Circulating extracellular vesicles as novel biomarkers for pulmonary arterial hypertension in patients with systemic lupus erythematosus.

Introduction: Pulmonary arterial hypertension (PAH) is a serious complication of systemic lupus erythematosus (SLE) with increased mortality. A prothrombotic state may contribute to pathogenesis of SLE-PAH. Extracellular vesicles (EVs) are known to be associated with thrombosis. Here, we investigated circulating EVs and their associations with SLE-PAH. Methods: Eighteen SLE-PAH patients, 36 SLE-non-PAH patients, and 36 healthy controls (HCs) were enrolled. Flow cytometry was used to analyze circulating EVs from leukocytes (LEVs), red blood cells (REVs), platelets (PEVs), endothelial cells (EEVs), and Annexin V+ EVs with membrane phosphatidylserine (PS) exposure. Results: Plasma levels of all EV subgroups were elevated in SLE patients with or without PAH compared to HCs. Furthermore, plasma Annexin V+ EVs, LEVs, PEVs, REVs, EEVs, and Annexin V+ REVs were significantly elevated in SLE-PAH patients compared to SLE-non-PAH patients. Additionally, PAH patients with moderate/high SLE showed a significant increase in LEVs, PEVs, REVs, Annexin V+ EVs, and Annexin V+ REVs compared to SLE-non-PAH patients. However, PAH patients with inactive/mild SLE only exhibited elevations in Annexin V+ EVs, REVs, and Annexin V+ REVs. In the SLE-PAH patients, EEVs were positively correlated with pulmonary arterial systolic pressure, while PEVs and EEVs were positively correlated with right ventricular diameter. Moreover, the receiver operating characteristic curve indicated that Annexin V+ EVs, LEVs, PEVs, REVs, EEVs and Annexin V+ REVs could predict the presence of PAH in SLE patients. Importantly, multivariate logistic regression analysis showed that circulating levels of LEVs or REVs, anti-nRNP antibody, and serositis were independent risk factors for PAH in SLE patients. Discussion: Findings reveal that specific subgroups of circulating EVs contribute to the hypercoagulation state and the severity of SLE-PAH. Higher plasma levels of LEVs or REVs may serve as biomarkers for SLE-PAH.

Multimodal and multiscale feature fusion for weakly supervised video anomaly detection.

Weakly supervised video anomaly detection aims to detect anomalous events with only video-level labels. In the absence of boundary information for anomaly segments, most existing methods rely on multiple instance learning. In these approaches, the predictions for unlabeled video snippets are guided by the classification of labeled untrimmed videos. However, these methods do not account for issues such as video blur and visual occlusion, which can hinder accurate anomaly detection. To address these issues, we propose a novel weakly supervised video anomaly detection method that fuses multimodal and multiscale features. Firstly, RGB and optical flow snippets are input into pre-trained I3D to extract appearance and motion features. Then, we introduce an Attention De-redundancy (AD) module, which employs an attention mechanism to filter out task-irrelevant redundancy in these appearance and motion features. Next, to mitigate the effects of video blurring and visual occlusion, we propose a Multi-scale Feature Learning module. This module captures long-term and short-term temporal dependencies among video snippets to provide global and local guidance for blurred or occluded video snippets. Finally, to effectively utilize the discriminative features of different modalities, we propose an Adaptive Feature Fusion module. This module adaptively fuses appearance and motion features based on their respective feature weights. Extensive experimental results demonstrate that our proposed method outperforms mainstream unsupervised and weakly supervised methods in terms of AUC. Specifically, our proposed method achieves 97.00% AUC and 85.31% AUC on two benchmark datasets, i.e., ShanghaiTech and UCF-Crime, respectively.

Genome-level therapeutic targets identification and chimeric Vaccine designing against the Blastomyces dermatitidis.

Blastomyces dermatitidis is a thermally dimorphic fungus that can cause serious and sometimes fatal infections, including blastomycosis. After spore inhalation, a pulmonary infection develops, which can be asymptomatic and have lethal effects, such as acute respiratory distress syndrome. Its most common extra-pulmonary sites are the central nervous system, bones, skin, and genito-urinary systems. Currently, no vaccine has been approved by the FDA to prevent this infection. In the study, a peptide-based vaccine was developed against blastomycosis by using subtractive proteomics and reverse vaccinology approaches. It focuses on mining the whole genome of B. dermatitidis, identifying potential therapeutic targets, and pinpointing potential epitopes for both B- and T-cells that are immunogenic, non-allergenic, non-toxic, and highly antigenic. Multi-epitope constructs were generated by incorporating appropriate linker sequences. A linker (EAAAK) was also added to incorporate an adjuvant sequence to increase immunological potential. The addition of adjuvants and linkers ultimately resulted in the formation of a vaccine construct in which the number of amino acids was 243 and the molecular weight was 26.18 kDa. The designed antigenic and non-allergenic vaccine constructs showed suitable physicochemical properties. The vaccine's structures were predicted, and further analysis verified their interactions with the human TLR-4 receptor through protein-protein docking. Additionally, MD simulation showed a potent interaction between prioritized vaccine-receptor complexes. Immune simulation predicted that the final vaccine injections resulted in significant immune responses for the T- and B-cell immune responses. Moreover, in silico cloning ensured a high expression possibility of the lead vaccine in the E. coli (K12) vector. This study offers an initiative for the development of effective vaccines against B. dermatitidis; however, it is necessary to validate the designed vaccine's immunogenicity experimentally.

A synchronous-fluorescence analysis method combing with simple one-step extraction for determination of leonurine in traditional Chinese medicine.

Synchronous fluorescence spectroscopy (SFS) technology exhibits significant advantages in identifying target fluorescence signals within complex mixtures of multiple fluorescent compounds, owing to their closely overlapping spectra. In this study, a SFS method is reported for the first time for the direct analysis of leonurine in drugs containing concurrent natural products. By setting the wavelength interval (Δλ) to 30 nm, the characteristic emission peak of leonurine is observed at 307 nm, which increases proportionally with the concentration of leonurine without spectral overlap from other fluorescent species. The limit of detection (LOD) is estimated to be about 0.22 µM, and a low linear range of 0 to 20 µM is obtained. The common cations, anions and concomitant compounds display no interference with the SFS signal of leonurine, supporting the practical application of this method. Thus, we successfully applied this SFS method to detect leonurine in several real samples (leonurus granules, capsules, ointment and pills), in which the good relative standard deviation (RSD) values (0.04-4.24%) and recoveries (95.63-113%) were obtained. As a result, this work provides an efficient and convenient method to identify the target active compound from natural products without complex pre-treatment to diminish the fluorescent chaos that might be serving a potential role in the study of traditional Chinese medicine.

Occurrence and health risks of multiple emerging bisphenol S analogues in pregnant women from South China.

Recently, there has been increasing concern regarding the emergence of bisphenol S analogues (BPSs) due to their potential toxicity. However, their exposure levels and associated health risks in susceptible populations remain unknown. In our study, we analyzed bisphenol A (BPA), along with 11 common BPA analogues (BPAs), and nine emerging BPSs in urine samples collected from 381 pregnant women in South China. All nine BPSs were first detected in pregnant women's urine. In addition to BPA, two BPAs, three BPSs including Diphenylsulfone (DPS), Bis(phenylsulfonyl)phenol (DBSP) and Bis(3-allyl-4-hydroxyphenyl)sulfone (TGSA), were identified as the predominant bisphenols, with detection frequencies ranging from 53-100 %. BPA still exhibited the highest median concentration at 0.624 ng/mL, followed by DPS (0.169 ng/mL), BPS (0.063 ng/mL) and DBSP (0.023 ng/mL). Importantly, mothers with higher levels of BPA, DBSP, DPS, and TGSA in their urine are statistically more likely to give birth to premature infants with shorter lengths at birth or smaller head circumference (p < 0.05). Although the median exposure to 21 bisphenols did not exceed the tolerable daily intake (TDI) of BPA, it did surpass the recently proposed BPA TDI (0.2 ng/kg bw/day) by a factor ranging from 1.1-99 times. This study signifies the first report unveiling the prevalence of multiple bisphenols, particularly emerging BPSs, in the urine of pregnant women in South China.

Sustained-release of SOD from multivesicular liposomes accelerated the colonic mucosal healing of colitis mice by inhibiting oxidative stress.

Oxidative stress has long been known as a pathogenic factor of ulcerative colitis. Superoxide dismutase (SOD) has been demonstrated to mitigate gut mucosal injury via combating oxidative stress. Herein, we developed SOD-loaded multivesicular liposomes (S-MVLs) as sustained-release depot for ulcerative colitis treatment. S-MVLs were spherical honeycomb-like particles with average particle size of 27.3 ± 5.4 µm and encapsulating efficiency of 78.7 ± 2.6 %. Moreover, the two-phase release profiles of SOD from S-MVLs were exhibited, that was, the burst release phase within 4 h and the sustained-release phase within 96 h. After intraperitoneally injecting S-MVLs, in situ retention time of SOD at bowel cavity extended by 4-fold in comparison with SOD solution. In vitro cells experiment showed that S-MVLs had the protective effect on LPS-treated RAW 264.7 cells via scavenging ROS and inhibiting pro-inflammatory cytokines production. S-MVLs ameliorated the body weight loss, DAI score and the colon shortening of colitis mice. Meanwhile, the colonic morphology and the epithelial barrier of colitis mice were effectively recovered after S-MVLs treatment. The therapeutic mechanism might be associated with polymerizing M1 macrophages to M2 phenotypes and alleviating oxidative stress. Collectively, multivesicular liposomes might be a promising sustained-release depot of SOD for ulcerative colitis treatments.

Global estimates of ambient NO2 concentrations and long-term health effects during 2000-2019.

High concentrations of ambient NO2 causes serious air pollution and could also pose great threats to human health. However, the long-term trends (20-year) and potential health effects of ambient NO2 exposure globally still shows high uncertainties. In this work, the field measurements, satellite dataset, GEOS-Chem output, and multiple geographical covariates were incorporated into the multi-stage model to investigate the global evolutions of ambient NO2 during 2000-2019. The results indicated that the cross-validation (CV) R2 values of ambient NO2 based on multi-stage model displayed satisfied performance (R2 = 0.78), which was superior to the individual model. Besides, the out-of-bag R2 was 0.75, which suggested the multi-stage model showed the better transferability. At the spatial scale, the NO2 concentrations followed the order of China (16.9 ± 9.0 µg/m3) > India (15.5 ± 5.6 µg/m3) > United States (10.7 ± 5.6 µg/m3) > Europe (7.7 ± 4.5 µg/m3), which was in consistent with the anthropogenic NOx emission. At the temporal scale, the ambient NO2 levels in China experienced persistent increases (0.29 µg/m3/year) during 2000-2013, whereas they showed slight decreases (-0.23 µg/m3/year) during 2013-2019. The ambient NO2 levels in the United States experienced continuous decreases during 2000-2019 (-0.20 µg/m3/year), while both of India and Europe remained relatively stable. Long-term NO2 exposure inevitably increased premature mortalities. The global premature all-cause mortalities associated with the excessive NO2 exposure increased from 288,169 (95% CI: 43,650, 527,971) to 461,301 (95% CI: 69,973, 843,996) in the past 20 years. This study would provide sufficient policy support for future ambient NO2 mitigation.

Development and validation of a nomogram model of depression and sleep disorders and the risk of disease progression in patients with breast cancer.

BACKGROUND: In this study, we investigated the relationship between the risk of postoperative progressive disease (PD) in breast cancer and depression and sleep disorders in order to develop and validate a suitable risk prevention model. METHODS: A total of 750 postoperative patients with breast cancer were selected from the First People's Hospital of LianYunGang, and the indices of two groups (an event group and a non-event group) were compared to develop and validate a risk prediction model. The relationship between depression, sleep disorders, and PD events was investigated using the follow-up data of the 750 patients. RESULTS: SAS, SDS, and AIS scores differed in the group of patients who experienced postoperative disease progression versus those who did not; the differences were statistically significant and the ability to differentiate prognosis was high. The area under the receiver operating characteristic (ROC) curves (AUC) were: 0.8049 (0.7685-0.8613), 0.768 (0.727-0.809), and 0.7661 (0.724--0.808), with cut-off values of 43.5, 48.5, and 4.5, respectively. Significant variables were screened by single-factor analysis and multi-factor analysis to create model 1, by lasso regression and cross-lasso regression analysis to create model 2, by random forest calculation method to create model 3, by stepwise regression method (backward method) to create model 4, and by including all variables for Cox regression to include significant variables to create model 5. The AUC of model 2 was 0.883 (0.848-0.918) and 0.937 (0.893-0.981) in the training set and validation set, respectively. The clinical efficacy of the model was evaluated using decision curve analysis and clinical impact curve, and then the model 2 variables were transformed into scores, which were validated in two datasets, the training and validation sets, with AUCs of 0.884 (0.848-0.919) and 0.885 (0.818-0.951), respectively. CONCLUSION: We established and verified a model including SAS, SDS and AIS to predict the prognosis of breast cancer patients, and simplified it by scoring, making it convenient for clinical use, providing a theoretical basis for precise intervention in these patients. However, further research is needed to verify the generalization ability of our model.

The "4+4" Medical Doctor (MD) Pilot Program at PUMC: Implementation, Performance, and Prospects.

Peking Union Medical College (PUMC) launched the "4+4" Medical Doctor (MD) pilot program in 2018, admitting students with non-medical backgrounds from top universities, aligning with national medical talent training policies to foster diverse and eager learners in medicine. On the occasion of the graduation of the first class of the "4+4" MD pilot class at PUMC in 2023, we reviewed the teaching reform in the pilot program and carried out a systematic survey and interviews with students, faculties, and management staff of the pilot class. This article reports on the measures taken by the pilot class at PUMC in enrollment and curriculum setting, and demonstrates the achievements of the pilot class in terms of student academic background structure, knowledge acquisition and skill learning, scientific research ability, and course evaluation. The results indicated that the pilot class had met the national demand for the "Medicine + X" talent training model. More specifically, with a diverse academic backgrounds, the pilot class graduates had academic levels comparable to the eight-year medical education graduates, and their scientific research abilities were satisfactory. The pilot program at PUMC will optimize the curriculum setting, strengthen the construction of faculty, learning resources, and teaching facilities, and reform the academic evaluation methods, thus deepening the reform of medical education and improving the "4+4" MD program as a novel medical education model.

Comparative study of atmospheric brown carbon at Shanghai and the East China Sea: Molecular characterization and optical properties.

The pollution burdens and compositions of atmospheric brown carbon (BrC) that determine their impacts on climate-health-ecosystems have not been well studied, particularly in some mega-economic coastal areas. Herein, atmospheric BrC samples synchronously collected from urban Shanghai (SH) and Huaniao Island (HNI) in the East China Sea during winter were characterized through ultrahigh-performance liquid chromatography-diode array detector-high resolution mass spectrometry (UHPLC-DAD-HRMS). The three polarity-dependent BrC fractions exhibited significant differences in both light absorption and chromophore composition. The average light absorption coefficients of BrC subfractions at 365 nm in SH were 2.6-3.7 times higher than those in HNI. The water-insoluble BrC (WIS-BrC) and humic-likes BrC (HULIS-BrC) dominated the total BrC absorption in SH (45 ± 7 %) and HNI (43 ± 6 %), respectively. Compared with SH, the higher O/Cw, lower molecule conjugation degree, and reduced mass absorption efficiency at 365 nm (MAE365) in HNI imply a potential bleaching mechanism during the transportation oxidation process. Thousands of BrC chromophores were detected at both sites. >20 major chromophores with strong absorption were unambiguously identified in HULIS-BrC and accounted for ∼40 % of the HULIS light absorption at 365 nm at both sites. These chromophores in SH HULIS-BrC featured oxygenated aromatics and nitroaromatics, while alkyl benzenesulfonic acids with emissions from cargo ships were found in HNI HULIS-BrC. Moreover, 22 major chromophores identified in WIS-BrC included alkaloids, polyaromatic hydrocarbons (PAHs), and carbonyl oxygenated PAHs, contributing 39 % and 49 % of the WIS-BrC light absorption at 365 nm in SH and HNI, respectively. Ascertaining the molecular-specific optical properties of BrC chromophores over the mega-economic coastal area is helpful for the predictive understanding of the sources and evolution of BrC, as well as its atmospheric behavior from land to sea.

Association between pesticide exposure and thyroid function: analysis of Chinese and NHANES databases.

Background: Pesticides are widely used in agricultural activities. Although pesticide use is known to cause damage to the human body, its relationship with thyroid function remains unclear. Therefore, this study aimed to investigate the association between pesticide exposure and thyroid function. Methods: The Chinese database used included 60 patients with pyrethroid poisoning and 60 participants who underwent health checkups between June 2022 and June 2023. The NHANES database included 1,315 adults enrolled from 2007 to 2012. The assessed pesticide and their metabolites included 2,4-dichlorophenoxyacetic acid (2,4-D), 4-fluoro-3-phenoxybenzoic acid (4F3PB), para-nitrophenol (PN), 3-phenoxybenzoic acid (3P), and trans-dichlorovinyl-dimethylcyclopropane carboxylic acid (TDDC). The evaluated indicators of thyroid function were measured by the blood from the included population. The relationship between pesticide exposure and thyroid function indexes was investigated using linear regression, Bayesian kernel machine regression (BKMR), restricted cubic spline (RCS), and weighted quantile sum (WQS) models. Results: The Chinese data showed that pesticide exposure was negatively correlated with the thyroid function indicators FT4, TT4, TgAb, and TPOAb (all p < 0.05). The BKMR model analysis of the NHANES data showed that the metabolic mixture of multiple pesticides was negatively associated with FT4, TSH, and Tg, similar to the Chinese database findings. Additionally, linear regression analysis demonstrated positive correlations between 2,4-D and FT3 (p = 0.041) and 4F3PB and FT4 (p = 0.003), whereas negative associations were observed between 4F3PB and Tg (p = 0.001), 4F3PB and TgAb (p = 0.006), 3P and TgAB (p = 0.006), 3P and TPOAb (p = 0.03), PN and TSH (p = 0.003), PN and TT4 (p = 0.031), and TDDC and TPOAb (p < 0.001). RCS curves highlighted that most pesticide metabolites were negatively correlated with thyroid function indicators. Finally, WQS model analysis revealed significant differences in the weights of different pesticide metabolites on the thyroid function indexes. Conclusion: There is a significant negative correlation between pesticide metabolites and thyroid function indicators, and the influence weights of different pesticide metabolites on thyroid function indicators are significantly different. More research is needed to further validate the association between different pesticide metabolites and thyroid disease.

A population-based study on trajectories of HER2 status during neoadjuvant chemotherapy for early breast cancer and metastatic progression.

BACKGROUND: This study aimed to investigate the distribution and changes of HER2 status in untreated tumours, in residual disease and in metastasis, and their long-term prognostic implications. METHODS: This is a population-based cohort study of patients treated with neoadjuvant chemotherapy for breast cancer during 2007-2020 in the Stockholm-Gotland region which comprises 25% of the entire Swedish population. Information was extracted from the National Breast Cancer Registry and electronic patient charts to minimize data missingness and misclassification. RESULTS: In total, 2494 patients received neoadjuvant chemotherapy, of which 2309 had available pretreatment HER2 status. Discordance rates were 29.9% between primary and residual disease (kappa = 0.534), 31.2% between primary tumour and metastasis (kappa = 0.512) and 33.3% between residual disease to metastasis (kappa = 0.483). Adjusted survival curves differed between primary HER2 0 and HER2-low disease (p < 0.001), with the former exhibiting an early peak in risk for death which eventually declined below the risk of HER2-low. Across all disease settings, increasing the number of biopsies increased the likelihood of detecting HER2-low status. CONCLUSION: HER2 status changes during neoadjuvant chemotherapy and metastatic progression, and the long-term behaviours of HER2 0 and HER2-low disease differ, underscoring the need for obtaining tissue biopsies and for extended follow-up in breast cancer studies.

Small extracellular vesicle CA1 as a promising diagnostic biomarker for nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC), a malignant cancer originating from the epithelial cells of the nasopharynx, presents diagnostic challenges with current methods such as plasma Epstein-Barr virus (EBV) DNA testing showing limited efficacy. This study focused on identifying small extracellular vesicle (sEV) proteins as potential noninvasive biomarkers to enhance NPC diagnostic accuracy. We isolated sEVs from plasma and utilized 4D label-free proteomics to identify differentially expressed proteins (DEPs) among healthy controls (NC = 10), early-stage NPC (E-NPC = 10), and late-stage NPC (L-NPC = 10). Eighteen sEV proteins were identified as potential biomarkers. Subsequently, parallel reaction monitoring (PRM) proteomic analysis preliminarily confirmed sEV carbonic anhydrase 1 (CA1) as a highly promising biomarker for NPC, particularly in early-stage diagnosis (NC = 15; E-NPC = 10; L-NPC = 15). To facilitate this, we developed an automated, high-throughput and highly sensitive CA1 immune-chemiluminescence chip technology characterized by a broad linear detection range and robust controls. Further validation in an independent retrospective cohort (NC = 89; E-NPC = 39; L-NPC = 172) using this technology confirmed sEV CA1 as a reliable diagnostic biomarker for NPC (AUC = 0.9809) and E-NPC (AUC = 0.9893), independent of EBV-DNA testing. Notably, sEV CA1 exhibited superior diagnostic performance compared to EBV-DNA, with a significant incremental net reclassification improvement of 27.61 % for NPC and 72.11 % for E-NPC detection. Thus, this study identifies sEV CA1 as an innovative diagnostic biomarker for NPC and E-NPC independent of EBV-DNA. Additionally, it establishes an immune-chemiluminescence chip technology for the detection of sEV CA1 protein, paving the way for further validation and clinical application.

The synergistic impact of probiotics and dietary fiber on constipation management in chlorpromazine-induced schizophrenia patients: exploring the modulation of intestinal microbiota and neurotrophic factors.

OBJECTIVE: To explore the improvement effect of probiotics combined with dietary fiber on constipation in patients with schizophrenia. METHODS: To compare the improvement scores of constipation, constipation symptoms, quality of life, neurotrophic factors-related indicators, and clinical efficacy between the two groups. RESULTS: There was no statistically significant difference in Cleveland Constipation Scoring System (CCS) scores in the control group before and after treatment (p > 0.05), while the CCS scores in the observation group decreased significantly after treatment (p < 0.05); Patient Assessment of Constipation Symptoms scores significantly decreased in the observation group compared to the control group (p < 0.05), with no significant difference in Patient Assessment of Constipation Quality of Life scores between the two groups pre- and post-treatment; Neuron-specific enolase levels decreased significantly in both groups post-treatment, while brain-derived neurotrophic factor, neuregulin-1, and nerve growth factor levels increased significantly, with a more pronounced rise in the observation group (p < 0.05). Additionally, the total effective rate of clinical treatment in the observation group was higher than that in the control group (p < 0.05). CONCLUSION: Probiotics combined with dietary fiber can improve constipation symptoms in patients with schizophrenia accompanied by constipation, effectively maintain the balance of intestinal microbiota, and improve the quality of life of patients. Additionally, levels of neurotrophic factors associated with bowel function and neurological health increased significantly, with a higher total effective rate of clinical treatment observed in the probiotics and dietary fiber group. These findings suggest the potential efficacy of probiotics and dietary fiber in managing constipation in this patient population.

Clinical evaluation of deep learning-based risk profiling in breast cancer histopathology and comparison to an established multigene assay.

PURPOSE: To evaluate the Stratipath Breast tool for image-based risk profiling and compare it with an established prognostic multigene assay for risk profiling in a real-world case series of estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative early breast cancer patients categorized as intermediate risk based on classic clinicopathological variables and eligible for chemotherapy. METHODS: In a case series comprising 234 invasive ER-positive/HER2-negative tumors, clinicopathological data including Prosigna results and corresponding HE-stained tissue slides were retrieved. The digitized HE slides were analysed by Stratipath Breast. RESULTS: Our findings showed that the Stratipath Breast analysis identified 49.6% of the clinically intermediate tumors as low risk and 50.4% as high risk. The Prosigna assay classified 32.5%, 47.0% and 20.5% tumors as low, intermediate and high risk, respectively. Among Prosigna intermediate-risk tumors, 47.3% were stratified as Stratipath low risk and 52.7% as high risk. In addition, 89.7% of Stratipath low-risk cases were classified as Prosigna low/intermediate risk. The overall agreement between the two tests for low-risk and high-risk groups (N = 124) was 71.0%, with a Cohen's kappa of 0.42. For both risk profiling tests, grade and Ki67 differed significantly between risk groups. CONCLUSION: The results from this clinical evaluation of image-based risk stratification shows a considerable agreement to an established gene expression assay in routine breast pathology.

Neonicotinoid insecticides and metabolites levels in neonatal first urine from southern China: Exploring links to preterm birth.

Neonicotinoids (NEOs) have indeed become the most widely used insecticides worldwide. Concerns have been raised about their potential impact on newborns due to maternal exposure and their unique neurotoxic mode of action. However, it is still poorly understood whether in utero exposure of pregnant women to environmental NEOs and their metabolites can cause carryover effects on vulnerable newborns and subsequent health consequences. In this study, we determined the concentrations of 13 NEOs and their metabolites in the first urine collected from 92 newborns, both preterm and full-term, in southern China during 2020 and 2021. NEOs and their metabolites were identified in 91 urine samples, with over 93% of samples containing a cocktail of these compounds, confirming their maternal-fetal transfer. N-desmethyl-acetamiprid, imidaclothiz, clothianidin and flonicamid were the most commonly detected analytes, with detection frequencies of 59-87% and medians of 0.024-0.291 ng/mL in the urine. The relative abundance of imidaclothiz was significantly higher in preterm newborns, those with head circumferences below 33 cm, birth lengths less than 47 cm, and weights below 2500 g (p < 0.05). When comparing newborns in the 2nd quartile of imidaclothiz concentrations with those in the 1st quartile, we observed a significant increase in the odds of preterm outcomes in the unadjusted model (odds ratio = 3.24, 95% confidence interval = 1.02-10.3). These results suggest that exposure to elevated concentrations of imidaclothiz may be associated with preterm birth.

Primary epithelioid trophoblastic tumor of the lung: A case report.

ABSTRACT: Primary epithelioid trophoblastic tumor (ETT) of the lung is exceedingly rare. Only about three cases have been reported in Pubmed and worldwide literature. We presented a case of multiple primary ETT of the lung occurring in a 33-year-old Chinese female patient. Comprehensive physical examinations revealed no evidence of a primary lesion on the uterus or cervix uteri. Microscopic examination of the tumor demonstrated ETT of the lung, which was confirmed by immunohistochemical staining and declining level of beta-human choriogonadotropin ( ß -HCG) after the operation. Our case revealed that the ETT can occur in the lung and should be considered when a female had a tumor of lung with increasing ß -HCG.

Association between serum TSH levels and all-cause mortality in critically ill patients.

Thyroid dysfunction is common in critical illness and may influence prognosis. However, the value of TSH in patients with severe diseases remains unclear. The aim of this study was to investigate the association between TSH and the clinical prognosis of critically ill patients. Methods: This retrospective study identified patients who were admitted to the ICU in the Medical Information Mart for Intensive Care (MIMIC-IV) database (version 2.2). A total of 6432 patients were divided into four groups based on TSH quartiles (Q1, <0.92 mIU/L; Q2, 0.92-1.07 mIU/L; Q3, 1.07-3.10 mIU/L; Q4, >3.10 mIU/L). The clinical outcomes were defined as all-cause 7-, 30-, and 90-year mortality after ICU admission. Restricted cubic splines (RCSs) for nonlinear associations were generated to visualize the relationship between TSH levels and clinical outcomes. The survival differences among the four groups were also analyzed using Kaplan‒Meier curves and log rank tests. Univariable and multivariable Cox proportional hazards regression were further used to assess the association between TSH levels and clinical outcomes. Results: After multivariate adjustment, a U-shaped relationship was observed between TSH levels and all-cause 7-, 30-, and 90- mortality among patients with severe disease (all P < 0.05 for nonlinearity). The plot showed a risk reduction in the low range of TSH, which reached the lowest risk at approximately 2.9 µIU/mL and then increased thereafter. Compared with patients with Q3 TSH levels, those with Q1, Q2, and Q4 TSH levels had a significantly higher risk of all-cause 30-day mortality (Q1: hazard ratio, 1.28; 95% CI, 1.06-1.54; Q2: hazard ratio, 1.22; 95% CI, 1.01-1.48; Q4: hazard ratio, 1.25; 95% CI, 1.04-1.50). For all-cause 90-day mortality, only the Q4 group had a significantly higher mortality risk than the Q3 group (hazard ratio, 1.24; 95% CI, 1.07-1.44). In subgroup analyses, we found that Q1 TSH levels were associated with higher mortality risk in men and older (≥65 years) patients, while Q4 TSH had a greater risk in men and younger (<65 years) patients. Conclusions: TSH was significantly associated with all-cause 7-, 30-, and 90-day mortality in critically ill patients after admission to the ICU. TSH may serve as a valuable biomarker for risk stratification in critically ill patients.

Anti-parietal cell antibodies as a potential biomarker for interstitial lung disease associated with primary Sjögren's syndrome / Anticuerpos contra las células parietales como biomarcadores potenciales de enfermedad pulmonar intersticial relacionada con el síndrome de Sjögren primario

Background ILD is a common manifestation in pSS and is associated with an increased risk of death. APCA are strongly expressed by hyperplastic alveolar epithelial cells in the fibrotic lung and are associated with an accelerated decline in lung function in IPF. In the present study, we aimed to evaluate the clinical utility of APCA in ILD patients with pSS. Methods Clinical, laboratory, PFTs and imaging data from pSS patients were reviewed, and the ESSDAI was utilized to evaluate disease activity. HRCT semiquantitative scoring was conducted. We compared the clinical characteristics of pSS patients with and without ILD and carried out logistic regression analysis of risk factors for ILD in pSS. Results A total of 74 patients with pSS and 40 HCs were included in the study. ILD was more commonly observed in the APCA-positive group than in the APCA-negative group. The quantitative levels of APCA were positively correlated with the imaging score. Multivariate analysis found that the long disease duration, elevated APCA and elevated KL-6 level were independent risk factors for ILD in pSS patients. The area under ROC curve for APCA was 0.6618, and the threshold concentration was 153.82ng/ml (sensitivity 45.24%, specificity 87.50%). Conclusion APCA level is an independent risk factor and might be a potential biomarker for ILD in patients with pSS (AU)

Antecedentes La enfermedad pulmonar intersticial (EPI) es una manifestación común del síndrome de Sjögren primario (SSp) y está relacionada con un mayor riesgo de muerte. Los anticuerpos anticélulas parietales (AACP) están fuertemente expresados por células epiteliales alveolares proliferantes en los pulmones fibróticos y están relacionados con la disminución acelerada de la función pulmonar en la gibrosis pulmonar idiopática. En este estudio, pretendemos evaluar la aplicación clínica de la AACP en pacientes con EPI con SSp. Método Se revisaron los datos clínicos, de laboratorio, de función pulmonar e imágenes de los pacientes con SSp y se utilizó la ESSDAI para evaluar la actividad de la enfermedad en general. Se registraron 5 características principales de imagen pulmonar de la EPI y 2 radiólogos ciegos experimentados realizaron una puntuación semicuantitativa de HRCT de forma independiente. Comparamos las características clínicas de los pacientes con y sin EPI con SSp y realizamos un análisis de regresión logística de los factores de riesgo de EPI en SSp. Resultados Un total de 74 pacientes con SSp y 40 controles sanos fueron incluidos en el estudio. La EPI es más común en el grupo positivo de AACP que en el grupo negativo de APCA. El nivel cuantitativo de AACP, está positivamente relacionado con la puntuación de imagen. El análisis multifactorial encontró que la larga duración, el aumento de los niveles de AACP y el aumento de los niveles de KL-6 fueron factores de riesgo independientes para la EPI en pacientes con SSp. El área bajo la curva ROC de AACP es de 0,6618 y la concentración umbral fue de 153,82 ng/ml (sensibilidad 45,24% y especificidad 87,50%). Conclusiones Los niveles de AACP son un factor de riesgo independiente y pueden ser biomarcadores potenciales de EPI en pacientes con SSp (AU)