Public Heterogeneous Preferences for Low-Dose Computed Tomography Lung Cancer Screening Service Delivery in Western China: A Discrete Choice Experiment.

BACKGROUND: Lung cancer screening (LCS) with low-dose computed tomography (LDCT) is an efficient method that can reduce lung cancer mortality in high-risk individuals. However, few studies have attempted to measure the preferences for LDCT LCS service delivery. This study aimed to generate quantitative information on the Chinese population's preferences for LDCT LCS service delivery. METHODS: The general population aged 40 to 74 in the Sichuan province of China was invited to complete an online discrete choice experiment (DCE). The DCE required participants to answer 14 discrete choice questions comprising five attributes: facility levels, facility ownership, travel mode, travel time, and out-of-pocket cost. Choice data were analyzed using mixed logit and latent class logit (LCL) models. RESULTS: The study included 2529 respondents, with 746 (29.5%) identified as being at risk for lung cancer. Mixed logit model (MLM) analysis revealed that all five attributes significantly influenced respondents' choices. Facility levels had the highest relative importance (44.4%), followed by facility ownership (28.1%), while out-of-pocket cost had the lowest importance (6.4%). The at-risk group placed relatively more importance on price and facility ownership compared to the non-risk group. LCL model identified five distinct classes with varying preferences. CONCLUSION: This study revealed significant heterogeneity in preferences for LCS service attributes among the Chinese population, with facility level and facility ownership being the most important factors. The findings underscore the need for tailored strategies targeting different subgroup preferences to increase screening participation rates and improve early detection outcomes.

SFPL: Sample-specific fine-grained prototype learning for imbalanced medical image classification.

Imbalanced classification is a common and difficult task in many medical image analysis applications. However, most existing approaches focus on balancing feature distribution and classifier weights between classes, while ignoring the inner-class heterogeneity and the individuality of each sample. In this paper, we proposed a sample-specific fine-grained prototype learning (SFPL) method to learn the fine-grained representation of the majority class and learn a cosine classifier specifically for each sample such that the classification model is highly tuned to the individual's characteristic. SFPL first builds multiple prototypes to represent the majority class, and then updates the prototypes through a mixture weighting strategy. Moreover, we proposed a uniform loss based on set representations to make the fine-grained prototypes distribute uniformly. To establish associations between fine-grained prototypes and cosine classifier, we propose a selective attention aggregation module to select the effective fine-grained prototypes for final classification. Extensive experiments on three different tasks demonstrate that SFPL outperforms the state-of-the-art (SOTA) methods. Importantly, as the imbalance ratio increases from 10 to 100, the improvement of SFPL over SOTA methods increases from 2.2% to 2.4%; as the training data decreases from 800 to 100, the improvement of SFPL over SOTA methods increases from 2.2% to 3.8%.

CRISPR Screening and Comparative LC-MS Analysis Identify Genes Mediating Efficacy of Delamanid and Pretomanid against Mycobacterium tuberculosis.

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.

Incidence and risk factors of VTE in lung cancer: a meta-analysis.

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.

The pooled incidences of VTE and PE were 6% and 3% in lung cancer.LUAD, NSCLC and tumour stage III-IV have significant relevant with VTE in lung cancer.

What are the frequent complaints voiced by inpatients and physicians amidst the emerging infectious diseases? - An illustrative instance of the COVID-19.

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.

Single-cell transcriptome analysis deciphers the CD74-mediated immune evasion and tumour growth in lung squamous cell carcinoma with chronic obstructive pulmonary disease.

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.

The Impact of Early Antibiotic Use on Clinical Outcomes of Patients Hospitalized with COVID-19: A Propensity Score-Matched Analysis.

Purpose: Early empiric antibiotics were prescribed to numerous patients during the Coronavirus disease 2019 (COVID-19) pandemic. However, the potential impact of empiric antibiotic therapy on the clinical outcomes of patients hospitalized with COVID-19 is yet unknown. Methods: In this retrospective cohort study, early antibiotics use cohort was defined as control group, which was compared with no antibiotic use and delayed antibiotic use cohorts for all-cause mortality during hospitalization. The 1:2 propensity score matched patient populations were further developed to adjust confounding factors. Survival curves were compared between different cohorts using a Log rank test to assess the early antibiotic effectiveness. Results: We included a total of 1472 COVID-19 hospitalized patients, of whom 87.4% (1287 patients) received early antibiotic prescriptions. In propensity-score-matched datasets, our analysis comprised 139 patients with non-antibiotic use (with 278 matched controls) and 27 patients with deferred-antibiotic use (with 54 matched controls). Patients with older ages, multiple comorbidities, severe and critical COVID-19 subtypes, higher serum infection indicators, and inflammatory indicators at admission were more likely to receive early antibiotic prescriptions. After adjusting confounding factors likely to influence the prognosis, there is no significant difference in all-cause mortality (HR=1.000(0.246-4.060), p = 1.000) and ICU admission (HR=0.436(0.093-2.04), p = 0.293), need for mechanical ventilation (HR=0.723(0.296-1.763), p = 0.476) and tracheal intubation (HR=1.338(0.221-8.103), p = 0.751) were observed between early antibiotics use cohort and non-antibiotic use cohort. Conclusion: Early antibiotics were frequently prescribed to patients in more severe disease condition at admission. However, early antibiotic treatment failed to demonstrate better clinical outcomes in hospitalized patients with COVID-19 in the propensity-score-matched cohorts.

A multimodal integration pipeline for accurate diagnosis, pathogen identification, and prognosis prediction of pulmonary infections.

Pulmonary infections pose formidable challenges in clinical settings with high mortality rates across all age groups worldwide. Accurate diagnosis and early intervention are crucial to improve patient outcomes. Artificial intelligence (AI) has the capability to mine imaging features specific to different pathogens and fuse multimodal features to reach a synergistic diagnosis, enabling more precise investigation and individualized clinical management. In this study, we successfully developed a multimodal integration (MMI) pipeline to differentiate among bacterial, fungal, and viral pneumonia and pulmonary tuberculosis based on a real-world dataset of 24,107 patients. The area under the curve (AUC) of the MMI system comprising clinical text and computed tomography (CT) image scans yielded 0.910 (95% confidence interval [CI]: 0.904-0.916) and 0.887 (95% CI: 0.867-0.909) in the internal and external testing datasets respectively, which were comparable to those of experienced physicians. Furthermore, the MMI system was utilized to rapidly differentiate between viral subtypes with a mean AUC of 0.822 (95% CI: 0.805-0.837) and bacterial subtypes with a mean AUC of 0.803 (95% CI: 0.775-0.830). Here, the MMI system harbors the potential to guide tailored medication recommendations, thus mitigating the risk of antibiotic misuse. Additionally, the integration of multimodal factors in the AI-driven system also provided an evident advantage in predicting risks of developing critical illness, contributing to more informed clinical decision-making. To revolutionize medical care, embracing multimodal AI tools in pulmonary infections will pave the way to further facilitate early intervention and precise management in the foreseeable future.

Outcomes of clinical decision support systems in real-world perioperative care: A systematic review and meta-analysis.

BACKGROUND: Although clinical decision support systems (CDSS) have been developed to enhance the quality and efficiency of surgeries, little is known regarding the practical effects in real-world perioperative care. OBJECTIVE: To systematically review and meta-analyze the current impact of CDSS on various aspects of perioperative care, providing evidence support for future research on CDSS development and clinical implementation. METHODS: This systematic review and meta-analysis followed the Cochrane Handbook and PRISMA statement guidelines, searching databases up to February 2, 2024, including MEDLINE, PubMed, Embase, Cochrane, and Web of Science. It included studies on the effectiveness of CDSS in assisting perioperative decision-making, involving anaesthesiologists, doctors, or surgical patients, and reporting at least one outcome such as complications, mortality, length of stay, compliance, or cost. RESULTS: Forty studies met inclusion criteria, analyzing outcomes from 408,357 participants, predominantly in developed countries. Most perioperative CDSS use was associated with improved guideline adherence, decreased medication errors, and some improvements in patient safety measures such as reduced postoperative nausea and vomiting and myocardial injury. However, reported results varied widely, and no significant improvement in postoperative mortality was observed. CONCLUSION: The preliminary findings of this review offer an overview of the potential use of CDSS in real-world perioperative situations to enhance patient and anaesthesiologist outcomes, but further researches with broader outcome dimensions, involving more stakeholders, and with longer follow-up periods are warranted for the critical evaluation of CDSS and then in better facilitate clinical adoption.

Advanced Hydrogels in Breast Cancer Therapy.

Breast cancer is the most common malignancy among women and is the second leading cause of cancer-related death for women. Depending on the tumor grade and stage, breast cancer is primarily treated with surgery and antineoplastic therapy. Direct or indirect side effects, emotional trauma, and unpredictable outcomes accompany these traditional therapies, calling for therapies that could improve the overall treatment and recovery experiences of patients. Hydrogels, biomimetic materials with 3D network structures, have shown great promise for augmenting breast cancer therapy. Hydrogel implants can be made with adipogenic and angiogenic properties for tissue integration. 3D organoids of malignant breast tumors grown in hydrogels retain the physical and genetic characteristics of the native tumors, allowing for post-surgery recapitulation of the diseased tissues for precision medicine assessment of the responsiveness of patient-specific cancers to antineoplastic treatment. Hydrogels can also be used as carrier matrices for delivering chemotherapeutics and immunotherapeutics or as post-surgery prosthetic scaffolds. The hydrogel delivery systems could achieve localized and controlled medication release targeting the tumor site, enhancing efficacy and minimizing the adverse effects of therapeutic agents delivered by traditional procedures. This review aims to summarize the most recent advancements in hydrogel utilization for breast cancer post-surgery tissue reconstruction, tumor modeling, and therapy and discuss their limitations in clinical translation.

Astrocytic 5-HT1A receptor mediates age-dependent hippocampal LTD and fear memory extinction in male mice.

NMDA receptor-dependent long-term depression (LTD) in the hippocampus is a well-known form of synaptic plasticity that has been linked to different cognitive functions. Although the underlying mechanisms remain unclear, this form of LTD cannot be induced by low-frequency stimulation (LFS) in adult mice. In this study, we found that LFS-induced LTD was not easily induced in adult animals and was age dependent. Interestingly, the level of the 5-HT1A receptor was correspondingly increased and exhibited an inverse correlation with the magnitude of LFS-LTD during development. Knockout or pharmacological inhibition of the 5-HT1A receptor reversed impaired LFS-LTD in adult mice (P60), while activation or inhibition of this receptor disturbed or enhanced LFS-LTD in adolescent mice (P21), respectively. Furthermore, the astrocytic 5-HT1A receptor in the hippocampus predominantly mediated age-dependent LFS-LTD through enhancing GABAergic neurotransmission. Finally, fear memory extinction differed among the above conditions. These observations enrich our knowledge of LTD at the cellular level and suggest a therapeutic approach for LTD-related psychiatric disorders.

Increased risk of subsequent primary lung cancer among female hormone-related cancer patients: A meta-analysis based on over four million cases.

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 <0.001). Subgroup analysis revealed an obvious trend of increasing lung cancer risk over time (SIRs for <5 years, ≥5 years, ≥10 years, ≥20 years, and ≥30 years after FHRC: 1.32, 1.59, 1.57, 1.68, and 1.95, respectively). In addition, subgroup analysis stratified by tumor type indicated an increased risk of developing subsequent lung cancer after breast (SIR = 1.25, P <0.001), endometrial (SIR = 1.40, P = 0.019), cervical (SIR = 2.56, P <0.001), and ovarian cancer (SIR = 1.50, P = 0.010). CONCLUSION: FHRC patients are more likely to develop lung cancer than the general population. Furthermore, the increased risk of subsequent primary lung cancer is more obvious with a longer survival time and is observed in all types of hormone-related cancer. REGISTRATION: International Platform of Registered Systematic Review and Meta-analysis Protocols: No. INPLASY202270044; https://inplasy.com/.

Current status and progress of PD-L1 detection: guiding immunotherapy for non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths and represents a substantial disease burden worldwide. Immune checkpoint inhibitors combined with chemotherapy are the standard first-line therapy for advanced NSCLC without driver mutations. Programmed death-ligand 1 (PD-L1) is currently the only approved immunotherapy marker. PD-L1 detection methods are diverse and have developed rapidly in recent years, such as improved immunohistochemical detection methods, the application of liquid biopsy in PD-L1 detection, genetic testing, radionuclide imaging, and the use of machine learning methods to construct PD-L1 prediction models. This review focuses on the detection methods and challenges of PD-L1 from different sources, and discusses the influencing factors of PD-L1 detection and the value of combined biomarkers. Provide support for clinical screening of immunotherapy-advantage groups and formulation of personalized treatment decisions.

NGS and FISH for MET amplification detection in EGFR TKI resistant non-small cell lung cancer (NSCLC) patients: A prospective, multicenter study in China.

OBJECTIVES: Comprehensive data using Next-Generation Sequence (NGS) and fluorescence in situ hybridization (FISH) for detecting MET amplification is limited in Chinese patients, we evaluating NGS performance both in tissue and plasma samples using FISH as reference. We also sought to find optimal thresholds value for NGS in detecting MET amplification via bioinformatics methods. METHOD: Patients progressed after 1st-, 2nd-, or 3rd-generation (G) EGFR-TKIs were enrolled. Tissue biopsy samples were performed for MET amplification detection via both NGS and FISH. Paired plasma samples were collected for MET amplification detection by NGS. The sensitivity, specificity and agreement were analyzed between NGS and FISH. RESULTS: 116 eligible patients were analyzed. 44 patients were male. 82 patients were after 3rd generation EGFR-TKI. MET amplification was detected in 43 (37.1 %) patients by FISH, including 19 (16.4 %) polysomy and 24 (20.7 %) focal amplification. The positive rate of MET amplification in post 3rd generation EGFR-TKI and post 1st/2ndgeneration EGFR-TKI resistant patients was 42.7 % (35/82), and 23.5 % (8/34). The sensitivity, specificity and agreement of detecting MET amplification by NGS in tissue were 39.5 % (17/43), 98.6 % (72/73) and 76.7 % (89/116), respectively, 66.7 % (16/24), 98.6 % (72/73) and 90.7 % (88/97) for focal MET amplification in tissue and 29.2 % (7/24), 94.5 % (69/73), 78.4 % (76/97) for focal amplification in plasma. Results were shown in the table below. CONCLUSION: NGS is an alternative method for MET focal amplification detection in tissue. While the sensitivity of NGS testing in plasma needs further improvement to maximize identification of patients with potential benefit from dual-targeted therapy.

Medical Resource Management in Emergency Hierarchical Diagnosis and Treatment Systems: A Research Framework.

The occurrence of major public health crises, like the COVID-19 epidemic, present significant challenges to healthcare systems and the management of emergency medical resources worldwide. This study, by examining the practices of emergency medical resource management in select countries during the COVID-19 epidemic, and reviewing the relevant literature, finds that emergency hierarchical diagnosis and treatment systems (EHDTSs) play a crucial role in managing emergency resources effectively. To address key issues of emergency resource management in EHDTSs, we examine the features of EHDTSs and develop a research framework for emergency resource management in EHDTSs, especially focusing on the management of emergency medical personnel and medical supplies during evolving epidemics. The research framework identifies key issues of emergency medical resource management in EHDTSs, including the sharing and scheduling of emergency medical supplies, the establishment and sharing of emergency medical supply warehouses, and the integrated dispatch of emergency medical personnel. The proposed framework not only offers insights for future research but also can facilitate better emergency medical resource management in EHDTSs during major public health emergencies.

PPCRKB: a risk factor knowledge base of postoperative pulmonary complications.

Postoperative pulmonary complications (PPCs) are highly heterogeneous disorders with diverse risk factors frequently occurring after surgical interventions, resulting in significant financial burdens, prolonged hospitalization and elevated mortality rates. Despite the existence of multiple studies on PPCs, a comprehensive knowledge base that can effectively integrate and visualize the diverse risk factors associated with PPCs is currently lacking. This study aims to develop an online knowledge platform on risk factors for PPCs (Postoperative Pulmonary Complications Risk Factor Knowledge Base, PPCRKB) that categorizes and presents the risk and protective factors associated with PPCs, as well as to facilitate the development of individualized prevention and management strategies for PPCs based on the needs of each investigator. The PPCRKB is a novel knowledge base that encompasses all investigated potential risk factors linked to PPCs, offering users a web-based platform to access these risk factors. The PPCRKB contains 2673 entries, 915 risk factors that have been categorized into 11 distinct groups. These categories include habit and behavior, surgical factors, anesthetic factors, auxiliary examination, environmental factors, clinical status, medicines and treatment, demographic characteristics, psychosocial factors, genetic factors and miscellaneous factors. The PPCRKB holds significant value for PPC research. The inclusion of both quantitative and qualitative data in the PPCRKB enhances the ability to uncover new insights and solutions related to PPCs. It could provide clinicians with a more comprehensive perspective on research related to PPCs in future. Database URL: http://sysbio.org.cn/PPCs.

Impact of Pulmonary microbiota on lung cancer treatment-related pneumonia.

Background: The use of immunotherapy is progressively expanding for the treatment of lung cancer, either alone or in combination with radiotherapy. However, treatment-related adverse events, especially pneumonia, significantly limit the drug's effectiveness in treating lung cancer. The occurrence of lung cancer, immunotherapy, and pulmonary radiotherapy can all contribute to the imbalance in the pulmonary microbiota, rendering the lungs more susceptible to inflammatory reactions. Methods: Mouse models of lung transplantation tumor were treated with either PD-1 monoclonal antibody or radiotherapy alone, or in combination. The differences in lung inflammation among the different treatment groups were regularly observed by micro-CT. Further, bronchoalveolar lavage fluid was extracted for macrogenomic and cytokine detection. The transcriptional genome of tumor-filled lung tissue was also sequenced. Results: When treated with a combination of PD-1 and radiotherapy, the CT scans showed more severe pulmonary inflammation. However, with the addition of continuously administered antibiotics, no exacerbation of pneumonia signs was observed. Moreover, the differential gene expression and cytokine profiles in the combination treatment group differed from those in the PD-1 monotherapy group and the radiotherapy monotherapy group. This discrepancy does not seem to be a straightforward superimposition of radiation-induced pneumonia and immune-related pneumonia. Further exploration of changes in pulmonary microbiota revealed specific bacterial interactions with DEGs and cytokines. Conclusions: The underlying causes of this susceptibility are intricate and may be associated with the complexity of pulmonary microbiota imbalance, along with fluctuations in the abundance of specific microbiota species.

Selenite improves growth by modulating phytohormone pathways and reprogramming primary and secondary metabolism in tomato plants.

Selenium (Se) is an essential micronutrient in organisms that has a significant impact on physiological activity and gene expression in plants, thereby affecting growth and development. Humans and animals acquire Se from plants. Tomato (Solanum lycopersicum L.) is an important vegetable crop worldwide. Improving the Se nutrient level not only is beneficial for growth, development and stress resistance in tomato plants but also contributes to improving human health. However, the molecular basis of Se-mediated tomato plant growth has not been fully elucidated. In this study, using physiological and transcriptomic analyses, we investigated the effects of a low dosage of selenite [Se(Ⅳ)] on tomato seedling growth. Se(IV) enhanced the photosynthetic efficiency and increased the accumulation of soluble sugars, dry matter and organic matter, thereby promoting tomato plant growth. Transcriptome analysis revealed that Se(IV) reprogrammed primary and secondary metabolic pathways, thus modulating plant growth. Se(IV) also increased the concentrations of auxin, jasmonic acid and salicylic acid in leaves and the concentration of cytokinin in roots, thus altering phytohormone signaling pathways and affecting plant growth and stress resistance in tomato plants. Furthermore, exogenous Se(IV) alters the expression of genes involved in flavonoid biosynthesis, thereby modulating plant growth and development in tomato plants. Taken together, these findings provide important insights into the regulatory mechanisms of low-dose Se(IV) on tomato growth and contribute to the breeding of Se-accumulating tomato cultivars.