Background: Community‑acquired pneumonia (CAP) is a leading cause of acute respiratory infection‑related morbidity and mortality worldwide. Accurate severity assessment and risk stratification are essential for guiding treatment, allocating resources, and improving outcomes. This study compared the predictive performance of seven scoring systems for adverse outcomes in hospitalized CAP patients, with a focus on comorbidity subgroups. Methods: A retrospective cohort study was conducted at Shaoguan First People’s Hospital, enrolling 468 adult CAP patients admitted between January 2022 and December 2022. The predictive values of CURB‑65, CRB‑65, Pneumonia Severity Index (PSI), Modified Early Warning Score (MEWS), quick Sequential Organ Failure Assessment (qSOFA), A‑DROP, and SMART‑COP for in‑hospital mortality and mechanical ventilation (MV) requirement were evaluated using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. Comorbidity-stratified subgroup analyses were further conducted to validate the stability and generalisability of their predictive performance. Results: The in‑hospital mortality rate was 7.26% (34/468), and 15.38% (72/468) required MV. All seven scores showed significant positive correlations between risk strata and adverse outcomes. A‑DROP achieved the highest AUC for predicting mortality (0.920, 95%CI 0.878–0.962) and MV (0.700, 95%CI 0.629–0.771), and maintained robust predictive ability across comorbidity subgroups. Conclusions: A‑DROP demonstrates superior predictive efficacy for in‑hospital mortality and MV need in hospitalized CAP patients, with stable performance in those with comorbidities. It is a clinically feasible and reliable tool for routine risk stratification and clinical decision‑making in CAP management.

Exposure to microplastic (MPs) pollution may induce pulmonary fibrosis (PF). Macrophage pyroptosis has been directly implicated in the pathogenesis of PF. This study focused on the potential driving role of macrophage pyroptosis in polystyrene microplastics (PS-MPs) induced pulmonary fibrosis. Through a 56-day intranasal exposure model in mice, we demonstrate that chronic exposure to 5-μm PS-MPs induces significant pulmonary fibrosis characterized by collagen deposition, extracellular matrix remodeling, and substantial lung function impairment. PS-MPs specifically trigger GSDMD-dependent pyroptosis in alveolar macrophages, as evidenced by enhanced NLRP3 inflammasome assembly, caspase-1 activation, and GSDMD-NT pore formation. Genetic ablation of Gsdmd substantially attenuated fibrotic progression, improved pulmonary functional parameters, and reduced production of pro-fibrotic mediators including IL-1β. Crucially, we established a direct paracrine link between macrophage pyroptosis and fibrogenesis through conditioned medium experiments, demonstrating that GSDMD-dependent release of pyroptotic factors promotes fibroblast activation and extracellular matrix production. Our results delineate a complete pathogenic pathway wherein PS-MPs induce pulmonary fibrosis through macrophage pyroptosis, thereby positioning GSDMD as both a key mediator and promising therapeutic target for combating microplastic-associated lung disease. These findings provide crucial insights into the environmental health risks of microplastics and identify potential intervention strategies for plastic pollution-related respiratory disorders.

Background Epidermal growth factor receptor (EGFR) mutation status plays a critical role in guiding targeted therapy for non-small cell lung cancer (NSCLC). However, molecular testing in patients with stage IA NSCLC may be limited by insufficient tissue availability, procedural invasiveness, and resource constraints. Therefore, developing a non-invasive approach for EGFR mutation prediction is of substantial clinical interest. This study aimed to develop a computed tomography (CT) radiomics based model integrating clinical variables for non-invasive prediction of EGFR mutation status in stage IA NSCLC patients. Methods A total of 375 patients with stage IA NSCLC who underwent pre-treatment chest CT and EGFR mutation testing were retrospectively enrolled. Tumor volumes of interest (VOIs) were manually segmented on CT images, and radiomic features were extracted using the pyradiomics package. Clinical and radiomic features were selected through a feature selection pipeline, and multiple machine learning algorithms were evaluated for EGFR mutation prediction. Model performance was assessed using the Area Under Curve (AUC). Results Predictive performance varied across feature selection strategies and machine learning algorithms. Among all evaluated combinations, the Linear Regression (LR) model built using the Least Absolute Shrinkage and Selection Operator (LASSO)-30 feature set achieved the best performance, with a test-set AUC of 0.745. In this model, CT radiomic features served as the primary predictive component, while selected clinical variables provided complementary information and modestly improved predictive performance. These findings support the value of integrating radiomic and clinical features for non-invasive EGFR mutation prediction in early-stage NSCLC. Conclusions A CT radiomics based model demonstrated only moderate performance for the non-invasive prediction of EGFR mutation status in patients with stage IA NSCLC. When clinical variables were incorporated, predictive performance improved, suggesting that clinical features provide complementary information beyond radiomics alone. The combined model highlights the added value of integrating CT-derived radiomics with clinical data for more accurate individualized molecular assessment, particularly when tissue-based genotyping is unavailable or limited.

Background Mepolizumab is clinically beneficial for patients with severe asthma with an eosinophilic phenotype (SA-EP) but lacks randomised controlled trial efficacy data in those on medium-dose inhaled corticosteroids (ICS). This analysis assessed mepolizumab's efficacy in a subgroup of patients on medium-dose ICS from a Chinese phase 3 trial ( NCT03562195 ). Methods Eligible SA-EP patients had received daily ≥500 µg·day −1 fluticasone propionate or equivalent. In this post hoc evaluation, we included patients who were on baseline medium-dose ICS. Outcomes assessed were rate of clinically significant exacerbations (CSEs) at week 52, time to first CSE, St George's Respiratory Questionnaire (SGRQ) score, pre-bronchodilator forced expiratory volume in 1 s (FEV 1 ), asthma control questionnaire-5 (ACQ-5) score and rate of clinical remission. Results At week 52, in the medium-dose ICS subgroup, mepolizumab (n=115) versus placebo (n=104) significantly reduced the rate of CSEs (0.53 versus 1.30 events·yr −1 ; rate ratio 0.41 (95% CI 0.25–0.66); p<0.001), with a lower probability of CSE (Kaplan–Meier estimate, 27.0% versus 49.3%; HR 0.47 (95% CI 0.30–0.73); p<0.001), greater improvements, as measured by difference in least-square mean, in SGRQ score (−5.58, 95% CI −10.73 to −0.44), FEV 1 (119.06 mL, 95% CI 6.66–231.45) and ACQ-5 score (−0.25, 95% CI −0.46 to −0.04), and a higher proportion of patients achieving three- or four-component clinical remission (31.3–57.4% versus 13.5–36.5%). The rate of clinical remission was higher in patients on medium-dose ICS than those on high-dose ICS. Conclusions Mepolizumab provided greater clinical benefit across multiple outcomes including clinical remission versus placebo in Chinese SA-EP patients on medium-dose ICS. Earlier treatment could increase the chance of clinical remission.

Background:With the rapid development of medical technology and the emphasis on early lung cancer screening, the detection rate of multiple primary lung cancer (MPLC) has increased in recent years. However, the prognostic determinants and clinical characteristics of patients with MPLC remain poorly characterized. Objective:This study aimed to develop and validate a nomogram for predicting overall survival (OS) in patients with MPLC using data from the Surveillance, Epidemiology, and End Results database. Methods:This study was reported in accordance with the TRIPOD (Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis) guidelines. A cohort of 4177 patients with MPLC (2007-2015) was obtained from the Surveillance, Epidemiology, and End Results database. The patients were randomly divided into training (n=2923) and validation (n=1254) cohorts at a 7:3 ratio. Backward stepwise Cox regression identified 11 independent risk factors, which were integrated into a nomogram predicting 3-, 5-, and 8-year OS rates. Results:The nomogram demonstrated superior discriminative ability compared to the American Joint Committee on Cancer staging system, with higher area under the receiver operating characteristic curve values for 3-, 5-, and 8-year OS predictions in both cohorts (training cohort: 0.743, 0.751, and 0.759, respectively; validation cohort: 0.737, 0.734, and 0.695, respectively). Calibration curves and decision curve analysis confirmed its clinical utility. Conclusions:This study establishes a validated nomogram incorporating clinical and socioeconomic variables to optimize prognostic assessment and personalized treatment planning for patients with MPLC.

Background: KLF5 is closely related to tumour growth, proliferation, and blood vessel formation. Our study was designed to explore the role of KLF5 in non-small cell lung cancer (NSCLC) and its impact on clinical prognosis. Methods: Lung tissue specimens of patients diagnosed with NSCLC were collected, and KLF5 protein expression was detected in tissues. We then compared KLF5 expression levels in NSCLC patients of different sexes and its impact on clinical features using samples from the TCGA and GEPIA databases, and performed GO and KEGG enrichment analyses on KLF5, ESR1 and related genes. Finally, in vitro experiments using NSCLC PC-9 cells demonstrated estradiol mediated regulation of KLF5 expression and apoptosis were demonstrated at the cellular level. Results: KLF5 mRNA was 2.5-fold higher in NSCLC tissues vs. adjacent tissues (p = 0.003), and protein levels increased by 1.8-fold (p = 0.01), which indicated that KLF5 was significantly over-expressed in cancerous tissues of NSCLC patients. This consistent over-expression pattern was clinically consequential, as survival analysis revealed the poor prognosis of patients was related to the over-expression of KLF5. Further analysis showed that KLF5 expression was lower in female patients than in male patients. Multivariate regression analysis showed that high KLF5 expression (HR = 1.328, p < 0.05) was an independent risk factor for lung cancer prognosis, but only in female patients. Oestrogen and oestrogen receptor inhibitors were shown to mediate KLF5 protein expression at the cellular level. In addition, with increasing concentrations of oestrogen, the expression of Bcl2 was progressively increased, the expression of Bax was progressively down-regulated, and the apoptosis of NSCLC cells decreases, and that this effect was dependent on the regulation of KLF5. Conclusion: Estrogen upregulates KLF5, which suppresses pro-apoptotic Bax and enhances anti-apoptotic Bcl-2, reducing caspase-3 activation KLF5 may represent a potential therapeutic target for female NSCLC, warranting further preclinical and clinical investigation These findings are primarily derived from in vitro models; future in vivo studies are needed to confirm clinical relevance.

BACKGROUND:Preserved ratio impaired spirometry (PRISm) is regarded as a COPD precursor, but whether this varies by smoking status remains unclear. RESEARCH QUESTION:Are annual lung function decline and the risk of developing airflow limitation different among PRISm subtypes by smoking status? STUDY DESIGN AND METHODS:A total of 2,850 participants from a 15-year population-based prospective cohort were included in this analysis. Participants were categorized into 3 groups: patients with normal spirometry who do not smoke (normal control), patients with PRISm who do not smoke (NS-PRISm), and patients with PRISm who have ever smoked (ES-PRISm). We compared annual lung function decline and the risk of developing airflow limitation among the 3 groups. RESULTS:Participants in the normal control group exhibited the fastest decline in annual lung function, followed by the ES-PRISm group, with the NS-PRISm group showing the slowest decline. Participants in the ES-PRISm group had significantly faster annual lung function decline than the NS-PRISm group. Participants in the ES-PRISm group had a significantly increased risk of developing airflow limitation than the NS-PRISm group (95 of 256 [37.1%] vs 69 of 470 [14.7%]; adjusted hazard ratio [HR], 1.90; 95% CI, 1.31-2.77; P = .001) and normal control group (95 of 256 [37.1%] vs 193 of 2,124 [9.1%]; adjusted HR, 2.69; 95% CI, 1.96-3.69; P < .001). Participants in the NS-PRISm group also exhibited a higher risk of developing airflow limitation than those in the normal control group (69 of 470 [14.7%] vs 193 of 2,124 [9.1%]; adjusted HR, 1.41; 95% CI, 1.07-1.87; P = .016). When the ES-PRISm group was further divided into participants with PRISm who currently smoke and those who formerly smoked, both of these PRISm subtypes showed a faster annual lung function decline and a similarly higher risk of airflow limitation than the NS-PRISm group. INTERPRETATION:These findings suggest that both NS-PRISm and ES-PRISm may be potential precursors to COPD and indicate that PRISm should not be restricted to evaluating individuals with a history of smoking alone.

OBJECTIVE:This study aims to investigate the regulatory effects of cigarette smoke extract (CSE) on resistin-like molecule β (RELMβ) in chronic obstructive pulmonary disease (COPD) and to elucidate the mechanisms by which RELMβ modulates inflammatory factors. METHODS:The expression of RELMβ in 16HBE cells after CSE exposure was detected. The activation and nuclear translocation of NF-κB/p65, degradation of IκBα protein, and the expression of inflammatory factors were assessed in 16HBE cells with RELMβ overexpression or exogenous human recombinant RELMβ protein stimulation. RESULTS:CSE exposure promoted mRNA and protein expression of RELMβ in 16HBE cells. Both stable overexpression of RELMβ and exogenous recombinant RELMβ protein stimulation enhanced secretion of IL-1β, IL-8, IL-6, and TNF-α, upregulated mRNA expression of IL-1β and IL-8, increased phosphorylation of p-IKKα/β, p-IκBα, and p-NF-κB/p65, promoted nuclear translocation of NF-κB/p65, and accelerated the degradation of IκBα in a dose-dependent and time-dependent manner. Inhibition of the NF-κB signaling pathway using pyrrolidine dithiocarbamate and Bay 11-7082 blocked the promotion effect of CSE and RELMβ on expression of p-NF-κB/p65, IL-1β, and IL-8. CONCLUSION:CSE induces inflammation via RELMβ through NF-κB/p65 signaling pathway in COPD. This study provides new insights into the involvement of CSE in the progression of COPD from the perspective of RELMβ.

BACKGROUND AND OBJECTIVE:Asthma, a chronic inflammatory airway disease, presents a significant global health burden. This study aimed to elucidate the mechanism by which curcumin modulates tracheal epithelial cell autophagy in asthma, with a specific focus on its interplay with SCGB3A2 and the NF-κB pathway. METHODS:An in vitro asthma model was mimicked using 16HBE cells treated with TDI. Concurrently, a TDI-induced asthma model was built in Balb/c mice for in vivo investigations. Cells or mice were subjected to curcumin treatment, and SCGB3A2 was knockdown or overexpressed, to explore the function of SCGB3A2. TNF-α and TPCA-1 were also utilized to mediate activation of NF-κB in vitro. Western blot, qPCR, ELISA, immunofluorescence, and transmission electron microscopy were employed to assess SCGB3A2 expression, NF-κB pathway activation, autophagy, key inflammatory cytokines, and airway remodeling indicators. RESULTS:TDI stimulation reduced SCGB3A2 expression in 16HBE cells. SCGB3A2 overexpression mitigated TDI-induced inflammation and airway remodeling by inhibiting the NF-κB pathway and enhancing autophagy. Subsequent NF-κB activation partially abrogated these SCGB3A2-mediated protective effects on inflammation, airway remodeling, and autophagy. Curcumin treatment upregulated SCGB3A2, inhibited NF-κB activation, and promoted autophagy; these protective effects were substantially diminished upon SCGB3A2 knockdown. In vivo, curcumin administration ameliorated asthma features, evidenced by reduced airway inflammation, suppressed NF-κB, and enhanced autophagy in tracheal epithelial tissues. CONCLUSIONS:This study reveals that curcumin protects against asthma by modulating the SCGB3A2-NF-κB-autophagy axis. These findings highlight this axis as a novel therapeutic target for asthma.

INTRODUCTION:Chromatin regulators (CRs) are critical in cancer development, yet their prognostic value in lung squamous cell carcinoma (LUSC) remains unclear. This study aimed to develop a CR-based prognostic model and explore the role of APOBEC1 in LUSC progression. METHODS:Transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed. Gene Ontology and KEGG pathway enrichment were performed. Prognostic CRs were identified using univariate Cox and Lasso analyses. Drug sensitivity was assessed via the Drug Signatures Database. Key CRs were validated by PCR. APOBEC1 expression and prognosis were evaluated through pan-cancer analysis and experimentally validated in LUSC cell lines using colony formation, CCK-8, wound healing, and transwell assays. RESULTS:An eight-gene CR-based signature was established, achieving 5-year AUCs of 0.87, 0.92, and 0.73 in the TCGA training, validation, and GEO datasets, respectively. High-risk patients showed enrichment in cancer-related pathways, greater immune infiltration, and elevated immune checkpoint expression. They were also more sensitive to Dasatinib, Bexarotene, and Bicalutamide. APOBEC1 was overexpressed across multiple cancer types and promoted proliferation and migration in LUSC cell lines. CONCLUSIONS:This study presents a robust CR-based survival model and highlights APOBEC1 as a potential therapeutic target in LUSC.

With the rapid development of medical technology and the emphasis on early lung cancer screening, the incidence of multiple primary lung cancer (MPLC) has increased in recent years. However, the prognostic determinants and clinical characteristics of MPLC patients remain poorly characterized. This study aimed to develop and validate a nomogram for predicting overall survival (OS) in MPLC patients using data from the Surveillance, Epidemiology, and End Results (SEER) database. This study was reported in accordance with the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) guideline. A cohort of 4,177 MPLC patients (2007–2015) was collected from the Surveillance, Epidemiology and End Results (SEER) database. The patients were randomly divided into training (n=2,923) and validation (n=1,254) cohorts at a 7:3 ratio. Backward stepwise Cox regression identified 11 independent risk factors, which were integrated into a nomogram predicting 3-, 5-, and 8-year OS rates. The nomogram demonstrated superior discriminative ability compared to the AJCC staging system, with higher AUC values for 3-/5-/8-year overall survival (OS) predictions in both cohorts (training cohort: 0.743, 0.751, 0.759; validation cohort: 0.737, 0.734, 0.695). Calibration curves and decision curve analysis confirmed its clinical utility. This study establishes a validated nomogram incorporating clinical and socioeconomic variables to optimize prognostic assessment and personalized treatment planning for MPLC patients.

Small airway dysfunction (SAD) is common but little is known about the longitudinal prognosis of spirometry-defined SAD. Therefore, we aimed to evaluate the risk of lung function decline and incident chronic obstructive pulmonary disease (COPD) of spirometry-defined SAD. It was a population-based prospective cohort study conducted in Guangdong, China. Participants were enrolled in the years 2002, 2008, 2012, 2017, and 2019, and those who completed baseline demographic data, a standardized epidemiological questionnaire for COPD, and spirometry were included. Follow-up visits were conducted every three years after enrolment, with a maximum follow-up time of 15 years and a minimum follow-up time of 3 years. Spirometry-defined SAD was defined as having at least two out of three parameters (maximal mid-expiratory flow, forced expiratory flow 50

In this work, we present a novel microfluidic immunosensor for the detection of the lung cancer biomarker epithelial cell adhesion molecule (EpCAM). This sensor leverages the unique properties of graphene oxide (GO), silver nanoparticles (Ag NPs), and their composite (Ag NPs@GO) to achieve enhanced sensitivity and specificity. Ag NPs@GO composite is a sensitive and reasonably priced lung cancer biomarker sensor, and its integration into this sensor is innovative. This represents a major breakthrough in the field of biosensors for cancer detection. By acting as catalysts, the Ag NPs boost the electrochemical signal and enhance the sensor's functionality. The sensor shows a linear range of 0.005-100 pg/mL and a detection limit of 1.12 pg/mL, outperforming commercial ELISA (6.03 pg/mL). It demonstrates excellent sensitivity and specificity for EpCAM detection, with a relative standard deviation of less than 5 % for tampered blood samples, indicating good repeatability. Additionally, the sensor successfully identified circulating tumor cells (CTCs) in lung cancer patients' blood samples, showing a strong correlation between CTC count and EpCAM concentration. These findings suggest that the microfluidic immunosensor could be a powerful tool for lung cancer surveillance and early diagnosis.

Objective:This paper aimed to identify the factors related to Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection in neurosurgical patients, and to compare the therapeutic effects of tigecycline versus polymyxin B against CRKP infection, so as to provide a reliable reference for neurosurgery in future prevention and treatment of CRKP infection. Methods:One hundred and fifty cases of KPN treated in the neurosurgery department of our hospital from January 1, 2019 to December 31, 2021 were selected, 50 of which were found to be infected with CRKP and the other 100 were detected with carbapenem-sensitive Klebsiella pneumoniae (CSKP) by culture, analysis of factors associated with infection with CRKP. Subsequently, CRKP-infected patients were randomized into a group treated with Ti (group Ti) and a group treated with PB (group PB). The clinical efficacy, bacterial clearance, adverse reactions, and pre- and post-treatment hepatorenal function were comparatively analyzed. Results:Based on the Logistic regression analysis, tracheal intubation (or mechanical ventilation), combination of multiple underlying diseases, presence of impaired consciousness, and use of carbapenem antibiotics are independent risk factors for CRKP infection (P < .05). Ti and PB groups had no evident differences in clinical efficacy and bacterial clearance (P > .05); however, Ti group presented a worse hepatorenal function and a higher incidence of adverse reactions than PB group (P < .05). Conclusions:Tracheal intubation (or mechanical ventilation), multiple underlying diseases, consciousness disturbance, and use of carbapenem antibiotics are related factors affecting CRKP infection in neurosurgical patients. Both Ti and PB have excellent therapeutic efficacy, but the former has more obvious toxicity and side effects.

Background: Non-small cell lung cancer (NSCLC) is the most commonly occurring type of lung cancer. Previous studies have shown reduced expression of long noncoding RNA (lncRNA) RAMP2 antisense RNA1 ( RAMP2-AS1 ) in NSCLC; however, the mechanism of RAMP2-AS1 in NSCLC is not clear. Methods: Cell Counting Kit -8 was used to assess cell viability. Cell apoptosis was detected using flow cytometry. Western blot assay was used to examine protein levels. N6-methyladenosine (m 6 A)-RNA immunoprecipitation and Fluorescence in situ hybridization assays were used to detect the m 6 A modification and cellular location of RAMP2-AS1 , respectively. Glycolysis level was examined by commercial kits. Results: RAMP2-AS1 and large tumor suppressor 2 ( LATS2 ) were downregulated in NSCLC tissues. Knockdown of fat mass and obesity-associated protein ( FTO ) elevated the m 6 A modification RAMP2-AS1 . Overexpression of RAMP2-AS1 inhibited proliferation, glycolysis (indicated by high levels of glycolysis-related proteins, glucose consumption, lactate production, adenosine triphosphate content, and extracellular acidification rate) and induced cell apoptosis through Hippo signaling. RAMP2-AS1 transcriptionally activated LATS2 by binding with Kr & uuml;ppel-like factor 9 (KLF9). Downregulation of LATS2 reversed the suppressive impact of RAMP2-AS1 on cell glycolysis. Conclusion: FTO-mediated m 6 A demethylation of RAMP2-AS1 increased glycolysis by reducing the impact of KLF9 on LATS2 transcriptional activity. This study provides insights for developing novel therapeutic strategies for NSCLC.

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.

Background:This present work focused on predicting prognostic outcomes of inpatients developing acute exacerbation of chronic obstructive pulmonary disease (AECOPD), and enhancing patient monitoring and treatment by using objective clinical indicators. Methods:The present retrospective study enrolled 322 AECOPD patients. Registry data downloaded based on the chronic obstructive pulmonary disease (COPD) Pay-for-Performance Program database from January 2012 to December 2018 were used to check whether the enrolled patients were eligible. Our primary and secondary outcomes were intensive care unit (ICU) admission and in-hospital mortality, respectively. The best feature subset was chosen by recursive feature elimination. Moreover, 7 machine learning (ML) models were trained for forecasting ICU admission among AECOPD patients, and the model with the most excellent performance was used. Results:According to our findings, a random forest (RF) model showed superb discrimination performance, and the values of area under the receiver operating characteristic curve were 0.973 and 0.828 in training and test cohorts, separately. Additionally, according to decision curve analysis, the net benefit of the RF model was higher when differentiating patients with a high risk of ICU admission at a <0.55 threshold probability. Moreover, the ML-based prediction model was also constructed to predict in-hospital mortality, and it showed excellent calibration and discrimination capacities. Conclusion:The ML model was highly accurate in assessing the ICU admission and in-hospital mortality risk for AECOPD cases. Maintenance of model interpretability helped effectively provide accurate and lucid risk prediction of different individuals.

Objectives: This study analyzed the clinical characteristics and hematologic examination indexes to tell the type of influenza among patients and provide a basis for the early diagnosis and treatment of influenza patients. Methods: We collected demographic characteristics and clinical data from 726 influenza patients and analyzed the impact of different clinical manifestations and hematological tests on the measured values of influenza types. Results: The common clinical manifestations of influenza patients were fever (99.2%), pharyngeal congestion (97.1%) and cough (80.4%), et al. Those with oneset of illness with were 19-49 years of age (OR= 0.335, 95% CI: 0.196-0.573) or had nasal congestion (OR= 0.566, 95% CI: 0.349-0.919) and fever for more than 3 days (OR= 0.368, 95% CI: 0.214-0.632) tend to were diagnosed asprone to have influenza B. While those patients with symptoms of cough (OR=2.119, 95% CI: 1.322-3.389), headache (OR=1.834, 95% CI: 1.157-2.908), muscle pain (OR=1.811, 95% CI: 1.139-2.880), and blood CPR>8mg/L (OR=2.315, 95% CI: 1.501-3.589) were prone to have influenza A. Conclusion: By combining clinical manifestations and laboratory findings, it is possible to initially distinguish the type of influenza, which can provide assistance in the early treatment and prognosis of influenza.

Bronchial thermoplasty (BT), an effective treatment for severe asthma, requires heat to reach the airway to reduce the mass of airway smooth muscle cells (ASMCs). Autophagy is involved in the pathological process of airway remodeling in patients with asthma. However, it remains unclear whether autophagy participates in controlling airway remodeling induced by BT. In this study, we aim to elucidate the autophagy-mediated molecular mechanisms in BT. Our study reveal that the number of autophagosomes and the level of alpha-smooth muscle actin (α-SMA) fluorescence are significantly decreased in airway biopsy tissues after BT. As the temperature increased, BT causes a decrease in cell proliferation and a concomitant increase in the apoptosis of human airway smooth muscle cells (HASMCs). Furthermore, increase in temperature significantly downregulates cellular autophagy, autophagosome accumulation, the LC3II/LC3I ratio, and Beclin-1 expression, upregulates p62 expression, and inhibits the AMPK/mTOR pathway. Furthermore, cotreatment with AICAR (an AMPK agonist) or RAPA (an mTOR antagonist) abolishes the inhibition of autophagy and attenuates the increase in the apoptosis rate of HASMCs induced by the thermal effect. Therefore, we conclude that BT decreases airway remodeling by blocking autophagy induced by the AMPK/mTOR signaling pathway in HASMCs.

This research was designed to demonstrate the pre-treatment prevalence of drug resistance (DR) and resistance mutation sites (MSs) in highly resistant human immunodeficiency virus (HIV) infected patients, along with assessing the differences between HIV -1 DNA and HIV -1 RNA resistance, and evaluating the efficacy of lopinavir and ritonavir application. The study focused on 420 newly diagnosed HIV -1 -infected patients. Prior to antiviral therapy, HIV -1 RNA resistance testing was performed to analyse the prevalence of resistance and resistance mutations. In addition, HIV -1 DNA genotypic resistance was simultaneously assessed in treatment -naive patients to evaluate its clinical significance. The effect of lopinavir/ritonavir treatment was observed on CD4+ cell count, HIV -1 RNA load and safety indicators (aspartate aminotransferase (AST), blood glucose (BG), triglyceride (TG), cholesterol (Cho)) before and after treatment. The results showed that the success rate of HIV -1 RNA pol region amplification (73.10%) was lower than that of HIV -1 DNA pol region amplification (92.86%). The median CD4+ cell count before treatment was 213 cells/mu L, and after 12, 24 , 36, 48 and 96 weeks of treatment, the median CD4+ cell counts were 303 cells/mu L, 352 cells/mu L, 381 cells/mu L, 399 cells/mu L and 476 cells/mu L, respectively. The virologic suppression rate of HIV RNA < 50 copies/mL with lopinavir/ritonavir was greater than 75% at all time points. In conclusion, lopinavir/ritonavir demonstrated remarkable efficacy in the treatment of highly resistant HIV infection and HIV -1 DNA resistance testing provided comprehensive information for resistance monitoring.