9.3, 9.4-11.0, 11.1-13.2, 13.3-15.8, 15.9-17.7, and 17.8-35.9 mg/L, respectively. The GDM rate was 15.96%, 13.10%, 13.64%, and 12.87% among women with gestational VE change of <0, 0-0.19, 0.20-0.29, ≥0.30 mg/L per week, respectively. Multivariable adjusted GAM analyses found that the first-trimester VE concentration was associated with the FPG levels and GDM risk in an L-shaped pattern; the FPG levels and GDM risk decreased sharply to a threshold (around 7 mg/L), and then were keep flat. Gestational VE decreases when the first-trimester VE level was less than 11 mg/L were related to increased FPG levels and GDM risk. CONCLUSIONS: Both low first-trimester VE levels and subsequent gestational VE decrease were related with increased risk of GDM. The findings suggest the necessity of having VE-rich foods and appropriate VE supplementation to prevent GDM for pregnant women with low baseline VE levels.

Variation Patterns of Hemoglobin Levels by Gestational Age during Pregnancy: A Cross-Sectional Analysis of a Multi-Center Retrospective Cohort Study in China.

BACKGROUND: Pregnancy anemia is a global health concern. However, to our knowledge, there still has little consensus on the reference value of hemoglobin levels. Particularly, little evidence from China was accessible in most existing guidelines. OBJECTIVE: To evaluate hemoglobin levels and anemia prevalence of pregnant women in China and offer evidence for anemia and its reference values in China. METHODS: A multi-center retrospective cohort study was conducted among 143,307 singleton pregnant women aged 15-49 at 139 hospitals in China, with hemoglobin concentrations routinely tested at each prenatal visit. Subsequently, a restricted cubic spline was performed to reveal a non-linear variation of hemoglobin concentrations during the gestational week. The Loess model was used to describe the changes in the prevalence of different degrees of anemia with gestational age. Multivariate linear regression model and Logistic regression model were applied to explore influencing factors of gestational changes in hemoglobin level and anemia prevalence, respectively. RESULTS: Hemoglobin varied nonlinearly with gestational age, and the mean hemoglobin levels decreased from 125.75 g/L in the first trimester to 118.71 g/L in the third trimester. By analyzing hemoglobin levels with gestational age and pregnancy period, we proposed new criteria according to 5th percentile hemoglobin concentration in each trimester as a reference for anemia, with 108 g/L, 103 g/L, and 99 g/L, respectively. According to WHO's criteria, the prevalence of anemia sustainably increased with gestational age, with 6.2% (4083/65,691) in the first trimester, 11.5% (7974/69,184) in the second trimester and 21.9% (12,295/56,042) in the third trimester, respectively. In subsequent analysis, pregnant women in non-urban residents, multiparity, and pre-pregnancy underweight tended to have lower hemoglobin levels. CONCLUSIONS: This research, the first large-sample study to present a set of gestational age-specific reference centiles for hemoglobin levels in China, could be used to obtain a better understanding of the overall levels of hemoglobin in Chinese healthy pregnant women and ultimately offer clues for a more precise hemoglobin reference value of anemia in China.

Privacy-Preserving Multi-Source Domain Adaptation for Medical Data.

Great progress has been made in diagnosing medical diseases based on deep learning. Large-scale medical data are expected to improve deep learning performance further. It is almost impossible for a single institution to collect so much data due to the time-consuming and costly collection and labeling of medical data. Many studies have turned attention to data sharing among multiple medical institutions. However, due to different data acquiring and processing procedures, multiple institutions' medical data is characterized by distribution heterogeneity. Besides, the protection of patient privacy in medical data sharing has also been a common concern. To simultaneously address the problems of heterogeneous data distribution and privacy protection, we propose a novel multi-source source free domain adaptation. When aligning distributed heterogeneous data, our method only require to transfer the pre-trained source models rather than the direct source domain data, thus protecting patients' privacy. In addition, it has the advantages of being efficient and less costly in network resources. The proposed method is evaluated on the multi-site fMRI database Autism Brain Imaging Data Exchange (ABIDE) and yields an average accuracy of 69.37%. We also analyzed its effectiveness on network resource-saving and conducted additional experiments on Camelyon17 to validate the generalization.

The role and mechanism of tryptophan - kynurenine metabolic pathway in depression.

Major depressive disorder (MDD) is a common mental illness characterized by persistent low mood and anhedonia, normally accompanied with cognitive impairment. Due to its rising incidence and high rate of recurrence and disability, MDD poses a substantial threat to patients' physical and mental health, as well as a significant economic cost to society. However, the etiology and pathogenesis of MDD are still unclear. Chronic inflammation may cause indoleamine-2,3-dioxygenase (IDO) to become overactive throughout the body and brain, resulting in excess quinolinic acid (QUIN) and less kynuric acid (KYNA) in the brain. QUIN's neurotoxicity damages glial cells and neurons, accelerates neuronal apoptosis, hinders neuroplasticity, and causes depression due to inflammation. Therefore, abnormal TRP-KYN metabolic pathway and its metabolites have been closely related to MDD, suggesting changes in the TRP-KYN metabolic pathway might contribute to MDD. In addition, targeting TRP-KYN with traditional Chinese medicine showed promising treatment effects for MDD. This review summarizes the recent studies on the TRP-KYN metabolic pathway and its metabolites in depression, which would provide a theoretical basis for exploring the etiology and pathogenesis of depression.

An Evaluation of Exposure to 18 Toxic and/or Essential Trace Elements Exposure in Maternal and Cord Plasma during Pregnancy at Advanced Maternal Age.

Pregnant women of advanced maternal age (AMA) are vulnerable to exposure to the surrounding environment. Assessment of trace elements in pregnant women living in specific areas is important for biomonitoring. However, exposure levels and variation patterns during pregnancy remains controversial and attracts extensive public concern. Therefore, we aimed to evaluate exposure of 18 toxic and/or essential trace elements in maternal plasma and in paired cord plasma during pregnancy at AMA. A total of 48 pregnant women of AMA were recruited in Peking University Third Hospital from 2018 to 2021. Eighteen elements found in maternal plasma during the 1st, 2nd, or 3rd trimester of pregnancy and paired cord plasma were measured by 7700x ICP-MS (Agilent Technologies, Palo Alto, CA, USA) and Elan DRC type II ICP-MS (The Perkin-Elmer Corporation, Waltham, MA USA). Concentrations of Pb, Se, Fe, Zn, and Mo all decreased during pregnancy, while Cu increased. Interestingly, concentrations of Rb decreased initially but then increased. Elements as Al, Co, Se, Cu, and Ni showed significantly lower levels in cord than in maternal plasma, while elements as Sr, Fe, Rb, Mn and Zn displayed significantly higher levels in cord than in maternal plasma. Moreover, positively- interacted clusters were found in Ni-Co-Cu-Al-Rb-Zn and Zn-Mn-Al-Pb in maternal blood. Similar positively-interacted clusters were found in Zn-Ni-Co, Zn-Ni-Fe, Mn-Al-Pb, Fe-Pb-Mn, Fe-Ni-Cu, and Rb-Cu-Sb-Fe-Mn in cord plasma. Furthermore, correlations between paired maternal and cord blood samples for As, Sr, and Mo were statistically significant, indicating that the fetus burden may reflect maternal exposure to some extent. Admittedly, levels of toxic and essential elements in our cohort study were comparatively lower than those in the scientific literature.

Risk of preeclampsia by gestational weight gain in women with varied prepregnancy BMI: A retrospective cohort study.

Introduction: Despite the important clinical significance, limited data on the joint contribution of prepregnancy body mass index (BMI) and gestational weight gain (GWG) to preeclampsia, the second leading cause of maternal mortality worldwide. This study aimed to estimate the risk of preeclampsia by GWG among women with varied prepregnancy BMI. Methods: We conducted a retrospective cohort study using data of 117 738 singleton pregnant women aged 18-49 years from 150 maternity hospitals in China between 2015 and 2018. GWG was calculated as the measured weight at the time of preeclampsia assessment minus prepregnancy weight; GWG velocity was calculated as the GWG divided by the gestational age at weighing. The non-linear associations of GWG with preeclampsia were examined by restricted cubic spline regression analysis according to prepregnancy BMI. The association of the GWG categories with preeclampsia was further examined by performing robust Poisson regression stratified by the prepregnancy BMI categories. Results: Among participants, 2426 (2.06%) were diagnosed with preeclampsia. Compared to women with normal BMI, those who were overweight and obese had 1.92- fold (95%CI, 1.73-2.14) and 5.06- fold (95%CI, 4.43-5.78) increased risks for preeclampsia, respectively. The association of GWG velocity with preeclampsia was presented as a J-shaped curve with the varied inflexion point (where the rate of preeclampsia was 2%), which was 0.54, 0.38, and 0.25 kg/week in women with normal BMI, overweight, and obesity, respectively; a steep risk rise was observed along with GWG velocity beyond the inflexion points. The overall adjusted relative risk for preeclampsia was calculated among women with the different GWG categories of GWG. Conclusions: The findings highlight that high prepregnancy BMI and exceed GWG contributed to increased risk of preeclampsia with a superimposed effect and underscore the need to optimize the recommendations for GWG for women with different prepregnancy BMI.