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Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation and chronic airway inflammation, traditionally managed with inhaled bronchodilators and corticosteroids. However, a significant subset of patients exhibits suboptimal response to these inhaled therapies, and disease progression remains challenging to control effectively. Recent advances in understanding the inflammatory pathways underlying COPD have led to the development of biologic agents targeting critical cytokines and their receptors, including IL-4 receptor (IL-4R), IL-5, IL-5 receptor (IL-5R), IL-33, ST2, and thymic stromal lymphopoietin (TSLP). Emerging drugs such as JKN2401, TQC2731, and tezepelumab demonstrate promising therapeutic potential by modulating these specific inflammatory mediators. This review comprehensively summarizes the pathophysiological roles of these cytokines in COPD, the current progress in biologic drug development targeting these molecules, and the outcomes of recent clinical trials. By elucidating these novel therapeutic avenues, the article aims to provide a theoretical foundation and clinical guidance for precision medicine approaches in COPD management beyond conventional inhaled treatments.

INTRODUCTION: Airway foreign bodies are time-sensitive otolaryngologic emergencies that can occur in persons of any age. We describe a unique case of complete aphonia caused by the impaction of a crayfish (Procambarus clarkii) claw at the level of the vocal cords.CASE PRESENTATION: A 65-year-old man developed abrupt throat discomfort and loss of voice while eating crayfish. Indirect laryngoscopy showed a foreign body resting across the vocal cords with absent vibration. Cervical CT demonstrated a tubular hyperdense structure within the glottic region, and flexible transoral bronchoscopy confirmed a mucus-coated object adherent to the vocal cords. The object was removed en bloc with grasping forceps under topical anesthesia, after which phonation returned immediately. The patient was discharged the next day without complications. The retrieved foreign body was identified as a crayfish claw.CONCLUSIONS: Crayfish claw impaction at the vocal cords is an exceedingly rare cause of aphonia. Incorporating a targeted dietary history—particularly of regional or seasonal foods—can expedite the diagnosis and management of unusual airway foreign bodies.

Introduction Obstructive sleep apnea (OSA) affects nearly 1 billion adults worldwide. Treatment options include positive airway pressure (PAP), oral appliance therapy, and positional therapy. Few studies have comprehensively compared these treatments using network meta-analysis. This study aimed to compare the effectiveness of different non-surgical OSA treatments across several clinically relevant outcomes. Methods A systematic review and network meta-analysis were conducted following PRISMA guidelines. We searched MEDLINE, Embase, CENTRAL, Web of Science, and ClinicalTrials.gov through October 2025. Randomized controlled trials comparing PAP therapy, oral appliance therapy, positional therapy, or control in adults with OSA were included. Primary outcomes were AHI reduction and Epworth Sleepiness Scale (ESS) improvement. Secondary outcomes included oxygen saturation. Bayesian network meta-analysis was performed, with treatment rankings using surface under the cumulative ranking curve (SUCRA). Results Eighteen trials involving 1,520 participants were included. For AHI reduction, PAP therapy was most effective (mean difference: -17.39 events/hour, 95% CI: -23.13 to -12.74), followed by oral appliance therapy (-10.76 events/hour) and positional therapy (-10.05 events/hour). PAP therapy ranked first with 100% probability, while oral appliance therapy and positional therapy showed similar effectiveness. For ESS improvement, PAP showed slight superiority. In position-dependent OSA, oral appliance therapy ranked first with 40% probability. Moderate heterogeneity was found (I² = 32–52%). Conclusions PAP therapy is the most effective treatment for OSA, while oral appliance and positional therapies offer viable alternatives, especially for position-dependent OSA patients. However, moderate heterogeneity (I² = 32–52%) was observed across analyses, which may affect the certainty of these conclusions. Treatment selection should consider patient-specific factors, and findings should be interpreted acknowledging this methodological limitation.

Background PANoptosis, a newly identified form of cell death, has been linked to both the destruction of cancer cells and the regulation of antitumor immunity. This study aimed to establish a PANoptosis-related signature associated with lung adenocarcinoma (LUAD), highlighting its role in LUAD pathogenesis. Methods Transcriptome data from the TCGA-LUAD dataset were analyzed to identify PANoptosis-related differentially expressed genes (PANR-DEGs). A LUAD gene signature was developed using Cox regression and LASSO analyses. The study also evaluated somatic mutations, the immune microenvironment, and immunotherapy potential across two risk groups. Additionally, prognostic gene expression was validated clinically by reverse transcription-quantitative PCR (RT-qPCR). Results The TCGA-LUAD dataset revealed 520 PANR-DEGs. A prognostic signature based on six key genes—CDCP1, CLIC6, FURIN, KRT6A, MFI2, and P2RY13—was constructed. Prognostic analysis indicated that pathological T and N statuses, along with the risk score, could serve as independent prognostic markers. Significant differences in the immune microenvironment were observed between the two risk groups, with TP53 showing the highest mutation frequency. Drug sensitivity assays suggested that the PANoptosis-related gene signature could serve as a predictive tool for therapy. Elevated expression levels of CDCP1, CLIC6, FURIN, KRT6A, and MFI2 were observed in tumor tissues compared to normal tissues. RT-qPCR results confirmed the findings from the bioinformatic analysis. Conclusion A prognostic signature composed of CDCP1, CLIC6, FURIN, KRT6A, MFI2, and P2RY13, based on PANR-DEGs, provides a theoretical framework and reference for further LUAD research.

RationaleCurrently available PDE2 inhibitors have poor brain penetration that limits their therapeutic utility in the treatment of depression. Hcyb1 is a novel selective PDE2 inhibitor that was introduced more lipophilic groups with polar functionality to the scaffold pyrazolopyrimidinone to improve the blood-brain barrier (BBB) penetration. Our previous study suggested that Hcyb1 increased the neuronal cell viability and exhibited antidepressant-like effects, which were parallel to the currently available PDE2 inhibitor Bay 60-7550.ObjectivesThe present study investigated whether Hcyb1 protected HT-22 cells against corticosterone-induced neurotoxicity and produced antidepressant-like effects in behavioral tests in stressed mice.MethodsThe neuroprotective effects of Hcyb1 against corticosterone-induced cell lesion were examined by cell viability (MTS) assay. The enzyme-linked immunosorbent assay (ELISA) and immunoblot analysis were used to determine the levels of cAMP or cGMP and expression of pCREB or BDNF, respectively, in the corticosterone-treated HT-22 cells. The antidepressant-like effects of Hcyb1 were determined in the tail suspension and novelty suppressed feeding tests in stressed mice.ResultsIn the cell-based assay, Hcyb1 significantly increased cell viability of HT-22 cells against corticosterone-induced neurotoxicity in a time- and dose-dependent manner. Hcyb1 also rescued corticosterone-induced decreases in both cGMP and cAMP levels, pCREB/CREB and BDNF expression. These protective effects of Hcyb1 were prevented by pretreatment with either the PKA inhibitor H89 or the PKG inhibitor KT5823. Moreover, Hcyb1 reversed acute stress–induced increases in immobility time and the latency to feed in the tail suspension and novelty suppressed feeding tests, respectively, which were prevented by pretreatment with H89 or KT5823.ConclusionThese findings provide evidence that the neuroprotective effects of Hcyb1 are mediated by PDE2-dependent cAMP/cGMP signaling.

This study aimed to evaluate the potential role of hydrogen in rats after cerebral ischemic/reperfusion (I/R) injury. The experimental samples were composed of sham group, model group of rats that received middle cerebral artery occlusion (MCAO) for 2 hr followed by reperfusion for 24 hr, and the hydrogen saline group treated by hydro¬gen-rich saline (1 ml/kg) after MCAO. Hydrogen sulfide (H2S), S100-βprotein (S100-β), and neuron-specific enolase (NSE) levels were measured; the levels of malondialdehyde (MDA), reactive oxygen species (ROS), and superoxide dismutase (SOD) were detected; the histologic structure and apoptotic cells of hippocampus were observed; the expressions of cystathionine β-synthase (CBS), nuclear factor erythroid 2-related factor 2 (Nrf2), and hemeoxygenase-1 (HO-1) were measured. Statistical analyses were performed using one-way analysis of variance (ANOVA) followed by Fisher's least significant difference (LSD) test. Our results showed that hydrogen up-regulated H2S levels via promoting the expression of CBS in the hippocampus, and its treatment alleviated oxidative stress via activating the expression of Nrf2 and HO-1, and then cell apoptosis reduced, furthermore, brain function improved by down-regulating the levels of S100-βand NSE. This study showed that hydrogen-rich saline ameliorates cell injury through up-regulating the expression of CBS in the hippocampus after cerebral ischemia reperfusion (I/R) in rats, this provides new experimental evidence for the treatment of stroke with hydrogen saline.

Background and objectiveThe diagnosis of obstructive sleep apnea (OSA) relies on polysomnography which is time-consuming and expensive. We therefore aimed to develop two simple, non-invasive models to screen adults for OSA.MethodsThe effectiveness of using body mass index (BMI) and a new visual prediction model to screen for OSA was evaluated using a development set (1769 participants) and confirmed using an independent validation set (642 participants).ResultsBased on the development set, the best BMI cut-off value for diagnosing OSA was 26.45 kg/m2, with an area under the curve (AUC) of 0.7213 (95% confidence interval (CI), 0.6861–0.7566), a sensitivity of 57% and a specificity of 78%. Through forward conditional logistic regression analysis using a stepwise selection model developed from observed data, seven clinical variables were evaluated as independent predictors of OSA: age, BMI, sex, Epworth Sleepiness Scale score, witnessed apnoeas, dry mouth and arrhythmias. With this new model, the AUC was 0.7991 (95% CI, 0.7668–0.8314) for diagnosing OSA (sensitivity, 75%; specificity, 71%). The results were confirmed using the validation set. A nomogram for predicting OSA was generated based on this new model using statistical software.ConclusionsBMI can be used as an indicator to screen for OSA in the community. We created an internally validated, highly distinguishable, visual and parsimonious prediction model comprising BMI and other parameters that can be used to identify patients with OSA among outpatients. Use of this prediction model may help to improve clinical decision-making.

We obtain the global existence of weak solutions for the Cauchy problem of the nonhomogeneous, resonant system. First, by using the technique given in Tsuge (2006), we obtain the uniformly bounded L ∞ estimates z ( ρ δ , ε , u δ , ε ) ≤ B ( x ) and w ( ρ δ , ε , u δ , ε ) ≤ β when a ( x ) is increasing (similarly, w ( ρ δ , ε , u δ , ε ) ≤ B ( x ) and z ( ρ δ , ε , u δ , ε ) ≤ β when a ( x ) is decreasing) for the ε -viscosity and δ -flux approximation solutions of nonhomogeneous, resonant system without the restriction z 0 ( x ) ≤ 0 or w 0 ( x ) ≤ 0 as given in Klingenberg and Lu (1997), where z and w are Riemann invariants of nonhomogeneous, resonant system; B ( x ) > 0 is a uniformly bounded function of x depending only on the function a ( x ) given in nonhomogeneous, resonant system, and β is the bound of B ( x ) . Second, we use the compensated compactness theory, Murat (1978) and Tartar (1979), to prove the convergence of the approximation solutions.

Ultrafine composite fibers were fabricated by electrospinning of chloroform solutions of organic-soluble chitosan (O-CS) and poly-vinylpyrrolidone (PVP). The composite fibers were subjected to detailed analysis by Fourier transformed infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The FT-IR showed that the composite fibers contained the two polymers. The SEM image results confirmed that the morphology and diameter of the fibers were remarkably affected by the process and the parameters of the electrospinning. The governing parameters included the applied voltage, the viscosity of the electrospun solution and tip-to-collector distance, and were further investigated.

Background： Our previous studies have shown that Tongxinluo （TXL）, a compound Chinese medicine, can decrease myocardial ischemia-reperfusion injury, protect capillary endothelium function, and lessen cardiac ventricle reconstitution in animal models. The aim of this study was to illuminate whether TXL can improve hypercholesterolemia-impaired heart function by protecting artery endothelial function and increasing microvascular density （MVD） in heart. Furthermore, we will explore the underlying molecular mechanism of TXL cardiovascular protection. Methods： After intragastric administration of TXL （0.1 ml/10 g body weight） to C57BL/6J wild-type mice （n = 8） and ApoE-/- mice （n=8）, total cholesterol, high-density lipoprotein-cholesterol, very-low-density lipoprotein （VLDL）-cholesterol, triglyceride, and blood glucose levels in serum were measured. The parameters of heart rate （HR）, lelt ventricular diastolic end diameter, and left ventricular systolic end diameter were harvested by ultrasonic cardiogram. The left ventricular ejection fraction, stroke volume, cardiac output, and let1 ventricular fractional shortening were calculated. Meanwhile, aorta peak systolic flow velocity （PSV）, end diastolic flow velocity, and mean flow velocity （MFV） were measured. The pulsatility index （PI） and resistant index were calculated in order to evaluate the vascular elasticity and resistance. Tile endothelium-dependent vasodilatation was evaluated by relaxation of aortic rings in response to acetylcholine. Western blotting and real-time quantitative reverse transcription polymerase chain reaction were performed for protein and gene analyses of vascular endothelial growth factor （VEGF）. lnamunohistochenaical detection was perlbrmed for myocardial CD34 expression. Data in this study were compared by one-way analysis of variance between groups. A value of P 〈 0.05 was considered statistically significant. Results： Although there was no significant decrease of cholesterol level （F = 2.300, P = 0.240）, TXL inhibited the level of triglyceride and VLDL （F- 9.209, P- 0.024 and F = 9.786, P ： 0.020, respectively） in ApoE-/- mice. TXL improved heart function of ApoE-/- mice owing to the elevations of LVEF, SV, CO, and LVFS （all P 〈 0.05）. TXL enhanced aortic PSV and MFV （F = 10.774, P = 0.024 and F = 11.354, P - 0.020, respectively） and reduced PI of ApoE-/- mice （1.41 ± 0.17 vs. 1.60 ± 0.17; P= 0.037）. After incubation with 10μmol/L acetylcholine, the ApoE-/- mice treated with TXL aortic segment relaxed by 44% - 3%, significantly higher than control group mice （F = 9.280, P = 0.040）. TXL also restrain the angiogenesis of ApoE-/- mice aorta （F = 21.223, P = 0.010）. Compared with C57BL/6J mice, the MVD was decreased in heart tissue of untreated ApoE-/- mice （54.0 ± 3.0/mm2 vs. 75.0 ± 2.0/mm2; F = 16.054, P - 0.010）. However, TXL could significantly enhance MVD （65.0 ± 5.0/mm2 vs. 54.0 ±3.0/mm2; F- 11.929, P = 0.020） in treated ApoE-/- mice. In addition, TXL obviously increased the expression of VEGF protein determined by Western blot （F = 20.247, P = 0.004）. Conclusions： TXL obviously improves the ApoE-/- mouse heart function from different pathways, including reduces blood fat tolessen atherosclerosis; enhances aortic impulsivity, blood supply capacity, and vessel elasticity： improves endothelium-dependent vasodilatation： restraines angiogenesis of aorta-contained plaque; and enhances MVD of heart. The molecular mechanism of MVD enhancement maybe relate with increased VEGF expression.