Background Exposure to benzo[a]pyrene (BaP) may impair lung function through various mechanisms; however, it remains uncertain whether BaP induces ferroptosis in lung tissue cells, resulting in lung function impairment. Objective To investigate the ferroptosis of lung tissue cells triggered by subchronic BaP exposure in mice and its correlation with lung injury, and to explore the function of ferroptosis in BaP-induced lung tissue damage. Method Seventy-two healthy 3-weeks-old male C57BL/6J mice were acclimatized for 1 week and then randomly divided into six groups: control group (corn oil 10 mL·kg⁻¹), low-dose BaP group (2.5 mg·kg⁻¹), medium-dose BaP group (5 mg·kg⁻¹), high-dose BaP group (10 mg·kg⁻¹), BaP+ferrostatin-1 (Fer-1) group (10 mg·kg⁻¹+1 mg·kg⁻¹), and Fer-1 group (1 mg·kg⁻¹), with 12 mice each group. Corn oil and BaP were administered via gavage every other day, followed by an intraperitoneal injection of Fer-1 the subsequent day, throughout a period of 90 d. Whole-body plethysmography was applied to detect lung function; hematoxylin-eosin staining (HE) and Masson staining were used to observe lung tissue injury and fibrosis; microscopy of alveolar epithelial cells was conducted to reveal mitochondrial morphology; biochemical assays were used to measure the content of tissue iron, malondialdehyde (MDA), and glutathione (GSH), as well as the activity of glutathione peroxidase (GSH-Px); Western blotting and real-time quantitative PCR (RT-qPCR) analyses were performed to reveal the protein and mRNA expression of ferroptosis markers. Results Compared to the control group, the high-dose BaP group showed a significant increase in expiration time (Te) (P<0.01), and a significant decrease in ratio rate of achieving peak expiratory flow (Rpef), tidal volume (TVb), peak inspiratory flow (PIF), minute volume (MVb), and peak expiratory flow (PEF) (P<0.05 or 0.01). Based on the results of HE and Masson staining, partial destruction of alveolar structures, thickening of alveolar walls, infiltration of inflammatory cells, significant thickening of tracheal walls and a large deposition of collagen fibers in lung tissue were observed in the medium- and high-dose BaP groups. By microscopy, the alveolar epithelial cells exposed to low-dose BaP showed condensed chromatin, and the mitochondria exposed to medium and high-dose BaP showed wrinkles, increased mitochondrial membrane density, and diminished mitochondrial cristae. Compared to the control group, in the medium- and high-dose BaP groups, the lung tissue iron content and the expression levels of ACSL4 protein and mRNA significantly elevated (P<0.01 or 0.05), while the mRNA expression level of SLC7A11 significantly decreased (P<0.05); in the high-dose BaP group, the MDA content, COX2 protein, and PTGS2 mRNA expression levels significantly increased (P<0.05 or 0.01), GSH content and GSH-Px activity, GPX4 protein and mRNA expression levels, and the expression level of SLC7A11 protein significantly decreased (P<0.01 or 0.05). The ferroptosis inhibitor Fer-1 markedly reversed respiratory function, morphology, mitochondrial alterations, and the aforementioned ferroptosis-related biochemical indicators. Conclusion Subchronic exposure to BaP can induce ferroptosis in mice lung tissue cells, resulting in compromised lung function.

Objective To analyze the characteristics of HIV-1 pretreatment drug resistance(PDR)and molecular transmission networks in Yubei District,Chongqing,providing evidence for targeted interventions.Methods Using a cross-sectional design,plasma samples were collected from HIV/AIDS patients receiving antiretroviral therapy(ART)in Yubei District from January 2022 to December 2023.Pol gene fragments were extracted and amplified for HIV-1 genotyping and drug resistance analysis.Molecular transmission networks were constructed based on genetic distance calculations.Results Among 478 HIV-1 pol sequences,eight geno-types were identified:with CRF07_BC(60.4%,289/478),CRF08_BC(15.5%,74/478),CRF01_AE(11.7%,56/478),and CRF85_BC(5.9%,28/478).The overall PDR rate was 6.3%(30/478),with resistance to nucleoside reverse transcriptase inhibitors(NRTIs)and non-nucleoside reverse transcriptase inhibitors(NNRTIs)at 1.7%(8/478)and 5.2%(25/478),respectively.No protease inhibitor(PI)resistance was de-tected.The molecular network included 177 cases(37.0%network entry rate),forming 53 clusters with 198 connections.Cluster sizes ranged from 2 to 17 nodes,and 75.3%(149/198)of connections were associated with five subdistricts/towns:Shuanglonghu Street,Huixing Street,Luoqi Town,Gulu Town,and Baoshenghu Street.Conclusion HIV-1 genotypes in Yubei District exhibit diversity and complexity,with moderate PDR prevalence.Regional clustering of transmission networks suggests the need for enhanced molecular surveil-lance and targeted interventions based on analytical findings.

Objective To investigate the role of circular RNAs(circRNA)in Alzheimer's disease(AD)and its potential mechanism.Methods Six-month-old APP/PS1 mouse model of AD and wild type(WT)mice were subjected and then randomly divided into WT group,WT+circ-Olfm1 knockout group,AD group(transgenic APP/PS1 mice),AD+circ-Olfm1 knockout group,AD+FOXO3a knockout group,with 3 mice in each group.① The total RNA of mouse brain was extracted,and the differential expression of circRNAs and mRNAs between the AD mice and WT mice was detected,and the obtained circRNAs and mRNAs were analyzed with gene ontology(GO)analysis.② RT-qPCR was used to detect the expression of the top 10 up-regulated and down-regulated circRNAs,as well as the expression of circ-Olfm1 and miR-330-5p.③ Lentiviral vectors were prepared and stereotaxically injected into the cortex or hippocampus of WT and AD mice to knock out circ-Olfm1 gene.Water maze test was used to evaluate the effect of circ-Olfm1 knockout on cognitive function,and immunofluorescence assay was employed to observe the deposition of amyloid β(Aβ)plaque in the brain.④ The interaction between circ-Olfm1 and miR-330-5p was verified by double luciferase reporter gene analysis.⑤ The protein levels of AMPK and FOXO3a were detected by Western blotting.⑥ Transmission electron microscopy was utilized to observe the mitochondria of the hippocampus.⑦ The levels of inflammatory factors IL-6,IL-1β and TNF-α were detected by ELISA.Results There were totally 52 differentially expressed circRNAs identified between the AD and WT mice,including 28 up-regulated and 24 down-regulated(fold change>1.5,P<0.05).These differentially expressed genes are mainly involved in signal transduction,learning and memory and other functions.circ-Olfm1 was identified as the most significantly differentially expressed circRNA,which is highly expressed in the neurons and up-regulated in the cerebral cortex and hippocampus of the AD mice.Knockout of circ-Olfm1 reduced the number of Aβ plaques in the cerebral cortex and hippocampus of AD mice(P<0.01).In starBase database,there are complementary sequences observed between circ-Olfm1 and miR-330-5p.Western blotting showed that the addition of Aβ42 significantly increased the expression of AMPK and FOXO3a in the neuronal cells(P<0.01).And silencing circ-Olfm1 led to decreased expression of AMPK and FOXO3a in neuronal cells+Aβ42(P<0.01).ELISA revealed that knockout of FOXO3a significantly increased the levels of inflammatory factors IL-6,IL-1β,and TNF-α(P<0.01).Transmission electron microscopy displayed that knocking FOXO3a out significantly aggravated mitochondrial damage(P<0.01).Conclusion circ-Olfm1 is up-regulated in the brain tissue and neurons+Aβ42 of AD rats,and the mechanism of cognitive impairment in AD rats may be through its regulating FOXO3a protein.

Humans ; Adolescent ; Acne Vulgaris/therapy* ; Skin Care ; Surveys and Questionnaires ; Cognition ; China ; Skin

Taking into consideration the characteristics and current development status of air medical rescue,an analysis is conducted from the perspective of hospitals to examine the focal points and challenges in establishing the capability of hospital air medical rescue.A capability framework comprising five modules,namely planning system,service model,professional teams,hardware platform,and operational procedures,is proposed.The key tasks for each module are sorted out.Furthermore,the ex-ploration and practical experience of The First Affiliated Hospital of Sun Yat-sen University are shared,with the aim of providing a reference for the construction of hospital air medical rescue capabilities in the modern era.

Objective To evaluate the clinical use of the baseline CT angiography(CTA)quantitative score(self-designed collateral circulation quantitative,SD-CCQ)in determining the collateral circulation compensation status in patients with acute ischemic stroke(AIS),as well as the reliability and accuracy of the SD-CCQ score and the Alberta Stroke Program Early CT Score(ASPECTS).Methods Retrospective analysis was made on the clinical and imaging data,including CT,CTA and DWI image data,of 84 patients who were admitted for acute ischemic stroke to the Department of Neurorehabilitation of Zhongshan Hospital of Traditional Chinese Medicine from January 2020 to December 2022.Their CTA source images were annotated using a multi-task deep learning method for vascular segmentation.The ASPECTS score and SD-CCQ score were then applied to the CTA images following vascular segmentation in order to assess the collateral circulation compensation of AIS patients.The Kappa test was used to assess the consistency of the two methods used to assess collateral circulation,and the multifactorial Logistic regression analysis was used to examine the relationship between the SD-CCQ and the prognosis of the AIS patients.Results ASPECTS score had good consistency with SD-CCQ score in evaluating collateral circulation in AIS patients(κ=0.65,P＜0.001),and the diagnostic accuracy of the latter for benign collateral circulation in AIS was 96.15％.Logistic regression analysis showed that the new collateral circulation score,baseline NIHSS,and DWI infarct volume were the main factors affecting the long-term prognosis of AIS patients.Conclusion The new scoring system SD-CCQ can be used to evaluate the compensatory status of collateral circulation in AIS patients,which may help in clinical treatment decision-making and prognosis prediction.

OBJECTIVE To explore the predictive factors of cefoperazone/sulbactam-induced thrombocytopenia in adult inpatients， and to establish and validate the nomogram prediction model. METHODS Data of adult inpatients treated with cefoperazone/sulbactam in Xi’an Central Hospital from Jun. 30th， 2021 to Jun. 30th， 2023 were retrospectively collected. The training set and internal validation set were randomly constructed in a 7∶3 ratio. Singler factor and multifactor Logistic regression analysis were used to screen the independent predictors of cefoperazone/sulbactam-induced thrombocytopenia. The nomogram was drawn by using “RMS” of R 4.0.3 software， and the predictive performance of the model was evaluated by the receiver operating characteristic curve and C-index curve. Hosmer-Lemeshow goodness-of-fit test was used to evaluate the calibration degree of the model. Using the same standard， the clinical data of hospitalized patients receiving cefoperazone/sulbactam in Xi’an First Hospital in the same period were collected for external validation of the nomogram prediction model. RESULTS A total of 1 045 patients in Xi’an Central Hospital were included in this study， among which 67 patients suffered from cefoperazone/sulbactam-induced thrombocytopenia， with an incidence of 6.41%. After the false positive patients were excluded， 473 patients were included finally， including 331 in the training set and 142 in theinternal validation set. Multifactor Logistic regression analysis showed that age [OR＝1.043， 95%CI （1.017， 1.070）]， estimated glomerular filtration rate （eGFR） [OR＝0.988，95%CI（0.977， 0.998）]， baseline platelet （PLT） [OR＝0.989， 95%CI（0.982， 0.996）]， nutritional risk [OR＝3.863， 95%CI（1.884， 7.921）] and cumulative defined daily doses （DDDs） [OR＝1.082， 95%CI（1.020， 1.147）] were independent predictors for cefoperazone/sulbactam-induced thrombocytopenia （P＜0.05）. The C-index values of the training set and the internal validation set were 0.824 [95%CI （0.759， 0.890）] and 0.828 [95%CI （0.749， 0.933）]， respectively. The results of the Hosmer-Lemeshow test showed that χ 2 values were 0.441 （P＝0.802） and 1.804 （P＝0.406）. In the external validation set， the C-index value was 0.808 [95%CI （0.672， 0.945）]， the χ 2 value of the Hosmer-Lemeshow test was 0.899 （P＝0.638）. CONCLUSIONS The independent predictors of cefoperazone/sulbactam-induced thrombocytopenia include age， baseline PLT， eGFR， nutritional risk and cumulative DDDs. The model has good predictive efficacy and extrapolation ability， which can help clinic identify the potential risk of cefoperazone/sulbactam-induced thrombocytopenia quickly and accurately.

Objective:To examine the correlation between serum 25-hydroxyvitaminD [25(OH)D] levels and all-cause mortality risk among adult women in the United States.Methods:Data for this retrospective cohort study were obtained from the National Health and Nutrition Examination Survey 2011—2016. A total of 6 452 women with complete data were enrolled and the end point event was all-cause mortality. The subjects were categorized into four groups based on serum 25(OH)D levels: severe deficiency group [25(OH)D<25.0 nmol/L, n=285], deficiency group [25(OH)D 25.0-49.9 nmol/L, n=1 695], insufficient group [25(OH)D 50.0-74.9 nmol/L, n=2 119], and sufficient group [25(OH)D≥75.0 nmol/L, n=2 353]. The serum 25 (OH) D level was included in cox proportional hazards model as a continuous variables and a categorical variables, respectively, to estimate the risk of all-cause mortality. Cox regression model based on restricted cubic splines was used to observe the curve relationship between the continuous change of serum 25(OH)D and the risk of all-cause mortality. A two-piecewise linear regression model was used to analyze the saturation threshold effect and examine the correlation between serum 25(OH)D levels and all-cause mortality risk among adult women in the United States. Results:A total of 6 452 women were enrolled. The mean level of serum 25(OH)D was (68.2±31.6) nmol/L, and only 36.5% (2 353/6 452) of the women had sufficient vitamin D. During the follow-up time of (5.8±1.8) years, 375 women died, and the all-cause mortality rate of 5.8%. After multivariate adjustment, for every 10 nmol/L increase in serum 25(OH)D level, the risk of all-cause mortality was reduced by 5% ( HR=0.95, 95% CI: 0.91-0.98) ( P<0.05). Compared with serum 25(OH)D severe deficiency group, the risk of all-cause mortality in 25(OH)D sufficient group was 54% lower ( HR=0.46, 95% CI: 0.29-0.75) ( P<0.05, Ptrend<0.001). The association between serum 25(OH)D levels and all-cause mortality risk exhibited an L-shaped curve ( P=0.007) and the inflection point was 128.5 nmol/L; when the serum level of 25(OH)D was less than 128.5 nmol/L, for every 10 nmol/L increase in 25(OH)D, the risk of all-cause mortality was reduced by 8% ( HR=0.92, 95% CI: 0.88-0.96) ( P<0.001). Conclusion:High serum 25(OH)D concentrations are non-linearly associated with low risk of all-cause mortality. These findings suggest that maintaining adequate vitamin D status may lower mortality risk in American women individuals.

Objective:The aim of this study is to examine the impact of inosine pretreatment in pregnant rats on as-trocyte(Ast)responses in the maternal inflammation-induced periventricular leukomalacia(PVL)model in offspring.Methods:The pregnant rats were divided into Control,PVL,and IN-PVL groups.In the PVL group,pregnant rats at gestational day 17(E17)received intraperitoneal injections of lipopolysaccharide(LPS)at a dose of 350 μg/kg for 2 days.In the IN-PVL group,pregnant rats at E1 were administered an inosine solution(1 mg/ml,25 ml/day)for 16 days followed by intraperitoneal injections of LPS for 2 days.Newborn 7-day-old rat brains from each group of pregnant rats were collected,and the protein expression of myelin basic protein(MBP),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-1 β(IL-1β),interleukin-4(IL-4),interleukin-10(IL-10),glial fibrillary acidic protein(GFAP),complement 3(C3),S100 calcium binding protein A10(S100A10),platelet-derived growth factor(PDGF),chemokine ligand 1(CXCL1),and connexin 43(Cx43)were detected by immunofluorescence staining or Western Blot.Results:The PVL group exhibited a decrease in myelin MBP color area and an increase in hypertrophic Ast in contrast to the Control group.Additionally,protein expression levels of proinflammatory factors(TNF-α,IL-6,IL-1β),GFAP,A1 Ast marker C3,and Ast linker Cx43 were significantly elevated in the PVL group compared to the Control group(P＜0.05).Conversely,protein expression levels of anti-inflammatory factors(IL-4,IL-10),MBP,A2 Ast marker S100A10,and Ast secreted products(PDGF,CXCL 1)were significantly decreased in the PVL group com-pared to the Control group(P＜0.05).Inosine pretreatment effectively reversed the expression levels of these proteins(P＜0.05).Conclusion:Inosine pretreatment of pregnant rats improved cerebral hypomyelination in offspring PVL neonatal rats by regulation of Ast responsiveness and the secretion of pro-myelinating substances.