BACKGROUND: Asthma is a common chronic inflammatory airway disease and intermittent hypoxia is increasingly recognized as a factor that may impact disease progression. The present study investigated whether intermittent hypoxia (IH) could aggravate asthma by promoting hypoxia-inducible factor-1α (HIF-1α)/nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing protein 3 (NLRP3)/interleukin (IL)-1β-dependent pyroptosis and the inflammatory response and further elucidated the underlying molecular mechanisms involved. METHODS: A total of 49 patients diagnosed with severe bronchial asthma and diagnosed by polysomnography were enrolled at Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, between January 2022 and December 2022, and their general data and induced sputum were collected. BEAS-2B cells were treated with IL-13 and subjected to IH. An ovalbumin (OVA)-treated mouse model was also used to assess the effects of chronic intermittent hypoxia (CIH) on asthma. Pyroptosis, the inflammatory response, and related signalling pathways were assessed in vivo and in vitro . RESULTS: In this study, as the apnoea and hypopnea index (AHI) increased, the proportion of patients with uncontrolled asthma increased. The proportions of neutrophils and the levels of IL-6, IL-8, HIF-1α and NLRP3 in induced sputum were related to the AHI. NLRP3-mediated pyroptosis, which could be mediated by the HIF-1α signalling pathway, was activated in IL-13 plus IH-treated BEAS-2B cells and in the lungs of OVA/CIH mice. HIF-1α downregulation significantly reduced lung pyroptosis and ameliorated neutrophil inflammation by modulating the NLRP3/IL-1β pathway both in vitro and in vivo . Similarly, pretreatment with LW6, an inhibitor of HIF-1α, effectively blocked the generation of inflammatory cytokines in neutrophils. In addition, administration of the NLRP3 activator nigericin obviously increased lung neutrophil inflammation. CONCLUSIONS Obstructive sleep apnoea-hypopnea syndrome (OSAHS) is a risk factor for asthma exacerbation. IH aggravates neutrophil inflammation in asthma via NLRP3/IL-1β-dependent pyroptosis mediated by the HIF-1α signalling pathway, which should be considered a potential therapeutic target for the treatment of asthma with OSAHS.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Humans ; Asthma/metabolism* ; Animals ; Pyroptosis/physiology* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Mice ; Signal Transduction/physiology* ; Male ; Hypoxia/metabolism* ; Female ; Interleukin-1beta/metabolism* ; Adult ; Inflammation/metabolism* ; Middle Aged ; Mice, Inbred C57BL

OBJECTIVES: To investigate the predictive factors for plastic bronchitis (PB) in children with Mycoplasma pneumoniae pneumonia (MPP) and to establish a nomogram prediction model for PB occurrence. METHODS: A retrospective analysis was conducted on children with MPP hospitalized at The Affiliated Hospital of Xuzhou Medical University from January 2023 to June 2024. The patients were randomly divided into a training set (n=562) and a validation set (n=240) at a ratio of 7:3 using simple random sampling. In the training set, patients were categorized into a PB group (n=70) and a non-PB group (n=492) based on the occurrence of PB. Spearman correlation analysis was performed to exclude collinearity among variables, followed by univariate analysis and LASSO regression to identify predictive factors. A nomogram prediction model for PB in children with MPP was constructed. The discriminative ability of the model was assessed using receiver operating characteristic (ROC) curve analysis, model calibration was evaluated with calibration curves, and clinical utility was appraised through decision curve analysis. RESULTS: Compared with the non-PB group, the PB group exhibited significantly longer disease duration prior to bronchoscopy, prolonged fever duration, higher fever peaks, higher proportions of patients with a family history of allergy and personal allergy history, and a higher proportion of patients with pleural effusion, as well as significantly elevated levels of white blood cell count, neutrophil percentage, C-reactive protein, procalcitonin, fibrinogen, D-dimer, aspartate aminotransferase, alanine aminotransferase, creatine kinase, lactate dehydrogenase, immunoglobulin A, and interleukin-6, along with a significantly lower lymphocyte percentage (all P<0.05). LASSO regression analysis identified pleural effusion, procalcitonin, D-dimer, and lactate dehydrogenase as major predictive factors for PB occurrence in children with MPP. The nomogram model based on these factors demonstrated good discriminative ability (area under the ROC curve: 0.852 in the training set and 0.830 in the validation set), with satisfactory calibration and clinical benefit. CONCLUSIONS The nomogram prediction model based on pleural effusion, procalcitonin, D-dimer, and lactate dehydrogenase provides effective predictive performance for the occurrence of PB in children with MPP.
Humans ; Pneumonia, Mycoplasma/complications* ; Nomograms ; Male ; Female ; Child ; Child, Preschool ; Retrospective Studies ; Bronchitis/etiology* ; Infant ; ROC Curve ; Adolescent

Objective:To analyze the perceptions, attitudes toward cognitive screening and associated factors in Chinese population.Methods:It was a cross-sectional study, a total of 1 246 Chinese residents who used smartphones and completed the cognitive screening survey in the Sojump application from February 22 to March 7, 2024 were consecutively selected as the study subjects. The questionnaire content included demographic data, physical examination information, perceptions of cognitive disorders, perceptions, attitudes and suggestions of cognitive screening. A total of 1 273 questionnaires were distributed, and 1 273 were retrieved, of which 1 246 were valid (97.9%). The logistic regression analysis was used to evaluate factors associated with the attitudes toward cognitive screening in the subjects.Results:Of the 1 246 respondents included in the study, 468 were male and 778 were female, with a mean age of (43.9±13.8) years. The respondents covered 26 provincial-level administrative regions in China, including 347 (27.8%) in the east, 429 (34.4%) in the middle and 470 (37.7%) in the west. While 943 respondents failed to comprehend the cognitive screening, 914 considered it necessary. Additionally, 447 respondents recommended initiating cognitive screening at age 50, 927 respondents recommended annual screening, and 924 respondents preferred scale assessment. Female ( OR=2.121, 95% CI: 1.599-2.815), middle-aged and elderly ( OR=1.681, 95% CI: 1.223-2.310), urban residents ( OR=1.426, 95% CI: 1.002-2.029), high per capita monthly household income ( OR=1.253, 95% CI: 1.063-1.477), had complete physical examination ( OR=1.404, 95% CI: 1.015-1.943), better understanding of cognitive disorders ( OR=2.202, 95% CI: 1.750-2.772), and better understanding of cognitive screening ( OR=3.313, 95% CI: 2.227-4.931) showed positive correlations with the attitude favoring cognitive screening (all P<0.05). Conclusion:The perception levels of cognitive screening among Chinese residents are relatively low, but their attitudes are positive. Socio-economic factors, behavioral experiences, and knowledge levels are associated with residents′ attitudes toward cognitive screening.

Objective:To investigate the acute effects of persistent high exposure to atmospheric fine particulate matter (PM 2.5) on residents' outpatient visits for respiratory diseases. Methods:We collected daily outpatient records from 92 hospitals in 13 cities across the Beijing-Tianjin-Hebei region, along with daily PM 2.5, nitrogen dioxide (NO 2), and meteorological data from 2013 to 2018. Five persistent high PM 2.5 exposure scenarios were defined in terms of daily mean PM 2.5 concentrations (>75 μg/m 3 and >150 μg/m 3), duration (≥2 days and ≥3 days), and whether or not there was concurrent exposure to high levels of NO 2 (daily mean NO 2 concentration >50 μg/m 3). A two-stage statistical analysis strategy based on a generalized linear model was applied to conduct a time-series analysis to assess the exposure-response relationship between persistent high PM 2.5 exposure scenarios and residents' outpatient visits for a variety of respiratory diseases, and to estimate excess outpatient visits. Results:During the period, M ( Q1, Q3) PM 2.5 and NO 2 concentrations were 61.2 (42.3, 95.1) μg/m 3 and 40.2 (31.4, 54.4) μg/m 3, respectively, and the daily respiratory disease outpatient visits were 57 (52, 66) cases. When compared with non-permanent high PM 2.5 exposure periods, exposure scenarios with PM 2.5 >75 μg/m 3 and lasting for ≥2 days caused an increased risk of outpatient visits for respiratory diseases by 2.10% (95% CI: 1.44%-2.77%), and resulted in 43 787 (95% CI: 30 025-57 757) excess visits; in this scenario, the concurrent exposure to high levels of NO 2 had a greater acute effect on respiratory disease visits than the absence of exposure to high levels of NO 2 ( P<0.001). The risk of respiratory disease visits increased substantially by 4.41% (95% CI: 3.15%-5.68%) when the daily mean PM 2.5 concentration exceeded 150 μg/m 3 for ≥2 days. Subgroup disease analyses showed that scenarios with daily mean PM 2.5 concentrations exceeding 75 μg/m 3 for ≥3 days caused a significant increase in the risk of lower respiratory tract infections, chronic lower respiratory disease, and asthma visits. Conclusions:Sustained persistent high PM 2.5 exposure increases the risk of outpatient visits for various respiratory diseases; concurrent exposure to high concentrations of NO 2 leads to a greater risk of visiting the clinic, suggesting that the prevention and control of PM 2.5 pollution should be synchronized with the control of mobile source emissions, to synergistically manage the compound pollution of PM 2.5 and NO 2 in the atmosphere.

Objective : To evaluate the coverage and spatial clustering of 13-valent pneumococcal conjugate vaccine(PCV13) among the 2017—2023 birth cohorts in Anhui Province. Methods : Obtained vaccination data of PCV13 for children born in 2017—2023 from the Anhui Immunization Information Management System.We estimated coverage levels and described characteristics of coverage.The spatial autocorrelation analysis of coverage was conducted. Results : Cumulative coverage,cumulative primary immunization coverage and cumulative full-series coverage of PCV13 were 17.19%,12.12% and 9.09% among the 2017—2023 birth cohort in Anhui Province.The coverage of PCV13 increased from 1.14% in the 2017 birth cohort to 41.59% in the 2022 birth cohort.The first dose of PCV13 at ages under 3,3—6,7—11,12—23 and not less than 24 months were 45.35%,29.84%,5.52%,10.75% and 8.53%,respectively.There were significant differences in the ages of the first dose between children of different years of born and kinds of PCV13(P<0.001).Significant differences were also observed in the cumulative coverage,cumulative primary immunization coverage,cumulative full-series coverage of PCV13 and ages of the first dose among children from various residence regions(P<0.001).From 2018 to 2023 birth cohort,the coverage of PCV13 in Anhui Province showed obvious positive spatial autocorrelation.Local spatial autocorrelation analysis showed that the "high-high" agglomeration areas were concentrated in the central area of Anhui. Conclusion The coverage of PCV13 was low in Anhui Province with significant regional differences.

Objective:To analyze the clinical characteristics and identify predictive factors for spontaneous passage of common bile duct (CBD) stones.Methods:A retrospective analysis was conducted on patients diagnosed as having choledocholithiasis via abdominal imaging at outpatient and emergency departments of Jiangsu Province Hospital of Chinese Medicine and other medical institutions from January 2021 to November 2023. Participants were stratified into spontaneous passage versus non-passage groups. Multivariate logistic regression analysis was used to identify predictors for the spontaneous passage of common bile duct stones.Results:Spontaneous stone passage were confirmed in 70 cases (15.5%). Multivariate logistic regression analysis identified that an admission diagnosis of acute biliary pancreatitis ( OR=3.317, 95% CI: 1.427-7.713, P=0.005), larger common bile duct diameter ( OR=1.117, 95% CI: 1.000-1.248, P=0.049), and solitary stones ( OR=11.135, 95% CI: 3.602-34.418, P<0.001) significantly increased the probability of spontaneous stones. In contrast, larger stone long diameter ( OR=0.539, 95% CI: 0.441-0.659, P<0.001) markedly decreased passage likelihood. Receiver operator characteristic (ROC) curve analysis demonstrated that the common bile duct diameter predicted spontaneous stone passage with an area under the curve (AUC) of 0.662, yielding sensitivity of 52.9% (37/70) and specificity of 73.6% (51/70) at a cutoff value of 9.5 mm. The common bile duct stone diameter achieved an AUC of 0.852 for predicting spontaneous stone passage, with sensitivity of 75.7% (53/70) and specificity of 89.0% (62/70) at a cutoff value of 4.5 mm. Conclusion:Solitary small stones, ductal dilation, and an admission diagnosis of acute biliary pancreatitis are key predictive factors for spontaneous common bile duct stone passage. A common bile duct diameter ≥9.5 mm and stone long diameter ≤4.5 mm are more likely to result in spontaneous stone passage.

Objective:To investigate multi-system involvement in Kennedy′s disease and its association with disease progression.Methods:We retrospectively reviewed the clinical, laboratory, and electrophysiological data from 48 genetically confirmed patients with Kennedy′s disease at the Department of Neurology, First Medical Center of the Chinese PLA General Hospital, between February 2016 and February 2024. The disease progression rate was calculated based on the functional scores at baseline and follow-up. Correlation analyses and multiple linear regression models were employed to assess the relationships among clinical variables and to identify potential predictors of disease progression.Results:The age of muscle weakness onset ranged from 16 to 66 years (mean 42±11 years), with a diagnostic delay of 5.0 (3.0, 9.8) years. Lower limb weakness was the most common initial symptom in 72.9% (35/48) of patients, and 37.5% (18/48) exhibited non-motor manifestations prior to the onset of weakness. Core motor manifestations included bulbar weakness (89.6%, 43/48) and symmetric proximal limb weakness (83.3%, 40/48), frequently accompanied by gynecomastia (74.2%, 23/31) and sexual dysfunction (64.6%, 31/48). The median CAG repeat length was 43 (42, 46), which showed a significant negative correlation with the age at onset ( r=-0.406, P=0.004). Patients with CAG repeats > 43 had a higher prevalence of sexual dysfunction. Elevated serum muscle enzymes were observed in 97.9% (47/48), and abnormal sex hormone levels were detected in 81.2% (39/48). Sensory neuropathy was present in 68.1% (32/47), with CAG repeat length inversely correlating with compound muscle action potential (CMAP) amplitudes in the median ( β=-0.29; t=-2.27, P=0.029) and ulnar ( β=-0.22; t=-2.23, P=0.031) nerves. Low-frequency repetitive nerve stimulation (RNS) revealed a decrement in 43.3% (13/30) of patients, most commonly affecting the axillary and spinal accessory nerves. The disease progression rate was 1.3±0.3 (range: 0.5-2.0). Furthermore, serum creatine kinase-MB (CK-MB) levels were negatively correlated with disease progression rate ( r=-0.303, P=0.036). Conclusions:Kennedy′s disease presents with diverse initial manifestations and frequent multi-system involvement. Non-motor manifestations may precede muscle weakness, serving as valuable clues for early diagnosis. Widespread sex hormone abnormalities (particularly testosterone/luteinizing hormone dysregulation) support the role of androgen insensitivity in disease pathogenesis. Sensory neuropathies are frequent and not length-dependent. The presence of decremental responses on low-frequency RNS suggests neuromuscular junction dysfunction, which may underlie motor impairment in patients with Kennedy′s disease. Finally, serum CK-MB may serve as a potential biomarker for disease progression.

Objective:To investigate the risk factors associated with 90-day mortality in critically ill patients receiving continuous renal replacement therapy (CRRT), with a particular focus on the association between hypotension within the first hour of CRRT initiation and 90-day mortality after hospital admission.Methods:This study was a post hoc analysis of a prospective cohort study investigating the impact of colloid versus crystalloid priming solutions on early hemodynamics in critically ill patients undergoing CRRT. The study enrolled intensive care unit patients who received CRRT at West China Hospital of Sichuan University from January 2024 to May 2024. The data were collected including demographic characteristics, laboratory tests, CRRT-related parameters, blood pressure, heart rate, sequential organ failure assessment scores, and vasoactive-inotropic score, etc. The 90-day survival outcome after hospital admission of critically ill patients aged 18-80 years who received continuous veno-venous hemodiafiltration was used as the primary outcome indicator. A Cox proportional hazards model analysis was conducted, and the predictive ability of the model was evaluated along with the test of the proportional hazards assumption. The risk factors associated with the 90-day mortality after hospital admission of critically ill patients receiving CRRT were explored, with a particular focus on whether hypotension occurring within the first hour of CRRT initiation was one of these risk factors.Results:A total of 208 patients were included in this study. Within 90 days after hospital admission, 141 patients (67.8%) died, among whom 102 were male (72.3%) and the median age was 61.0 (50.0, 71.5) years; 67 patients (32.2%) survived, among whom 53 were males (79.1%) and the median age was 56.0 (47.0, 68.0) years. The incidence of hypotension within the first hour of CRRT initiation was significantly higher in the death group than in the survival group [29.8% (42/141) vs. 16.4% (11/67), χ2=4.275, P=0.039]. Moreover, The mortality rate of the group with hypotension within the first hour of CRRT initiation was higher than that of the group without hypotension [79.2% (42/53) vs. 63.9% (99/155), χ2=4.275, P=0.039]. The Kaplan-Meier survival analysis showed that the median survival time of patients without hypotension within the first hour of CRRT initiation [39.0 d (95% CI 23.2-54.8)] was longer than that of patients with hypotension [26.0 d (95% CI 18.9-33.1)], and the 90-day cumulative survival rate after hospital admission of patients without hypotension was significantly higher than that of patients with hypotension (Log-rank test, χ2=5.100, P=0.024). Univariate and multivariate Cox proportional hazards analyses demonstrated that serum albumin ( HR=0.964, 95% CI 0.933-0.997, P=0.030), sequential organ failure assessment score ( HR=1.064, 95% CI 1.012-1.118, P=0.015), and the use of mechanical ventilation ( HR=8.272, 95% CI 1.145-59.743, P=0.036) were significantly associated with 90-day mortality in critically ill patients undergoing CRRT. In contrast, the vasoactive-inotropic score ( HR=1.004, 95% CI 0.999-1.008, P=0.079) and the presence of hypotension within the first hour of CRRT initiation ( HR=1.236, 95% CI 0.833-1.835, P=0.293) were not significantly associated with 90-day mortality in critically ill patients undergoing CRRT. The consistency index of this model was 0.654 (95% CI 0.617-0.691), the area under the receiver operating characteristic curve was 0.724 (95% CI 0.658-0.800), and the calibration curve showed that the predicted values of the model were well fitted to the actual observations, suggesting that the predictive effect of this model was relatively ideal. Conclusions:In critically ill patients undergoing CRRT, the occurrence of hypotension within the first hour of CRRT initiation was not significantly associated with 90-day mortality after hospital admission. Lower serum albumin levels, higher sequential organ failure assessment scores, and the use of mechanical ventilation may be the risk factors for 90-day mortality in this population.

Objective To investigate the characteristics of changes in pain-anxiety-depression-fatigue symptom clusters and their possible associated factors in adolescents with acute lymphoblastic leukemia(ALL)during early chemotherapy.Methods A prospective longitudinal study was conducted from Nov 2019 to Oct 2021,enrolling newly diagnosed adolescent ALL patients from 5 tertiary or pediatric specialty hospitals in Shanghai,Zhejiang Province,Sichuan Province,Anhui Province and Guangdong Province.Patient-reported pain,anxiety,depression,and fatigue were collected at five time points within the first nine weeks of chemotherapy using the PROMIS Pediatric-25 instrument.Latent profile analysis(LPA)and latent transition analysis(LTA)were applied to explore the latent classes of symptom clusters,their transition probabilities over time,and possible risk or protective factors associated with class membership.Results A total of 134 ALL cases were enrolled,and symptom clusters at all the 5 time points(T1-T5)were consistently classified into three groups of mild,moderate and severe symptoms.The severe symptoms group accounted for the largest proportion at each time point(54.5%,59.7%,66.4%,49.3%,and 47.0%,respectively),while the mild and moderate symptoms groups showed an initial decline followed by an increase.Among participants,40.2%maintained the same symptom status,and 77.4%experienced at least one episode of severe symptom status during the trajectory.Religious affiliation(T5)and family monthly income>5 000 Yuan(T2,T4 and T5)served as protective factors against severe symptoms.Higher baseline fatigue(T1)was associated with membership in the severe symptoms group at subsequent time points.Conclusion Pain-anxiety-depression-fatigue symptoms in adolescents with ALL during early chemotherapy can be categorized into mild,moderate and severe symptoms with dynamic transitions over time.Higher baseline fatigue was associated with increased risk of severe symptoms,whereas higher family income and religious affiliation appeared protective effects.

This study aims to investigate the protective effect of naringenin(Nar)on cadmium(Cd)-induced liver injury in chickens and its regulatory role in endoplasmic reticulum stress(ERS)and autophagy.Forty-eight 1-day-old Hyland Brown egg roosters were divided into four groups:The control group,the Cd group(150 mg/kg CdCl2),the Nar group(250 mg/kg Nar),and the Cd+Nar group(150 mg/kg CdCl2+250 mg/kg Nar),and the rearing period was 60 days.On the 60th day,6 chickens were randomly selected from each group,and after fasting for 24 hours,blood was collected via vein and then removed from the neck and executed,the livers were collected and organ coefficients were calculated,changes in the content of liver function-related indexes were de-termined,pathological sections were made and observed,and the expression of mRNA and protein of related genes were detected by fluorescence quantitative PCR and Western blot method.The re-sults showed that Cd treatment resulted in a highly significant decrease(P＜0.01)in body mass,a highly significant increase(P＜0.01)in liver coefficient,a highly significant increase(P＜0.01)in serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),and lactate dehydrogenase(LDH)levels were highly significantly increased(P＜0.01),hepatic antioxidant capacity was highly significantly reduced(P＜0.01),and ERS-related genes(GRP-78,PERK,eIF-2α,CHOP,ATF-4,ATF-6)and autophagy-related genes(Atg-5,Beclin-1,LC3)mRNA expression was highly significantly up-regulated(P＜0.01),and the expression of mRNA for p62 was highly significantly reduced(P＜0.01).After the addition of Nar,Cd-induced liver injury was significantly alleviated,liver function indexes improved,hepatic antioxidant capacity was highly significantly el-evated(P＜0.01),mRNA expression of ERS-related genes(GRP-78,PERK,eIF-2α,CHOP,ATF-4,ATF-6)and autophagy-related genes(Atg-5,Beclin-1,LC3)was highly significantly decreased(P＜0.01)and mRNA expression of P62 was highly significantly increased(P＜0.01).This study suggests that Nar has potential in alleviating Cd-induced liver damage in chickens through the reg-ulation of ERS and autophagy,providing theoretical support for its application in livestock health.