Chronic obstructive pulmonary disease (COPD) commonly coexists with coronary heart disease (CHD). This retrospective study aimed to examine the association between the triglyceride-total cholesterol-body mass index (TCBI) and the CHD in COPD patients. This study included 407 participants recruited from the Second Affiliated Hospital of Chongqing Medical University. Logistic regression models were employed to evaluate the association between TCBI and CHD among hospitalized COPD patients undergoing coronary angiography for chest pain. Restricted cubic spline (RCS) analysis was conducted to investigate potential non-linear relationships. Additionally, subgroup analyses were performed to identify variations across different population groups. The study included 407 participants with a median age of 72 years. After adjusting After adjustment for covariates, each 100-unit increase in TCBI was associated with a significantly lower likelihood of CHD in COPD patients (odds ratio [OR] = 0.927; 95

Sirtuin 1 (SIRT1), a nicotinamide adenine dinucleotide (NAD+)-dependent class III histone deacetylase, functions as a central metabolic sensor and stress-responsive regulator in the cardiovascular system. Unlike its well-characterized role in atherosclerosis, SIRT1 exerts multifaceted protective effects directly on cardiac tissue. This review synthesizes recent advances in understanding SIRT1-mediated cardioprotection across a spectrum of heart diseases, including myocardial ischemia/reperfusion (I/R) injury, heart failure (HF), diabetic cardiomyopathy (DCM), cardiac hypertrophy, aging-related cardiac dysfunction and circadian rhythm disruption. Mechanistically, SIRT1 orchestrates antioxidant defense through nuclear factor erythroid 2-related factor 2 (Nrf2) and Forkhead box O (FoxO) transcription factors activation, suppresses inflammatory signaling via nuclear factor kappa B (NF-κB) deacetylation, inhibits apoptosis by targeting p53, promotes autophagic flux and mitophagy, regulates mitochondrial biogenesis through peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and controls ferroptosis via the Nrf2/glutathione peroxidase 4 (GPX4) axis. Preclinical studies demonstrate that natural compounds (resveratrol, quercetin, curcumin, ginsenosides, tanshinone IIA, bergenin, swietenine) and synthetic SIRT1 activators (SRT1720, anilinopyridine derivatives) attenuate cardiac injury and improve function. Moreover, SIRT1 serves as a prognostic biomarker in HF and diabetic patients. However, context-dependent dual roles, where excessive SIRT1 expression may be detrimental, underscore the need for precise modulation. Challenges remain in achieving cardiac-specific targeting, optimizing NAD+ availability, and translating preclinical findings into clinical practice. Future research should integrate multi-omics approaches, single-cell transcriptomics, and precision medicine strategies to unlock the therapeutic potential of SIRT1 in cardiac diseases.

Lung cancer is one of the most prevalent and lethal malignant tumors worldwide. In recent years, immune checkpoint inhibitors have significantly improved the survival outcomes of some patients with advanced non-small cell lung cancer; however, primary and acquired resistance remain important barriers limiting their clinical efficacy. Research has revealed that structural remodeling of the tumor microenvironment (TME) is one of the key factors involved in immunotherapy resistance. Efferocytosis is an important process by which tumor-associated macrophages clear apoptotic cells. In the lung cancer TME, the high apoptotic cell burden can lead to persistent activation of efferocytosis. Studies have shown that sustained efferocytosis is not merely a process of cellular debris clearance, but can also induce metabolic reprogramming in macrophages, including dysregulated lipid metabolism and enhanced glycolysis, and promote the secretion of immunosuppressive and tissue-repair-related factors. These changes further promote pathological angiogenesis, activation of cancer-associated fibroblasts, and excessive extracellular matrix deposition, thereby driving structural remodeling of the TME and forming an immune-excluded microenvironment characterized by vascular abnormalities and stromal fibrosis. This process restricts effector T-cell infiltration and impairs the efficacy of immune checkpoint inhibitors. This review describes the molecular mechanisms of macrophage efferocytosis in the lung cancer TME, focusing on its regulatory roles in metabolic reprogramming, pathological angiogenesis, and stromal fibrosis, and discusses potential therapeutic strategies targeting efferocytosis-related signaling pathways and TME structural remodeling, aiming to provide new insights into overcoming immunotherapy resistance in lung cancer.

A substantial body of evidence links frailty to a wide range of chronic diseases (CCD); however, the direction and strength of this causal relationship remain insufficiently understood. In this study, we systematically assess the relationship between the frailty index (FI) and CCD by integrating large-scale observational analyses with Mendelian randomization (MR) to provide more robust causal inference. This national cross-sectional study used data from the first wave of the China health and retirement longitudinal study conducted in 2011. Multivariable logistic regression models were applied to examine the association between FI and CCD. Restricted cubic splines were used to characterize the dose–response relationship. In addition, a two-sample MR analysis was performed to explore the potential causal effect of FI on CCD, with the inverse-variance weighted (IVW) method serving as the primary analytical approach. Tests for heterogeneity and multiple sensitivity analyses were also carried out to ensure the robustness of the findings. In our analysis, the FI remained independently associated with an increased risk of multiple CCDs after adjustment for relevant covariates. Specifically, higher FI values were linked to elevated odds of hypertension (OR = 1.055, 95

Cognitive dysfunction, characterized by memory impairment, attentional deficits, and executive dysfunction, represents a critical clinical manifestation in post-acute sequelae of COVID-19 that significantly compromises patients' quality of life. The lung-brain axis, as a bidirectional regulatory network connecting the respiratory system to the central nervous system, interacts through neural circuits, humoral pathways, and microbial pathways, and may play a central role in the cognitive impairments occurring in long COVID (LC). This paper systematically reviews the multidimensional pathways of the lung-brain axis and their pathological mechanisms in the cognitive impairment of LC, including direct viral neuroinvasion during the acute phase, chronic injury triggered by viral persistence, immune homeostasis dysregulation, hypoxaemia, microbiome disruption, and renin- angiotensin system imbalance. It then explores clinical intervention strategies based on the lungbrain axis, integrating supportive treatments, such as oxygen therapy, exercise therapy, and cognitive training, with treatments targeting the lung-brain axis, including antiviral drugs, immunomodulation, probiotics, and neuromodulation techniques. It is also suggested that future research should favour the integration of multi-omics technologies and the development of individualised therapeutic targets.

Atherosclerosis is a chronic inflammatory and metabolic disease driven by endothelial dysfunction, immune activation, vascular smooth muscle cell remodeling and aging-associated mitochondrial decline. Although lipid lowering remains the cornerstone of therapy, substantial residual inflammatory risk persists, highlighting the need for integrative regulatory targets. Sirtuin 1 (SIRT1), a NAD+-dependent deacetylase, has emerged as a central metabolic sensor linking energy availability to transcriptional control of inflammation, oxidative stress, mitochondrial biogenesis and cellular senescence. Experimental studies across endothelial cells, macrophages and vascular smooth muscle cells consistently demonstrate that SIRT1 activation preserves nitric oxide bioavailability, suppresses ROS-dependent inflammasome signaling, modulates macrophage polarization, inhibits ferroptosis and maintains mitochondrial integrity. These cell-type-specific effects converge to reduce plaque progression and enhance fibrous cap stability in preclinical models. However, SIRT1 activity is hierarchically regulated by AMPK signaling and NAD+ availability and is influenced by aging, metabolic dysfunction and environmental stressors, underscoring its context-dependent function. Despite promising mechanistic data, clinical translation remains limited, suggesting that precision modulation strategies may be required. This review synthesizes current evidence and proposes that SIRT1 functions as a metabolic-inflammatory integrator within the atherosclerotic arterial wall, representing a potential but context-sensitive target for future cardiovascular therapies.

Obstructive sleep apnea syndrome (OSAS) is a prevalent sleep-related breathing disorder characterized by intermittent hypoxia (IH). Myocardial injury is a common complication associated with OSAS. Alpha-lipoic acid (LA), a potent antioxidant, has been utilized in various disease contexts and has demonstrated significant protective effects in myocardial infarction models. Given the limited treatment options available for OSAS-related myocardial injury, this study aimed to demonstrate the potential therapeutic effects of LA and to investigate the underlying mechanisms. IH is a widely employed method to simulate the pathophysiological conditions associated with OSAS. In vivo experiments were conducted using mice placed in a specialized hypoxic chamber to replicate IH conditions. Echocardiography indicated that exposure to IH severely impaired cardiac function. Treatment with LA activated the Nrf2 pathway and autophagy, which contributed to the improvement of cardiac function in mice with OSAS. Additionally, in vitro studies demonstrated that IH induced apoptosis and decreased cell viability in H9C2 cardiomyocytes. LA enhanced Nrf2 nuclear translocation and its downstream signaling pathways, thereby promoting autophagy, inhibiting apoptosis, and alleviating injury in H9C2 cardiomyocytes. Furthermore, in vitro inhibition of Nrf2 using ML385 reduced autophagy levels and attenuated the protective effects of LA against apoptosis in H9C2 cardiomyocytes. These findings suggest that LA may provide a promising therapeutic strategy for myocardial injury associated with OSAS. By elucidating these findings, new insights into the protective mechanisms of LA against IH-induced myocardial injury are provided, highlighting its potential as a therapeutic agent for diseases associated with OSAS.

PurposeThe incidence of lung cancer is closely associated with diabetes; however, it remains unclear whether diabetes influences the genetic mutations present in lung cancer. Therefore, we will compare the genetic mutations in patients with lung adenocarcinoma (ADC) who have diabetes against those who do not.MethodsWe included 279 patients diagnosed with lung adenocarcinoma (143 with diabetes and 136 without diabetes) at the Second Affiliated Hospital of Chongqing Medical University between 2016 and 2023, and analyzed the clinical characteristics and genetic mutation profiles of all participants.ResultsIn comparison to ADC patients without diabetes, those with diabetes exhibited a lower overall gene mutation rate (49.7% vs. 65.4%, P = 0.008). Female ADC patients demonstrated a higher total gene mutation rate and EGFR gene mutation rate than their male counterparts (49.3% vs. 66.9%, P = 0.003; 27.6% vs. 58.3%, P < 0.001, respectively), although their TP53 gene mutation rate was lower (8.6% vs. 2.4%, P = 0.027). ADC patients without a smoking history had a higher gene mutation rate and EGFR gene mutation rate than those with a smoking history (62.6% vs. 47.4%, P = 0.014; 51.6% vs. 22.7%, P < 0.001, respectively), but a lower KRAS gene mutation rate (4.4% vs. 14.4%, P = 0.003). Conversely, ADC patients with a drinking history had a lower EGFR gene mutation rate than those without (48% vs. 62.6%, P = 0.018; 31.0% vs. 47.5%, P = 0.007), yet a higher KRAS gene mutation rate (14.0% vs. 4.5%, P = 0.005). Univariate and multivariate linear regression analyses revealed that being female, having no smoking history, and being in phase II or IV of tumor stage were associated with gene mutation. Subgroup analysis indicated that the rate of gene mutation in male smoking lung adenocarcinoma patients with diabetes was significantly lower than in those without diabetes.ConclusionThis retrospective study of real-world data suggests that patients with lung adenocarcinoma and diabetes may have a reduced likelihood of developing genetic mutations, particularly among male smokers. Furthermore, gender, smoking history, and tumor stage may be correlated with the presence of gene mutations.

Diabetes mellitus (DM) exhibits a strong association with tumorigenesis, yet its impact on tumor gene mutations remains poorly understood. Consequently, the present study was conducted to delve into the influence of DM on tumor gene mutations. This study enrolled 397 lung adenocarcinoma (ADC), 312 colorectal cancer (CRC), and 210 breast cancer (BC) patients between 2016 and 2024. All participants underwent next-generation sequencing (NGS) to detect tumor mutation genes (including point mutations, insertion, deletion, inversion, and duplication) and had their clinical characteristics evaluated. Linear regression analysis and Spearman correlation analysis were carried out to evaluate the association between DM and tumor gene mutations. Herein, tumor patients with DM exhibited significantly lower genetic mutation rates than non-DM individuals across all analyzed cancer types: ADC (49.76

Obstructive sleep apnea (OSA) drives immune dysregulation through its hallmark stressors—intermittent hypoxia (IH) and sleep fragmentation (SF). Beyond impaired sleep, OSA acts as a systemic inflammatory trigger that disrupts immune homeostasis and reshapes both innate and adaptive responses. Recent evidence shows that OSA activates hypoxia-inducible factor-1α (HIF-1α), NF-κB signaling, and the NLRP3 inflammasome, promoting chronic inflammation and immune-cell dysfunction. These alterations mechanistically contribute to OSA-associated cardiovascular disease, metabolic disorders, cognitive impairment, and tumor progression. Reframing OSA as an immune-modulating disorder highlights the need for diagnostics and therapies guided by immunology rather than airway management alone.

Early Growth Response 1 (EGR1) is a crucial transcription factor that regulates diverse cellular processes, including growth, differentiation, proliferation, inflammation, apoptosis, and autophagy. It plays a vital role in maintaining cardiac homeostasis and is deeply implicated in the pathological mechanisms leading to cardiomyocyte death, making it a promising therapeutic target for cardiovascular diseases. To better understand the research landscape of EGR1 in this context, we conducted a bibliometric analysis using data from the Web of Science Core Collection (WoSCC) covering the period from 2014 to 2024, retrieved on 31 December 2024. A total of 2,112 publications related to EGR1 were identified, of which 173 specifically addressed cardiovascular disease and were published across 126 journals. Global research output on this topic has shown fluctuating growth over the past decade, with China contributing the most publications and citations. The Institut national de la santé et de la recherche médicale (Inserm) emerged as the most productive institution. Zhang Y authored the highest number of papers, while Wang J received the most citations. Scientific Reports was the most prolific journal, whereas the Journal of Biological Chemistry was the most influential in terms of citation metrics. Keyword co-occurrence and cluster analysis revealed major research themes such as apoptosis, inflammation, oxidative stress, angiogenesis, and autophagy. These findings provide a comprehensive overview of EGR1-related cardiovascular research and offer a valuable reference for future investigations into its mechanisms and therapeutic potential.

Intermittent hypoxia (IH) is a hallmark pathological feature of obstructive sleep apnea (OSA) and a key contributor to cardiovascular and myocardial injury in affected patients. Despite its clinical importance, the molecular mechanisms linking OSA to cardiovascular diseases remain poorly understood. Early Growth Response 1 (EGR1) has been shown to aggravate myocardial injury by regulating autophagy and apoptosis during hypoxia/reoxygenation (H/R) and ischemia-reperfusion (IR) injury. However, its role in IH-induced myocardial injury has not been elucidated. miR-199a-3p, a microRNA implicated in the regulation of cardiovascular disease progression and myocardial repair, has not been investigated under IH conditions. In this study, We explored the functions of EGR1 and miR-199a-3p in IH-induced myocardial injury using an in vitro model. We found that silencing EGR1 promoted autophagy, suppressed apoptosis, and alleviating IH-induced myocardial injury. Upregulation of miR-199a-3p inhibited mTOR signaling and enhanced autophagy, thereby mitigating the detrimental effects of IH on myocardial cells. Moreover, Our findings demonstrate that EGR1, as a transcription factor, regulates the miR-199a-3p/mTOR pathway to exacerbate IH-induced myocardial injury. These results suggest that the EGR1/miR-199a-3p/mTOR axis represents a promising therapeutic target for OSA associated myocardial injury.

Obstructive sleep apnea (OSA) is a sleep-related hypoxia/reoxygenation disorder, characterized by repeated upper airway obstruction during sleep, leading to intermittent hypoxia (IH) and a series of systemic health issues. OSA is considered a chronic systemic disease with a high prevalence that severely impacts patients' quality of life and may lead to cardiovascular and cerebrovascular diseases, lipid metabolism disorders, and even multiple organ damage, posing a significant threat to human health. Autophagy, an important cellular degradation process, relies on the lysosomal pathway to degrade damaged proteins and organelles, maintaining cellular homeostasis and enabling cellular renewal. A growing body of evidence has highlighted the critical influence of autophagy in the pathophysiology of OSA and its associated multi-organ dysfunction. This review aims to elucidate the mechanisms of autophagy involved in OSA and its impact on heart, brain, kidneys, among other organs, discussing IH 's impact on autophagy activity and the potential consequences of autophagy dysregulation in OSA-related organ damage. Furthermore, we propose the therapeutic potential of targeting autophagy as a new strategy for managing OSA and mitigating its systemic effects. Our findings suggest that understanding the interaction between autophagy and OSA may pave the way for novel therapeutic approaches, thereby improving patient outcomes.

OBJECTIVE:To explore the impact of hypertension-induced cardiorenal disease on disability rates and mortality, this study reported the burden of cardiorenal disease caused by hypertension (including hypertensive heart disease [HHD] and hypertensive kidney disease) between 1990 and 2021. METHODS:Utilizing data from the Global Burden of Disease (GBD) database, this study delivered a comprehensive analysis of the burden of hypertension-induced cardiorenal disease. Hypertension was estimated in terms of disability-adjusted life years (DALYs) and mortality, age-standardized death rates (ASDRs), and age-standardized DALY rates (ASRs), considering age, gender, geographical distribution, socio-demographic index (SDI), and cardiorenal disease. Additionally, the estimated annual percentage change (EAPC) was calculated to assess trends in ASDRs and ASRs from 1990 to 2021. RESULTS:In comparison with 1990, the mortality and DALYs of hypertension-induced cardiorenal disease rose in 2021, resulting in 1,332,099 deaths and 25,462,184 DALYs of HHD, as well as 454,358 deaths and 10,850,728 DALYs of chronic kidney disease(CKD). Between 1990 and 2021, the ASDRs and ASRs of hypertensive heart disease decreased by 21.99%(95% UI, -31.92-6.74%) and 25.81%(95% U, -34.45- -10.07%), respectively. In contrast, the ASDRs and ASRs of hypertension-attributable CKD decreased by 29.21%(95%UI, 11.55-39.65%) and 19.15%(95% UI, 4.31-27.76%), respectively. In 2021, the highest ASDR and ASR of HHD were recorded in Central Sub-Saharan Africa and Southern Sub-Saharan Africa, while those of hypertension-attributable CKD peaked in Western Sub-Saharan Africa and Southeast Asia. Projections indicate a continued decline in HHD ASDRs through 2050, whereas hypertension-attributable CKD is expected to exhibit an upward trend over the same period. CONCLUSION:Despite the declining mortality rate of HHD, the increasing incidence of hypertension-induced CKD underscores that hypertension-attributable cardiovascular and kidney diseases remain a globally urgent public health concern.

Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder that is closely associated with metabolic conditions. The Blood Urea Nitrogen to Creatinine Ratio(BUCR) is commonly utilized as a tool for evaluating renal function, particularly in cases where there are concerns about pre-renal or renal causes of azotemia. However, the connection between OSA and BUCR is not yet fully understood. This study examined the link between BUCR and OSA in adults over 20 using National Health and Nutrition Examination Surveys(NHANES) data from 2005–2008. Logistic regression models adjusted for multiple variables were used to analyze the relationship. The non-direct correspondence relationship were explored with a smooth curve and a two-part linear regression model, which revealed a threshold effect. Subgroup analyses were conducted to assess variations among different populations. The survey, encompassing a total of 8826 participants, revealed that the median age of all respondents was 48 years, with a notable OSA prevalence of 51.3

Ambroxol is a widely used mucoactive agent, but the efficacy of inhaled ambroxol in patients with lower respiratory tract infectious (LRTI) disease is poorly understood. This trial aimed to compare the efficacy and safety of inhaled ambroxol with those of placebo in patients with LRTI diseases. In this randomized, double-blind, placebo-controlled, multicentre clinical trial, 240 patients with LRTI diseases were randomized to receive inhaled ambroxol hydrochloride solution (ambroxol group, N = 120) or placebo (placebo group, N = 120) twice daily for 7 days. Compared with the placebo group, the ambroxol group had lower sputum trait scores and greater changes in sputum trait scores from Day 2 to Day 8. Compared with the placebo group, the ambroxol group presented lower expectoration difficulty scores and greater changes in expectoration difficulty scores on Days 2, 3, and 6. The sputum volume scores on Days 6, 7, and 8 were lower in the ambroxol group than in the placebo group, but the change in the sputum volume score was not different between the groups. Compared with the placebo group, the ambroxol group had lower cough scores on Days 3, 5, 6, and 7, as well as greater changes in cough scores on Days 2, 3, and 5. The incidences of adverse events (10.8

Chronic obstructive pulmonary disease (COPD), a respiratory disease characterized by inflammation due to neutrophil infiltration, has become the third leading cause of death worldwide. After the occurrence of COPD, the persistent accumulation of neutrophils can promote the excessive formation of neutrophil extracellular traps (NETs), which plays an important role in local capture and clearance of pathogens, rapid control of infection, and immune regulation. This article mainly introduces the mechanism of COPD occurrence and NETs formation as well as the research progress of NETs in COPD, and summarizes the relevant drug targets for COPD treatment based on NETs, aiming to provide a reference for further research.

Objectives The prognosis of patients with Small Cell Lung Cancer (SCLC) can be predicted by their Lymph Node (LN) status. The authors aimed to assess the correlations between SCLC survival and number of LN Ratio (LNR), positive LN (pLNs), and Logarithmic Odds of positive LN (LODDS). Methods This cohort study retrospectively included 1,762 patients with SCLC from the SEER database 2004‒2015. The X-tile software was used to determine the cutoff values for pLNs, LNR, and LODDS. The correlations between pLNs, LNR, and LODDS with Overall Survival (OS) and Cancer-Specific Survival (CSS) were explored using Cox regression analysis. The study used the C-index to assess the predictive value of LNR, pLNs, and LODDS on survival. Results Among these 1,762 patients, 121 (6.87%) were alive, 1,641 (93.13%) died, and 1,532 (86.95%) died of SCLC. In univariable COX analysis, LNR, pLNs, and LODDS all showed a correlation with CSS and OS (p < 0.05). In multivariable COX analysis, only patients with LODDS (> 0.3 vs. ≤ 0.3) were related to both worse OS (HR = 1.28, 95% CI 1.10‒1.50) and CSS (HR = 1.29, 95% CI 1.10‒1.51), but no correction was observed between LNR and pLNs and survival (p > 0.05). The C-indices for predicting OS for LODDS were 0.552 (95% CI 0.541‒0.563), for LNR 0.504 (95% CI 0.501‒0.507), and for pLNs 0.527 (95% CI 0.514‒0.540). Moreover, the association between LODDS and prognosis in SCLC patients was significant only in patients with LN stage N1 and N2, but not in stage N3. Conclusion LODDS may be better than other LN assessment tools at predicting survival in SCLC patients.

BackgroundPenpulimab is a novel programmed death (PD)-1 inhibitor. This study aimed to establish the efficacy and safety of first line penpulimab plus chemotherapy for advanced squamous non-small-cell lung cancer.MethodsThis multicentre, randomised, double-blind, placebo-controlled, phase 3 clinical trial enrolled patients with locally advanced or metastatic squamous non-small-cell lung cancer from 74 hospitals in China. Eligible participants were aged 18–75 years, had histologically or cytologically confirmed locally advanced (stage IIIb or IIIc) or metastatic (stage IV) squamous non-small-cell lung cancer, were ineligible to complete surgical resection and concurrent or sequential chemoradiotherapy, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1, did not have previous systemic chemotherapy for locally advanced or metastatic non-small-cell lung cancer, and had one or more measurable lesions according to RECIST (version 1.1). Participants were randomly assigned (1:1) to receive intravenous penpulimab 200 mg or placebo (excipient of penpulimab injection), plus paclitaxel 175 mg/m2 and carboplatin AUC of 5 intravenously on day 1 every 3 weeks for four cycles, followed by penpulimab or placebo as maintenance therapy. Stratification was done according to the PD-L1 tumour proportion score (<1% vs 1–49% vs ≥50%) and sex (male vs female). The participants, investigators, and other research staff were masked to group assignment. The primary outcome was progression-free survival assessed by the masked Independent Radiology Review Committee in the intention-to-treat population and patients with a PD-L1 tumour proportion score of 1% or more (PD-L1-positive subgroup). The primary analysis was based on the intention-to-treat analysis set (ie, all randomly assigned participants) and the PD-L1-positive subgroup. The safety analysis included all participants who received at least one dose of study drug after enrolment. This trial was registered with ClinicalTrials.gov (NCT03866993).FindingsBetween Dec 20, 2018, and Oct 10, 2020, 485 patients were screened, and 350 participants were randomly assigned (175 in the penpulimab group and 175 in the placebo group). Of 350 participants, 324 (93%) were male and 26 (7%) were female, and 347 (99%) were of Han ethnicity. In the final analysis (June 1, 2022; median follow-up, 24·7 months [IQR 0–41·4]), the penpulimab group showed an improved progression-free survival compared with the placebo group, both in the intention-to-treat population (median 7·6 months, 95% CI 6·8–-9·6 vs 4·2 months, 95% CI 4·2–4·3; HR 0·43, 95% CI 0·33–0·56; p<0·0001) and in the PD-L1-positive subgroup (8·1 months, 5·7–9·7 vs 4·2 months, 4·1–4·3; HR 0·37, 0·27–0·52, p<0·0001). Grade 3 or worse treatment-emergent adverse events occurred in 120 (69%) 173 patients in the penpulimab group and 119 (68%) of 175 in the placebo group.InterpretationPenpulimab plus chemotherapy significantly improved progression-free survival in patients with advanced squamous non-small-cell lung cancer compared with chemotherapy alone. The treatment was safe and tolerable. Penpulimab combined with paclitaxel and carboplatin is a new option for first-line treatment in patients with this advanced disease.FundingThe National Natural Science Foundation of China, Shanghai Municipal Health Commission, Chia Tai Tianqing Pharmaceutical, Akeso.

The objective of this study was to explore the molecular basis through which Curcumin (Cur) mitigates neuronal damage caused by obstructive sleep apnea (OSA). HT22 was used to simulate intermittent hypoxia (IH) injury and explore the effect of Cur on these cells. We evaluated the cell viability, cytotoxicity, apoptosis, proliferation, and Wnt/β-catenin (WβC) pathway. IWR-1 was used to block the pathway and investigate the protective mechanism of Cur. We constructed an in vivo model of IH to validate the results of the cellular experiments. IH accelerated apoptosis and cytotoxicity, suppressed proliferation, and decreased the activity of the WβC pathway. Cur can significantly improve cell viability, reduce apoptosis rate and cell toxicity, promote cell proliferation, and up-regulate the WβC. After blocking the WβC pathway, the proliferative effect of Cur was observably weakened. In vivo, IH caused hippocampal damage and inhibited WβC pathway activity in mice, which was ameliorated by Cur treatment. This implies that Cur could be a novel treatment option for neurological impairment brought on by OSA.