BACKGROUND:The impact of neoadjuvant chemo-immunotherapy (nCIT) on perioperative cardiac safety in patients undergoing lung cancer resection remains unclear. This study aimed to evaluate the incidence and risk factors of postoperative cardiac adverse events (PCAEs) in patients receiving nCIT compared with neoadjuvant chemotherapy (nCT). METHODS:We conducted a bidirectional cohort study including 310 patients who received neoadjuvant therapy (nCT = 115; nCIT = 195), comprising both retrospective and prospective cases. Propensity score matching (PSM) at a 1:1 ratio was applied to balance baseline characteristics. Univariable and multivariable logistic regression analyses were performed to identify independent predictors of PCAEs, including clinically important perioperative atrial fibrillation, myocardial injury after non-cardiac surgery, myocardial infarction, and heart failure. Variance inflation factors were calculated to assess multicollinearity, and model goodness-of-fit was evaluated. Subgroup and sensitivity analyses were conducted to examine the robustness of findings. RESULTS:Before PSM, the overall incidence of PCAEs was comparable between the nCT and nCIT groups [20.9% vs. 25.6%; odds ratio (OR) 1.307, 95% confidence interval (CI) 0.759-2.300; P = 0.342]. After PSM (n = 166), no significant difference in PCAEs was observed (19.3% vs. 18.1%; OR 0.924, 95% CI 0.423-2.017; P = 0.842). Multivariable analyses confirmed that nCIT was not independently associated with increased PCAEs before (Model 3 OR 1.137, 95% CI 0.573-2.299) or after PSM (Model 3 OR 1.462, 95% CI 0.510-4.387). Hypertension (OR 11.024, 95% CI 3.518-38.380; P < 0.001) and pericardial window creation (OR 8.310, 95% CI 2.186-34.139; P = 0.002) were identified as strong independent predictors of PCAEs. Subgroup and sensitivity analyses consistently showed no elevated cardiac risk associated with nCIT across sex, hypertension status, surgical approach, ACEI/ARB use, CCB use, or treatment era. CONCLUSIONS:In this bidirectional cohort study, nCIT did not increase the risk of postoperative cardiac adverse events compared with nCT. Hypertension and pericardial window creation were significant independent risk factors for PCAEs. These findings support the perioperative cardiac safety of nCIT in lung cancer surgery.

Neutrophils, which represent about 50–70

Background A subset of CD4+ T cells with cytotoxic activity has been identified, and these cells exert their effects by expressing perforin and granzymes. Despite the progress made in characterizing cytotoxic CD4+ T cells in various diseases, the status of cytotoxic CD4+ T cells in non-small cell lung cancer (NSCLC) and the underlying mechanisms involved in promoting intratumoral cytotoxic CD4+ T-cell activation remain unclear.Methods We used flow cytometry to examine the phenotypic and functional properties of CD4+GzmB+ T cells in the peripheral blood and tumor tissues of patients with NSCLC. Loss-of-function analyses and RNA sequencing were used to identify the underlying mechanisms involved in the effects of interleukin (IL)-15 on the restoration of CD4+GzmB+ T-cell function in vitro. A patient-derived lung cancer explant model and an animal model were used to verify the effects of immune checkpoint inhibitors on CD4+GzmB+ T-cell activation.Results In patients with NSCLC, impaired cytolytic function of tumor-infiltrated granzyme B (GzmB)-expressing CD4+ T cells was restored by IL-15 through activation of the AKT-FOXO1-T-bet axis. Moreover, IL-15 stimulation increased solute carrier family 7 member 5 (SLC7A5) expression in CD4+GzmB+ T cells in an Protein Kinase B (AKT)-dependent manner, and inhibition of SLC7A5 abrogated the effect of IL-15 on CD4+GzmB+ T cells. Additionally, we showed that the immune checkpoint molecules programmed cell death-1 (PD-1) and CD85j were mutually exclusively expressed in CD4+GzmB+ T cells and that dual targeting of PD-1 and CD85j enhanced the effector function of CD4+GzmB+ T cells by activating the AKT pathway. Notably, tumor cells expressing major histocompatibility complex (MHC)-II and IL-15 determine the effectiveness of CD4+GzmB+ T-cell-mediated antitumor immunity in response to immunotherapy.Conclusions Our study demonstrated that tumor-infiltrating CD4+GzmB+ T cells fail to eliminate tumors. Dual blockade of PD-1 and CD85j alongside IL-15 restores the effector function of CD4+GzmB+ T cells and drives CD4+GzmB+ T-cell transformation in the tumor microenvironment to combat MHC-II-expressing tumors.

Glutamine metabolism is emerging as a target for improving immunotherapy efficacy. However, the outcomes remain inconclusive. Given that the tumor-intrinsic response to interferon-γ (IFN-γ) is a key determinant of immunotherapy efficacy, we investigated whether and how glutamine deprivation in cancer cells affects their response to IFN-γ. By using human lung cancer cell lines, patient-derived tumor explants, and a syngeneic mouse model of lung cancer, we demonstrated that glutamine deprivation reduced the IFN-γ-driven response in cancer cells by promoting autophagy-dependent IFN-γ receptor (IFNGR1) degradation and rendering tumors resistant to anti-PD-1 or anti-PD-L1 therapy. Treatment with V9302, an inhibitor of the alanine-serine-cysteine transporter (ASCT2), enhanced the IFN-γ-driven response of cancer cells and increased the efficacy of PD-1 blockade therapy. Mechanistic analysis revealed that V9302 inhibited autophagy by impairing lysosomal activity independent of glutamine deprivation, likely because of its physiochemical properties, thereby preventing IFNGR1 degradation. Moreover, V9302 also increased Glut1 expression through the inhibition of lysosomal pathway-dependent degradation of Glut1 and consequently increased cancer cell glucose uptake, in turn retaining the levels of intracellular alpha-ketoglutarate (α-KG) and ATP, which are involved in maintaining IFN-γ signal transduction in cancer cells. In support of these findings, targeting lysosomal activity with chloroquine (CQ) also increased IFNGR1 expression and the IFN-γ-driven response in cancer cells. The administration of CQ increased the sensitivity of ASCT2-deficient tumors to anti-PD-L1 therapy. Glutamine deprivation per se leads to resistance to immunotherapy, whereas V9302 treatment results in increased immunotherapy efficacy through impaired lysosomal activity, which is independent of glutamine deprivation.

Background:Distinguishing multiple primary lung adenocarcinomas (MPLAs) from intrapulmonary metastases (IPMs) is essential for accurate staging and treatment planning. However, existing histologic and molecular criteria remain limited in diagnostic accuracy. Spread through air spaces (STAS) has been recognized as a marker of tumor aggressiveness, but its role in differentiating MPLA from IPM remains unclear. This study aimed to assess whether STAS can serve as a supportive marker to differentiate IPM from MPLA under both histologic and molecular frameworks. Methods:We retrospectively enrolled 170 patients who were preoperatively diagnosed with MPLA and underwent surgical resection of multiple lung lesions. Clinical, histopathologic, and molecular data-including broad-panel next-generation sequencing (NGS) results [e.g., epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS), tumor protein p53 (TP53), among others]-were collected. Tumors were classified as MPLA or IPM using histologic criteria alone and a combined histologic-molecular algorithm. The presence and quantity of STAS were evaluated and analyzed as potential predictors of IPM. Results:STAS was more frequent in the IPM group across both classification methods and was an independent predictor of IPM. Driver gene mutations (e.g., EGFR, KRAS) differed significantly between MPLA and IPM. The 83.5% concordance between histologic and combined classifications suggests potential bias in histology alone. In resource-limited settings, STAS may offer a cost-effective adjunct to support IPM diagnosis when molecular data are unavailable. Conclusions:STAS is associated with IPM and may serve as a supportive diagnostic marker when distinguishing IPM from MPLA. In resource-limited settings where molecular testing is not always available, STAS may offer a practical, cost-effective histologic adjunct to guide clinical decision-making.

Lung cancer remains the leading cause of cancer-related mortality worldwide, with limited treatment efficacy and frequent resistance to conventional therapies. Recent advances have uncovered the critical influence of the human microbiota—complex communities of bacteria, viruses, fungi, and other microorganisms—on lung cancer pathogenesis and therapeutic responses. This review synthesizes current knowledge on the compositional and functional roles of microbiota across multiple body sites, including the gut, lung, tumor microenvironment, circulation, and oral cavity, highlighting their contributions to tumor initiation, progression, metastasis, and immune regulation. We emphasize the bidirectional communication between microbial metabolites and host immune pathways, particularly the gut–lung axis, which modulates systemic and local antitumor immunity. Importantly, microbiota composition has been linked to differential responses and toxicities in chemotherapy, radiotherapy, targeted therapy, and immune checkpoint blockade. Microbiota-targeted interventions, such as probiotics, fecal microbiota transplantation, and selective antibiotics, show promising potential to enhance treatment efficacy and mitigate adverse effects. However, challenges remain in clinical translation due to interindividual microbiome variability, mechanistic complexities, and limited longitudinal data. Future research integrating multi-omics, microbial functional profiling, and controlled clinical trials is essential to harness the microbiome as a precision medicine tool in lung cancer management. This review provides a comprehensive overview of the emerging role of microbiota in lung cancer development and therapy, offering new perspectives for innovative therapeutic strategies.

Abstract Background IL-15 plays a vital role in enhancing NK cell- and T-cell-mediated antitumor immune responses; however, the direct effect of IL-15 on tumor cells has not been fully elucidated. Herein, we investigated the effect of IL-15 on lung adenocarcinoma cells. Methods Silencing and overexpression techniques were used to modify endogenous IL-15 expression in tumor cells. Transwell assays were used to assess tumor cell migration and invasion; a live-cell analysis system was used to evaluate cell motility; cellular morphological changes were quantified by confocal fluorescence microscopy; the molecular mechanisms underlying the effect of IL-15 on tumor cells were analyzed by western blotting; and RhoA and Cdc42 activities were evaluated by a pulldown assay. NCG and C57BL/6 mouse models were used to evaluate the functions of IL-15 in vivo. Results Cancer cell-intrinsic IL-15 promoted cell motility and migration in vitro and metastasis in vivo via activation of the AKT-mTORC1 pathway; however, exogenous IL-15 inhibited cell motility and migration via suppression of the RhoA-MLC2 axis. Mechanistic analysis revealed that both the intracellular and extracellular IL-15-mediated effects required the expression of IL-15Rα by tumor cells. Detailed analyses revealed that the IL-2/IL-15Rβ and IL-2Rγ chains were undetected in the complex formed by intracellular IL-15 and IL-15Rα. However, when exogenous IL-15 engaged tumor cells, a complex containing the IL-15Rα, IL-2/IL-15Rβ, and IL-2Rγ chains was formed, indicating that the differential actions of intracellular and extracellular IL-15 on tumor cells might be caused by their distinctive modes of IL-15 receptor engagement. Using a Lewis lung carcinoma (LLC) metastasis model, we showed that although IL-15 overexpression facilitated the lung metastasis of LLC cells, IL-15-overexpressing LLC tumors were more sensitive to anti-PD-L1 therapy than were IL-15-wild-type LLC tumors via an enhanced antitumor immune response, as evidenced by their increased CD8+ T-cell infiltration compared to that of their counterparts. Conclusions Cancer cell-intrinsic IL-15 and exogenous IL-15 differentially regulate cell motility and migration. Thus, cancer cell-intrinsic IL-15 acts as a double-edged sword in tumor progression. Additionally, high levels of IL-15 expressed by tumor cells might improve the responsiveness of tumors to immunotherapies.

Abstract IFNγ-mediated signaling in tumor cells can induce immunosuppressive responses and cause tumor resistance to immunotherapy. Blocking TGFβ promotes T lymphocyte infiltration and turns immunologically cold tumors into hot tumors, thereby improving the efficacy of immunotherapy. Several studies have shown that TGFβ inhibits IFNγ signaling in immune cells. We thus sought to determine whether TGFβ affects IFNγ signaling in tumor cells and plays a role in the development of acquired resistance to immunotherapy. TGFβ stimulation of tumor cells increased SHP1 phosphatase activity in an AKT–Smad3-dependent manner, decreased IFNγ-mediated tyrosine phosphorylation of JAK1/2 and STAT1, and suppressed the expression of STAT1-dependent immune evasion–related molecules, e.g., PD-L1, IDO1, herpes virus entry mediator (HVEM), and galectin-9 (Gal-9). In a lung cancer mouse model, dual blockade of TGFβ and PD-L1 led to superior antitumor activity and prolonged survival compared with anti–PD-L1 therapy alone. However, prolonged combined treatment resulted in tumor resistance to immunotherapy and increased expression of PD-L1, IDO1, HVEM, and Gal-9. Interestingly, after initial anti–PD-L1 monotherapy, dual TGFβ and PD-L1 blockade promoted both immune evasion gene expression and tumor growth compared with that in tumors treated with continuous PD-L1 monotherapy. Alternatively, treatment with JAK1/2 inhibitor following initial anti–PD-L1 therapy effectively suppressed tumor growth and downregulated immune evasion gene expression in tumors, indicating the involvement of IFNγ signaling in immunotherapy resistance development. These results demonstrate an unappreciated effect of TGFβ on the development of IFNγ-mediated tumor resistance to immunotherapy. Significance: Blocking TGFβ facilitates IFNγ-mediated resistance to anti–PD-L1 therapy due to the role of TGFβ in inhibiting IFNγ-induced immunoevasion by increasing SHP1 phosphatase activity in tumor cells.

Early detection of skin cancer is very important and can prevent some skin cancers, such as focal cell carcinoma and melanoma. Although there are several reasons that have bad impacts on the detection precision. Recently, the utilization of image processing and machine vision in medical applications is increasing. In this paper, a new image processing based method has been proposed for the early detection of skin cancer. The method utilizes an optimal Convolutional neural network (CNN) for this purpose. In this paper, improved whale optimization algorithm is utilized for optimizing the CNN. For evaluation of the proposed method, it is compared with some different methods on two different datasets. Simulation results show that the proposed method has superiority toward the other compared methods.

BACKGROUND:The incidence rates of early-stage non-small cell lung cancer (NSCLC) are now increasing, and therapies such as thermal ablation have shown potential therapeutic promise. This study aimed to determine the influence of different surgical methods on overall survival (OS) and cancer-specific survival (CSS) in patients with stage I NSCLC. METHODS:Patients diagnosed with stage I NSCLC who had received thermal ablation or wedge resection between 2004 and 2014 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was performed according to the surgical method. Kaplan-Meier curves and a Cox proportional hazard model were used to evaluate OS and CSS. RESULTS:In all, 4,372 patients with stage I NSCLC were included. Before PSM, the respective 3- and 5-year OS rates were 68.9 and 52.7% in the wedge resection group and 68.5 and 47.8% in the thermal ablation group (p < 0.0001); the corresponding CSS rates were 79.1 and 69.4% and 62.6 and 46.0% (p < 0.0001). After PSM, survival analysis showed that wedge resection had better OS (44.5% vs. 30.1%, p = 0.033) and CSS (63.5% vs. 46%, p = 0.038) than thermal ablation. After PSM, Cox regression showed that treatment was not associated with OS or CSS. For patients aged >75 years, thermal ablation showed similar OS and CSS as wedge resection (OS: 30.6% vs. 41.7%, p = 0.470; CSS: 46.4% vs. 64.1%, p = 0.100). After PSM, thermal ablation still had OS (30.6% vs. 41.0%, p = 0.470) and CSS (46.4% vs. 59.8%, p = 0.100) comparable to wedge resection. CONCLUSION:For patients with stage I NSCLC who are unfit for lobectomy, thermal ablation could be a potential therapeutic option, especially for those >75 years old.

目的 分析2019新型冠状病毒肺炎(COVID-19)治愈出院患者的临床特征.方法 选取2020年2月3日至2月22日于华中科技大学同济医学院附属同济医院治愈出院的76例COVID-19患者为研究对象,其中轻症组42例,重症组34例.对比分析2组患者的临床症状、实验室检查、影像学资料间的差异及其与病情严重程度的关系.结果 76例患者的平均年龄为(53.3±15.1)岁.男性39例,女性37例,其中男性较女性发生重症肺炎的比例更高[61.5％(24/39)vs.27.0％(10/37),P=0.003].重症组中合并高血压的比例更高(P<0.05).重症组患者的发热比例(100.0％)高于轻症组(73.8％)(P<0.01).重症组CT提示双肺弥漫感染的比例(95.2％)高于轻症组(73.5％)(P<0.05).重症患者的白细胞计数平均值[(6.19±3.22)×109/L]较轻症患者[(4.90±1.57)×109/L]高(P<0.05).重症患者的超敏C反应蛋白(hsCRP)、铁蛋白、D-D二聚体、乳酸脱氢酶(LDH)、IL-2R、IL-6、IL-10、TNF-α水平明显高于轻症患者(均P<0.01).ROC曲线分析提示,IL-2R预测患者疾病严重程度的价值最高,其曲线下面积(AUC)为0.908,灵敏度为91.7％,特异度为82.4％.结论 男性、合并基础疾病、发热、CT提示双肺感染是COVID-19发展为重症的高危因素,而hsCRP、铁蛋白、D-D二聚体、LDH、IL-2R等指标有助于预测COVID-19病情的进展,其中IL-2R预测效果最佳.

男,53岁,胸部隐痛不适1个月余.无呼吸困难、心慌、胸闷、咳嗽、咳痰、四肢乏力等不适.无慢性基础疾病史,体格检查未见明显异常.既往体健.入院查心电图、甲状腺B超及甲状腺功能(TSH、fT3、fT4)均未见明显异常.胸部增强CT及MRI检查提示:左心房上方,升主动脉后方见一大小约53 mm× 36mm的不规则混杂密度肿块,考虑心包内肿瘤(图1,图2).然而,心脏彩超检查显示此肿块并未造成右心室流出道受阻以及肺动脉受压,心脏内未见结构异常.为进一步的临床及病理诊断,完善术前检查后,于2015年9月1日在全麻下行右后外侧切口开胸心包内肿瘤切除术,切开心包,见肿块位于升主动脉后方,左心房上方,大小约60 mm×36 mm,包膜完整,质韧硬,与升主动脉外膜粘连,与左心房无明显粘连,5ml注射器穿刺肿瘤无液体抽出,排除血管瘤可能,逐步分离粘连,完整切除肿瘤.

Background/Aims: KRas is usually mutated in non-small cell lung cancer (NSCLC). The mutated KRas gene is a negative prognostic indicator that promotes tumor proliferation, metastasis, and drug resistance in NSCLC, and thus has become a target for cancer therapy. This study is focused on the effects of the microRNA (miR)-202/KRas axis in regulating chemosensitivity in NSCLC. Methods: Quantitative reverse transcriptase real-time PCR analysis was performed to examine the expression of miR-202. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays were performed to evaluate the sensitivity of cisplatin against NSCLC cells. The miR-202/KRas axis was confirmed by western blot and luciferase reporter assays. Cell apoptosis was measured by flow cytometry. KRas expression, MEK1/2 and ERK1/2 phosphorylation, and activation of caspase-9 and caspase-3 were detected by western blot. Results: A significant decrease in miR-202 expression was observed in NSCLC cells both in vivo and in vitro. In addition, miR-202 expression was associated with drug resistance. Recovery of miR-202 expression levels was found to increase the sensitivity of both NCI-H441 and A549 NSCLC cells to cisplatin treatment. Mechanically, as the Ras/mitogen-activated protein kinase (MAPK) pathway was aberrantly activated in NCI-H441 and A549 NSCLC cells, the overexpression of miR-202 was found to inhibit the Ras/MAPK pathway by targeting the KRas gene. As a result, increased miR-202 expression expanded apoptosis signaling induced by cisplatin in NSCLC cells. Conclusion: The miR-202/KRas axis controlled the chemosensitivity of NSCLC by mediating the Ras/MAPK pathway. Thus, the combination of platinum-based drugs with miR-202 may represent a novel strategy to enhance the anti-tumor effect against NSCLC.

目的:探讨微信Webquest教学模式在胸外科临床教学中的应用.方法:选取武汉市某大学附属医院2011级胸外科硕士研究生以及2013级八年制学生共74人,随机分为微信Webquest教学组和传统教学组进行胸外科临床教学,结课时采用结课考试、问卷调查等方式评价教学效果.结果:Webquest教学组与传统教学组学生教学背景无差异;结课考试中Webquest教学组成绩显著优于传统教学组(87.78±.2.405 VS 81.92±3.475,P＜0.05);Webquest教学组中82.4％的学生喜欢该教学模式,89.2％的学生认为该教学模式使掌握知识的程度得以提高,75.7％的学生对该教学模式满意.结论:基于微信的Webquest教学模式不仅利用了微信平台的沟通实时性,还具备Webquest教学模式的学习自主性优势,教学效果优于传统教学模式.

目的:食管癌术前评估对淋巴结的影像学检查是很有临床意义的,特别是颈部淋巴结的检查.传统检查方式为颈部淋巴结超声(EU)和对应部位的CT,为了提高颈部淋巴结的检查效率,往往会同时进行上述两种检查.而PET/CT在评估术前分期上优于CT或PET,那么PET/CT的价值有多大?另外,已经行过PET/CT的病患是否还有需要行颈部超声的必要?颈部超声对于PET/CT在术前评估上是否存在附加价值,这将是我们研究的目的.方法:收集2012年—2014年54例食管癌病患资料,均行PET/CT及颈部超声检查评估颈部淋巴结情况.其中52例均行手术治疗.颈部淋巴结穿刺活检(FNA)或行颈部淋巴结活检术,通过细胞学及病理学验证.结果:54例病患中20例病患术前颈部超声及PET/CT均提示无明显异常,8例颈部超声及PET/CT均提示淋巴结转移可能(术后病检提示6例为恶性,2例为良性),23例颈部超声提示淋巴结转移可能但PET/CT未提示异常(其中术后病检提示4例为恶性,19例为良性),3例PET/CT提示淋巴结转移可能但颈部超声未提示异常.结论:本研究中PET/CT对食管癌淋巴结转移的特异性较高,但在敏感性及准确性上较低,而对于术前已经行PET/CT并提示颈部淋巴结无明显转移的情况下,再行颈部淋巴结超声是没有必要的,然而在PET/CT提示颈部淋巴结转移时,即使颈部超声未提示转移可能的情况下,仍然建议行颈部淋巴结切除术以排除假阳性.

BACKGROUND AND OBJECTIVE:Despite undergoing curative resection, the 5-year survival rate for stage III non-small cell lung cancer (NSCLC) patients is less than 25%. There is a need for biomarkers for prediction of survival and guiding individual therapy. MiR-155 is one of most commonly upregulated miRNAs in malignancies, and regulates multiple pro-oncogenic pathways. We aimed to investigate the prognostic impact of miR-155 in resected stage III NSCLC patients.METHODS:Tumor formalin-fixed, paraffin-embedded (FFPE) from 162 resected stage III NSCLC patients were collected. Total RNA including miRNA was extracted, and qRT-PCR was used to determine the expression of miR-155.RESULTS:Spearman rank correlation test showed a positive correlation between miR-155 expression and nodal status (r=0.169, P=0.032). MiR-155 expression had a significant prognostic impact in the total cohort (P<0.001), in squamous cell carcinomas (P=0.002) and in adenocarcinomas (P=0.003). In N0-1 subgroup, miR-155 expression did not have a significant prognostic on overall survival in univariate analysis (P=0.319). In N2 subgroup, miR-155 had a negative prognostic effect on OS in univariate analysis (P<0.001). Cox regression analysis revealed that miR-155 expression was unfavorable prognostic factors of OS (RR=2.311, 95%CI: 1.479-3.611, P<0.001).CONCLUSIONS:High expression of miR-155 represents a valuable marker of poor clinical outcomes in patients with stage III NSCLC.