Re-analysis of single-cell RNA-seq data reveals the origin and roles of cycling myeloid cells.

Cycling myeloid cells (CMCs) are often detected from various tissues using single-cell RNA sequencing (scRNA-seq) datasets, however, their research value was not noticed before. For the first time, our study preliminarily revealed the origin, differentiation, and roles of CMCs in physiological processes. Particularly, subgroup a of cycling myeloid cells (aCMCs) were conclusively identified as belonging to a specific cell type. In an active state, aCMCs rapidly proliferate during the early stages of an embryonic development. With an individual maturing, most aCMCs differentiate into specialized cells, while a small portion of them enter an inactive or dormant state. Under pathological conditions, aCMCs restore their proliferative and differentiation capacities via activation or revival. The present study has set the stage for future research on CMCs by linking them with progenitors of immune cells, and provided a crucial starting point to understand the origin, differentiation, and roles of CMCs in various physiological and pathological processes, particularly those related to traumatic injury, cancer, and pathogen infection, leading to develop targeted therapies or interventions.

ALKBH1 promotes HIF-1α-mediated glycolysis by inhibiting N-glycosylation of LAMP2A.

ALKBH1 is a typical demethylase of nucleic acids, which is correlated with multiple types of biological processes and human diseases. Recent studies are focused on the demethylation of ALKBH1, but little is known about its non-demethylase function. Here, we demonstrate that ALKBH1 regulates the glycolysis process through HIF-1α signaling in a demethylase-independent manner. We observed that depletion of ALKBH1 inhibits glycolysis flux and extracellular acidification, which is attributable to reduced HIF-1α protein levels, and it can be rescued by reintroducing HIF-1α. Mechanistically, ALKBH1 knockdown enhances chaperone-mediated autophagy (CMA)-mediated HIF-1α degradation by facilitating the interaction between HIF-1α and LAMP2A. Furthermore, we identify that ALKBH1 competitively binds to the OST48, resulting in compromised structural integrity of oligosaccharyltransferase (OST) complex and subsequent defective N-glycosylation of LAMPs, particularly LAMP2A. Abnormal glycosylation of LAMP2A disrupts lysosomal homeostasis and hinders the efficient degradation of HIF-1α through CMA. Moreover, NGI-1, a small-molecule inhibitor that selectively targets the OST complex, could inhibit the glycosylation of LAMPs caused by ALKBH1 silencing, leading to impaired CMA activity and disruption of lysosomal homeostasis. In conclusion, we have revealed a non-demethylation role of ALKBH1 in regulating N-glycosylation of LAMPs by interacting with OST subunits and CMA-mediated degradation of HIF-1α.

Long-Acting Heterodimeric Paclitaxel-Idebenone Prodrug-Based Nanomedicine Promotes Functional Recovery after Spinal Cord Injury.

After spinal cord injury (SCI), successive systemic administration of microtubule-stabilizing agents has been shown to promote axon regeneration. However, this approach is limited by poor drug bioavailability, especially given the rapid restoration of the blood-spinal cord barrier. There is a pressing need for long-acting formulations of microtubule-stabilizing agents in treating SCI. Here, we conjugated the antioxidant idebenone with microtubule-stabilizing paclitaxel to create a heterodimeric paclitaxel-idebenone prodrug via an acid-activatable, self-immolative ketal linker and then fabricated it into chondroitin sulfate proteoglycan-binding nanomedicine, enabling drug retention within the spinal cord for at least 2 weeks and notable enhancement in hindlimb motor function and axon regeneration after a single intraspinal administration. Additional investigations uncovered that idebenone can suppress the activation of microglia and neuronal ferroptosis, thereby amplifying the therapeutic effect of paclitaxel. This prodrug-based nanomedicine simultaneously accomplishes neuroprotection and axon regeneration, offering a promising therapeutic strategy for SCI.

LRRK2 regulates ferroptosis through the system Xc-GSH-GPX4 pathway in the neuroinflammatory mechanism of Parkinson's disease.

Parkinson's disease (PD) is the most prevalent neurodegenerative disorder. Neuroinflammation mediated by activated microglia and apoptosis of dopaminergic (DA) neurons in the midbrain are its primary pathological manifestations. Leucine-rich repeat protein kinase 2 (LRRK2) kinase has been observed to increase expression during neuroinflammation, however, the effect of LRRK2 on microglia activation remains poorly understood. In this study, we have established lipopolysaccharide (LPS) treated BV2 cells and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) models for both in vivo and in vitro investigation. Our data in vivo reveal that LRRK2 can promote microglia activation by regulating ferroptosis and activating nuclear factor-κB. Inhibition of LRRK2 expression effectively suppressed the LPS-induced pro-inflammatory cytokines and facilitated the secretion of neuroprotective factors. Importantly, by co-overexpressing LRRK2 and glutathione peroxidase 4 (GPX4), we identified the system Xc-GSH-GPX4 pathway as a crucial component in LRRK2-mediated microglial ferroptosis and inflammatory responses. Using a microglial culture supernatant (MCS) transfer model, we found that inhibiting LRRK2 or downregulating ferroptosis in BV2 cells prevented SH-SY5Y cell apoptosis. Additionally, we observed abundant expression of LRRK2 and P-P65 in the midbrain, which was elevated in the MPTP-induced PD model, along with microglia activation. LRRK2 and P-P65 expression inhibition with PF-06447475 attenuated microglia activation in the nigrostriatal dense part of MPTP-treated mice. Based on our findings, it is evident that LRRK2 plays a critical role in promoting the neuroinflammatory response during the pathogenesis of PD by regulating the system Xc-GSH-GPX4 pathway. Taken together, our data highlights the potential research and therapeutic value of targeting LRRK2 to regulate neuroinflammatory response in PD through ferroptosis.

Exploring Metabolic Aberrations after Intracerebral Hemorrhage In Vivo with Deuterium Metabolic Spectroscopy Imaging.

Aberrations in metabolism after intracerebral hemorrhage (ICH), particularly lactate metabolism, play a crucial role in the pathophysiology and patient outcome. To date, the evaluation of metabolism relies heavily on invasive methods such as microdialysis, restricting a comprehensive understanding of the metabolic mechanisms associated with ICH. This study proposes a noninvasive metabolic imaging method based on 2H magnetic resonance spectroscopy and imaging (2H-MRS/MRSI) to detect metabolic changes after ICH in vivo. To overcome the low-sensitivity limitation of 2H, we designed a new 1H-2H double-resonance coil with 2H-channel active detuning and proposed chemical shift imaging based on the balanced steady-state free precession method (CSI-bSSFP). Compared with the volume coil, the signal-to-noise ratio (SNR) of the new coil was increased by 4.5 times. In addition, the SNR of CSI-bSSFP was 1.5 times higher than that of conventional CSI. These two technologies were applied to measure lactate metabolic flux at different phases of ICH. The results show a higher lactate concentration in ICH rats than in control rats, which is in line with the increased expression of lactate dehydrogenase measured via immunohistochemistry staining (AUCLac_area/Glc_area: control, 0.08 ± 0.02 vs ICH-3d, 0.39 ± 0.05 vs ICH-7d, 0.18 ± 0.02, P < 0.01; H-score: control, 126.4 ± 5.03 vs ICH-3d, 168.4 ± 5.71 vs ICH-7d,133.6 ± 7.70, P < 0.05). A higher lactate signal also appeared near the ICH region than in normal brain tissue. In conclusion, 2H-MRS/MRSI shows potential as a useful method for in vivo metabolic imaging and noninvasive assessment of ICH.

Unsupervised deep learning model for correcting Nyquist ghosts of single-shot spatiotemporal encoding.

PURPOSE: To design an unsupervised deep learning (DL) model for correcting Nyquist ghosts of single-shot spatiotemporal encoding (SPEN) and evaluate the model for real MRI applications. METHODS: The proposed method consists of three main components: (1) an unsupervised network that combines Residual Encoder and Restricted Subspace Mapping (RERSM-net) and is trained to generate a phase-difference map based on the even and odd SPEN images; (2) a spin physical forward model to obtain the corrected image with the learned phase difference map; and (3) cycle-consistency loss that is explored for training the RERSM-net. RESULTS: The proposed RERSM-net could effectively generate smooth phase difference maps and correct Nyquist ghosts of single-shot SPEN. Both simulation and real in vivo MRI experiments demonstrated that our method outperforms the state-of-the-art SPEN Nyquist ghost correction method. Furthermore, the ablation experiments of generating phase-difference maps show the advantages of the proposed unsupervised model. CONCLUSION: The proposed method can effectively correct Nyquist ghosts for the single-shot SPEN sequence.

Rheumatoid arthritis and adverse pregnancy outcomes: a bidirectional two-sample mendelian randomization study.

BACKGROUND: There is growing evidence of bidirectional associations between rheumatoid arthritis and adverse pregnancy outcomes (APOs) in observational studies, but little is known about the causal direction of these associations. Therefore, we explored the potential causal relationships between rheumatoid arthritis and APOs using a bidirectional two-sample Mendelian randomization (MR) in European and Asian populations. METHODS: We conducted a bidirectional two-sample Mendelian randomization analysis using available summary statistics from released genome-wide association studies. Summary statistics for instrument-outcome associations were retrieved from two separate databases for rheumatoid arthritis and adverse pregnancy outcomes, respectively. The inverse-variance weighted method was used as the primary MR analysis, and cML-MA-BIC was used as the supplementary analysis. MR-Egger, MR pleiotropy residual sum and outlier (MR-PRESSO), and Cochran Q statistic method were implemented as sensitivity analyses approach to ensure the robustness of the results. RESULTS: Our study showed that a higher risk of rheumatoid arthritis in the European population was associated with gestational hypertension (OR: 1.04, 95%CI: 1.02-1.06), pre-eclampsia (OR: 1.06, 95%CI: 1.01-1.11), fetal growth restriction (OR: 1.08, 95%CI: 1.04-1.12), preterm delivery (OR:1.04, 95%CI: 1.01-1.07). Furthermore, we found no evidence that APOs had causal effects on rheumatoid arthritis in the reverse MR analysis. No association between rheumatoid arthritis and APOs was found in East Asian population. There was no heterogeneity or horizontal pleiotropy. CONCLUSIONS: This MR analysis provides the positive causal association from rheumatoid arthritis to gestational hypertension, pre-eclampsia, fetal growth restriction and preterm delivery genetically. It highlights the importance of more intensive prenatal care and early intervention among pregnant women with rheumatoid arthritis to prevent potential adverse obstetric outcomes.

Meta-Analysis on the Therapeutic Effect of Transcatheter Arterial Chemoembolization Combined with Portal Vein Embolization.

INTRODUCTION: The aim of the study was to conduct a systematic review to explore the therapeutic effect of transcatheter arterial chemoembolization (TACE) combined with portal vein embolization (PVE) for patients with hepatocellular carcinoma (HCC). METHODS: Chinese and English databases (PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang database, and VIP database) were searched from database inception to August 15, 2023. Studies comparing TACE combined with PVE versus TACE alone for patients with HCC were included. The degree of heterogeneity was assessed using I2 statistics and a Q test. The effect size was represented by risk ratio and mean difference (MD), and the effect size range was estimated using a 95% confidence interval (CI). RESULTS: Eight eligible studies were included in the systematic review, involving 689 participants. The results showed that the future liver residual (FLR) of patients treated with TACE combined with PVE was significantly higher than that of those treated with PVE alone (MD = 3.99%; 95% CI: 1.03-6.94). Furthermore, compared with PVE alone, TACE combined with PVE had a positive effect on disease-free survival (odds ratio [OR] = 2.16; 95% CI: 1.20-3.88), recurrence rate (OR = 0.79; 95% CI: 0.07-9.42), and complications (OR = 0.53; 95% CI: 0.30-0.96). There was no statistically significant impact on mortality with TACE combined with PVE treatment. CONCLUSION: The combination of TACE with PVE can significantly reduce the FLR of patients with HCC, with higher disease-free survival, lower recurrence rate, and fewer complications.

Mammographically detected breast clustered microcalcifications localized by chest thin-section computed tomography.

BACKGROUND: To explore the capability and clinical significance of chest thin-section computed tomography (CT) for localization of mammographically detected clustered microcalcifications. METHODS: A total of 69 patients with 71 mammographically detected clustered microcalcifications received surgical biopsy under the guidance of mammography (MG), CT was used to localize calcifications combined with MG if calcifications can be seen on CT. Intraoperative mammography of the specimens were performed in all cases for identification of the resected microcalcifications. The clinical, imaging and pathological information of these patients were analyzed. RESULTS: A total of 42 (59.15%) cases of calcifications were localized by CT + MG, 29 (40.85%) cases were guided only by the mammography. All suspicious calcifications on the mammography were successfully removed. Pathological results showed 42 cases were cancer, 23 cases were benign, and 6 cases were atypical hyperplasia. The mean age in the CT + MG group was older than that of the MG group (54.12 vs. 49.27 years; P = 0.014). The maximum diameter of clusters of microcalcifications on mammography in the CT + MG group was larger than that of the MG group [(cranio-caudal view, 1.52 vs. 0.61 mm, P = 0.000; mediolateral oblique (MLO) view, 1.53 vs. 0.62 mm, P = 0.000)]. The gray value ratio (calcified area / paraglandular; MLO, P = 0.004) and the gray value difference (calcified area - paraglandular; MLO, P = 0.005) in the CT + MG group was higher than that of the MG group. Multivariate analysis showed that the max diameter of clusters of microcalcifications (MLO view) was a significant predictive factor of localization by CT in total patients (P = 0.001). CONCLUSIONS: About half of the mammographically detected clustered microcalcifications could be localized by thin-section CT. Maximum diameter of clusters of microcalcifications (MLO view) was a predictor of visibility of calcifications by CT. Chest thin-section CT may be useful for localization of calcifications in some patients, especially for calcifications that are only visible in one view on the mammography.

Causal relationships between genetically predicted particulate air pollutants and neurodegenerative diseases: A two-sample Mendelian randomization study.

Accumulating observational studies have linked particulate air pollutants to neurodegenerative diseases (NDDs). However, the causal links and the direction of their associations remain unclear. Therefore, we adopted a two-sample Mendelian randomization (TSMR) design using the GWAS-based genetic instruments of particulate air pollutants (PM2.5 and PM10) from the UK Biobank to explore their causal influence on four common neurodegenerative diseases. Estimates of causative relationships were generated by the Inverse variance weighted (IVW) method with multiple sensitive analyses. The heterogeneity and pleiotropy tests were additionally performed to verify whether our findings were robust. Genetically predicted PM2.5 and PM10 could elevate the occurrence of AD (odds ratio [OR] = 2.22, 95 % confidence interval [CI] 1.53-3.22, PIVW = 2.85×10-5, PFalsediscovery rate[FDR]= 2.85×10-4 and OR = 2.41, 95 % CI: 1.26-4.60, PIVW = 0.008, PFDR=0.039, respectively). The results were robust in sensitive analysis. However, no evidence of causality was found for other NDDs. Our present study suggests that PM2.5 and PM10 have a detrimental effect on AD, which indicates that improving air quality to prevent AD may have pivotal public health implications.

Tryptophan metabolites and gut microbiota play an important role in pediatric migraine diagnosis.

BACKGROUND: The pathogenesis of pediatric migraine remains unclear and presents challenges in diagnosis. Recently, growing evidence has indicated that the gut microbiota can exert modulatory functions at the gut-brain axis by directly or indirectly regulating tryptophan metabolism. Consequently, we aimed to elucidate the potential association among gut microbiota, tryptophan metabolism, and pediatric migraine while also identifying diagnostic biomarkers for pediatric migraine. METHODS: The gut microbiota composition of 33 migraine children and 42 healthy children, aged less than ten years, from the GMrepo database, was analyzed using the Shannon index, Simpson index, principal coordinates analysis, and Wilcoxon rank-sum test. Microbial diagnostic biomarkers were identified using linear discriminant analysis effect size, ridge regression, and random forest. Plasma concentrations of tryptophan metabolites investigated by enzyme-linked immunosorbent assay were compared between 51 migraine children and 120 healthy children, aged less than eighteen years, using t tests and analysis of variance. The receiver operating characteristic curve was performed to evaluate the diagnostic value of microbial and metabolite biomarkers in pediatric migraine. RESULTS: Differences in the composition of gut microbiota, notably the genera that regulate tryptophan metabolism, were observed in pediatric migraine children. Further investigations revealed a significant decrease in plasma kynurenic acid levels (p < 0.001) among migraine children, along with a significant increase in serotonin (p < 0.05) and quinolinic acid (p < 0.001). Subsequently, we established the normal reference intervals for plasma concentrations of tryptophan metabolites in children. More importantly, the ratio of kynurenic acid to quinolinic acid (AUC: 0.871, sensitivity: 86.3%, specificity: 83.3%) exhibited excellent diagnostic efficacy for pediatric migraine. CONCLUSION: Our study suggests that the gut microbiota may play an important role in the development of pediatric migraine by regulating tryptophan metabolism. We believe that microbial and metabolite biomarkers are sensitive diagnostic tests for pediatric migraine. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (NCT05969990).

Unsupervised cycle-consistent network using restricted subspace field map for removing susceptibility artifacts in EPI.

PURPOSE: To design an unsupervised deep neural model for correcting susceptibility artifacts in single-shot Echo Planar Imaging (EPI) and evaluate the model for preclinical and clinical applications. METHODS: This work proposes an unsupervised cycle-consistent model based on the restricted subspace field map to take advantage of both the deep learning (DL) and the reverse polarity-gradient (RPG) method for single-shot EPI. The proposed model consists of three main components: (1) DLRPG neural network (DLRPG-net) to obtain field maps based on a pair of images acquired with reversed phase encoding; (2) spin physical model-based modules to obtain the corrected undistorted images based on the learned field map; and (3) cycle-consistency loss between the input images and back-calculated images from each cycle is explored for network training. In addition, the field maps generated by DLRPG-net belong to a restricted subspace, which is a span of predefined cubic splines to ensure the smoothness of the field maps and avoid blurring in the corrected images. This new method is trained and validated on both preclinical and clinical datasets for diffusion MRI. RESULTS: The proposed network could effectively generate smooth field maps and correct susceptibility artifacts in single-shot EPI. Simulated and in vivo preclinical/clinical experiments demonstrated that our method outperforms the state-of-the-art susceptibility artifact correction methods. Furthermore, the ablation experiments of the cycle-consistent network and the restricted subspace in generating field maps did show the advantages of DLRPG-net. CONCLUSION: The proposed method (DLRPG-net) can effectively correct susceptibility artifacts for preclinical and clinical single-shot EPI sequences.

Enhancing Leaf Area Index Estimation for Maize with Tower-Based Multi-Angular Spectral Observations.

The leaf area index (LAI) played a crucial role in ecological, hydrological, and climate models. The normalized difference vegetation index (NDVI) has been a widely used tool for LAI estimation. However, the NDVI quickly saturates in dense vegetation and is susceptible to soil background interference in sparse vegetation. We proposed a multi-angular NDVI (MAVI) to enhance LAI estimation using tower-based multi-angular observations, aiming to minimize the interference of soil background and saturation effects. Our methodology involved collecting continuous tower-based multi-angular reflectance and the LAI over a three-year period in maize cropland. Then we proposed the MAVI based on an analysis of how canopy reflectance varies with solar zenith angle (SZA). Finally, we quantitatively evaluated the MAVI's performance in LAI retrieval by comparing it to eight other vegetation indices (VIs). Statistical tests revealed that the MAVI exhibited an improved curvilinear relationship with the LAI when the NDVI is corrected using multi-angular observations (R2 = 0.945, RMSE = 0.345, rRMSE = 0.147). Furthermore, the MAVI-based model effectively mitigated soil background effects in sparse vegetation (R2 = 0.934, RMSE = 0.155, rRMSE = 0.157). Our findings demonstrated the utility of tower-based multi-angular spectral observations in LAI retrieval, having the potential to provide continuous data for validating space-borne LAI products. This research significantly expanded the potential applications of multi-angular observations.

Delayed administration of nafamostat mesylate inhibits thrombin-mediated blood-spinal cord barrier breakdown during acute spinal cord injury in rats.

BACKGROUND: Nafamostat mesylate (nafamostat, NM) is an FDA-approved serine protease inhibitor that exerts anti-neuroinflammation and neuroprotective effects following rat spinal cord injury (SCI). However, clinical translation of nafamostat has been limited by an unclear administration time window and mechanism of action. METHODS: Time to first dose of nafamostat administration was tested on rats after contusive SCI. The optimal time window of nafamostat was screened by evaluating hindlimb locomotion and electrophysiology. As nafamostat is a serine protease inhibitor known to target thrombin, we used argatroban (Arg), a thrombin-specific inhibitor, as a positive control in the time window experiments. Western blot and immunofluorescence of thrombin expression level and its enzymatic activity were assayed at different time points, as well its receptor, the protease activated receptor 1 (PAR1) and downstream protein matrix metalloproteinase-9 (MMP9). Blood-spinal cord barrier (BSCB) permeability leakage indicator Evans Blue and fibrinogen were analyzed along these time points. The infiltration of peripheral inflammatory cell was observed by immunofluorescence. RESULTS: The optimal administration time window of nafamostat was 2-12 h post-injury. Argatroban, the thrombin-specific inhibitor, had a similar pattern. Thrombin expression peaked at 12 h and returned to normal level at 7 days post-SCI. PAR1, the thrombin receptor, and MMP9 were significantly upregulated after SCI. The most significant increase of thrombin expression was detected in vascular endothelial cells (ECs). Nafamostat and argatroban significantly downregulated thrombin and MMP9 expression as well as thrombin activity in the spinal cord. Nafamostat inhibited thrombin enrichment in endothelial cells. Nafamostat administration at 2-12 h after SCI inhibited the leakage of Evans Blue in the epicenter and upregulated tight junction proteins (TJPs) expression. Nafamostat administration 8 h post-SCI effectively inhibited the infiltration of peripheral macrophages and neutrophils to the injury site. CONCLUSIONS: Our study provides preclinical information of nafamostat about the administration time window of 2-12 h post-injury in contusive SCI. We revealed that nafamostat functions through inhibiting the thrombin-mediated BSCB breakdown and subsequent peripheral immune cells infiltration.

Solar-induced chlorophyll fluorescence imperfectly tracks the temperature response of photosynthesis in winter wheat.

Solar-induced fluorescence (SIF) is a promising proxy for photosynthesis, but it is unclear whether it performs well in tracking the gross primary productivity (GPP) under different environmental conditions. In this study, we investigated the dynamics of the two parameters from October 2020 to June 2021 in field-grown winter wheat (Triticum aestivum) and found that the ability of SIF to track GPP was weakened at low temperatures. Accounting for the coupling of light and temperature at a seasonal scale, we found that SIF yield showed a lower temperature sensitivity and had a lower but broader optimal temperature range compared with light-use efficiency (LUE), although both SIF yield and LUE decreased in low-temperature conditions. The discrepancy between the temperature responses of SIF yield and GPP caused an increase in the ratio of SIF/GPP in winter, which indicated the variation in the relationship between them during this period. The results of our study highlight the impact of low temperature on the relationship between SIF and GPP and show the necessity of reconsidering the dynamics of energy distribution inside plants under changing environments.

Enrofloxacin Induces Intestinal Microbiota-Mediated Immunosuppression in Zebrafish.

The immunosuppressive effects of antibiotics and the potential associations with the intestinal microbiota of the host have been increasingly recognized in recent years. However, the detailed underlying mechanisms of immune interference of antibiotics in environmental organisms remain unclear, particularly at the early life stage of high sensitivity. To better understand the gut microbiome and immune function interactions, the vertebrate model, zebrafish, was treated with environmentally relevant concentrations of a frequently detected antibiotic, enrofloxacin (ENR), ranging from 0.01 to 100 µg/L. 16S ribosomal RNA sequencing indicated diminished diversity, richness, and evenness of intestinal flora following ENR treatment. Twenty-two taxa of gut bacteria including Rickettsiales, Pseudomonadales, and Flavobacteriales were significantly correlated with immunosuppressive biomarkers, including a significant decrease in the abundance of macrophages and neutrophils. To validate the immunomodulatory effects due to altered intestinal microbial populations, zebrafish reared under sterile and non-sterile husbandry conditions were compared after ENR treatment. A significant inhibitory effect was induced by ENR treatment under non-sterile conditions, while the number of macrophages and neutrophils, as well as biomarkers of immunosuppressive effects, were significantly salved in zebrafish under sterile conditions, confirming for the first time that immunosuppression by ENR was closely mediated through alterations of the intestinal microbiome in fish.

The risk of perchlorate and iodine on the incidence of thyroid tumors and nodular goiter: a case-control study in southeastern China.

BACKGROUND: The incidence rates of thyroid tumors and nodular goiter show an upward trend worldwide. There are limited reports on the risk of perchlorate and iodine on thyroid tumors, but evidence from population studies is scarce, and their impact on thyroid function is still uncertain. Therefore, the objective of this study was to investigate the association of perchlorate and iodine with the risk of nodular goiter (NG), papillary thyroid microcarcinoma (PTMC), and papillary thyroid carcinoma (PTC) and to assess the correlation between perchlorate and iodine with thyroid function indicators. METHODS: A case-control population consisting of 184 pairs of thyroid tumors and nodular goiter matched by gender and age (±2 years) was recruited in this study. Serum and urine samples were collected from each participant. Thyroid function indicators in serum were tested by automatic chemical immunofluorescence, and perchlorate and iodine levels in urine were determined by ultra-high performance liquid chromatography tandem-mass spectrometry and inductively coupled plasma-mass spectrometry, respectively. Conditional logistic regressions and multiple linear regressions were used to analyze the associations. RESULTS: Urinary perchlorate concentration was significantly higher in total cases, NG and PTC than in the corresponding controls (P < 0.05). Perchlorate was positively associated with PTC (OR = 1.058, 95% CI: 1.009, 1.110) in a non-linear dose-response relationship, but there was no association between perchlorate and NG or PTMC. Iodine was not associated with the risk of thyroid tumors and NG and did not correlate with the thyroid function indicators. Furthermore, perchlorate showed a positive correlation with thyroid stimulating hormone (TSH) at iodine adequate levels (P < 0.05), and a negative correlation with free triiodothyronine (FT3) and a positive correlation with thyroglobulin antibody (TgAb) at iodine more than adequate or excess levels (P < 0.05). CONCLUSIONS: Perchlorate can increase the risk of PTC in a non-linear dose-response relationship and disturb the thyroid hormone homeostasis and thyroid autoantibody levels.

Stimulant use and bone health in US children and adolescents: analysis of the NHANES data.

Stimulants have become the most popular psychopharmacologic drugs used in therapy for attention-deficit/hyperactivity disorder (ADHD). Childhood and adolescence are crucial periods for optimizing bone health to prevent osteoporosis-related fractures in old age. However, controversy remains regarding the relationship between stimulant use and bone health. The present study was designed to examine the bone mineral content (BMC) and bone mineral density (BMD) of 5472 individuals aged 8-16 years with or without stimulant use based on National Health and Nutrition Examination Survey (NHANES) 2011-2018 data and to further assess the association between stimulant use and bone health. Among these, 284 (5.2%) participants were using stimulants. In analyses stratified by sex, the BMC and BMD at the level of the lumbar spine, pelvis, and total body were generally lower among stimulant users than among nonusers in males (all P < 0.001), while the differences were not statistically significant in females. In multivariable linear regression models, the increasing range of BMCs and BMDs with age was lower in participants using stimulants than in those not using stimulants after fully adjusting for potential confounding factors. Compared to participants not using stimulants, stimulant use ≥ 3 months was associated with significantly lower BMCs [lumbar spine: ß = - 1.35, (95% CI: - 2.56, - 0.14); pelvis: ß = - 9.06, (95% CI: - 15.21, - 2.91); and total: ß = - 52.96, (95% CI: - 85.87, - 20.04)] and BMDs [pelvis: ß = - 0.03, (95% CI: - 0.04, - 0.01), total: ß = - 0.01, (95% CI: - 0.02, - 0.00)]. CONCLUSIONS: Children and adolescents using stimulants exhibited reductions in BMC and BMD at the lumbar spine, pelvis, and total body compared to those who were not using stimulants, especially among males. WHAT IS KNOWN: • Childhood and adolescence are crucial periods for optimizing bone health to prevent osteoporosis-related fractures in old age. • Controversy remains regarding the relationship between stimulant use and bone health. WHAT IS NEW: • The bone mineral content and bone mineral density at the level of the lumbar spine, pelvis, and total body were generally lower among stimulant users than among nonusers in males, while the differences were not statistically significant in females. • Body mass index and serum alkaline phosphatase may be predictors for loss of bone mineral content and bone mineral density in stimulant users.

Lactate/albumin ratio as a predictor of in-hospital mortality in critically ill children.

OBJECTIVE: Managing critically ill patients with high mortality can be difficult for clinicians in pediatric intensive care units (PICU), which need to identify appropriate predictive biomarkers. The lactate/albumin (L/A) ratio can precisely stratify critically ill adults. However, the role of the L/A ratio in predicting the outcomes of critically ill children remains unclear. Therefore, this study aimed to evaluate the prognostic performance of the L/A ratio in predicting in-hospital mortality in unselected critically ill patients in the PICU. METHODS: This was a single-center retrospective study. Clinical data of 8,832 critical patients aged between 28 days and 18 years were collected from the pediatric intensive care (PIC) database from 2010 to 2018. The primary outcome was the in-hospital mortality rate. RESULTS: There was a higher level of L/A ratio in non-survivors than survivors (P < 0.001). Logistic regression indicated that the association between the L/A ratio and in-hospital mortality was statistically significant (OR 1.44, 95% CI 1.31-1.59, P < 0.001). The AUROC of the L/A ratio for predicting in-hospital mortality was higher than lactate level alone (0.74 vs 0.70, P < 0.001). Stratification analysis showed a significant association between the L/A ratio and in-hospital mortality in the age and primary disease groups (P < 0.05). CONCLUSIONS: Our study suggested that the L/A ratio was a clinical tool to predict in-hospital mortality in critically ill children better than lactate level alone. However, given that the study was retrospective, more prospective studies should be conducted to test the predictive value of the L/A ratio in critical illness.

The cerebrospinal fluid neutrophil to lymphocyte ratio is a sensitive biomarker for bacterial meningitis in children.

BACKGROUND: The cerebrospinal fluid neutrophil-to-lymphocyte ratio (CSF NLR) as a diagnostic biomarker of bacterial meningitis has been reported in adult trials. The aim of this study was to evaluate the CSF NLR as a diagnostic biomarker of bacterial meningitis in children and to define an optimal CSF NLR concentration. METHODS: We performed a retrospective cohort study of children with clinical findings compatible with meningitis. CSF NLR was calculated as the ratio of neutrophil count to lymphocyte count in cerebrospinal fluid (CSF). Initial data included clinical, radiological, and laboratory diagnostics. RESULTS: We determined CSF parameters from children with infectious meningitis (n = 348) and subdivided them into bacterial meningitis (n = 112) and viral meningitis (n = 236). CSF NLR was significantly higher in bacterial meningitis than in viral meningitis (P < 0.001), and its level was higher in Gram-negative bacterial infections than in Gram-positive bacterial infections (P = 0.01). In the receiver operating characteristic curve analysis, CSF NLR was better than CSF protein/sugar/WBC in the ability to distinguish bacterial meningitis from viral meningitis (AUC 0.91 ± 0.02 versus 0.88 ± 0.03/0.87 ± 0.03/0.86 ± 0.03), and using a cutoff point of 0.68, the sensitivity was 0.90, and the specificity was 0.75. Compared with Gram-positive infection, CSF NLR with Gram-negative infection was higher (media, IQR (1.18 (0.19-2.33) versus 3.90 (1.50-8.91), P = 0.01). CONCLUSION: CSF NLR is a more useful diagnostic tool to distinguish between bacterial meningitis and viral meningitis in children. While at a cutoff value of 0.68, CSF NLR has better sensitivity and specificity for bacterial meningitis, and the higher level of CSF NLR could be related to Gram-negative bacterial infection.