Imaging of lung cancer with molecular beacons delivered by octreotide-modified chitosan nanoparticles / 天津医药

Objective To investigate the identification of octreotide(OCT)modified chitosan(CS)miR-155 molecular beacon nanoparticles(CS-miR-155-MB-OCT)and imaging of lung cancer cells for the early screening of lung cancer.Methods A nude mouse model of lung transplantation tumor was established by injecting A549 lung cancer cells into tail veins to establish lung xenograft models.Cre adenovirus was injected through nasal cavity,and mice were killed at 4,6,8 and 12 weeks after adenovirus injection to establish lung cancer models of atypical hyperplasia,adenoma,carcinoma in situ and adenocarcinoma of lung in LSL K-ras G12D transgenic mice at different pathological stages.Lung tissue samples were taken and observed by HE staining.Immunohistochemistry were used to detect the expression of somatostatin receptor 2(SSTR2).Real-time fluorescence quantitative PCR was used to detect miR-155 expression levels in lung xenograft models and transgenic mice at different stages of lung cancer.Then CS-miR-155-MB and CS-miR-155-MB-OCT were injected via tail vein in lung xenograft models.CS-miR-155-MB-OCT was injected via tail vein in transgenic mice models.The fluorescence signals of lung in nude mice and transgenic mice at different disease stages were imaged by living imaging system.Frozen slices of lung tissue were made.The source of fluorescence signal was detected by laser confocal scanning microscope(CLSM).Results HE staining showed that lung transplantation tumor models and lung cancer models of atypical hyperplasia,adenoma,carcinoma in situ and lung adenocarcinoma at different pathological stages were successfully constructed.Immunohistochemical analysis showed somatostatin receptor 2(SSTR2)was expressed in transplanted lung tumor and tissue at different pathological stages.In transgenic mouse models,the expression of miR-155 was gradually increased as the disease progressed(P＜0.05).In lung xenograft models,the fluorescence signals were significantly higher in the CS-miR-155-MB-OCT group than those of the CS-miR-155-MB group(P＜0.05).In transgenic mouse models,the fluorescence signals gradually increased with the gradual progression of lesions(P＜0.05).After re-imaging the lung tissue,it was found that the fluorescence signal came from lung,and CLSM showed that the fluorescence signal came from cancer cells and some normal alveolar epithelial cells.Conclusion CS-miR-155-MB-OCT can dynamically reflect the occurrence and development of lung cancer according to changes of different fluorescence intensity,thus providing a new technology for the early diagnosis of lung cancer.

Caracterización de pacientes con cáncer de pulmón en un servicio de neumología / Characterization of patients with lung cancer in a pneumology service i: en

Introducción: El cáncer de pulmón es un problema de salud pública a escala mundial y Cuba no está exenta de este. Objetivo: Caracterizar a los pacientes diagnosticados con cáncer de pulmón según variables clínicas, epidemiológicas y morfológicas. Métodos: Se realizó un estudio transversal, descriptivo y retrospectivo de los 145 adultos diagnosticados con cáncer de pulmón en el Servicio de Neumología del Hospital General Docente Dr. Juan Bruno Zayas Alfonso de Santiago de Cuba, desde enero del 2018 hasta diciembre del 2019. A tal efecto, en el procesamiento estadístico se emplearon como medidas de resumen el porcentaje y la media para variables cualitativas y cuantitativas, respectivamente; asimismo, se aplicaron el coeficiente kappa para establecer el grado de concordancia entre datos y la prueba de independencia de la Χ2 para identificar asociación significativa entre los criterios de interés seleccionados (con p<0,05). Resultados: Se obtuvo un predominio del sexo masculino (62,1 %) y el grupo etario de 65-75 años (37,9 %). Respecto a la variedad histológica, resultó más frecuente el carcinoma epidermoide (42,7 %). El pulmón derecho fue el más afectado, específicamente su lóbulo superior (33,8 %); del mismo modo, existieron alteraciones morfológicas, como la infiltración bronquial (100,0 %), la irregularidad y el edema de la mucosa (con 98,5 % en cada caso) y la inflamación con engrosamiento de la pared bronquial (90,3 %). Conclusiones: La determinación de las características clínicas, epidemiológicas y morfológicas relacionadas con el cáncer de pulmón permite efectuar el correcto seguimiento de los pacientes y aplicar un adecuado protocolo terapéutico.

Introduction: Lung cancer is a public health problem worldwide and Cuba is not exempt from it. Objective: Characterize patients diagnosed with lung cancer according to clinical, epidemiological and morphological variables. Methods: A cross-sectional, descriptive and retrospective study was carried out on 145 adults diagnosed with lung cancer in the Pneumology Service of Dr. Juan Bruno Zayas Alfonso Teaching General Hospital in Santiago de Cuba, from January, 2018 to December, 2019. For this purpose, in the statistical processing, the percentage and mean were used as summary measures for qualitative and quantitative variables, respectively; Likewise, there were applied the kappa coefficient to establish the degree of agreement between data and the Χ2 independence test to identify a significant association between the selected criteria of interest (with p<0.05). Results: There was a predominance of the male sex (62.1%) and the age group of 65-75 years (37.9%). Regarding the histological type, squamous cell carcinoma was more common (42.7%). The right lung was the most affected, specifically its upper lobe (33.8%); also, there were morphological alterations, such as bronchial infiltration (100.0%), mucosal irregularity and edema (with 98.5% in each case), and inflammation with bronchial wall thickening (90.3%). Conclusions: The determination of the clinical, epidemiological and morphological characteristics related to lung cancer makes it possible to carry out the correct follow-up of the patients and apply an appropriate therapeutic protocol.

Role of active screening in the diagnosis and treatment of early lung cancer and suggestions for health management / 中华健康管理学杂志

Objective:To explore the role of active screening in the diagnosis and treatment of early lung cancer, and give health management recommendations.Methods:A retrospective study was conducted to collect lung cancer patients who had complete population sociology, clinical information, pathology and imaging characteristics in the Thoracic Surgery in Xiangya Hospital of Central South University from 2016 to 2019. According to different diagnostic modes, they were divided into an active screening group (1082 cases) and a passive case finding group (974 cases), to analyze their differences in demographic sociological, clinical information, pathology and imaging characteristics, and to discuss the key points of population management in the active screening group.Results:From 2016 to 2019, the proportion of lung cancer patients in the active screening group increased from 36.1% to 54.2%, and the proportion of patients found to have lung cancer by CT examination in the active screening group increased from 82.2% to 96.8%. Compared with the passive case finding group, the active screening group had a higher proportion of women, non-smokers, patients with precursor glandular lesions and adenocarcinoma, patients in stage 0 and stage I, patients with lesion diameter (d)≤1 cm and 1<d≤2 cm, patients with sublobectomy and lymph node sampling (46.9% vs 32.9%, 59.2% vs 43.8%, 4.0% vs 2.1%, 80.5% vs 56.8%, 4.0% vs 2.1%, 72.0% vs 56.8%, 14.5% vs 7.6%, 42.5% vs 33.3%, 6.3% vs 2.9%, 2.4% vs 1.0%, respectively, all P<0.05). Conclusion:Active screening is helpful to find early lung cancer, and the health management and physical examination center should pay attention to the management of such physical examination population.

Application of ALK antibody clone 1A4 in the diagnosis of non-small cell lung cancer with ALK fusion / 临床与实验病理学杂志

Purpose The aim of this study is to explore the application value of ALK(1A4)in ALK fused non-small cell lung cancer(NSCLC).Methods A total of 1 035 NSCLC specimens were collected.The expression of ALK(1A4)and ALK(D5F3)antibodies was detected by immunohistochemical(IHC)staining,and their consistency was analyzed.FISH and next-generation sequencing(NGS)were used to detect ALK positive,and the sensitivity and specificity of ALK in the two groups were evaluated.Results ALK fused NSCLC patients accounted for about 5.4％(56/1 035).The positive rate of ALK(1A4)was 7.2％(75/1 035),and that of ALK(D5F3)was 5.7％(59/1 035).The consistency between them was high,with a Kappa value of 0.874.The consistency of ALK(1A4)and ALK(D5 F3)antibodies with FISH was high,with Kappa values of 0.845 and 0.954,respectively.The consisten-cy of ALK(1A4)and ALK(D5F3)with NGS was also high,with Kappa values of 0.836 and 0.988,respectively.According to the FISH results,the sensitivities of ALK(1A4)and ALK(D5F3)antibodies were 100％and 98.2％,and the specifici-ties were 98.1％and 99.6％,respectively.Conclusion ALK(1A4)antibody has high sensitivity and slightly low specificity,and can be used for clinical screening of ALK fused NSCLC.

Clinicopathological features of non-small cell lung cancer with high PD-L1 expression and positive driver gene mutation / 临床与实验病理学杂志

Purpose To investigate the clinicopathological and histological features of non-small cell lung cancer(NSCLC)patients with high expression of PD-L1 and positive driver muta-tion.Methods The clinical data of 141 patients with PD-L1 high expression and driver mutation-positive NSCLC were col-lected.Immunohistochemical methods,ARMS-PCR,and next-generation sequencing(NGS)were used to detect PD-L1 ex-pression and driver gene mutations.The clinicopathological fea-tures were analyzed and the related literatures were reviewed.Results There were 141 cases NSCLC patients with high ex-pression of PD-L1 in tumor cells,of which 57 cases were≥50％,＜60％;≥60％,＜70％in 18 cases;≥70％,＜80％in 35 cases;≥80％in 31 cases.Among 141 cases NSCLC patients with high PD-L1 expression,53 cases(37.6％)had driver gene mutations,including 4 cases BRAF 15 exon mutations,9 cases MET-associated mutations,17 cases EGFR-associated mutations,16 cases KRAS 2 exon mutations,4 cases EML4-ALK fusion mutations,and 3 cases other rare mu-tations.The high expression of PD-L1 and the occurrence of driver gene mutation were related to the gender,smoking history and pathological type of patients(P＜0.05).MET-related mu-tations and KRAS 2 exon mutations were more common in males than in females.All BRAF 15 exon mutations were female.The mean percentage of PD-L1 expression was highest in patients with MET mutation,KRAS 2 exon mutation,and 3 cases rare mutations.In 33 cases with BRAF 15 exon mutation,MET am-plification or mutation,EGFR-related mutation,and 3 cases oth-er rare mutations,PD-L1 was highly expressed in solid,glandu-lar,and micropapillary tumor cells.In 20 cases with KRAS 2 exon mutation and EML4-ALK fusion mutation,PD-L1 was highly expressed in solid nested tumor cells.Conclusion In NSCLC,high expression of PD-L1 and positive driver gene mu-tation are negatively correlated with the degree of tumor differen-tiation.In the poorly differentiated surgical specimens of lung adenocarcinoma,solid,micropapillary,or glandular tubular tumor tissues should be selected as far as possible for PD-L1 ex-pression and driver gene mutation detection.

Immune microenvironment and clinicopathological features in brain metastases of non-small cell lung cancer / 临床与实验病理学杂志

Purpose To investigate the expression of PD-1,PD-L1,CD3 and CD8 in the immune microenvironment of non-small cell lung cancer(NSCLC)and their clinical signifi-cance.Methods The clinical data of 39 patients with NSCLC brain metastasis(BM)were collected.The expression of PD-1,PD-L1,CD3 and CD8 in the tumor and stroma of BM was detec-ted using an immunofluorescence-based tissue microenvironment analysis panel.Targeted sequencing was carried out to catalog cancer-related genes.The clinical pathological features were an-alyzed with review of relevant literature.Results Thity-nine patients with NSCLC presented with tumor-infiltrating lympho-cytes(TIL)in different degree.CD3+TIL(P=0.000 7)and CD8+TIL(P=0.0006)were more prominent in the tumor stroma,and the positive PD-L1 expression was significantly higher in the interstitial tissues of tumor(P=0.025 8).Com-pared with the whole wild-type driver gene cohort,the expres-sion of PD-L1 in the stroma of BM was significantly increased in the EGFR mutation cohort(P=0.039).Patients with high in-filtration of stroma CD8+TIL had longer median overall survival than those with low infiltration(16 months vs 6 months,P=0.032);PD-L1-positive patients(36 months)were longer sur-vival time than PD-L1-negative patients(5.5 months,P=0.056).Compared with lung primary lesions,the variant allele frequencies(VAFs)in BM generally increased,and samples with higher VAFs corresponded to higher expression of PD-1,PD-L1,CD3 and CD8.Conclusion The TIL infiltration is most prominent in the stroma of NSCLC BM.The EGFR muta-tion of a tumor might affect the immune microenvironment of me-tastases;PD-L1 expression and TIL infiltration were correlated with overall survival.

Clinical significance of adhesion G protein-coupled receptor GPR110 in distinguishing acinar and solid lung adenocarcinoma / 临床与实验病理学杂志

Purpose To explore the differential expression of GPR110,an adherent G protein-coupled receptor,and its role in the differential diagnosis of acinar and solid adenocarcinoma of the lung.Methods The expression level of GPR110 was de-termined by immunohistochemistry(IHC),qRT-PCR and ELISA,and ROC and area under the curve(AUC)were ana-lyzed to distinguish the acinar predominant and solid predomi-nant of lung adenocarcinoma,so as to evaluate the role of differ-ential GPR110 expression in the differential diagnosis of these two histopathological subtypes with different prognosis.Results The expression of GPR110 in lung adenocarcinoma tumor tis-sue was significantly higher than that in adjacent tissue,and its expression in solid predominant lung adenocarcinoma was signifi-cantly higher than that in acinar predominant.The average con-centrations of GPR110 protein in 100 pairs of acinar predominant lung adenocarcinoma tumor tissues and its adjacent tissues were 430.53 and 313.26 ng/L by ELISA.The average concentrations of GPR110 protein in 53 pairs of solid predominant lung adeno-carcinoma tumor tissues and its adjacent tissues were 716.56 and 368.46 ng/L,and the differences were statistically signifi-cant(P＜0.001).At the same time,the ROC curve showed that the GPR110 protein had a sensitivity of 77.36％,a speci-ficity of 83.00％,an optimal Cut-off value of 582.27 ng/L,and an AUC of 0.865(0.802-0.927).Conclusion GPR110 has potential application value in the differential diagnosis of acinar type and solid type of adenocarcinoma of the lung,and it is ex-pected to become a new biomarker for differential diagnosis

Invasive mucinous adenocarcinoma of the lungs versus mixed invasive mucinous and non-mucinous adenocarcinoma:a clinicopathological analysis / 临床与实验病理学杂志

Purpose To investigate the clinicopathological characteristics,diagnosis,and differential diagnosis of invasive mucinous adenocarcinoma(IMA)and mixed invasive mucinous and non-mucinous adenocarcinoma(mIMA).Methods The clinical data were collected in 36 patients with primary IMA and 17 patients with mIMA,and the expression of TTF-1,CK7,CK20,SATB2,CDX2,EGFR,HNF4a,etc.was detected by immunohistochemical EnVision two-step method.The Sanger se-quencing and the FISH were used for KRAS mutation and NRG1 gene rearrangement detection.The clinicopathological character-istics were analyzed with review of relevant literature.Results There were 9 cases(25.0％)and 3(8.3％)cases of papillary and micropapillary structures in IMA,while 13 cases(76.5％)(P＜0.001)and 9 cases(52.9％)(P=0.001)were present in mIMA.There were 5 cases(13.9％)of high nuclear grade of IMA and 10 cases(58.8％)of high nuclear grade of mIMA(P=0.002).TTF-1 had a positive rate of 37.5％in IMA,but 60.0％and 80.0％in the mucinous adenocarcinoma and non-mucinous adenocarcinoma components of mIMA(P=0.021),respectively.The positive rates of CK7,CK20,and CDX2 in IMA were 90.6％,21.9％,and 9.4％,and the positive rates in mucinous adenocarcinoma and non-mucinous adenocarcinoma components of mIMA were 100％,20％,20％and 100％,6.7％,6.7％,respectively and no SATB2 expression was found in all cases.There was no significant difference in the expres-sion of total EGFR and two EGFR mutation-specific antibodies(L858R,DEL19)between IMA and mIMA.There were 3 cases of mucinous adenocarcinoma with L858R positive in mIMA,and 2 of them were negative for non-mueinous adenocarcinoma.In another case,the non-mueinous adenocarcinoma component of mIMA expressed DEL19,but the mucinous adenocarcinoma component was not expressed.The positive rate of HNF4a in IMA was 72.0％(18/25),and those of HNF4a in mucinous adenocarcinoma and non-mucinous adenocarcinoma in mIMA were 41.7％(5/12)and 33.3％(4/12),respectively(P=0.048).KRAS gene sequencing was carried out in 19 cases of IMA,among which 9 cases(47.4％)had mutations,G12D and G12V were most commonly detected,and 4 cases of mIMA were sequenced,but none of them showed KRAS mutations.FISH detection showed that 2 cases(7.1％)IMAs had NRG1 translocation rearrangement.Conclusion Pulmonary mIMA is more aggressive than IMA.For example,mIMA has significantly more papillary structure,micropapillary structure,and high nu-clear grade cases than IMA.The differences in immunohisto-chemical expression and KRAS mutation between the two are sta-tistically significant.

Correlation of different high-grade components with clinicopathological characteristics and genetic variations in stage Ⅰ lung adenocarcinoma / 临床与实验病理学杂志

Purpose To investigate the clinicopathological characteristics and genetic variations of stage Ⅰ lung adenocarci-noma with high-grade components,according to the new grading system of the WHO classification of thoracic tumors(2021).Methods A retrospective analysis was conducted on the clini-cal data of 785 patients with stage Ⅰ lung adenocarcinoma.HE,EnVision immunohistochemistry and Victoria blue staining were used,common genetic variation(EGFR/KRAS/ALK/ROS1/RET)were detected by PCR method.The correlation between different high-grade components and clinical pathological charac-teristics as well as genetic variations in stage Ⅰ lung adenocarci-noma were analyzed.Results A total of 785 cases of stage Ⅰlung adenocarcinoma were enrolled,including 332 cases with high-grade components and 453 cases without high-grade compo-nents.Among the adenocarcinomas with high-grade components,there were 7 cases of grade 1,150 cases of grade 2,and 175 ca-ses of grade 3.The positive rates of tumor cells spreading through airspace(STAS),vascular invasion,and pleural inva-sion in grade 2 adenocarcinoma with two high-grade components(61.5％,21.2％,26.9％)were significantly higher than that of the adenocarcinomas with only one high-grade component(20.4％,7.1％,5.1％),but there was no significant differ-ence in grade 3 adenocarcinoma.The positive rate(39.0％)of STAS in the micropapillary group with one high-grade component in grade 2 adenocarcinoma was significantly higher than that in the complex glandular group(9.3％)and the solid group(0),while there was no significant difference between the latter two groups.Among the three groups there were no statistically signif-icant differences in grade 3 adenocarcinoma.In 167 cases of ad-enocarcinoma with two or more high-grade components,there were 74 cases(44.3％)of complex glands combined with mi-cropapillary components,67 cases(40.1％)of complex glands combined with solid components,8 cases(4.8％)of micropap-illary combined with solid components,and 18 cases(10.8％)of three types of components.The positive rates of pleural inva-sion and KRAS gene mutation or fusion gene(ALK/ROS1/RET)in the group of complex glands combined with solid(49.3％,28.3％)were significantly higher as compared to those in the group of complex glands combined with micropapil-lary(27.0％,8.6％).The positive rate of psammoma bodies in the group with high-grade components(24.7％)was significant-ly higher than that in those without high-grade components(3.5％,P＜0.001),and the positive rate of psammoma bodies in group of gene mutation(EGFR/KRAS)(40.4％)was higher than that in the no-gene mutation group(26.7％,P＜0.05).Conclusion The clinicopathological features of different high-grade components in stage Ⅰ lung adenocarcinoma are not identi-cal,suggesting that their invasiveness may have different biologi-cal backgrounds.Characteristic morphological observations are helpful.

Relationship between the expression of PNCK,EGFR and EGFR gene mutation in non-small cell lung cancer / 临床与实验病理学杂志

Purpose To investigate the correlation of PNCK and EGFR expression with EGFR gene mutation status in non-small cell lung cancer(NSCLC).Methods Immunohisto-chemical staining was used to detect the expression of PNCK and EGFR in 256 cases of invasive lung carcinoma,42 cases of inva-sive precancerous lesions and 40 cases of paracancerous lung tis-sues,EGFR gene amplification and mutation were detected by next-generation sequencing.The relationship between the ex-pression of PNCK and EGFR protein and the clinicopathological features of NSCLC,the mutation status of EGFR gene and the correlation between them were analyzed.GEPIA database was used to analyze the correlation between PNCK and EGFR gene expression in lung adenocarcinoma and lung squamous cell carci-noma,and Kaplan-Meier Plotter database was used to analyze the effect of PNCK on the prognosis of lung cancer.Results Expression of PNCK and EGFR in lung invasive carcinoma(53.5％,137/256;47.7％,122/256)was higher than those of pre-invasive lesions(47.6％,20/42;31.0％,13/42)and paracancer tissue(22.5％,9/40;7.5％,3/40),pair-to-pair comparison among the three groups had statistical significance(P＜0.05).The high expression of PNCK protein was correla-ted with the degree of cancer differentiation,TNM stage,lymph node metastasis and distant metastasis(P＜0.05).The high expression of EGFR protein was correlated with TNM stage,lymph node metastasis and distant metastasis(P＜0.05).There was a negative correlation between PNCK and EGFR pro-tein expression in NSCLC tissues(r=-0.208,P＜0.05).The expression of EGFR protein in NSCLC with EGFR gene mu-tation and amplification was higher than that of wild type(P＜0.05).There was no correlation between PNCK protein expres-sion and EGFR gene mutation and amplification(P＞0.05).Bioinformatics database showed that PNCK and EGFR gene ex-pression were positively correlated in lung adenocarcinoma and lung squamous cell carcinoma(r=0.15,P＜0.05;r=0.30,P＜0.05),PNCK high expression group had a shorter overall survival rate in lung cancer(HR:1.28,95％CI:1.09-1.51,P=0.003 1).Conclusion The high expression of PNCK is associated with the occurrence,development,and poor prognosis of NSCLC,and negatively correlated with EGFR pro-tein expression.It is expected to become a potential therapeutic target for EGFR mutations in NSCLC.

Clinicopathological characteristics and prognostic correlation of stage Ⅰ pulmonary adenocarcinoma:analysis of 447 cases of invasive pulmonary adenocarcinoma by using WHO new grading system(2021) / 临床与实验病理学杂志

Purpose To investigate the clinicopathological characteristics and prognostic correlation of the WHO(2021)new grading system of invasive pulmonary adenocarcinoma in stageⅠ pulmonary adenocarcinoma.Methods The clinical data of 447 patients with stage Ⅰ pulmonary adenocarcinoma were collect-ed,and all cases were evaluated according to the new grading system for invasive pulmonary adenocarcinoma.The immunohis-tochemical EnVision two-step method and elastic fiber staining were used to analyze the clinicopathological features with review of the relevant literature.Results In 447 patients with stage Ⅰlung adenocarcinoma,Napsin A and TTF-1 expression were posi-tive,p40 expression was negative,and Ki-67 proliferation index was higher than 5％in 177 patients(39.6％).There were 39 cases(8.7％)of positive pleural invasion in the visceral layer revealed by elastic fiber staining.The pleural invasion in stage Ⅰpulmonary adenocarcinoma patients was significantly higher than that in grades 2 and 3,the difference was statistically significant(P＜0.05).Patients with different grades of stage Ⅰ pulmonary adenocarcinoma were associated with gender,smoking history,surgical mode,chemotherapy,targeted medication,clinical stage,pathological classification,degree of differentiation,tumor size,vascular invasion,visceral pleural invasion,spread through air space(STAS)and Ki-67 index(P＜0.05).Survival analy-sis showed that there were statistically significant differences in disease free survival(DFS)and overall survival(OS)among different grades(grade 1＞grade 2＞grade 3)(P＜0.05).Cox regression analysis showed that WHO(2021)new grading of invasive pulmonary adenocarcinoma,visceral pleural invasion and Ki-67 proliferation index were independent risk factors for prognosis of patients with stage Ⅰ pulmonary adenocarcinoma.Conclusion The WHO(2021)new grading system of invasive pulmonary adenocarcinoma has good prognostic significance for stage Ⅰ pulmonary adenocarcinoma,and appropriate intervention for high-risk patients.It can effectively assist its postoperative treatment and has application value.

Expression of histone demethylase JMJD2D in lung adenocarcinoma and its prognostic implication / 临床与实验病理学杂志

Purpose To analyze the expression and prog-nostic role of JMJD2D in lung adenocarcinoma.Methods In this study,the expression of JMJD2D mRNA in lung adenocarci-noma and prognosis were analyzed using TCGA and GEO data-bases.The protein expression and prognostic value of JMJD2D in lung adenocarcinoma were further validated by immunohisto-chemistry.GSEA analysis was performed to identify signaling pathways associated with JMJD2D,with review of the relevant literature.Results The expression of JMJD2D mRNA in lung adenocarcinoma in TCGA database(513 cases of lung adenocar-cinoma and 59 cases of paracancerous tissue)and GEO database(46 cases of lung adenocarcinoma and 45 cases of adjacent tis-sue)were significantly higher than those in the paracancerous tissues.Survival analysis showed that the overall survival of pa-tients with low expression of JMJD2D mRNA was significantly higher than that of patients with high expression,and high ex-pression of JMJD2D mRNA was associated with poor prognosis in patients with lung adenocarcinoma.The expression of JMJD2D in 208 cases of lung adenocarcinoma was higher(96.15％)than that in adjacent tissues(9.13％)(P＜0.001),and its high expression was related to the prognosis.The results of GSEA analysis showed that JMJD2D high expression was signifi-cantly enriched in DNA damage repair,DNA replication and cell cycle regulation.Conclusion This study identifies high expres-sion of JMJD2D as an adverse prognostic factor in lung adenocar-cinoma.Further research on JMJD2D may provide new thera-peutic targets for lung adenocarcinoma.

Tracheobronchopathia Osteochondroplastica and Lung Carcinoma: A Rare Combination

Tracheobronchopathia osteochondroplastica is a rare benign idiopathic disorder of unknown cause affecting the large airways. Bronchoscopy and computed tomography (CT) of the thorax establish the diagnosis, but biopsy is confirmatory. We describe a case of tracheobronchopathia osteochondroplastica, rarely associated with lung cancer. There should be a high index of suspicion of tracheobronchopathia osteochondroplastica, especially in patients with malignancy; as it can easily be missed in a patient with lung malignancy.

Application and basic application process of MR accelerator in lung cancer / 中华放射肿瘤学杂志

Radiotherapy is one of the most important components of cancer treatment. Image-guided radiotherapy (IGRT) is the mainstream tool in the precision radiation oncology. Magnetic resonance (MR) accelerator can perform MRI for tumors during radiotherapy, deliver real-time tracing and monitoring of tumors and thus realize the MRI-guided adaptive radiotherapy. Here, the latest research status and clinical application of MR accelerator in lung cancer were reviewed.

Application value of low-dose 4DCT scanning in simulation and target delineation for solitary pulmonary tumors / 中华放射肿瘤学杂志

Objective:To explore the feasibility of low-dose 4DCT scanning in simulation and target delineation for solitary pulmonary tumors (SPTs).Methods:23 patients with SPTs received 4DCT scanning simulation with the conventional scanning (CON), low voltage (LV), low current (LA) and low voltage combined with low current (LVA) in sequence. Based on the 4DCT images derived from the four sets of scanning parameters, the internal gross tumor volume (IGTV CON, IGTV V, IGTV A, IGTV VA) of SPTs were delineated and matched. Taking IGTV CON as reference, the tumor displacement and the centroid position of IGTV V, IGTV A and IGTV VA were compared with IGTV CON. The radiation doses under different scanning parameters were compared. Results:The volumes of IGTV CON, IGTV V and IGTV A were (12.26±12.30) cm 3, (12.21±12.16) cm 3 and (11.87±11.70) cm 3, respectively ( P=0.337). IGTV VA was (11.34±11.07) cm 3, significantly smaller than IGTV CON ( P=0.005). There was no significant difference in the centroid positions of IGTV CON, IGTV V, IGTV A and IGTV VA in three directions ( P=0.491, 0.360, 0.136). The Dice′s similarity coefficient (DSC VA) was significantly lower than DSC V and DSC A ( P=0.004, 0.030). The tumor displacement measured by the four sets of 4DCT images was similar in the LR direction ( P=0.470), and also in the AP direction ( P=0.108). For the displacement in the SI direction, LVA scanning was smaller than CON ( P=0.015). The radiation doses under four different scanning conditions were (397.0±140.3) mGy·cm, (175.0±61.8) mGy·cm, (264.8±95.3) mGy·cm and (116.8±41.2) mGy·cm, respectively ( P<0.001). Conclusions:LV or LA scanning exert no significant effect on the volume, centroid position of IGTV and the tumor displacement in 4DCT simulation for SPTs. The radiation dose that patients receive under LV and LV scanning is lower than that of CON. Consequently, LV or LA scanning is feasible in 4DCT simulation and target delineation for SPTs.

Uncertainty of active breathing coordinator technology for liver and lung cancer therapy using proton and heavy ion / 中华放射肿瘤学杂志

Objective:To study and analyze the uncertainty of active breathing coordinator (ABC) technology for liver and lung cancer therapy using proton and heavy ion.Methods:Before each treatment, each patient received a verification radiograph through the supporting imaging frame in treatment room. 200 verification radiographs were taken for 20 lung cancer patients and 200 for 20 liver cancer patients. Ipiodol markers, which were fixed relative to the location of the tumor, were injected into the liver cancer patients. The position changes of ipiodol markers could reflect the position changes of liver tumors. Verification radiographs were registered with the vertebral body as the main target, and the change value of tumor location was recorded.Results:For liver cancer cases, the values of position change in the left and right, head and foot, and dorsal abdomendirection were (-0.05± 0.28) cm, (0.15±0.33) cm, (-0.12±0.27) cm, and (-0.03±0.13) cm, (-0.05±0.14) cm and (0.02±0.16) cmfor lung cancer cases, respectively ( P=0.280, <0.001, <0.001). For liver cancer cases, the dispersionin the left and right, head and foot, and dorsal abdomendirectionwas (0.20±0.09) cm, (0.25±0.06) cm, (0.19±0.09) cm, and (0.09±0.03) cm, (0.10±0.03) cm and (0.13±0.03) cm for lung cancer cases, respectively ( P<0.001, <0.001, 0.008). The proportion of tumor location changes of≤5 mm in three directions in liver and lung cancer patientswas (92%, 83%, 93%) vs. (99%, 99%, 100%)( P=0.030, 0.002, 0.007). Conclusion:The application of ABC technology in the proton heavy ion therapy of lung and liver cancer has good reproducibility, and the stability of ABC technology in the treatment of lung cancer is better than that of liver cancer.

Comparison of setup errors in supraclavicular regions of lung and esophageal cancer treated with radiotherapy / 中华放射肿瘤学杂志

Objective:To compare the setup errors in the supraclavicular regions of two different postures (arms placed on each side of the body, namely the body side group; arms crossed and elbows placed above forehead, namely the uplifted group) using the chest and abdomen flat frame fixation device in lung and esophageal cancer.Methods:Clinical data of patients with stage Ⅰ to Ⅳ lung or esophageal cancer who received three-dimensional radiotherapy with chest and abdomen flat frame fixation device in our institution from November 2020 to April 2021 were retrospectively analyzed. The setup errors of two postures were compared.Results:A total of 56 patients were included, including 31 patients (55%) in the body side group and 25 patients (45%) in the uplifted group. A total of 424 CBCTs were performed in the whole group. The overall setup errors in the X, Y and Z directions were similar in both groups ( P>0.05). The setup errors of sternoclavicular joint in the X and RZ directions in the body side group were significantly smaller than those in the uplifted group [(0.163±0.120) cm vs. (0.209 ±0.152) cm, P=0.033; 0.715°±0.628° vs. 0.910°±0.753°, P=0.011]. The setup errors of acromioclavicular joint in the Y, Z and RZ directions in the body side group were significantly smaller than those in the uplifted group [(0.233±0.135) cm vs. (0.284±0.193) cm, P=0.033; (0.202±0.140) cm vs. (0.252±0.173) cm, P=0.005; 0.671°±0.639° vs. 0.885°±0.822°, P=0.023]. The margins of target volume for setup errors were smaller in the X (0.45 cm vs. 0.54 cm) and Y (0.54 cm vs. 0.65 cm) directions of the sternoclavicular joint, as well as in the Y (0.59 cm vs. 0.78 cm) and Z directions (0.53 cm vs. 0.72 cm) of the acromioclavicular joint in the body side group. Conclusions:For lung and esophageal cancer patients requiring supraclavicular irradiation, the body side group yields smaller setup errors and corresponding margins of target volume than the uplifted group. In clinical practice, it is necessary to take comprehensive consideration of the accuracy of radiotherapy and additional radiation of the limbs to select appropriate posture.

Research progress on immune checkpoint inhibitors combined with stereotactic ablative body radiotherapy for advanced non-small cell lung cancer / 中华放射肿瘤学杂志

The effect of radiotherapy on anti-tumor immunity is bidirectional, immunotherapy, especially the combination of immune checkpoint inhibitors (ICIs) and radiotherapy, can produce synergistic effects on anti-tumor immunity. Compared with conventional radiotherapy, stereotactic ablative body radiotherapy (SABR) can achieve high-precision and high-dose irradiation on target lesions, and has stronger anti-tumor immune activation effect. At the same time, due to the steep dose gradient, SABR can better protect the surrounding normal tissues, which is an effective means for the rapid control of local lesions in advanced non-small cell lung cancer (NSCLC). ICIs are an important component of standard treatment for advanced NSCLC. There is growing evidence that SABR in combination with ICIs can benefit patients with advanced NSCLC. This article reviews the biological basis and clinical research progress on the combination of these two therapies, aiming to provide reference for the domestic counterparts to better use this new treatment model.

Comparison of aspirin and low molecular weight heparin in pulmonary lobectomy after percutaneous coronary intervention / 中华胸心血管外科杂志

Objective:To compare the clinical application of aspirin and low molecular weight heparin in pulmonary lobectomy after percutaneous coronary intervention(PCI), and to explore the effect of aspirin monotherapy in anti-platelet therapy.Methods:From January 2018 to December 2019, the clinical data of 48 patients with coronary atherosclerotic heart disease(coronary heart disease) who underwent lobectomy in the Thoracic Surgery Department of Beijing Anzhen Hospital within 12 months after PCI were retrospectively analyzed. There were 37 males and 11 females. The age ranged from 41 to 76(67.6±10.4) years. There were 22 cases with hypertension, 18 cases with diabetes and 2 cases with cerebrovascular disease. Iliac artery stents were inserted in 2 cases and vertebral artery stents in 1 case. Preoperative atrial fibrillation in 2 cases. There were 46 patients with gradeⅠand 2 patients with gradeⅡcardiac function(NYHA). According to the preoperative antiplatelet treatment, the patients were divided into aspirin group(25 cases) and low molecular weight heparin group(LMWH group, 23 cases). In the aspirin group, clopidogrel or ticagrelor was stopped 5 days before lobectomy, and aspirin single drug antiplatelet therapy was used, orally 100 mg every day until the morning of operation. In the LMWH group, aspirin, clopidogrel or ticagrelor were stopped 7 days before surgery, and 0.6 ml LMWH calcium was injected subcutaneously, once every 12 hours, and stopped 12 hours before surgery. Perioperative clinical data of the two groups were recorded and analyzed, and major adverse cardiac event(MACE) and bleeding events were observed.Results:There was no death in all groups. MACE and bleeding occurred in 1 case respectively in LMWH group. There were no significant differences between the two groups in length of hospital stay, duration of operation, diameter of lesion, total postoperative thoracic drainage and retention time of thoracic drainage tube( P>0.05). The intraoperative blood loss and chest drainage in the aspirin group were significantly lower than those in the LMWH group in the first 3 days after surgery, with statistical significance( P<0.05). Conclusion:The incidence of MACE increases after lobectomy for coronary heart disease within 12 months after PCI, and aspirin monotherapy is safe and effective in antiplatelet therapy.

Analysis of life quality related to cough and influencing factors in lung cancer patients after video-assisted thoracoscopic surgery based on enhanced recovery after surgery / 中国实用护理杂志

Objective:To understand the status of life quality related to cough in lung cancer patients after video-assisted thoracoscopic surgery (VATS) and to explore its influencing factors based on enhanced recovery after surgery(ERAS).Methods:By using the convenience sample way, a total of 140 patients in lung cancer who were admitted to the VATS from Chinese Academy of Medical Science, Cancer Hospital were selected as study objects from June to August 2020. Mandarin Chinese version of the Leicester cough questionnaire(LCQ-MC) was used to measure the status of life quality related to cough in lung cancer patients after surgery.The influencing factors were analyzed by single factor analysis and multivariate linear regression analysis.Results:The score of LCQ-MC of patients after VATS (15.83±1.93) was significantly lower than before (19.03±1.64) ( t value was 17.149, P<0.01) . In terms of physiology,psychology and society, the score of LCQ-MC after VATS (4.88±0.84, 5.25±0.71, 5.70±0.73) was also apparently lower than before (6.23±0.77, 6.20±0.84, 6.60±0.72) ( t values were 14.816, 11.338,11.276, P<0.01).The single factor analysis indicated that life quality related to cough had some connections with age( F value was 3.274), cough condition before surgery ( t value was -2.174), operation methods ( F value was 2.837), the time of chest tube retained ( F value was 3.690) and drinking ( t value was -3.033) after VATS( P<0.05). The multiple-factor result showed that age, cough condition before surgery and the time of chest tube retained were the independent factors affecting the life quality related to cough in lung cancer patients after VATS( P<0.05). Conclusion:The lung cancer patients after VATS cough obviously, and their life quality is lower. At the same time, it has some effect on physiology, psychology and society to a certain extent. Medical staff should pay more attention to the elderly and who cough obviously and develop individual interventions before the surgery.After that, in order to remove the chest tube as early as possible, the guidance of pulmonary rehabilitation and mental nursing should be suggested to patients to improve their life quality.