To develop and validate a model for predicting intensive care unit (ICU) mortality risk in patients with malignant tumors complicated by acute respiratory failure (ARF) based on an explainable machine learning framework.

Objective To quantitatively assess the association of short-term exposure to polycyclic aromatic hydrocarbons (PAHs) in ambient fine particulate matter (PM2.5) with residents mortality. Methods A time-stratified case-crossover study was conducted from 2020 to 2022 among 10606 non-accidental residents by using the Guangzhou Cause of Death Surveillance System in Conghua District, Guangzhou. Exposure levels of PAHs in PM_2.5 and meteorological data during the study period were obtained from the Center for Disease Control and Prevention in Conghua District and the China Meteorological Administration Land Data Assimilation System (CLDAS-V2.0), respectively. Conditional Poisson regression model was used to estimate the exposure-response association between PAHs and the mortality risk. Results Fluoranthene, chrysene, benzo[k]fluoranthene, benzo[a]pyrene, and indeno[1,2,3-cd]pyrene were significantly associated with an increased risk of mortality. For every one interquartile range increase in exposure levels, the non-accidental mortality risks increased by 8.33% (95% CI: 1.80%, 15.27%), 4.67% (95% CI: 1.86%, 7.57%), 6.07% (95% CI: 2.08%, 10.21%), 4.62% (95% CI: 1.85%, 7.47%), and 4.70% (95% CI: 0.53%, 9.03%), respectively. The estimated non accidental deaths attributable to exposure to fluoranthene, chrysene, benzo[k]fluorine, benzo[a]pyrene and indine[1,2,3-cd]pyrene were 5.91%, 6.08%, 6.51%, 6.46%, and 4.21%, respectively. Conclusions Short-term exposure to PAHs in PM_2.5, including fluoranthene, chrysene, benzo[k]fluoranthene, benzo[a]pyrene and indine[1,2,3-cd]pyrene, was significantly associated with an increased risk of mortality among residents.

Acute lung injury (ALI) is a severe disease caused by viral infection that triggers an uncontrolled inflammatory response. This study investigated the capacity of jasurolignoside (JO), a natural compound, to bind to Toll-like receptor 4 (TLR4) and treat ALI. The anti-inflammatory properties of JO were evaluated in vitro through Western blotting, enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining, and co-immunoprecipitation. The investigation utilized a lipopolysaccharide (LPS)-induced ALI animal model to examine the therapeutic efficacy and mechanism of JO in vivo. JO attenuated inflammatory symptoms in infected cells and tissues by modulating the NOD-like receptor family pyrin domain containing protein 3 (NLRP3) inflammasome and the nuclear factor κB (NF-κB)/mitogen-activated protein kinase (MAPK) pathway. Molecular docking simulations revealed JO binding to TLR4 active sites, confirmed by cellular thermal shift assay. Surface plasmon resonance (SPR) demonstrated direct interaction between JO and TLR4 with a Kd value of 35.1 μmol·L^-1. Moreover, JO inhibited tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and IL-6 secretion and reduced leukocyte, neutrophil, lymphocyte, and macrophage infiltration in ALI-affected mice. JO also enhanced lung function and reduced ALI-related mortality. Immunohistochemical staining demonstrated JO's ability to suppress TLR4 expression in ALI-affected mouse lung tissue. This study establishes that JO can bind to TLR4 and effectively treat ALI, indicating its potential as a therapeutic agent for clinical applications.
Toll-Like Receptor 4/chemistry* ; Animals ; Acute Lung Injury/chemically induced* ; Mice ; Humans ; Ilex/chemistry* ; Molecular Docking Simulation ; Male ; NF-kappa B/immunology* ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology* ; Tumor Necrosis Factor-alpha/genetics* ; Interleukin-1beta/genetics* ; RAW 264.7 Cells ; Disease Models, Animal

Background Exposure to air pollutants increases the risk of diseases in multiple systems, including respiratory and cardiovascular systems, yet its association with neurological diseases remains unclear. Objective To quantitatively evaluate the association between short-term exposure to air pollutants and outpatient and emergency visits for neurological diseases, identify potential susceptible populations, and quantify associated disease burden. Methods Daily 24-hour average concentrations of fine particulate matter (PM_2.5), inhalable particulate matter (PM₁₀), sulfur dioxide (SO₂), nitrogen dioxide (NO₂), and carbon monoxide (CO), daily maximum 8-hour average concentration of ozone (O₃), daily meteorological data (24-hour average temperature, 24-hour average relative humidity), and data on daily outpatient and emergency department visits for neurological diseases from two hospitals in Conghua District, Guangzhou, China, were collected from 2015 to 2022. A time-stratified case-crossover design was adopted, and a conditional Poisson regression model was constructed to analyze the association between air pollution exposure and neurological disease visits. Two-pollutant models and sensitivity analysis were used to validate model stability. Stratified analyses by season (cold season: from November to March; warm season: from April to October), sex (male, female), and age (≤45 years, 46–60 years, ≥61 years) were performed to identify vulnerable group. Additionally, the number and proportion of neurological disease visits attributable to short-term air pollutant exposure were calculated. Results A total of 72 673 outpatient and emergency department visits for neurological diseases were included during the study period. Most of the patients were middle-aged and elderly individuals (69.89% were over 45 years old) and females (60.25%). The results of single-pollutant models showed that for each interquartile range (IQR) increase in exposure to PM_2.5, PM₁₀, SO₂, NO₂, CO, and O₃, the risk of outpatient and emergency department visits for neurological diseases increased by 7.54% (95%CI: 4.69%, 10.46%), 6.66% (95%CI: 3.92%, 9.46%), 16.72% (95%CI: 10.58%, 23.19%), 8.12% (95%CI: 4.82%, 11.53%), 5.60% (95%CI: 2.34%, 8.97%), and 6.11% (95%CI: 2.91%, 9.40%), respectively. The results of the two-pollutant model showed that the association between PM_2.5 and SO₂ exposure and outpatient and emergency department visits for neurological diseases were relatively stable. The stratified analyses showed that the effect of SO₂ was stronger in the cold season. It was estimated that 8.32% (95%CI: 5.55%, 10.96%) and 6.65% (95%CI: 4.27%, 8.96%) of the outpatient and emergency department visits were attributable to short-term exposure to SO₂ and PM_2.5, respectively. Conclusion Exposure to PM_2.5 and SO₂ is associated with increased risks of outpatient and emergency visits for neurological diseases. SO₂ shows stronger effects during the cold season, and exposure to air pollution contributes to up to 8.32% of neurological disease visits.

Objective:To investigate the application of 18F-FDG PET/MR and its derived parameters in the diagnosis and staging of bladder cancer. Methods:Forty patients (32 males, 8 females; age (66.8±11.2) years) with suspected bladder cancer between December 2019 and March 2022 were retrospectively included and underwent 18F-FDG PET/MR in Nanjing First Hospital. Parameters including SUV max, SUV mean, maximum tumor diameter and mean of apparent diffusion coefficient (ADC mean) were obtained, and bladder cancer muscle invasiveness and lymph node involvement were determined. The efficacy of 18F-FDG PET/MR and its derived parameters for tumor diagnosis and staging was analyzed using transurethral resection of bladder tumor (TUR-BT) or radical cystectomy (RC) and extended pelvic lymph node dissection (ePLND) histopathology as the " gold standard". Independent-sample t test, Mann-Whitney U test or χ2 test was used to analyze the data, and Delong test was used to compare different AUCs. Results:Of 40 patients, 8 were non-muscle invasive bladder cancer (NMIBC), 32 were muscle invasive bladder cancer (MIBC), and 5 were pathologically confirmed to have lymph node metastasis. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 18F-FDG PET/MR for identifying MIBC were 96.9%(31/32), 7/8, 96.9%(31/32), 7/8, 95.0%(38/40), respectively, and those for lymph node metastasis were 4/5, 90.0%(18/20), 4/6, 18/19, 88.0%(22/25), respectively. For pathological tumor (pT) staging, significant differences were observed between pT2-3 and pT1 groups in maximum tumor diameter ( t=-2.37, P=0.024), SUV mean( Z=-2.11, P=0.035), and ADC mean( t=2.91, P=0.006). The AUCs of maximum tumor diameter, SUV mean and ADC mean in distinguishing MIBC were 0.781, 0.746, and 0.825, respectively. The sensitivity, specificity, PPV, NPV, and accuracy of MRI alone in identifying MIBC were 87.5%(28/32), 1/8, 80.0%(28/35), 1/5 and 72.5%(29/40), respectively, with the AUC of 0.500. The AUC of 18F-FDG PET/MR in identifying MIBC was 0.796, which was better than MRI alone ( Z=5.54, P<0.001), and the accuracy of PET/MR was also higher than MRI alone ( χ2=7.44, P=0.006). Conclusion:Compared with MRI alone, 18F-FDG PET/MR significantly improves the diagnostic efficacy of bladder cancer and the accuracy of pT staging.

Objective:To explore the effect of transcranial direct current stimulation (tDCS) on dysphagia in hemispheric stroke patients.Methods:Sixty-two hemispheric stroke patients with dysphagia were randomized into an ipsilateral group, a contralateral group and a bilateral group with 20 in each group. The ipsilateral and contralateral groups received tDCS over their ipsilesional and contralesional hemispheres, respectively, while in the bilateral group it was over both hemispheres. That was followed by conventional swallowing therapy. Before and after 2 weeks of the treatment, swallowing function was assessed using the modified Mann Assessment of Swallowing Ability (MMASA) and a Swallow Severity scale (SSS). Linear regressions were evaluated to highlight the factors most influencing recovery from post-stroke hemispheric dysphagia.Results:After the treatments, the average MMASA and SSS scores had increased significantly in all three groups. There was no significant difference in the average post-treatment MMASA and SSS scores between the ipsilateral and contralateral groups, but the bilateral group showed significantly better average post-treatment MMASA and SSS scores compared to the other two groups. Linear regression analysis confirmed that the tDCS protocol (group allocation) was a significant predictor of recovery.Conclusion:Bilateral tDCS can effectively promote the recovery of swallowing function after a hemispheric stroke. It demonstrates greater therapeutic benefits than unilateral tDCS.

Objective: To reveal the molecular biological mechanism of a rare Dc-variant individual using PacBio third-generation sequencing technology. Methods: ABO and Rh blood type identification, DAT, unexpected antibody screening and D antigen enhancement test were conducted by serological testing. The absorption-elution test was used to detect the e antigen. RHCE gene typing was performed by PCR-SSP, and the 1-10 exons of RHCE were sequenced by Sanger sequencing. The full-length sequences of RHCE, RHD and RHAG were detected by PacBio third-generation sequencing technology. Results: Serological findings: Blood type O, Dc-phenotype, DAT negative, unexpected antibody screening negative; enhanced D antigen expression; no detection of e antigen in the absorption-elution test. PCR-SSP genotyping indicated the presence of only the RHCE c allele. Sanger sequencing results: Exons 5-9 of RHCE were deleted, exon 1 had a heterozygous mutation at c. 48G/C, and exon 2 had five heterozygous mutations at c. 150C/T, c. 178C/A, c. 201A/G, c. 203A/G and c. 307C/T. Third-generation sequencing results: RHCE genotype was RHCE 02N. 08/RHCE-D(5-9)-CE; RHD genotype was RHD 01/RHD 01; RHAG genotype was RHAG 01/RHAG 01 (c. 808G>A and c. 861G>A). Conclusion: This Dc-individual carries the allele RHCE 02N. 08 and the novel allele RHCE-D(5-9)-CE. The findings of this study provide data support and a theoretical basis for elucidating the molecular mechanisms underlying RhCE deficiency phenotypes.