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Project-based learning (PBL) is a transformative approach to college education with the potential to develop comprehensive skills such as critical thinking, problem-solving, and teamwork. This study explores factors influencing the effectiveness of PBL and proposes strategies for its enhancement among Chinese college students. Utilizing the Input-Environment-Output (IEO) model as a theoretical framework, we conducted an empirical analysis of PBL outcomes and their determinants. The study employed advanced data analysis techniques, including structural equation modeling (SEM), to demonstrate the positive impact of PBL on knowledge integration, project skills, and self-efficacy. The effectiveness of PBL, however, is influenced by various factors, including instructional design, teacher guidance, student participation, and the disciplinary and institutional contexts. Based on a survey of 553 Chinese college students, the findings suggest that targeted improvements in these areas can optimize PBL to better meet students' educational needs. The results provide actionable insights for educators and policymakers on enhancing PBL strategies to foster a more engaging and effective learning environment.

Abstract Post-operative recurrence rates of stage I non-small cell lung cancer (NSCLC) range from 20% to 40%. Nonetheless, the molecular mechanisms underlying recurrence hitherto remain largely elusive. Here, we generate genomic, epigenomic and transcriptomic profiles of paired tumors and adjacent tissues from 122 stage I NSCLC patients, among which 57 patients develop recurrence after surgery during follow-up. Integrated analyses illustrate that the presence of predominantly solid or micropapillary histological subtypes, increased genomic instability, and APOBEC-related signature are associated with recurrence. Furthermore, TP53 missense mutation in DNA-binding domain could contribute to shorter time to recurrence. DNA hypomethylation is pronounced in recurrent NSCLC, and PRAME is the significantly hypomethylated and overexpressed gene in recurrent lung adenocarcinoma (LUAD). Mechanistically, hypomethylation at TEAD1 binding site facilitates the transcriptional activation of PRAME. Inhibition of PRAME restrains the tumor metastasis via downregulation of epithelial–mesenchymal transition-related genes. We also identify that enrichment of AT2 cells with higher copy number variation burden, exhausted CD8 + T cells and Macro_SPP1, along with the reduced interaction between AT2 and immune cells, is essential for the formation of ecosystem in recurrent LUAD. Finally, multi-omics clustering could stratify the NSCLC patients into 4 subclusters with varying recurrence risk and subcluster-specific therapeutic vulnerabilities. Collectively, this study constitutes a promising resource enabling insights into the biological mechanisms and clinical management for post-operative recurrence of stage I NSCLC.

Abstract Background Pleural diseases is a common respiratory disorder, mainly characterized as pleural effusion and patients with pleural effusion caused by pneumonia and empyema constituted 29% of the cohort, which suggests pleural infection as the predominant etiology of pleural effusion in China. Medical thoracoscopy (MT) combined with intrapleural injection of Urokinase holds significant therapeutic value for patients with early to moderate-stage empyema. However, there remains a lack of high-quality evidence regarding the efficacy and safety of combining MT with intrapleural injection of Urokinase administration in patients with pleural infections. Methods This study is a prospective, multicenter, randomized controlled clinical trial involving patients with pleural infections. The intervention involves medical thoracoscopy. The control group receives conventional treatment involving intrapleural urokinase injection followed by chest tube placement for drainage. The study outcomes include efficacy and health economic benefits. The estimated minimum sample size for each group is 64 cases, totaling 128 cases. The study groups are delineated as follows: patients in group A receives intrapleural urokinase injection followed by chest tube placement for drainage, while patients in group B undergoes MT to remove multiple septa and necrotic tissue followed by chest tube placement for drainage, and then intrapleural urokinase injection the day after MT. It is recommended that the diameter of the chest tube be 12–14 F, with three daily flushes of 30 ml normal saline to ensure optimal drainage. Subsequently, comprehensive statistical analyses will be conducted to compare treatment effects and complications across all groups, ultimately leading to conclusive findings. Discussion The study is the first prospective, multicenter clinical trial on the efficacy and safety of medical thoracoscopy combined with intrapleural urokinase injection for the treatment of pleural infection. This study aims to offer clinical guidance for the management of pleural infection. Registration number ChiCTR2300078352 (Registration Date: 2023/12/06).

Abstract Malignant pleural mesothelioma (MPM) is a rare form of thoracic malignancy with a poor prognosis. Pleural effusion (PE) occurs in the majority of patients with MPM; however, its impact on MPM outcomes remains controversial. We searched for eligible patients from the Surveillance, Epidemiology, and End Results (SEER) database, and clinicopathological information and outcomes were collected. Cox proportional hazard regression analyses were utilized to evaluate the association of PE and other factors with overall survival (OS) and cancer-specific survival (CSS) in patients with MPM. A total of 4185 patients were extracted from the SEER database from 2000 to 2021. The median age of the cohort was 73 years, with a predominance of male patients and epithelioid MPM as the main histological subtype. Univariate Cox regression revealed associations between PE, age, sex, marital status, histology, stage, and treatment with both OS and CSS. Besides, multivariate analyses indicated that PE was independently associated with poorer OS and CSS in patients with MPM, regardless of age, sex, histology, stage, and treatment. Subgroup analyses suggested that PE has a remarkable impact on patients undergoing surgery. PE might serve as an independent prognostic factor in patients with MPM, especially in surgery recipients. Consequently, the development of pleural effusion in these patients should receive increased attention. Future studies are needed to validate these findings, particularly concerning the effect of PE in other clinical settings, such as immunotherapy.

Background and objective A prognostic nutritional index (PNI) developed by nutritional status and inflammation are closely associated with poor prognosis in malignant tumors. However, the predictive impact of PNI in patients with malignant pleural effusion (MPE) remains inconclusive. The study aimed to determine the predictive value of PNI in prognosis and spontaneous pleurodesis among patients with MPE. Methods The patients diagnosed with advanced non-small cell lung cancer (NSCLC) with MPE in West China Hospital between January 2015 and December 2022 were reviewed and allocated randomly to development set(60%) and validation set(40%). After collecting clinical data, peripheral blood inflammation indices and calculating systemic inflammation indices, the effects of PNI on prognosis and spontaneous pleurodesis have been evaluated by Cox proportional hazards models, Kaplan-Meier method and Nelson-Aalen cumulative risk curve. Results In total, 261 patients diagnosed NSCLC with MPE were selected (development set: n=157; validation set: n=104), of whom 58.2% were aged

The incidence and mortality of lung cancer are extremely high, and the 5-year survival rate of patients after diagnosis is less than 20%; as such, early screening and intervention are important. However, doctors are overwhelmed with a large workload of CT scan review in a short period of time and should ensure that the rate of missed diagnosis and misdiagnosis is low. Artificial intelligence can assist doctors in early diagnosis and precise treatment of lung cancer, but this technology has problems. This paper reviews the application of artificial intelligence in the prediction of benign and malignant lung nodules, pathology, gene mutation, intervention scheme, treatment response, and prognosis and presents the corresponding challenges.

Abstract The immune escape capacities of XBB variants necessitate the authorization of vaccines with these antigens. In this study, we produce three recombinant trimeric proteins from the RBD sequences of Delta, BA.5, and XBB.1.5, formulating a trivalent vaccine (Tri-Vac) with an MF59-like adjuvant at a 1:1:4 ratio. Tri-Vac demonstrates immunogenicity in female NIH mice, inducing cross-neutralization against various SARS-CoV-2 variants, including pre-Omicron and Omicron BA.2.75, BA.5, and XBB lineages. It elicits measurable antigen-specific T cell responses, germinal center B cell responses, and T follicular helper responses, effectively protecting against live Omicron XBB.1.16 challenges. Protective immunity is maintained long-term, with sustained neutralizing antibodies and T cell responses, as well as memory B cells and long-lived plasma cells observed by day 210 post-immunization. Tri-Vac also serves as a candidate booster for enhancing immunity after three doses of inactivated virus or mRNA vaccines. A phase 1 investigator-initiated trial was initiated to assess safety and immunogenicity in humans, focusing on the primary endpoint of adverse reactions within 7 days and key secondary endpoints including the geometric mean titers (GMTs) of serum neutralizing antibodies within 30 days and 6 months post-vaccination, as well as adverse events within 30 days and serious adverse events within 6 months post-vaccination. Preliminary data indicate Tri-Vac has good safety and immunogenicity, improving neutralization against multiple variants, including JN.1, in previously vaccinated individuals, highlighting its clinical potential for protecting against SARS-CoV-2 variants. The registration number of this clinical trial is ChiCTR2200067245.

Abstract Although an ideal bandgap matching with 0.96 eV and 1.62 eV for a double-junction tandem is hard to realize practically, among all mature photovoltaic systems, Cu(In,Ga)Se2 (CIGSe) can provide the closest bandgap of 1.00 eV for the bottom sub-cell by adjusting its composition. However, pure CuInSe2 (CISe) solar cell suffers strong interfacial carrier recombination. We hereby present approaches to introduce appropriate Ga gradients in both the back and front parts of absorber while maintaining the absorption spectrum close to CISe. With an appropriate front Ga gradient, the open circuit voltage can be enhanced by ~30 mV. With a pre-deposited CIGSe layer and a high copper excess deposition during absorber growth, the Ga diffusion can be well suppressed and a wide U-shaped Ga grading with a minimum bandgap of 1.01 eV has been created. Our optimized narrow-bandgap CIGSe solar cell has achieved a certified record PCE of 20.26%, with a record-low open circuit voltage deficit of 368 mV and a record-high contribution of 10% absolute efficiency to a four-terminal tandem. This work demonstrates the potential of controlling gallium diffusion to improve the performance of narrow bandgap CIGSe solar cells for tandem applications.

Water-holding capacity, texture and color are important indicators of fresh meat quality. In China, drip loss and textural deterioration of fresh meat are critical problems in the meat industry, causing greater quality loss than that in developed countries. Recently, researchers have identified a series of potential biomarkers for the water-holding capacity and tenderness of meat and have studied the effect of cell apoptosis on meat tenderness. However, the relationship between ferroptosis and fresh meat quality has been researched little. After slaughter, the intramuscular environment alters and ferroptosis occurs, which is characterized by the accumulation of iron, an increase in lipid oxidation and disruption of redox equilibrium. These changes are closely related to meat quality. This paper reviews the characteristics, metabolic pathways and regulatory mechanisms of ferroptosis, and the crosslinks between ferroptosis and other modes of cell death. Moreover, it elaborates on how ferroptosis affects fresh meat quality through iron homeostasis imbalance, redox imbalance and lipoperoxidation. Overall, this review provides deeper insights into the mechanism of meat quality formation during postmortem aging.

Abstract Medical thoracoscopy has been extensively utilized in the diagnosis of pleural disease, yet its potential therapeutic applications remain underutilized. This article presents a comprehensive overview of the various uses of medical thoracoscopy in managing pleural diseases. It has been employed to facilitate thoracic drainage and reduce hospitalization duration of patients with complicated parapneumonic effusions and empyema. Additionally, medical thoracoscopic occlusion therapy can be used for bronchoscopic closure and refractory pneumothorax. However, there is currently a lack of standardized protocols for utilizing medical thoracoscopy to reduce the volume of giant emphysematous bullae. Furthermore, medical thoracoscopy allows for pleurodesis or photodynamic therapy in patients with malignant pleural effusion. Nevertheless, further high-quality clinical research is needed to validate these findings.

The response of an anti-Compton phoswich detector to gamma rays was investigated using Monte-Carlo method, and the pulses from different crystal cases, including gamma deposition only in the LaBr3(Ce) or CsI(Tl) crystal and coincidence in both crystals, were analyzed. A novel pulse discrimination method for gamma deposition events based on wavelet transform analysis, called SSD (Scale Shape Discrimination), was developed in this study. Compared to the traditional PSD (Pulse Shape Discrimination) method, SSD has the advantage of transforming one-dimensional pulses in the time-domain into two-dimensional time-frequency spectra, providing the more useful features for pulse discrimination. The performances of the Compton suppression and Full-energy peak loss using PSD and SSD methods was studied. The results show that the Compton suppression factor IPSD = 5.12 and ISSD = 5.32, and FEP loss factor PLPSD = 0.0554 and PLSSD = 0.0587. Meanwhile, the influences of the cutoff values for pulse discrimination on the results of I and PL with different method were analyzed.

Abstract Background With the rapid increase of chest computed tomography (CT) images, the workload faced by radiologists has increased dramatically. It is undeniable that the use of artificial intelligence (AI) image‐assisted diagnosis system in clinical treatment is a major trend in medical development. Therefore, in order to explore the value and diagnostic accuracy of the current AI system in clinical application, we aim to compare the detection and differentiation of benign and malignant pulmonary nodules between AI system and physicians, so as to provide a theoretical basis for clinical application. Methods Our study encompassed a cohort of 23 336 patients who underwent chest low‐dose spiral CT screening for lung cancer at the Health Management Center of West China Hospital. We conducted a comparative analysis between AI‐assisted reading and manual interpretation, focusing on the detection and differentiation of benign and malignant pulmonary nodules. Results The AI‐assisted reading exhibited a significantly higher screening positive rate and probability of diagnosing malignant pulmonary nodules compared with manual interpretation (p

Abstract Background Although the imaging manifestations of pulmonary sarcoidosis have been described in detail in previous studies, a consensus has not been reached on the imaging presentation of non-specific interstitial pneumonia (NSIP) lookalike pattern as a distinct pattern in the diagnosis of pulmonary sarcoidosis in high-resolution computed tomography (HRCT). No cases of pulmonary sarcoidosis comorbid with NSIP have been reported. Case presentation A 53-year-old male presented to the hospital with a five-year history of recurrent coughing up sputum and a four-year history of shortness of breath. In addition to the typical features of pulmonary sarcoidosis, the patient’s HRCT also showed unexpected interstitial changes in the lower lobes of both lungs, suggesting an NSIP pattern. Histopathology of the lung tissue in this region confirmed well-formed noncaseating epithelioid granulomas and pathological modifications of NSIP. After a rigorous exclusion diagnosis combining the patient’s clinical features, radiological and pathological findings, we diagnosed this patient with pulmonary sarcoidosis comorbid with NSIP. Conclusions This suggests that NSIP may act as a rare comorbidity of pulmonary sarcoidosis thereby resulting in the patient’s HRCT presenting differently from routine sarcoidosis imaging.

ABSTRACT Chronic obstructive pulmonary disease (COPD) is confirmed as an independent risk factor for the development of lung cancer. Although low‐dose CT screening significantly reduces the mortality rate of lung cancer, the misdiagnosis and missed diagnosis rates remain high in the COPD population. Additionally, several COPD patients are unable to undergo invasive histological examinations. Therefore, there is an urgent need for minimally invasive biomarkers to screen or diagnose lung cancer in COPD patients. In this study, peripheral blood samples were collected from COPD patients with and without lung cancer. Plasma exosomes (EVs) were extracted for proteomic analysis. Sixteen differentially expressed proteins (DEPs) were preliminarily selected via label‐free quantification (LFQ) proteomic technology and comprehensive bioinformatics analysis. Parallel reaction monitoring (PRM) targeted validation identified five candidate proteins associated with COPD with lung cancer. Compared to the COPD group, KRT1, KRT9, and KRT10 were significantly upregulated in the COPD with lung cancer group, while GPLD1 and TF were downregulated. The biomarkers identified in our study provide a foundation for non‐invasive screening and diagnosis of lung cancer in COPD patients and exploration of the mechanisms shared between COPD and lung cancer.

BackgroundAlarmins mediate type 2 T helper cell (Th2) inflammation and serve as upstream signaling elements in allergic inflammation and autoimmune responses. The alarmin interleukin (IL)-25 binds to a multi-domain receptor consisting of IL-17RA and IL-17RB subunits, resulting in the release of Th2 cytokines IL-4, IL-5, IL-9 and IL-13 to drive an inflammatory response. Therefore, the blockage of IL-17RB via SM17, a novel humanized monoclonal antibody, offers an attractive therapeutic target for Th2-mediated diseases, such as asthma.MethodsWild-type mice were stimulated with house dust mite (HDM) extracts for evaluation of SM17’s pre-clinical efficacy in allergic asthma. The safety, pharmacokinectics (PK), pharmacodynamics (PD), and immunogenicity of intravenous (IV) doses of SM17 were assessed in a 2-part clinical study in healthy adult subjects. In Part A, 53 healthy participants were enrolled to receive a single IV dose of SM17 (2, 20, 70, 200, 400, 600, 1200 mg) or placebo. In Part B, 24 healthy subjects were enrolled to receive a single IV dose of SM17 every two weeks (Q2W; 200, 400, 600 mg) or placebo for a total of 3 doses.ResultsAnimal studies demonstrated that SM17 significantly suppressed Th2 inflammation in the bronchoalveolar lavage fluid and infiltration of immune cells into the lungs. In the Phase I clinical study, no drug-related serious adverse events were observed. Total SM17 exposure increased by approximately 60- to 188-fold with a 60-fold increase in dose from 20 to 1200 mg SM17. Upon administration of the third dose, mean accumulation ratios over 200-600 mg was 1.5 to 2.1, which confirms moderate accumulation of SM17. After Q2W dosing of SM17 over 4 weeks, total exposure increased in a dose-proportional manner from 200 mg to 600 mg SM17.ConclusionIn the pre-clinical studies, we demonstrated that SM17 is a potential therapeutic agent to treat allergic asthma. In the Phase 1 clinical trial, a single IV dose of SM17 up to 1200 mg and three Q2W doses up to 600 mg were well tolerated in healthy participants and demonstrated a favorable safety profile. The pre-clinical efficacy and clinical PK and immunogenicity results of SM17 support further clinical development.Clinical trial registrationhttps://clinicaltrials.gov/, identifier NCT05332834.

Background Lung cancer has maintained a high prevalence and mortality. Besides, venous thromboembolism (VTE) is the third most common disease of cardiovascular disease. Lung cancer with VTE usually influenced the overall survival in the follow-up. In the development of lung cancer, vigilance against and early diagnosis of VTE is of significance.Methods We searched the databases of PubMed, Web of Science, Embase and Cochrane for related research up to 30 November 2023 and extracted information of incidence, odds ratio (OR), hazard ratio (HR) and their 95% confidence intervals (CIs), for evaluating the incidence of VTE and its risk factors.Results A total of 54 articles and 873,292 records were included in our study. The pooled incidences of VTE and PE were 6% and 3%, respectively. Subgroup analysis revealed that the tumour, node and metastasis (TNM) stage (HR= 5.43, 95% CI: 2.42, 12.22), metastasis (HR= 2.67, 95% CI: 1.35, 5.29) and chemotherapy (HR= 2.27, 95% CI: 1.11, 4.65) had major influence on VTE occurrence.Conclusions Lung cancer complicated with VTE is unignorable, and its occurrence varies widely by tumour staging, tissue type and treatment. The results may aid in clinical decision-making about lung cancer in higher risk with VTE and weather receiving anticoagulant prophylaxis.

Abstract Introduction Emerging infectious diseases (EIDs) can disrupt the healthcare system, causing regulatory changes that affect the healthcare-seeking process and potentially increase patient-physician dissatisfaction. This study aimed to collect and analyze patients’ and physicians’ complaints during an EID outbreak to inform potential clues regarding medical quality and patient safety enhancement in future dealing with EIDs, employing text mining methodologies. Methods In this descriptive study, complaint records from January 2020 to February 2023 at West China Hospital, a national medical facility in China, were analyzed. Patient and physician complaints have been retrospectively retrieved from the record from the medical department, and then categorized into distinct groups based on reporting reasons, encompassing COVID-19-related policies, healthcare access, availability of medical resources, and financial concerns. Results During the COVID-19 pandemic, 541 COVID-19-related complaints were identified: 330 (61.00%) from patients and 211 (39.00%) from physicians. The monthly volume of complaints fluctuated, starting at 10 in 2020, peaking at 21 in 2022, and dropping to 14 in 2023. Most complaints from inpatients were expressed by older males aged 40 to 65 (38.82%, 210/541). The primary source of complaints was related to mandatory COVID-19 policies (79.30%, 429/541), followed by concerns regarding timely healthcare services (31.61%, 171/541). Few complaints were expressed regarding the insufficiency of medical resources (2.77%, 15/541) and the high costs (4.25%, 23/541). The frequency of complaints expressed by doctors and patients in the emergency department was higher compared with other departments (24.58%, 133/541). Conclusions Increased complaints may serve as a primitive and timely resource for investigating the potential hazards and drawbacks associated with policies pertaining to EIDs. Prompt collection and systematical analysis of patient and physician feedback could help us accurately evaluate the efficacy and repercussions of these policies. Implementing complaints-based assessment might improve care standards in forthcoming healthcare environments grappling with EIDs.

Abstract. Background:. The incidence rate of lung cancer in women has significantly increased over the past decade, and previous evidence has indicated a significant relationship between the elevated levels of sex hormones and the risk of lung cancer. Therefore, we hypothesized that female hormone-related cancer (FHRC) patients, including breast, endometrial, cervical, and ovarian cancer patients, may experience a higher risk of developing subsequent lung cancer. This meta-analysis aimed to identify the risk of lung cancer among FHRC patients compared to the general population. Methods:. The PubMed, Web of Science, EMBASE, Cochrane Library, and CNKI databases were searched up to May 11, 2022. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were used to identify the risk of subsequent lung cancer after FHRC. Subgroup analyses based on the follow-up time and tumor type were also conducted. Results:. A total of 58 retrospective cohort studies involving 4,360,723 FHRC participants were included. The pooled results demonstrated that FHRC patients had a significantly increased risk of developing subsequent primary lung cancer (SIR = 1.61, 95% CI: 1.48–1.76, P

Large cell neuroendocrine carcinoma (LCNEC) of lung is a rare neuroendocrine carcinoma subtype with difficulty in early diagnosis and poor prognosis which is treated with standard strategies of small cell lung cancer and non-small cell lung cancer. In recent years, the precise types of LCNEC and its response to therapy have been identified by next-generation sequencing. Some researches have also found the correlation between different subtypes of LCNEC and the efficacy of chemotherapy regimens. However, there is no consensual agreement of its therapy. Recently, immune checkpoint inhibitors (ICIs) has provided a new option for LCNEC patients based on some retrospective research data and case reports. In this review, we aimed to summarize the epidemiological characteristics, standard therapy, the advances of molecular subtypes and clinical applications of ICIs of LCNEC, so as to provide optimal systemic clinical decision-making for LCNEC patients.

Abstract Objectives Lung cancer is one of the most common malignant tumors threatening human life and health. At present, low‐dose computed tomography (LDCT) screening for the high‐risk population to achieve early diagnosis and treatment of lung cancer has become the first choice recommended by many authoritative international medical organizations. To further optimize the lung cancer screening method, we conducted a real‐world study of LDCT lung cancer screening in a large sample of a healthy physical examination population, comparing differences in lung nodules and lung cancer detection between thin and thick‐slice LDCT scanning. Methods A total of 29 296 subjects who underwent low‐dose thick‐slice CT scanning (5 mm thickness) from January 2015 to December 2015 and 28 058 subjects who underwent low‐dose thin‐slice CT scanning (1 mm thickness) from January 2018 to December 2018 in West China Hospital were included. The positive detection rate, detection rate of lung cancer, pathological stage of lung cancer, and mortality rate of lung cancer were analyzed and compared between the two groups. Results The positive rate of LDCT screening in the thin‐slice scanning group was significantly higher than that in the thick‐slice scanning group (20.1% vs. 14.4%, p

Abstract The relationship between tissue-specific DNA methylation and cancer risk remains inadequately elucidated. Leveraging resources from the Genotype-Tissue Expression consortium, here we develop genetic models to predict DNA methylation at CpG sites across the genome for seven tissues and apply these models to genome-wide association study data of corresponding cancers, namely breast, colorectal, renal cell, lung, ovarian, prostate, and testicular germ cell cancers. At Bonferroni-corrected P

Abstract Background Pneumonia and lung cancer are both major respiratory diseases, and observational studies have explored the association between their susceptibility. However, due to the presence of potential confounders and reverse causality, the comprehensive causal relationships between pneumonia and lung cancer require further exploration. Methods Genome-wide association study (GWAS) summary-level data were obtained from the hitherto latest FinnGen database, COVID-19 Host Genetics Initiative resource, and International Lung Cancer Consortium. We implemented a bidirectional Mendelian randomization (MR) framework to evaluate the causal relationships between several specific types of pneumonia and lung cancer. The causal estimates were mainly calculated by inverse-variance weighted (IVW) approach. Additionally, sensitivity analyses were also conducted to validate the robustness of the causalty. Results In the MR analyses, overall pneumonia demonstrated a suggestive but modest association with overall lung cancer risk (Odds ratio [OR]: 1.21, 95% confidence interval [CI]: 1.01 − 1.44, P = 0.037). The correlations between specific pneumonia types and overall lung cancer were not as significant, including bacterial pneumonia (OR: 1.07, 95% CI: 0.91 − 1.26, P = 0.386), viral pneumonia (OR: 1.00, 95% CI: 0.95 − 1.06, P = 0.891), asthma-related pneumonia (OR: 1.18, 95% CI: 0.92 − 1.52, P = 0.181), and COVID-19 (OR: 1.01, 95% CI: 0.78 − 1.30, P = 0.952). Reversely, with lung cancer as the exposure, we observed that overall lung cancer had statistically crucial associations with bacterial pneumonia (OR: 1.08, 95% CI: 1.03 − 1.13, P = 0.001) and viral pneumonia (OR: 1.09, 95% CI: 1.01 − 1.19, P = 0.037). Sensitivity analysis also confirmed the robustness of these findings. Conclusion This study has presented a systematic investigation into the causal relationships between pneumonia and lung cancer subtypes. Further prospective study is warranted to verify these findings.

ABSTRACT: Objectives: Nocardia gipuzkoensis was first described as a novel and distinct species in 2020 by Imen Nouioui and pulmonary nocardiosis associated with N. gipuzkoensis was once reported in two bronchiectasis patients. Noteworthy, both reported N. gipuzkoensis cases showed sensitivity to trimethoprim/sulfamethoxazol (TMP-SMZ), which are usually recommended for empirical therapy. Methods: We reported the third case of N. gipuzkoensis infection in a 16-year-old girl with chief complaints of cough and persistent chest and back pain. No underlying immuno-suppressive conditions and glucocorticoid use was revealed. Patchy lesions next to the spine and located in the posterior basal segment of the lower lobes of the left lung were seen in thorax computed tomography (CT), but no pathogenic bacteria were detected according to routine laboratory testings. Results: Metagenomic next-generation sequencing (mNGS) combined with whole-genome sequencing (WGS) was used to classified our isolate from bronchoalveolar lavage fluid (BALF) as N. gipuzkoensis. It is worth mentioning that drug susceptibility testing of our isolate showed resistance to TMP-SMZ, which was never reported before. The patient improved remarkably both clinically and radiographically according to the treatment with imipenem-cilastatin infusion alone. Conclusion: mNGS and WGS showed excellent performance in identifying the Nocardia genus to the species level and improving the detection rate of N. gipuzkoensis ignored by traditional culture. Different from previously reported cases, the N. gipuzkoensis infection case showed resistance to TMP-SMZ, which is an unprecedented finding and a crucial addition to our understanding of the antibacterial spectrum of N. gipuzkoensis. The successful treatment with imipenem-cilastatin infusion alone in this case is a testament to the importance of precise identification and tailored antibiotic therapy.

Trisomy 21, characterized by the presence of an additional chromosome 21, leads to a set of clinical features commonly referred to as Down syndrome (DS). The pathological phenotypes observed in DS are caused by a combination of factors, such as mitochondrial dysfunction, neuroinflammation, oxidative stress, disrupted metabolic patterns, and changes in protein homeostasis and signal transduction, and these factors collectively induce neurological alterations. In DS, the triplication of chromosome 21 and the micronuclei arising from the missegregation of chromosomes are closely associated with inflammation and the development of redox imbalance. Autophagy, an essential biological process that affects cellular homeostasis, is a powerful tool to facilitate the degradation of redundant or dysfunctional cytoplasmic components, thereby enabling the recycling of their constituents. Targeting the autophagy process has been suggested as a promising method to balance intracellular inflammation and oxidative stress and improve mitochondrial dysfunction. In this review, we summarize the role of autophagy in regulating inflammation and redox homeostasis in DS and discuss their crosslinks. A comprehensive elucidation of the roles of autophagy in DS offers novel insights for the development of therapeutic strategies aimed at aneuploidy-associated diseases.

BackgroundThe modified Glasgow Prognosis Score (mGPS), which considers both inflammatory response and nutritional status, has been linked to the prognosis of various tumors. The relationship between mGPS and non-small cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitors (ICIs) is still a subject of debate. This meta-analysis aims to comprehensively assess the association between mGPS and survival in NSCLC treated with ICIs.MethodsA thorough review of studies from PubMed, Web of Science, Scopus, and Embase was conducted up to June 4, 2024. Fixed-effect or random-effect models were employed, combining hazard ratios (HRs) and 95% confidence intervals (CI), to assess the prognostic value of mGPS for OS and PFS in patients with NSCLC receiving immunotherapy.ResultsA total of 1,022 patients from 11 studies were recruited. Combined results showed that mGPS elevation was significantly associated with poor OS (HR = 1.63, 95%CI: 1.42-1.87, P < 0.01) and PFS (HR = 1.71, 95%CI: 1.31-2.24, P < 0.01). Subgroup analysis and sensitivity analysis further determined the predictive effect of elevated mGPS on OS and PFS deterioration in NSCLC patients receiving immunotherapy.ConclusionmGPS can be used as a good noninvasive biomarker to demonstrate prognostic and clinical significance in patients with NSCLC undergoing immunotherapy.Systematic review registrationhttp://www.crd.york.ac.uk/prospero/ PROSPERO, identifier CRD42023432661.

Abstract Tuberculosis (TB), the leading cause of death from bacterial infections worldwide, results from infection with Mycobacterium tuberculosis (Mtb). The antitubercular agents delamanid (DLM) and pretomanid (PMD) are nitroimidazole prodrugs that require activation by an enzyme intrinsic to Mtb; however, the mechanism(s) of action and the associated metabolic pathways are largely unclear. Profiling of the chemical‐genetic interactions of PMD and DLM in Mtb using combined CRISPR screening reveals that the mutation of rv2073c increases susceptibility of Mtb to these nitroimidazole drugs both in vitro and in infected mice, whereas mutation of rv0078 increases drug resistance. Further assays show that Rv2073c might confer intrinsic resistance to DLM/PMD by interfering with inhibition of the drug target, decaprenylphophoryl‐2‐keto‐b‐D‐erythro‐pentose reductase (DprE2), by active nicotinamide adenine dinucleotide (NAD) adducts. Characterization of the metabolic pathways of DLM/PMD in Mtb using a combination of chemical genetics and comparative liquid chromatography‐mass spectrometry (LC‐MS) analysis of DLM/PMD metabolites reveals that Rv0077c, which is negatively regulated by Rv0078, mediates drug resistance by metabolizing activated DLM/PMD. These results might guide development of new nitroimidazole prodrugs and new regimens for TB treatment.

The ecological environment of wetlands in semi-arid regions has deteriorated, and vegetation succession has accelerated due to climate warming-induced aridification and human interference. The nutrient acquisition strategies and biomass allocation patterns reflect plant growth strategies in response to environmental changes. However, the impact of nutrient acquisition strategies on biomass allocation in successional vegetation remains unclear. We investigated 87 plant communities from 13 wetland sites in the semi-arid upper Yellow River basin. These communities were divided into three successional sequences: the herbaceous community (HC), the herbaceous–shrub mixed community (HSC), and the shrub community (SC). The nutrient composition of stems and leaves, as well as the biomass distribution above and belowground, were investigated. Results revealed that aboveground biomass increased with succession while belowground biomass decreased. Specifically, SC exhibited the highest stem biomass of 1,194.53 g m−2, while HC had the highest belowground biomass of 2,054.37 g m−2. Additionally, significant positive correlations were observed between leaf and stem biomasses in both HC and SC. The nitrogen (N) and phosphorus (P) contents within aboveground parts displayed an evident upward trend along the succession sequence. The highest N and P contents were found in SC, followed by HSC, and the lowest in HC. Stem N was negatively correlated with stem, leaf, and belowground biomass but positively correlated with root–shoot ratio. Leaf P displayed positive correlations with aboveground biomass while showing negative correlations with belowground biomass and root–shoot ratio. The ratios of C:N, C:P, and N:P in stem and leaf exhibited positive correlations with belowground biomass. The random forest model further demonstrated that stem N and leaf P exerted significant effects on aboveground biomass, while leaf P, stem N and P, and leaf C:P ratio had significant effects on belowground components. Additionally, the root–shoot ratio was significantly influenced by leaf P, leaf C:P ratio, and stem N, P, and C:P ratio. Therefore, the aboveground and belowground biomasses exhibited asynchronism across successional sequences, while plant nutrient acquisition strategies, involving nutrient levels and stoichiometric ratios, determined the biomass allocation pattern. This study offers valuable insights for assessing vegetation adaptability and formulating restoration plans in the semi-arid upper Yellow River basin.

Abstract Nickel (Ni), a component of urease, is a micronutrient essential for plant growth and development, but excess Ni is toxic to plants. Tomato (Solanum lycopersicum L.) is one of the important vegetables worldwide. Excessive use of fertilizers and pesticides led to Ni contamination in agricultural soils, thus reducing yield and quality of tomatoes. However, the molecular regulatory mechanisms of Ni toxicity responses in tomato plants have largely not been elucidated. Here, we investigated the molecular mechanisms underlying the Ni toxicity response in tomato plants by physio-biochemical, transcriptomic and molecular regulatory network analyses. Ni toxicity repressed photosynthesis, induced the formation of brush-like lateral roots and interfered with micronutrient accumulation in tomato seedlings. Ni toxicity also induced reactive oxygen species accumulation and oxidative stress responses in plants. Furthermore, Ni toxicity reduced the phytohormone concentrations, including auxin, cytokinin and gibberellic acid, thereby retarding plant growth. Transcriptome analysis revealed that Ni toxicity altered the expression of genes involved in carbon/nitrogen metabolism pathways. Taken together, these results provide a theoretical basis for identifying key genes that could reduce excess Ni accumulation in tomato plants and are helpful for ensuring food safety and sustainable agricultural development.

Abstract Septated pleural effusion is very common. The presence of septations in pleural effusion determines the local treatment strategy for such patients. Therefore, there is a pressing need for imaging techniques to assess the presence of septations. The objective of this research was to assess the diagnostic efficacy of computed tomography (CT) and chest ultrasound in identifying septated pleural effusion. We delineated the ultrasound and enhanced chest CT manifestations for diagnosing septated pleural effusions, and subsequently, we conducted a comparative analysis to assess the diagnostic efficacy of enhanced chest CT and ultrasound in identifying septated pleural effusions. Medical thoracoscopy served as the gold standard for confirming the diagnosis of septated pleural effusions. Ultrasound demonstrated a sensitivity of 82.6% (95% CI 73.3–89.7%) and a specificity of 100.0% (95% CI 98.1–NaN) for diagnosing septated pleural effusion. In comparison, enhanced chest CT exhibited a sensitivity of 59.8% (95% CI 49.0–69.9%) and a specificity of 87.0% (95% CI 81.5–91.4%). The positive predictive value for ultrasound was 100.0% (95% CI 95.3–100.0%), while for enhanced chest CT, it was 68.8% (95% CI 59.0–77.4%). Ultrasound yielded a negative predictive value of 92.3% (95% CI 87.5–NaN), and enhanced chest CT had a negative predictive value of 82.0% (95% CI 74.6–87.8%) in diagnosing septated pleural effusion. Thoracic ultrasound exhibits superior sensitivity and specificity compared to enhanced chest CT in diagnosing septated pleural effusions. Therefore, chest ultrasound is highly recommended as an adjunct for determining septated pleural effusion.

Abstract Background While circulating metabolites have been increasingly linked to cancer risk, the causality underlying these associations remains largely uninterrogated. Methods We conducted a comprehensive 2-sample Mendelian randomization (MR) study to evaluate the potential causal relationship between 913 plasma metabolites and the risk of seven cancers among European-ancestry individuals. Data on variant-metabolite associations were obtained from a genome-wide association study (GWAS) of plasma metabolites among 14,296 subjects. Data on variant-cancer associations were gathered from large-scale GWAS consortia for breast (N = 266,081), colorectal (N = 185,616), lung (N = 85,716), ovarian (N = 63,347), prostate (N = 140,306), renal cell (N = 31,190), and testicular germ cell (N = 28,135) cancers. MR analyses were performed with the inverse variance-weighted (IVW) method as the primary strategy to identify significant associations at Bonferroni-corrected P

Abstract Background Multimorbidity is becoming an increasingly serious public health challenge in the aging population. The impact of nutrients on multimorbidity remains to be determined and was explored using data from a UK cohort study. Method Our research analysis is mainly based on the data collected by the United Kingdom Women’s Cohort Study (UKWCS), which recruited 35,372 women aged 35–69 years at baseline (1995 to 1998), aiming to explore potential associations between diet and chronic diseases. Daily intakes of energy and nutrients were estimated using a validated 217-item food frequency questionnaire at recruitment. Multimorbidity was assessed using the Charlson comorbidity index (CCI) through electronic linkages to Hospital Episode Statistics up to March 2019. Cox’s proportional hazards models were used to estimate associations between daily intakes of nutrients and risk of multimorbidity. Those associations were also analyzed in multinomial logistic regression as a sensitivity analysis. In addition, a stratified analysis was conducted with age 60 as the cutoff point. Results Among the 25,389 participants, 7,799 subjects (30.7%) were confirmed with multimorbidity over a median follow-up of 22 years. Compared with the lowest quintile, the highest quintile of daily intakes of energy and protein were associated with 8% and 12% increased risk of multimorbidity respectively (HR 1.08 (95% CI 1.01, 1.16), p-linearity = 0.022 for energy; 1.12 (1.04, 1.21), p-linearity = 0.003 for protein). Higher quintiles of daily intakes of vitamin C and iron had a slightly lowered risk of multimorbidity, compared to the lowest quintile. A significantly higher risk of multimorbidity was found to be linearly associated with higher intake quintiles of vitamin B12 and vitamin D (p-linearity = 0.001 and 0.002, respectively) in Cox models, which became insignificant in multinomial logistic regression. There was some evidence of effect modification by age in intakes of iron and vitamin B1 associated with the risk of multimorbidity (p-interaction = 0.006 and 0.025, respectively). Conclusions Our findings highlight a link between nutrient intake and multimorbidity risk. However, there is uncertainty in our results, and more research is needed before definite conclusions can be reached.

Abstract Background Immune checkpoint inhibitors (ICI) combined with chemotherapy are efficacious for treating advanced non-small cell lung cancer (NSCLC); however, the effectiveness of this approach in the malignant pleural effusion (MPE) population is unclear. This study evaluated ICI plus chemotherapy in NSCLC patients with MPE. Methods Patients from 3 centers in China with NSCLC and MPE who received ICI plus chemotherapy (ICI Plus Chemo) or chemotherapy alone (Chemo) between December 2014 and June 2023 were enrolled. Clinical outcomes and adverse events (AEs) were compared. Results Of 155 eligible patients, the median age was 61.0 years old. Males and never-smokers accounted for 73.5% and 39.4%, respectively. Fifty-seven and 98 patients received ICI Plus Chemo or Chemo, respectively. With a median study follow-up of 10.8 months, progression-free survival (PFS) was significantly longer with ICI Plus Chemo than with Chemo (median PFS: 7.4 versus 5.7 months; HR = 0.594 [95% CI: 0.403–0.874], P = 0.008). Median overall survival (OS) did not differ between groups (ICI Plus Chemo: 34.2 versus Chemo: 28.3 months; HR = 0.746 [95% CI: 0.420–1.325], P = 0.317). The most common grade 3 or worse AEs included decreased neutrophil count (3 [5.3%] patients in the ICI Plus Chemo group vs. 5 [5.1%] patients in the Chemo group) and decreased hemoglobin (3 [5.3%] versus 10 [10.2%]). Conclusions In patients with untreated NSCLC with MPE, ICI plus chemotherapy resulted in significantly longer PFS than chemotherapy and had a manageable tolerability profile, but the effect on OS may be limited.

This study aims to construct a predictive model for assessing the risk of cognitive decline among elderly patients diagnosed with type 2 diabetes and validate its effectiveness. A total of 480 elderly patients with type 2 diabetes who signed a family doctor and underwent chronic disease management were selected and divided into a cognitive decline group (n = 62) and a non-cognitive decline group (n = 418) based on cognitive decline. Various clinical variables, lifestyle choices, medication regimens, complications, and medical histories were subjected to statistical analysis for both groups. Univariate and multivariate logistic regression analyses were performed to identify risk factors, based on which a risk prediction model was constructed. Hosmer and Lemeshow were used to investigate the goodness of fit of the risk prediction model, and Statistical Product and Service Solutions (SPSS) was used to draw Receiver Operating Characteristic (ROC) curves to assess the predictive value of the risk prediction model. Age, infrequent exercise, inadequate sleep, and the presence of depression emerged as significant risk factors for cognitive decline. The goodness-of-fit test using the Hosmer and Lemeshow statistic yielded χ2 = 0.041 and p = 0.855, confirming the model’s appropriateness. ROC curve analysis demonstrated an Area Under the Curve (AUC) of 0.912 (95% CI: 0.874 to 0.950), underscoring the model’s predictive capability. Age, infrequent exercise, inadequate sleep and depression could be risk factors for cognitive decline in elderly individuals with type 2 diabetes, and the proposed risk prediction model displays robust predictive accuracy for identifying those at risk of cognitive decline.

Abstract Background Chronic obstructive pulmonary disease (COPD) contributes to the incidence and prognosis of lung cancer. The presence of COPD significantly increases the risk of lung squamous cell carcinoma (LSCC). COPD may promote an immunosuppressive microenvironment in LSCC by regulating the expression of immune‐inhibitory factors in T cells, although the mechanisms remain unclear. In this study, we aimed to decipher the tumour microenvironment signature for LSCC with COPD at a single‐cell level. Methods We performed single‐cell RNA sequencing on tumour tissues from LSCC with or without COPD, then investigated the features of the immune and tumour cells. We employed multiple techniques, including multispectral imaging, flow cytometry, tissue microarray analysis, survival analysis, co‐culture systems and in vitro and in vivo treatment experiments, to validate the findings obtained from single‐cell analyses. Results LSCC with COPD showed increased proportions of tumour‐associated macrophages (TAMs) and higher levels of CD8+ T cell exhaustion molecules, which contributed to an immunosuppressive microenvironment. Further analysis revealed a critical cluster of CD74+ tumour cells that expressed both epithelial and immune cell signatures, exhibited a stronger capacity for tumorigenesis and predicted worse overall survival. Notably, migration inhibitory factor (MIF) secreted by TAMs from LSCC with COPD may promote the activation of CD74. MIF‐CD74 may interact with CD8+ T cells and impair their anti‐tumour activity by regulating the PI3K‐STAT3‐programmed cell death‐1 ligand 1 signalling pathway, facilitating tumour proliferation and immune evasion. Conclusions Our comprehensive picture of the tumour ecosystem in LSCC with COPD provides deeper insights into relevant immune evasion mechanisms and potential targets for immunotherapy. Highlight Our results demonstrated higher proportions of tumour‐associated macrophages (TAMs) and higher levels of exhaustion molecules in CD8+ T cells in the microenvironment of LSCC with COPD. CD74+tumour cells were associated with poor disease prognosis. Migration inhibitory factor (MIF)‐CD74 may interact with CD8+ T cells and impair their anti‐tumour activity by regulating the PI3K‐STAT3‐PD‐L1 signalling pathway, facilitating immune evasion.