Background The mechanisms underlying the early progression of lung adenocarcinoma (LUAD) remain unclear, and the interaction between circular RNAs (circRNAs) and the immune microenvironment lacks systematic investigation. While circHIF1A has been reported to possess oncogenic functions in colorectal and breast cancers, its specific role in LUAD and whether it regulates the tumor microenvironment via a competing endogenous RNA (ceRNA) mechanism remain to be elucidated. Methods Tumor and paired paratumorous normal tissues were collected from 80 LUAD patients. Using A549 and H1299 cell lines and the nude mouse subcutaneous xenograft model, we systematically analyzed the expression characteristics, biological functions, and molecular mechanisms of circHIF1A. Results circHIF1A was significantly upregulated in LUAD, and its expression level was positively correlated with advanced TNM stage and poor patient prognosis. Mechanistically, circHIF1A functions as the ceRNA to specifically sponge miR-486-5p, thereby relieving the transcriptional repression of its downstream target gene, GRHL2, forming the circHIF1A/miR-486-5p/GRHL2 regulatory axis. This axis not only directly enhances LUAD cell proliferation, stemness maintenance, migration, and invasion but also induces macrophage M2 polarization by promoting IL-10 secretion, thereby establishing an immunosuppressive microenvironment. In vivo experiments confirmed that intervening in the circHIF1A/miR-486-5p/GRHL2 axis significantly inhibits LUAD tumor growth. Conclusion circHIF1A regulates malignant phenotypes of LUAD cells and tumor microenvironment remodeling through a ceRNA network. The mediated circHIF1A/miR-486-5p/GRHL2 axis provides a novel molecular biomarker for LUAD prognostic assessment and represents a potential target for therapeutic intervention.

The efficacy of neoantigen-reactive T cells (NRT) therapy in solid tumors, encompassing aspects such as infiltration, recognition, cytotoxicity, and enduring persistence, is notably influenced by the immunological microenvironment. This study endeavors to investigate whether the co-administration of pemetrexed and cisplatin augments the therapeutic efficacy of NRT therapy in lung cancer. Neoantigens were predicted using a comprehensive analysis of mutation data from Lewis lung carcinoma cells and mouse tail tissues. The immunogenicity of NRT cells was assessed through flow cytometry and IFN-γ ELISpot assays. A mouse model of NSCLC was used to investigate the anti-tumor effects of NRT combined with chemotherapy. The combination of NRT cells and chemotherapy significantly inhibited tumor growth in a mouse model, increased CD3+/CD137+ T cells to promote IFN-γ secretion from NRT cells, and up-regulated the levels of inflammatory cytokine proteins including IFN-γ, TNF, IL-6 and IL-10. Immunofluorescence analysis confirmed increased T-cell infiltration in tumor tissues without adverse effects on vital organs. In addition, transcriptome analyses indicated that the tumor microenvironment was altered to favor M1-like macrophages with an increased M1/M2 ratio, creating a pro-inflammatory environment. The integration of NRT with frontline chemotherapy for lung cancer could yield profoundly ideal therapeutic outcomes.

The rapid advancement of flexible electronics has driven innovation in wearable respiratory monitoring devices, yet challenges remain in achieving medical-grade precision for quantitative pulmonary function assessment. This study integrates water molecule-responsive flexible sensing technology, wearable devices, and a cloud-based intelligent analysis platform to develop the first medical-grade flexible respiratory sensing system (SFMS). By leveraging the synergistic effect of bionic microcavity differential pressure sensing and humidity-sensitive interfaces, combined with a pressure difference-flux dynamic model, the system enables simultaneous resolution of peak expiratory flow (PEF) and forced vital capacity (FVC), accurately deriving core pulmonary function indicators such as FEV1/FVC. Clinical validation across 454 cases demonstrated high consistency with gold-standard spirometry (intraclass correlation coefficient [ICC] = 0.93–0.97), with 89.7% sensitivity and 92.3% specificity in differentiating chronic obstructive pulmonary disease (COPD) from asthma. Technologically, this work pioneers medical-grade flexible sensing for quantitative pulmonary testing, eliminating dependence on specialized operators through an embedded edge computing architecture that supports real-time cloud data interaction. The system establishes disease-specific profiles through multi-parametric physiological correlation analysis. Practically, its low cost, portability, and user-friendly operation facilitate seamless integration into primary healthcare and home health management, providing technical tools for hierarchical diagnosis and treatment of chronic respiratory diseases. Aligned with WHO's Respiratory Health Action Plan, this innovation enables universal monitoring to advance early screening and long-term disease management. With significant clinical translation potential, it offers a groundbreaking solution for building a comprehensive prevention and control framework for respiratory diseases.

Purpose:Our aim was to illustrate mutational characteristic in non-smoking lung adenocarcinoma (LUAD) and to explore its relationship with clinical factors. Materials and Methods:We included 86 non-smokers with LUAD and downloaded the clinical information, whole exon sequencing (WES), and RNA sequencing (RNA-seq) data from cBioPortal and TCGA website. NMF algorithm, "SomaticSignatures", and "DeconstructSigs" were used to re-construct and infer new mutational signature. The similarity between COSMIC and re-constructed mutational signature was measured by cosine similarity. The enrichment status of signaling pathways was derived by GSEA. "pRRophetic" package was used to predict the sensitivity of adjuvant drug for cancer treatments. Results:The most frequent driver genes in non-smoking LUAD were EGFR (59% in cBioPortal cohort, 68% in Fujian non-smoking LUAD cohort). We identified three new mutation signatures of LUAD in non-smokers and identified S2 as the most enriched signature in these non-smokers with LUAD. In cBioPortal and Fujian non-smoking LUAD cohort, the proportion of S2 was higher in females (p<0.05) and patients with TMB (p<0.01). Similar results were observed in non-smoking TCGA-LUAD cohort (Pfemale=0.0013, PTMB<0.001). OXIDATIVE_PHOSPHORYLATION signaling pathway were most enriched in S2-enriched group (NES= 1.63). S2-enriched group had higher mutation rate of EGFR (p=0.003) and more drug sensitivity to metformin (p=0.035). Conclusion:We identified a new mutational signature (S2) which is most enriched in LUAD in non-smokers and related to female and low-TMB. S2 mutational signature may help revealed female-related mutagenesis mechanisms and develop strategies for therapeutic of never-smoker lung adenocarcinoma.

Flexible sensing technologies for dynamic respiratory monitoring face critical limitations in environmental robustness and signal resolution accuracy. To address these challenges, a humidity-sensitive dielectric material was developed through intermolecular force modulation, synergistically integrated with a hermetically sealed digital mask to establish a medical-grade respiratory monitoring platform. A novel quantitative respiratory waveform analytical model was proposed, transcending conventional flexible sensors’ capability of merely tracking respiratory rhythms to enable precise quantification of pulmonary function parameters, including peak expiratory flow (PEF) and forced vital capacity (FVC). Leveraging a Darcy’s law-based porous media gas dynamics model, a linear response mechanism was identified between sensing signals and airflow/volume parameters (R2 > 0.995). Time–frequency characteristics of respiratory waveforms were extracted via synchrosqueezed wavelet transforms, revealing robust correlations between spectral signatures and physical activity intensity. Clinical validation in chronic obstructive pulmonary disease (COPD) cohorts demonstrated the system’s efficacy in detecting characteristic patterns of airway obstruction and diminished pulmonary elasticity, enabling early-stage diagnostics. Furthermore, a 1-dimensional convolutional neural network (1D-CNN) achieved high-accuracy cough event recognition (95.24

The rapid monitoring devices,but there are still challenges in achieving medical-grade accuracy in quantitative pulmonary function assessment.This study integrates water molecule-responsive flexible sensing technology,wearable devices,and cloud-based intelligent analysis platform to develop the first medical-grade flexible respiratory sensing system(SFMS).By utilizing the synergistic effect of bionic microcavity differential pressure sensing and humidity-sensitive interfaces,combined with a pressure difference-flux dynamic model,the system can simultaneously resolve peak expiratory flow(PEF)and forced vital capacity(FVC),accurately obtaining core pulmonary function indicators such as FEV1/FVC.Clinical validation of 454 cases demonstrates high consistency with gold-standard spirometry(intraclass correlation coefficient[ICC]=0.93-0.97),with a sensitivity of 89.7％and specificity of 92.3％in differentiating chronic obstructive pulmonary disease(COPD)from asthma.Technologically,this work pioneers a medical-grade flexible sensor for quantitative pulmonary testing,and eliminates dependence on specialized operators through an embedded edge computing architecture that supports real-time cloud data interaction.The system establishes disease-specific profiles through multi-parametric physiological correlation analysis.Practically,its low cost,portability,and user-friendly operation facilitate seamless integration into primary healthcare and home health management,providing technical tools for hierarchical diagnosis and treatment of chronic respiratory diseases.Aligned with WHO's Respiratory Health Action Plan,this innovation enables universal monitoring to advance early screening and long-term disease management.As this innovation possesses significant clinical translation potential,it provides a groundbreaking solution for building a comprehensive prevention and control framework for respiratory diseases.

Emerging evidence suggests that tumor-specific neoantigens are ideal targets for cancer immunotherapy. However, how to predict tumor neoantigens based on translatome data remains obscure. Through the extraction of ribosome-nascent chain complexes (RNCs) from LLC cells, followed by RNC-mRNA extraction, RNC-mRNA sequencing, and comprehensive bioinformatic analysis, we successfully identified proteins undergoing translatome and exhibiting mutations in the cells. Subsequently, novel antigens identification was analyzed by the interaction between their high affinity and the Major Histocompatibility Complex (MHC). Neoantigens immunogenicity was analyzed by enzyme-linked immunospot assay (ELISpot). Finally, in vivo experiments in mice were conducted to evaluate the antitumor effects of translatome-derived neoantigen peptides on lung cancer. The results showed that ten neoantigen peptides were identified and synthesized by translatome data from LLC cells; 8 out of the 10 neoantigens had strong immunogenicity. The neoantigen peptide vaccine group exhibited significant tumor growth inhibition effect. In conclusion, neoantigen peptide vaccine derived from the translatome of lung cancer exhibited significant tumor growth inhibition effect.

Traditional lung function detectors are based on measuring the changes in airflow and pressure during expiration and inspiration to evaluate the respiratory function of the subject. These techniques are mainly based on mechanical differential pressure sensors or turbine sensors which evaluate the lung function of the subject by measuring the ability of the subject to blow and inhale and determine their lung function parameters, including peak expiratory flow (PEF) and forced vital capacity (FVC). In this study, we present a wearable respiratory function testing system called the wearable respiratory spectrometer, which is developed based on dynamic humidity sensing technology. By exploring the principles and quantitative design of respiratory detection and conducting simulations of humidity sensors, we investigate the comprehensive characteristics of the system. According to Darcy’s law, the gas flow measured by the wearable respiratory spectrometer is directly proportional to the pressure difference inside and outside the device, showing that the system follows the differential pressure sensing principle. According to this basis and combining the structural characteristics of the system, we establish a quantitative relationship among PEF, FVC, and the changes in sensor electrical signals.The experimental results validate a linear positive correlation between the maximum rate of relative humidity change inside the spectrometer and PEF. Additionally, the results of simulated moisture volume experiments of the spectrometer show that in the measurement range from 180 to 840 L/min, the indication error of PEF is less than 10%, the adjacent test error is less than 5%, and the frequency response test error is less than 12%, which meet the industry standards for peak expiratory flow meters. Moreover, we compare the spectrometer with traditional portable lung function testing devices in simulated moisture volume experiments at different PEFs (300 to 720 L/min) and FVCs (3 to 6 L) . The results demonstrate that the average indication error of measured PEF and FVC by the spectrometer are about 0.35% and 0.23%, respectively, both are much lower than those of the portable lung function testing devices, thus fully verifying the accuracy and reliability of this system for real-time lung function assessment. Importantly, under simulated free-breathing conditions (PEF from 12 to 24 L/min, FVC from 0.5 to 0.7 L), the changes in the electrical signals of the spectrometer maintain a linear relationship with the moisture volume. Therefore, the wearable respiratory spectrometer can provide the long-term, free, dynamic, and quantitative monitoring of natural and weak nasal breathing. The measured respiratory spectra of subjects have great potential in real-time monitoring of lung function and remote monitoring of respiratory system diseases.

BACKGROUND:Metastasis and disease refractoriness remain as major challenges for non-small cell lung cancer (NSCLC) treatment and understanding the underlying molecular mechanisms is of scientific and clinical value. Therefore, in this study, we aimed to explore the effects of circMED13L_012 on the proliferation, migration, invasion and drug-resistance of NSCLC tumor cells. METHODS:In this study, we utilized clinical samples and NSCLC cell lines to explore the association between circMED13L_012 expressions and tumor cell metastasis and chemo resistance. CCK8 and transwell assay were conducted to explore the impact of circMED13_012 on NSCLC tumor proliferation and migrative capabilities. Dual-luciferase reporter gene assay was conducted to validate the circMED13L_012 interaction network. RESULTS:Our results demonstrated that circMED13L_012 exhibited significantly elevated average level in our clinical samples of NSCLC, compared with normal tissues. circMED13L_012 level was positively correlated with disease stage and metastatic status. Increased circMED13L_012 expression was associated with the enhanced migration, proliferation and chemo resistance of NSCLC cell lines. Further experiments indicated that circMED13L_012 promoted malignant behavior of NSCLC tumor cells by targeting MAPK8 through modulation miR-433-3p expression. CONCLUSIONS:Our study for the first time demonstrated that circMED13L_012-miR-433-3p-MAPK8 axis played important role for NSCLC pathogenesis, which could be potential therapeutic target for the development of future NSCLC treatment.

Chemo-resistance and refractoriness remain challenges for Non-small cell lung cancer (NSCLC) patients and the underlying molecular mechanisms haven't been fully explained. In this study, we investigated the influence of circUBAP2 on the NSCLC tumor cells. This study might provide novel therapeutic targets for NSCLC treatment. Clinical samples and NSCLC cell lines were used to investigate circUBAP2 expressions and their impact on tumor cell chemo-resistance. CCK8 and transwell assays were conducted to explore the differences of NSCLC tumor proliferation and migration capabilities affected by circUBAP2. Dual-luciferase reporter gene assay was performed to explore the detailed molecular mechanism of circUBAP2 regulation network. circUBAP2 exhibited significantly elevated average level in our clinical samples of NSCLC, compared with normal tissues. CircUBAP2 level was positively correlated with disease stage and metastatic status. circUBAP2 significantly enhanced the migration, proliferation and chemo-resistance of NSCLC cell lines. Further experiments indicated that circUBAP2 promoted malignant biological behavior of NSCLC tumor cells by targeting KLF4 through modulating miR-3182 expression. Our study demonstrated for the first time that circUBAP2 played an important role exacerbating malignant capabilities of NSCLC. circUBAP2-miR3182-KLF4 regulative network demonstrated in this study could be a novel therapeutic target for future NSCLC treatment.

Long noncoding RNAs (lncRNAs) have been identified to be critical regulator for various human diseases and emerging evidence illustrate the essential function of lncRNAs in the non-small cell lung cancer (NSCLC). Here, our research team tried to identify the roles of lncRNA ferritin heavy chain 1 pseudogene 3 (FTH1P3) in the NSCLC, as well as its molecular mechanism. LncRNA microarray analysis revealed that ferritin heavy chain 1 pseudogene 3 (FTH1P3) was up-regulated in the gefitinib-resistant cells (PC9/GR). Clinically, lncRNA FTH1P3 high-expression was closely correlated with NSCLC patients' unfavorable prognosis. Gain and loss of functional experiments revealed that FTH1P3 promoted the proliferation and invasion of NSCLC cells in vitro, and FTH1P3 knockdown repressed the tumor growth in vivo. Mechanistically, transcription factor E2F1 accelerated the transcription of FTH1P3. RNA immunoprecipitation and chromatin immunoprecipitation experiments showed that FTH1P3 can recruit lysine-specific demethylase 1 (LSD1) and epigenetically repress the TIMP3, thereby accelerating the tumorigenesis of NSCLC. In summary, these findings suggest that FTH1P3 plays a critical role in the gefitinib resistance and progression of NSCLC, providing a potential novel prognostic marker for NSCLC.

目的 探讨气道内喷洒利多卡因联合含服达克罗宁胶浆在支气管镜诊疗中的安全性和有效性.方法 将2019年9月至2019年12月在福建省立医院接受支气管镜检查的100例患者,按随机数字表法分为两组:观察组50例,采用气道内喷洒利多卡因+含服达克罗宁胶浆局部麻醉;对照组50例,采用气道内滴注利多卡因+含服达克罗宁胶浆局部麻醉.记录各组在检查前、检查中(过声门后1 min)、检查结束时的心率、血压和血氧饱和度(SpO2)的变化,观察不良反应的发生情况,比较两组患者利多卡因用量的差别,并于检查后用视觉模拟评分(VAS)分别对患者和检查医师进行支气管镜检查的耐受性和满意度的评估.结果 观察组利多卡因用量明显低于对照组(P<0.01),差异具有统计学意义.两组患者在各时点的心率、收缩压、舒张压、血氧饱和度差异无统计学意义.在不良反应的发生率上,包括重度高血压(收缩压>180 mmHg)、气管痉挛、低氧血症(SpO2<90％)等,两组患者差异无统计学意义.在检查后患者评估显示,观察组患者的咳嗽VAS评分显著低于对照组(P<0.05),而疼痛VAS评分两组差异无统计学意义(P>0.05);检查医师的评估显示,观察组患者的术中咳嗽和通过声门难易程度的VAS评分均显著优于对照组(P<0.05).结论 在局麻支气管镜检查中,气道内喷洒利多卡因联合含服达克罗宁胶浆可以减少利多卡因用量,并提高患者在检查过程中的耐受性和满意度.该方法 安全可靠,有推广价值.

Objective To discuss the effect and mechanism of cytochrome P450 epoxygenase 2J2 (CYP2J2) overexpression on lung ischemia-reperfusion injury in rats.Methods CYP2J2 gene was transfected by pcDNA3.1 plasmid into Sprague Dawley (SD) rats,which increased the expression of CYP2J2 protein in lung tissue and the circulating level of corresponding metabolites.Then,a rat model of acute lung ischemia-reperfusion injury was structured by clamping the left lung hilar for 1 hour,followed by reperfusion for 2 hours.Animals were randomly divided into 5 groups:Blank (blank control group),Sham (sham group),IR (lung ischemia/reperfusion group),IR + GFP (lung ischemia/reperfusion and pcDNA3.1-GFP gene transfection group),and IR + CYP2J2 (lung ischemia/reperfusion and pcDNA3.1-CYP2J2 gene transfection group).Animals were sacrificed at the end of the experiment to evaluate lung injury and explore the mechanism.Results Lung ischemia-reperfusion led to acute lung injury,including increased lung weight/body weight(LW/BW) and lung wet/dry ratios (W/D),increased protein concentration in bronchoalveolar lavage fluid(BALF),increased level of inflammatory mediators in serum (including IL-1β,IL-8,TNF-α,sP-selectin,sE-selectin),and decreased level of IL-10 (a anti-inflammatory mediator).However,these effects were significantly relieved by CYP2J2 gene delivery [LW/BW:(4.720 ± 0.756) × 10-3 vs.(4.761 ± 0.905) × 10-3 vs.(7.331 ± 0.484) × 10-3 vs.(7.434±0.702) ×10-3 vs.(6.088 ±0.405) ×10-3,P＜0.01;W/D:3.762 ±0.537 vs.4.084± 0.517 vs.7.726 ±0.895 vs.7.941 ± 1.015 vs.5.633 ±0.543,P＜0.01;BALF:(664.827 ± 219.547) mg/L vs.(637.381 ± 83.860) mg/L vs.(2 138.503 ± 81.156) mg/L vs.(2 130.880 ± 473.470) mg/Lvs.(1208.030±256.255) mg/L,P＜0.01;IL-1β:(28.100±2.930) ng/L vs.(30.076±5.550) ng/L vs.(68.532 ±5.587) ng/L vs.(66.935 ±6.469) ng/L vs.(51.450± 6.300) ng/L,P＜0.01;IL-8:(38.949 ±6.441) ng/L vs.(45.212 ±5.814) ng/L vs.(64.661 ± 11.187) ng/L vs.(64.136 ±8.634) ng/L vs.(52.702 ±6.392) ng/L,P ＜0.01;TNF-α:(45.359 ± 6.531) ng/L vs.(98.797 ±6.610) ng/L vs.(188.368 ± 16.373) ng/L vs.(189.677 ± 19.264) ng/L vs.(121.861 ± 10.994) ng/L,P ＜ 0.01;sP-selectin:(4.855 ± 3.032) μg/L vs.(16.670 ± 8.177) μg/L vs.(59.428 ± 11.792) μg/L vs.(53.845 ±6.925) μg/L vs.(40.017 ±8.545) μg/L,P＜0.01;sE-selectin:(499.907 ± 151.751) ng/L vs.(985.640 ± 144.445) ng/L vs.(1 826.863 ± 370.931) ng/L vs.(1 684.189 ± 330.473) ng/L vs.(1 313.309± 197.700) ng/L,P＜ 0.01;IL-10:(128.995 ±3.114) ng/L vs.(126.487 ±9.532) ng/L vs.(47.992 ±9.730) ng/L vs.(55.497 ±4.755) ng/L vs.(91.854 ±4.166) ng/L,P ＜0.01].Moreover,isehemia-reperfusion induced activation of nuclear transcription factor kappa B (NF-κB) p65 and degradation of inhibitor of NF-κB (IκBα) in lung tissue,while,these effects were reversed by CYP2J2 overexpression (NF-κB p65:1.000±0.000 vs.1.090±0.078 vs.1.762 ±0.082 vs.1.681 ±0.057 vs.1.296±0.142,P＜0.01;IκBα:1.000 ±0.001 vs.0.904 ±0.060 vs.0.565 ±0.061 vs.0.601 ±0.070 vs.0.743 ±0.044,P ＜ 0.01).Conclusion CYP2J2 overexpression can protect against lung ischemia-reperfusion injury in rats,with a possible mechanism of peroxisome proliferator-activated receptor γ (PPARγ) activation.

Objective To investigate the effect of different cryoablation time on tracheal traumatic granulation formation and its mechanism .Methods A total of 32 rabbits were randomly assigned into four groups ( A-D) .Group A underwent tracheotomy alone .Group B, C and D received intra-tracheal brush rubbing to establish airway granulation model .Group C and D underwent 30 s and 2-minute cryoablation respectively.Tracheal specimens of all groups were collected to examine pathological changes using HE staining.Levels of transforming growth factor beta 1 ( TGF-β1 ) and CD34 in tracheal granulation were evaluated using immunohistochemistry ( IHC ) and real-time quantitative reverse transcription polymerase chain reaction (RT-qCR).Results Tracheal lumens of group A were smooth without granulation .While the growth of granulation and luminal stenosis were most severe in Group B , followed by Group D and C. Submucosa thickness of Group B was largest as compared with other groups (0.20 ±0.07, 0.77 ±0.28, 0.44 ±0.13 and 0.55 ±0.18 mm for Group A to D, respectively.P<0.05).And the submucosa layer of Group C was thinner than Group D (P<0.05).The expression and transcription levels of TGF-β1 of trachea were highest in Group B as detected by IHC and RT-qPCR (P<0.05), followed by Group D and C (IHC:0.48 ±0.01 vs 0.43 ±0.01, P<0.05;RT-qPCR:12.61 ±2.14 vs 2.38 ±0.10, P<0.05).Both protein and mRNA levels of CD34 were highest in Group B as detected by IHC and RT-qPCR (P<0.05).Tracheal mRNA levels of CD34 were more abundant in Group D than Group C (4.92 ±0.90 vs 2.09 ±0.10, P<0.05), while no significant difference was found between groups regarding protein levels measured by IHC . Conclusions Cryoablation could alleviate the hyperplasia of tracheal traumatic granulation , possibly due to the inhibition of TGF-β1 and CD34 expression. The effect of 30 s cryoablation for tracheal traumatic granulation is better.

Objective To explore the effect of CYP2J2 and EETs on lung ischemia-reperfusion injury and the related mech-anism.Methods CYP2J2 was stably transfected into lung tissue of rats.A rat model of lung ischemia-reperfusion injury and a human pulmonary artery endothelial cell(HPAEC)model of hypoxia-reoxygenation were established to observe the effect of CYP2J2 overexpression and EETs on oxidation stress and apoptosis induced by lung ischemia-reperfusion in vivo and in vitro.Results CYP2J2 overexpression significantly inhibited the level of oxidation stress and apoptosis in vivo induced by lung ischemia-reperfusion.Moreover,CYP2J2 gene was successfully transfected into human pulmonary artery endothelial cells,lead-ing to overexpression of CYP2J2 protein.In the HPAEC-based hypoxia-reoxygenation model,exogenous EETs enhanced cell vi-ability,inhibited the production of intracellular reactive oxygen species,mitigated mitochondrial dysfunction and attenuated sev-eral apoptotic related events,including collapse of mitochondrial transmembrane potential,activation of NADPH oxidase,pro-ap-optotic protein and Caspase-3.Conclusion CYP2J2 overexpression and exogenous EETs can protect against lung ischemia-reperfusion injury via anti-oxidative stress and antiapoptosis in vivo and in vitro.These effects may be mediated by PI3K/Akt signaling pathway.

目的:探讨液基细胞学检测技术(liquid-based cytology test,LCT)与支气管镜联合检查在肺癌诊断中的临床应用价值.方法:支气管镜检查联合LCT细胞病理诊断笔者所在医院2017年1-12月收集的肺癌患者131例,与2016年使用传统的直接涂片技术作细胞病理诊断的肺癌患者97例作为对比,进行分型比较,计算检出率.结果:在联合使用LCT技术组,细胞病理报告阳性率为82.4％(108/131),高于传统涂片组的54.6％(53/97),其中中央型肺癌阳性率为90.3％(93/103),高于传统涂片组的56.4％(44/78),差异均有统计学意义(P<0.01).另有31.5％的LCT细胞病理诊断可直接区分肿瘤的病理分型,高于传统涂片组的9.4％.结论:LCT技术支气管镜检查联合应用可以提高肺癌的诊断阳性率,尤其在中央型肺癌的诊断更具优势,且对肿瘤的分型的判断具有辅助意义.

目的 评估多索茶碱联合沙美特罗/氟替卡松在稳定期中重度慢性阻塞性肺疾病(COPD)治疗中的安全性和有效性.方法 将符合GOLD指南诊断标准的75例稳定期的中重度COPD患者随机分成3组,分别接受沙美特罗/氟替卡松(50/250 μg)+多索茶碱(A组)、沙美特罗/氟替卡松(50/500 μg)+维生素B6(B组)、沙美特罗/氟替卡松(50/250μg)+维生素B6(C组)治疗6个月.分别于治疗前、治疗后3、6个月,动态监测患者FEV1、FVC及6 min步行距离的变化.结果 与治疗前相比,3组FEV1、FVC及6 min步行距离得到显著提高(P＜0.05),尤其是A、B组,但组间差异无统计学意义;与治疗后3个月相比,同组患者治疗后6个月的肺功能指标有所下降,但差异无统计学意义(P＞0.05).组间对比显示,A组治疗后6个月FEV1明显优于C组(P＜0.05);不论是治疗后3或6个月,A、B组的FVC、6min步行距离较C组均有所改善,但差异无统计学意义(P＞0.05).结论 稳定期中重度以上COPD患者,在联合使用长效β2受体激动剂和吸入糖皮质激素的基础上,加用多索茶碱安全、有效并可减少吸入糖皮质激素的用量.

Idiopathic pulmonary fibrosis (IPF) is characterized by progressive interstitial fibrosis, and is associated with a fatal outcome. The critical pathological mechanisms underlying IPF are largely unknown; however, accumulating evidence has indicated similarities between IPF and cancer. Therefore, the present study examined the expression levels of the tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in Chinese patients with IPF, using an enzyme‑linked immunosorbent assay. To determine the effects of PTEN on the development of pulmonary fibrosis, PTEN was overexpressed in transforming growth factor (TGF)‑β1‑treated human embryonic lung fibroblasts (HFL‑I cells). The serum levels of PTEN were significantly lower in 42 patients with IPF, as compared with in the healthy controls. In addition, PTEN overexpression enhanced apoptosis, and suppressed basal levels of proliferation and migration in fibroblasts. Notably, PTEN was able to specifically inhibit TGF‑β1‑induced proliferation and migration of the cells. Overexpression of PTEN also suppressed phosphorylation of Akt and Smad3, and decreased the expression levels of numerous proteins with critical roles in TGF‑β1‑induced fibrosis, including α‑smooth muscle actin, matrix metalloproteinase (MMP)‑2 and MMP‑9. These results indicated that PTEN may inhibit TGF‑β1‑mediated myofibroblast differentiation of fibroblasts by attenuating signaling via the phosphatidylinositol 3‑kinase/Akt and TGF‑β/Smad3 pathways.

Objective To investigate serum levels of matrix metalloproteinase (MMP) 1,-2 and -9 in patients with idiopathic pulmonary fibrosis (IPF),and to assess their clinical value.Methods 39 clinically confirmed IPF cases and 36 healthy controls were recruited.A sample of 5 ml peripheral blood was collected from each individual and serum levels of MMP-1,-2 and 9 were detected by the enzyme-linked immunosorbent assay.Forced vital capacity (FVC) and diffusing capacity of carbon monoxide (DLCO) were measured in IPF patients.Serum levels of MMP 1,2 and-9 were compared between the groups.The correlations between serum levels of MMPs and lung function indicators were analyzed.Results The median serum levels of MMP 1,MMP-2 and MMP-9 were higher in the IPF group than in the control group [906.30 (613.50-1139.23) μg/L vs.808.38 (596.59 1249.36) μg/L,9.13 (5.95-11.92) μg/L vs.7.72 (5.28 10.35) μg/L,14.56 (8.24-18.96) μg/L vs.11.38 (8.07-17.14) μg/L,Z=-2.397,-3.564,-4.152,respectively,P=0.017,0.000,0.000].In patients with IPF,the serum level of MMP-2 was negatively correlated with DLCO％ (r=-0.53,P=0.011) and the serum level of MMP-9 had a negative correlation with FVC％ (r=-0.49,P=0.020) and DLCO％ (r=0.58,P=0.005).Conclusions Taken together,serum MMP-1,MMP-2 and MMP-9 levels may help in the clinical diagnosis of IPF.MMP 2 and MMP-9 may be important biomarkers to predict the prognosis of IPF.

BACKGROUND:Cytochrome P450 epoxygenase 2J2 (CYP2J2) metabolizes arachidonic acids to epoxyeicosatrienoic acids (EETs). EETs exert various biological effects, including anti-inflammatory, anti-apoptotic, pro-proliferation, pro-angiogenesis, anti-oxidation, and anti-fibrosis effects. However, little is known about the role of CYP2J2 and EETs in lung ischemia/reperfusion injury. In this study, we examined the effects of exogenous EETs or CYP2J2 overexpression on lung ischemia/reperfusion injury in vivo and in vitro.METHODS AND RESULTS:CYP2J2 gene was stably transfected into rat lungs via pcDNA3.1-CYP2J2 plasmid delivery, resulting in increased EETs levels in the serum and lung. A rat model of lung ischemia/reperfusion injury was developed by clamping the left lung hilum for 1 hour, followed by reperfusion for 2 hours. We found that CYP2J2 overexpression markedly decreased the levels of oxidative stress and cell apoptosis in lung tissues induced by ischemia/reperfusion. Moreover, we observed that exogenous EETs, or CYP2J2 overexpression, enhanced cell viability, decreased intracellular reactive oxygen species (ROS) generation, inhibited mitochondrial dysfunction, and attenuated several apoptotic signaling events in a human pulmonary artery endothelial cells (HPAECs)-based anoxia/reoxygenation model. These apoptotic events included activation of NADPH oxidase, collapse of mitochondrial transmembrane potential, and activation of pro-apoptotic proteins and caspase-3. These effects were mediated, at least partially, by the PI3K/Akt signaling pathway.CONCLUSION:These results reveal that CYP2J2 overexpression and exogenous EETs can protect against oxidative stress and apoptosis following lung ischemia/reperfusion in vivo and in vitro, suggesting that increasing the level of EETs may be a novel promising strategy to prevent and treat lung ischemia/reperfusion injury.