Lung transplantation is the definitive therapy for end-stage respiratory diseases. To expand the donor lung pool, ex vivo lung perfusion (EVLP) has been developed for the assessment of marginal donor lungs. However, current evaluation methods remain limited. This study aimed to develop non-invasive imaging and monitoring techniques for the quantitative and early assessment of pulmonary function during EVLP. Three novel approaches were established: (1) lung thermography during the initial reperfusion period to assess pulmonary function, (2) optical oxygen saturation (SaO₂) imaging to assess pulmonary oxygenation, and (3) real-time lung weight measurement as an early indicator of transplant suitability. Lung thermography revealed that lung surface temperature at 8 min after shunt closure was significantly lower in non-suitable cases than in suitable cases (25.1 ± 0.6 °C vs. 27.8 ± 1.2 °C, P < 0.01). Optical SaO₂ imaging demonstrated a strong correlation between lower lobe SaO₂ calculated from SaO₂ imaging and PaO2/FiO2 (P/F) ratio in the lower pulmonary vein (R = 0.855, P < 0.01), with SaO₂ being significantly lower in non-suitable cases. Real-time lung weight measurement showed that lung weight gain increased significantly after 40 min in non-suitable cases compared with suitable cases (51.6 ± 46.0 g vs. -8.8 ± 25.7 g, P < 0.01). These three approaches proved effective for the quantitative and early assessment of pulmonary function during EVLP. This review was created based on a translation of the Japanese review written in the Japanese Journal of Artificial Organs in 2024 (Vol. 53, No. 3, pp. 216-220).
Reexpansion pulmonary edema following pulmonary and mediastinal surgery presents a complex clinical challenge. Independent lung ventilation (ILV), which facilitates the application of distinct positive end-expiratory pressures (PEEP) and tidal volumes to each lung, may serve as an alternative therapeutic approach for managing reexpansion pulmonary edema. A 58-year-old female patient presented with a giant space-occupying lesion measuring 17.1*11.2*19.2 cm in the left lung and underwent mediastinal tumor resection under general anesthesia. Intraoperatively, following the resection of the tumor and the invaded upper lobe of the left lung, the left lung was manually reopened, resulting in the development of reexpansion pulmonary edema (RPE). To prevent exudate from the left lung from infiltrating the right lung and to avoid barotrauma to the right lung due to excessive airway pressure, a dual ventilator mechanical ventilation strategy was employed. This approach utilized a double-lumen endotracheal tube, allowing for differential ventilation modes tailored to each lung. The mechanical ventilation treatment involving double-lumen bronchial intubation with various ventilation modes serves as an effective ventilatory support for managing reexpansion pulmonary edema.
Objective: To analyze the mutation status of the PIK3CA gene and the clinicopathological characteristics in lung adenocarcinoma. Methods: Lung adenocarcinoma cases that underwent next-generation sequencing (NGS) for the PIK3CA gene at the Department of Pathology, the Third People's Hospital of Henan Province and the Henan Provincial People's Hospital from January 1, 2020 to December 31, 2024 were collected. Clinicopathological indicators were recorded for statistical analysis, and follow-up was conducted. Results: A total of 127 lung adenocarcinoma patients with PIK3CA mutations were detected. There was a slight female predominance (75/127, 59.1%), the majority were non-smokers (95/127, 74.8%), and age was 65.0(57.0, 71.0)years old. Most lung adenocarcinomas were moderately differentiated (56/127, 44.1%) or poorly differentiated (44/127, 34.6%), with clinical stage Ⅳ being the most common (60/127, 47.2%). Hotspot mutations in the PIK3CA gene were present in 77 cases (77/127, 60.6%), specifically manifesting as mutations in exon 9 (E9, p.E545K/Q, p.E542K) and exon 20 (E20, p.H1047R/L/Y). Compared with E9 mutations, E20 mutations were more frequently associated with lymph node metastasis, visceral pleural invasion, airspace dissemination, poorer differentiation, and higher staging, and had a worse prognosis. Multivariate Cox analysis showed that PIK3CA hotspot mutations did not significantly affect prognosis (HR=0.586,95%CI=0.343-1.002,P=0.051). Co-existing mutations in other genes were found in 105 cases (105/127, 82.7%), with 72 cases (72/105, 56.7%) harboring concomitant EGFR mutations. Of the 62 cases receiving targeted therapy, 11 developed drug resistance, primarily due to secondary EGFR exon 20 mutations (9/11). Conclusions: Lung adenocarcinomas with PIK3CA mutations exhibit distinct clinicopathological characteristics in terms of gender, age, smoking history, differentiation degree, and clinical stage. Acquired drug resistance in lung adenocarcinoma may be accompanied by PIK3CA mutations, but PIK3CA mutation is not the main mechanism of targeted therapy resistance in lung adenocarcinoma patients. 目的： 分析PIK3CA基因在肺腺癌中的变异情况及临床病理特征。 方法： 收集2020年1月1日至2024年12月31日经河南省直第三人民医院和河南省人民医院病理科对PIK3CA基因进行下一代测序的肺腺癌病例，收集临床病理学指标，行统计学分析，并随访。 结果： PIK3CA突变的肺腺癌患者127例，其中女性稍多（75/127，59.1%）、不吸烟者为主（95/127，74.8%），发病年龄65.0（57.0，71.0）岁；多数肺腺癌组织学分化程度呈中分化（56/127，44.1%）和低分化（44/127，34.6%），临床分期Ⅳ期多见（60/127，47.2%）。77例（77/127，60.6%）存在PIK3CA基因热点区突变，具体为第9号外显子（E9，p.E545K/Q、p.E542K）及第20号外显子（E20，p.H1047R/L/Y）；与E9突变相比，E20突变多见于淋巴结转移、脏层胸膜侵犯、气腔播散、较低分化、较高分期的人群，其预后亦较差。多因素Cox分析结果显示PIK3CA热点突变对预后无显著影响［HR=0.586，95%置信区间（CI）=0.343~1.002，P=0.051］。105例（105/127，82.7%）共存其他基因突变，其中72例（72/105，56.7%）伴EGFR突变，62例靶向治疗后，11例发生耐药，耐药机制多为继发EGFR基因第20号外显子突变（9/11）。 结论： PIK3CA突变的肺腺癌在性别、年龄、吸烟史、分化程度及临床分期方面具有独特的临床病理学特征，获得性耐药的肺腺癌可伴随PIK3CA基因突变，但PIK3CA突变并非肺腺癌患者靶向耐药的主要机制。.
Lung transplantation is the definitive treatment for end-stage pulmonary disease, but ongoing challenges remain in long-term survival. We report our single center experience of 2,000 adult lung transplants over a nearly 35-year period and assess trends in patient demographics, intraoperative management, and in perioperative and long-term outcomes. We retrospectively reviewed 2,000 lung transplants at our center performed between 1988 and 2023. Recipients and donors were separated into 3 eras: Era 1 (1988-2000), Era 2 (2001-2011), and Era 3 (2012-2023). Recipient outcomes were compared between the eras. There were differences in recipient demographics across the eras. Over time, we have increasingly transplanted patients with restrictive lung disease. Overall graft survival has improved, with median graft survival increasing from 5.5 years (Era 1) to 9.0 years (Era 3) (p < 0.0001). We observed similar trends when patients were stratified by transplant indication. The incidence of primary graft dysfunction grade 3 (PGD3) has remained stable at 28.7% in Era 2 and 26.7% in Era 3 (p = 0.4892). The median freedom from chronic lung allograft dysfunction (CLAD) has improved from 3.2 (Era 2) to 3.4 years (Era 3) (p = 0.0001). Lung graft survival has improved over time at our institution due to advances in perioperative and long-term management. However, PGD3 rates have not changed and CLAD is commonly diagnosed within the first 4 years after transplant. Further research is necessary to understand these disease processes and to generate new treatment strategies to address them.
Autophagy is a central cellular quality-control pathway that maintains metabolic and proteostatic homeostasis by degrading damaged organelles and proteins. In the lung, autophagy contributes to normal development, epithelial integrity, mitochondrial quality control, and immune regulation. Emerging evidence indicates that environmental exposures such as cigarette smoke (CS), electronic cigarette (EC) aerosols, and nicotine profoundly disrupt these processes, contributing to both chronic lung disease and developmental programming of respiratory pathology. In this review, we propose a unifying framework in which autophagy functions as a redox-modulated rheostat that integrates oxidative, metabolic, and epigenetic stress signals triggered by smoke and nicotine exposure. Under physiological conditions, autophagy mitigates oxidative stress by removing dysfunctional mitochondria and maintaining proteostasis. However, chronic exposure to CS or EC aerosols generates excessive reactive oxygen species, impairs lysosomal degradation, and disrupts mitochondrial quality control, shifting autophagy from an adaptive protective response to a maladaptive driver of epithelial injury, inflammation, and tissue remodeling. Integrating experimental and clinical evidence, we identify four mechanistic axes underlying smoke-induced autophagy dysregulation: lysosomal dysfunction with TFEB suppression, mitochondrial redox amplification, disruption of selective autophagy pathways (including mitophagy, ER-phagy, xenophagy, and lipophagy), and immune polarization associated with inflammasome activation and cellular senescence. Importantly, maternal smoke and EC exposure similarly perturb autophagy in the placenta and fetal lung, altering developmental trajectories and increasing susceptibility to asthma and chronic lung disease. Viewing autophagy as a dynamic, redox-sensitive rheostat highlights new therapeutic opportunities to restore autophagic flux, lysosomal competence, and mitochondrial quality control in smoke- and nicotine-related lung disease.
BackgroundLung adenocarcinoma is a multifaceted disease with diverse locations and timings of gene mutations, histology, and molecular pathogenesis. Thus, identifying therapeutic target genes for lung adenocarcinoma has become a major challenge.MethodWe downloaded the gene expression profiles of 220 patients with lung adenocarcinoma from the Gene Expression Omnibus database and identified the differentially expressed genes between noncancer tissue and cancer tissue groups. Mendelian randomization analysis was performed using the exposure gene expression quantitative trait locus dataset and outcome dataset (ieu-a-965) to obtain genome-wide association studies summary data. Sensitivity analysis was used to assess the presence of pleiotropy and heterogeneity in the instrumental variables. Additionally, we performed Mendelian randomization analysis to explore the potential intersecting genes between differentially expressed and specific genes. Moreover, gene set enrichment and overall survival analyses were performed on the intersection gene.ResultsWe combined Gene Expression Omnibus and genome-wide association studies data to identify one upregulated and two downregulated genes associated with lung adenocarcinoma risk using inverse variance weight analysis as the primary analytical method. We observed that survival was significantly higher in the groups with high expressions of ANGPT1 and CD36 than in those with low expressions of these genes. POU2AF1 demonstrated inconsistency with the results obtained using Kaplan-Meier analysis and lacked statistical significance in the GSE130779 cohort.ConclusionOur results confirmed two specific target genes, CD36 and ANGPT1, based on Mendelian randomization analysis, providing new insights into the role of these target genes in mediating the development of lung adenocarcinoma.
Acute lung injury (ALI) is a severe inflammatory syndrome characterized by epithelial and endothelial injury, increased pulmonary vascular permeability, and impaired gas exchange. ALI often involves ferroptosis, an iron-dependent form of oxidative cell death. Nuclear factor erythroid 2-related factor 2 (NRF2) is a key regulator of antioxidant defenses, but its role in ALI-related ferroptosis is not well understood. In this study, NRF2 knockout (KO) mice were utilized for transcriptomic analysis to investigate the role of NRF2 in ALI. NRF2 deficiency significantly exacerbated lung injury and ferroptosis, and upregulated the expression of the calcium transporter gene solute carrier family 24 member 2 (SLC24A2). Calcium overload was closely associated with increased SLC24A2 expression and contributed to the development of ferroptosis. These findings were validated in vitro: knockdown of NRF2 in lung epithelial cells enhanced susceptibility to ferroptosis, whereas overexpression of NRF2 attenuated ferroptotic cell death. Conversely, silencing SLC24A2 reduced intracellular calcium overload and suppressed ferroptosis. These results suggest that there may be a regulatory axis between NRF2 and SLC24A2, which has a potential association with inflammation and ferroptosis signals related to acute lung injury (ALI). However, further studies are required to clarify the causal relationship and its consistency across different models, thereby evaluating the feasibility of this axis as a potential therapeutic target.
Results from the MORPHEUS-Lung (NCT03337698) study suggest that atezolizumab + bevacizumab + stereotactic body radiotherapy (SBRT) was associated with numerically improved efficacy outcomes vs docetaxel (control) in immune checkpoint inhibitor-exposed patients with metastatic non-small cell lung cancer. We report exploratory analyses to identify potential biomarkers associated with this clinical response. Tumor samples were analyzed for differential gene expression and pathway/immune subset gene signatures by single cell RNA-sequencing and further validated with bulk RNA-sequencing. The biomarker-evaluable population included 58 patients from two cohorts (atezolizumab + bevacizumab + SBRT, n = 26; docetaxel [control], n = 32). In a discovery study, analyses of clinical benefit (CB) vs non-CB groups at baseline showed that resident-memory CD8 T cells (TRM) were significantly enriched (P = 0.027; Gini index: P = 0.018), and expression of CXCL10+ and FOLR2+ macrophages was increased in the CB group. Pre- and post-treatment analysis showed that expression of effector-memory CD45RA+ CD8 T cells(TEMRA), CD8 TRM, and FOLR2+ and FABP4+ macrophages were numerically increased post-treatment. Together these results led to the identification of curated T-cell- and macrophage-associated gene response signatures. Using a confirmatory cohort, gene signature expression aligned with survival outcomes for patients receiving atezolizumab + bevacizumab + SBRT. These results suggest that activation of T cells and macrophages are associated with a favorable clinical response to atezolizumab + bevacizumab + SBRT. Moreover, CD8 TRM, CD8 exhausted T cells, and CXCL10+ macrophages may serve as potential biomarkers of response to atezolizumab + bevacizumab + SBRT treatment and potentially aid in tailored, precision medicine for individual patients.
An effective treatment strategy is essential for metastatic Wilms tumor (WT) management. To improve prognostic accuracy, this study examined metastatic patterns and key prognostic factors. Children diagnosed with WT from 2010 to 2021 were identified from the SEER database. All patients underwent chemotherapy and surgical resection. Metastatic patterns, metastasis-related predictors, and prognostic factors were evaluated. Of the 1040 patients analyzed, 226 (21.7%) experienced lung metastasis, 31 (3.0%) liver metastasis, 6 (0.6%) bone metastasis, and 220 (21.2%) regional lymph node metastasis. Distant metastasis was associated with a higher incidence of lymph node metastasis (OR = 1.506, 95% CI 1.346-1.685, p < 0.001). Age 3-17 years (OR = 1.933, 95% CI 1.406-2.680, p < 0.001), left-sided (OR = 1.383, 95% CI 1.016-1.890, p = 0.040), bilateral (OR = 2.303, 95% CI 1.215-4.243, p = 0.009), and tumor size ≥135 mm (OR = 2.020, 95% CI 1.481-2.749, p < 0.001) were identified as predictors of metastasis. Both lymph node (p < 0.001) and lung metastasis (p < 0.001) were high-risk factors for WT. Radiotherapy provided long-term survival benefits for the metastatic population (p = 0.027), while postoperative chemotherapy showed better outcomes than preoperative or other strategies (p < 0.001). Further analysis demonstrated that the concurrent lung and lymph node metastasis group benefited more from postoperative chemoradiotherapy, with HRs of 0.226 (p = 0.028) for overall survival and 0.255 (p = 0.048) for cancer-specific survival. WT with concurrent lung and lymph node metastasis represents a distinct and aggressive metastatic phenotype associated with a significantly poor prognosis. Postoperative chemoradiotherapy may provide superior survival benefits for this high-risk population.
Osteoporosis and asthma are prevalent chronic conditions that significantly impact public health. Inflammatory cell merging, leading to reduced bone density, increases the risk of fractures, while asthma is a chronic respiratory disease characterized by airway inflammation and bronchoconstriction. More and more emerging research suggests a potential connection through shared pathways and biological mechanisms. In this study, we aim to investigate the causal effect of anti-osteoporosis drug treatment on chronic disease asthma through the Mendelian randomization (MR) analysis method. In our study, we employed a two-stage study design, utilizing observational data from the National Health and Nutrition Examination Survey (NHANES) and summary statistics data from genome-wide association studies (GWAS) with a large sample of European adults. Section-cross research was performed using NHANES datasets and analysis of the risk of asthma with bone mineral density (BMD) through a risk proportion regression model. After that, a two-sample MR analysis was performed to investigate the causal effect of anti-osteoporosis drug therapy on asthma. Finally, sensitivity analysis was conducted to evaluate the stability of the results. Our study revealed a non-linear association between femur BMD and asthma risk, with a critical inflection point at a BMD value of 1.114 g/cm2. MR analysis indicated that denosumab did not exert a causal effect on asthma risk (OR = 1.008, 95% CI: 0.994-1.022, P = 0.285) but was associated with improved lung function (β = 0.085, 95% CI: 0.006-0.164, P = 0.035). Conversely, calcitriol exhibited a protective effect against both asthma (OR = 0.931, 95% CI: 0.894-0.969, P < 0.001) and lung function decline (β = 0.294, 95% CI: 0.062-0.525, P = 0.013). These findings suggest a pleiotropic role for these anti-osteoporosis drugs in respiratory health. This study provides novel insights into the complex relationships between osteoporosis treatments, bone health, and asthma risk. The use of MR analysis enhances the reliability of our findings and highlights the potential benefits of osteoporosis treatments in reducing asthma risk and improving lung function. These results call for further research and may have implications for developing integrated treatment approaches for individuals managing osteoporosis and asthma.
Sepsis-induced acute lung injury (ALI) is a life-threatening condition associated with high mortality rates. While emerging evidence suggests that KIAA1199 (also known as cell migration-inducing protein, CEMIP) contributes to the pathogenesis of bacterial infections, its specific role in sepsis-induced ALI remains largely unexplored. In this study, we find that serum levels of KIAA1199 are significantly elevated in sepsis patients compared to healthy individuals, demonstrating a positive correlation with the SOFA scores. Additionally, we observe the expression of KIAA1199 increased in the lung tissue of septic mice, particularly in alveolar epithelial Type II (AT2) cells. We further generate AT2-specific KIAA1199 knockout mice on a male C57BL/6 J background and establish LPS-induced ALI model. The results indicate that KIAA1199-deficient mice exhibit improved survival rates, reduced lung injury, and decreased levels of proinflammatory cytokines. Transcriptomic analysis and functional validation reveal that KIAA1199 promotes pulmonary complement activation by downregulating complement factor H (CFH), a critical regulator of the alternative complement pathway. Mechanistically, KIAA1199 downregulates CFH expression by enhancing the ubiquitinated degradation of its transcription factor of p53. In conclusion, our data demonstrate that KIAA1199 exacerbates sepsis-induced ALI via promoting local complement activation through CFH suppression, which may serve as a potential therapeutic target for sepsis-induced ALI.
Small cell lung cancer (SCLC) is the most aggressive histological subtype of lung cancer and is characterized by rapid tumor proliferation, early dissemination, and poor prognosis. Currently, the standard first-line treatment for extensive-stage SCLC consists of platinum-based chemotherapy and immune checkpoint inhibitors. Although patients exhibit a high initial response rate to platinum-based chemotherapy, the majority develop acquired resistance within 6 months. Overcoming drug resistance and prolonging the duration of first-line therapy are critical for long-term survival in these patients. However, the definitive resistance mechanisms associated with chemotherapy and immunotherapy in SCLC remain unclear. In this context, we comprehensively review the diverse mechanisms contributing to therapeutic resistance in SCLC, including transcriptional subtype plasticity, the epithelial-mesenchymal transition, an enhanced DNA damage repair capacity, dysregulated autophagy and apoptosis, the presence of cancer stem cells, alterations in the tumor microenvironment, and the aberrant expression of cellular transporters. We particularly focus on the dynamic evolution of resistance from intrinsic to acquired states and the complex interplay among these mechanisms, aiming to provide an integrated theoretical framework to guide the development of rational combination strategies to overcome therapeutic resistance.
Lung adenocarcinoma (LUAD) is a highly heterogeneous disease, bringing daunting challenges in prognosis prediction. Alterations in mitochondrial dynamics (MD) are crucial in tumor generation and progression. Therefore, this study is the first to build a prognostic model based on mitochondrial dynamics-related genes (MDRGs) to predict microenvironment and potential drugs for LUAD. LUAD transcriptomic data were sourced from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO), respectively. First, differentially expressed genes (DEGs) were screened between normal and LUAD samples in the TCGA cohort. The intersection of DEGs and MDRGs yielded differentially expressed MDRGs (DE-MDRGs). Then, a prognostic model was constructed through univariate Cox regression, LASSO Cox regression, and multivariate Cox regression analysis. A nomogram was graphed using clinical factors and the MD-related risk score (MDRS). The predictive performance of the model and the nomogram was evaluated using ROC curves. Finally, analyses on tumor microenvironment (TME), mutation, and predicted in vitro drug response were undertaken. A prognostic model based on 8 MDRGs (SLC52A3, HMGA2, CPS1, GLS2, CYP27A1, CFTR, STAR, and DRP2) was established, demonstrating relatively accurate predictive ability. The low-MDRS group had higher levels of immune cell infiltration, such as aDCs, B cells, neutrophils, and tumor-infiltrating lymphocytes. We also discovered that the tumor mutation burden in the high-MDRS group was considerably higher than that in the low-MDRS group. Additionally, the low-MDRS group was more sensitive to AZD8055, ZM447439, ERK-6604, SB505124, Tozasertib, and BMS-754807, while the high-MDRS group was more sensitive to BI-2536 and Venetoclax. This work set up a prognostic model for LUAD based on 8 MDRGs, pinpointing promising biomarkers and targets for LUAD treatment.
Recently, a novel circular RNA (circRNA), circPTP4A2 (hsa_circ_0007364), was reported to promote cervical cancer progression. However, its specific role in non-small cell lung cancer (NSCLC) remains unclear. Here, we observed that circPTP4A2 is significantly upregulated in NSCLC tissues and cell lines. Furthermore, multivariate Cox proportional hazards regression analysis confirmed that high circPTP4A2 expression is independently associated with poor prognosis in NSCLC patients after adjusting for confounding clinicopathological covariates. Knockdown of circPTP4A2 significantly suppressed the proliferation, migration, and invasion capabilities of H1299 and A549 cells. Additionally, we identified miR-183-5p as a direct targeted of circPTP4A2. In NSCLC clinical samples, circPTP4A2 expression showed a negative correlation with miR-183-5p levels. Moreover, we demonstrated that circPTP4A2 enhances the expression of EEF2, a downstream target of miR-183-5p. Collectively, our findings elucidate that circPTP4A2 promotes NSCLC progression by sponging miR-183-5p to upregulate EEF2, suggesting it could be a promising therapeutic target for NSCLC.
Lung transplantation (LTx) is the solid organ transplantation with the comparatively worst prognosis. Therefore, improving candidate selection and risk stratification for these patients has become a high-priority research focus. Incorporating objective markers of frailty such as sarcopenia in the pre-transplant evaluation may help achieve this goal. We evaluated the association between CT-measured psoas muscle sarcopenia and early LTx outcomes. We performed a retrospective study including patients who underwent LTx from 2014 to 2018 at our institution with available chest and abdominal CT scans in the year prior to LTx. Psoas cross-sectional area was measured, and previously established sex-specific cutoffs were used to define sarcopenia. We compared sarcopenic and non-sarcopenic LTx recipients regarding 1-year mortality and perioperative outcomes. A total of 140 patients were included, who received LTx primarily for interstitial lung disease (ILD) (n = 75, 53%) or chronic obstructive pulmonary disease (n = 54, 39%). Forty-six (33%) were sarcopenic. We found no association between psoas sarcopenia and 1-year all-cause mortality (multivariable p=0.13) nor perioperative complications or FEV1 at 1-year post-LTx. Exploratory subgroup analysis revealed an association between psoas sarcopenia and 1-yer all-cause mortality in patients with ILD (multivariable p = 0.042). Pre-established sex-specific cutoffs for psoas sarcopenia did not reach statistical significance for 1-year mortality or perioperative outcomes in the overall cohort; given limited statistical power, a clinically meaningful association cannot be excluded. An exploratory signal in ILD patients warrants further investigation. Future studies may benefit from disease-specific threshold validation and the integration of muscle strength and physical performance alongside muscle mass assessment.
This study compared the local control (LC) and survival of patients with stage III lymph node-positive non-small-cell lung cancer (NSCLC) who received lymph node irradiation (LNs R+) and those who did not (LNs R-). We retrospectively reviewed patients with stage III LN-positive NSCLC who underwent stereotactic body radiotherapy (SBRT) with or without lymph node irradiation between January 2013 and December 2018. Using propensity score matching (PSM) analyses, we compared the rates of LC, progression-free survival (PFS), overall survival (OS), and acute/late toxicities between the two groups. We retrospectively analyzed 201 patients, of whom 52 received LN irradiation and 149 did not. The median LC and OS were 59.7 months (95% CI: 51.1-62.9 months) and 36.3 months (95% CI: 32.6-40.0 months), respectively. After the PSM analysis, 52 patients were included in each group. The median LC (30.6 months and not reached, HR 1.296, 95% CI: 0.733-2.294, p = 0.371) and OS (30.3 months and 31.6 months, HR 0.969, 95% CI: 0.628-1.496, p = 0.887) were similar between the LN R+ group and the LN R- group. Total tumor size, tumor location, and biologic equivalent dose (BED) were independently associated with LC (p < 0.05). The incidences of acute radiation esophagitis (p = 0.006) and late pulmonary interstitial fibrosis (p = 0.046) were significantly higher in the LN R+ group than in the LN R- group. SBRT is safe and effective in stage III LN-positive NSCLC patients. Omitting elective nodal irradiation achieves comparable survival to irradiating involved lymph nodes while significantly reducing toxicity. These findings support the development of novel combination strategies.
Immune checkpoint inhibitors (ICI), epitomized by PD-1/PD-L1 antibodies, have ushered in a new era in lung cancer treatment. However, ICI monotherapy is only applicable to a small subset of patients with high PD-L1 expression, while most patients with low expression require combination therapies. In this study, we found that β-elemene promotes M1 polarization of tumor-associated macrophages (TAMs) and enhances the efficacy of PD-L1 antibody (aPD-L1) in C57BL/6 mice. RNA sequencing and surface plasmon resonance revealed that β-elemene directly binds to FLT1 and inhibits the PI3K/AKT/FOXO1 signaling pathway, thereby mediating TAMs M1 polarization. Using Flt1 knockout mice, we further validated the critical role of Flt1 in TAMs polarization and confirmed that M1 polarization synergizes with aPD-L1 treatment. Furthermore, co-immunoprecipitation showed that the FLT1 intracellular domain binds to and phosphorylates the p85α subunit, triggering downstream signaling cascades. These findings elucidate the synergistic mechanism between β-elemene and aPD-L1. Moreover, given the clinical availability of both agents, they provide a strong rationale for further clinical evaluation of this combination therapy.
IntroductionTrastuzumab deruxtecan (T-DXd)-induced interstitial lung disease/pneumonitis (ILD) represents a clinically significant and potentially fatal toxicity. Discrepancies exist regarding its reported frequency and severity between clinical trials (CTs) and real-world data (RWD). This meta-analysis aims to evaluate the incidence of T-DXd-related ILD and investigate its differences between CTs and RWD.MethodsA systematic review and meta-analysis was conducted in accordance with the PRISMA guidelines. Databases were searched from their inception through January 2026. CTs and real-world studies reporting T-DXd-related ILD were included in the analysis. Pooled incidences for all-grade, grade ≥3, and fatal ILD were calculated using random-effects models. Subgroup analyses comparing CTs and RWD, and meta-regression analyses for relevant outcomes were performed.ResultsThirty-five studies (19 CTs, 16 RWD) including 6840 patients were analyzed. The pooled incidence was 8.8% for all-grade ILD, 1.6% for grade ≥3 ILD, and 0.26% for fatal ILD. RWD was independently associated with lower reported rates of all-grade and fatal ILD, while prior lines of therapy were the main predictor of grade ≥3 ILD.ConclusionILD risk with T-DXd differs by severity and data source. Vigilant monitoring is essential, particularly in heavily pretreated patients.
耐碳青霉烯类肺炎克雷伯菌（CRKP）已在全球范围内构成严重的公共健康威胁，而肺移植受者因供体来源性感染、移植肺局部防御机制削弱及免疫抑制状态，是CRKP感染的高危人群。尽管术后早期感染防控措施持续改进，CRKP感染仍是肺移植术后发病死亡的主要原因。目前防治方法采取涵盖术前、术中及术后的综合策略，在以新型酶抑制剂复合制剂为核心的抗感染治疗的基础上，探索噬菌体、免疫调节等新辅助疗法。未来应致力于新型药物研发，辅以精准免疫调控、感染快速诊断与多学科协作管理的综合防治模式，以提升CRKP感染防控成效并改善受者预后。.
肺癌是全球常见的恶性肿瘤之一，其中小细胞肺癌所致的副肿瘤综合征临床表现多样为诊断增加了困难，当患者以非呼吸系统症状为首发表现时，容易出现漏诊、误诊。本文报道青岛大学附属医院收治的1例以急性胰腺炎、假性肠梗阻为首发表现的小细胞肺癌病例，复习相关文献报道，以期提高临床医生对小细胞肺癌副肿瘤综合征的认识，减少误诊、漏诊。.