Neutrophil extracellular traps (NETs), intricate reticular structures released by activated neutrophils, play a pivotal regulatory role in the pathogenesis of malignant tumors. Lung cancer is one of the most prevalent malignancies globally, with persistently high incidence and mortality rates. Recent studies have revealed that NETs dynamically modulate the tumor microenvironment through unique pathological mechanisms, exhibiting complex immunoregulatory characteristics during the progression of lung cancer, and this discovery has increasingly become a focal point in tumor immunology research. This paper provides a comprehensive review of the latest advancements in NETs research related to lung cancer, offering an in-depth analysis of their impact on lung cancer progression, their potential diagnostic value, and the current state of research on targeting NETs for lung cancer prevention and treatment. The aim is to propose novel strategies to enhance therapeutic outcomes and improve the prognosis for lung cancer patients.
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Extracellular Traps/immunology* ; Humans ; Lung Neoplasms/metabolism* ; Neutrophils/metabolism* ; Animals ; Tumor Microenvironment

Objective:To explore the association between postoperative radiotherapy for bladder cancer and the risk of second primary rectal cancer.Methods:Eligible 75 120 patients with bladder cancer from the Surveillance, Epidemiology, and End Result database (SEER) of the National Cancer Institute (NCI) (1975-2017) were enrolled in this study. The second primary cancers referred to rectal cancers patients suffered after more than five years post-treatment for bladder cancer, and the cumulative incidence was estimated using Fine-Gray competing risk regression. The relative risk (RR) of rectal cancer in patients treated with or without radiotherapy (the RT group or the NRT group) was evaluated using Poisson regression.Results:Among the 75 120 patients, 70 045 (92.4%) were Caucasian, with a median age of 65.8 years (54-74 years). A total of 2 236 (3%) received postoperative radiotherapy, while 72 884 (97%) received surgery alone. The 30-year follow-up revealed a cumulative incidence of rectal cancer of 0.93% in the RT group and 0.43% in the NRT group ( P = 0.004). The competing risk regression analysis identified a significant association between radiotherapy and rectal cancer ( HR: 1.86; 95% CI 1.26-2.74, P < 0.009). Furthermore, the RR of radiotherapy-associated rectal cancer significantly increased as the diagnosis occurred earlier (1975-1985 vs. 1985-1994: RR 2.59; 95% CI 1.20-4.86, P < 0.001), and a lower age at the time of radiotherapy was associated with a higher probability of second primary tumors (≤50-year old vs. > 50 year old : RR 7.89, 95% CI 2.97-21.30, P < 0.001). As calculated using the Poisson distribution, the RR of second rectal tumors was higher in the RT group ( RR: 2.20, 95% CI 1.45-3.18, P < 0.001), even after adjusting the date of diagnosis ( RR: 1.77, 95% CI 1.17-2.57, P = 0.009). Conclusions:An increased risk of rectal cancer following bladder cancer radiotherapy necessitates aggressive follow-ups for the purpose of early detecting second primary rectal cancer associated with bladder cancer radiotherapy.

Objective·To study the alterations in vestibular hair cell morphology and function of ATPase plasma membrane Ca2+transporting 2 oblivion(Atp2b2 Oblivion)heterozygous mice at different ages.Methods·Atp2b2 Oblivion heterozygous male mice aged 2 months and 8 months were selected with ten in each kind and C57BL/6J wild-type mice with the same gender,age and number were selected as the control group.Expression patterns of ATP2B2 in vestibular hair cells and numbers of hair cells in the striola zone and the extra striola zone in the two groups of mice at different ages were observed and calculated respectively through immunofluorescence assay.Hair bundle structures were detected by scanning electron microscopy(SEM),and mitochondria and ribbon synapse structures were observed by transmission electron microscopy(TEM).Vestibular evoked potential(VsEP),vestibular evoked myogenic potential(VEMP),rotarod rod test,and balance beam test were adopted for the evaluation of vestibular functions.Results·ATP2B2 was mainly expressed in the hair bundle of vestibular hair cells in the two groups of mice.Hair cell numbers in the striola zone and the extra-striola zone did not exhibit any differences between Atp2b2 Oblivion heterozygous mutant mice and wild-type mice of 2-month-old and 8-month-old.No visible structural abnormality in the hair bundle could be seen through SEM.TEM results implied no morphological abnormality in mitochondria or ribbon synapses in the 2-month-old heterozygous mutant mice,while vacuolar degeneration was discovered in the mitochondria under the cuticular plate in the 8-month-old heterozygous mutant mice with the normal ribbon synapses and the normal mitochondria near the innervation site.VsEP and VEMP thresholds of 2-month-old and 8-month-old Atp2b2 Oblivion heterozygous mutant mice were significantly elevated compared with the wild-type mice.Analysis of VsEP waveform manifested prolonged P1 latency and declined P1N1 amplitude in heterozygous mutant mice(P＜0.05).Results of rotarod rod test and balance beam test acquired from 2-month-old Atp2b2 Oblivion heterozygous mutant mice were not significantly different from the wild-type mice,while the ability of the mutant mice to accomplish the tests descended significantly at 8 months of age compared with the wild-type mice(P＜0.05).Conclusion·Atp2b2 Oblivion heterozygous mutant mice showed defective vestibular electrophysiological function at 2 months old,and abnormalities in vestibule-related behaviors can be detected at 8 months old.The vestibular function ofAtp2b2 Oblivion heterozygous mutant mice deteriorate progressively.

Objective To investigate the role of miRNAs in maternal amniotic fluid exosomes in development of isolated ventriculomegaly(VM)in fetuses.Methods Amniotic fluid samples were collected from 9 cases of moderate isolated VM and 8 normal control cases to extract exosomal miRNA,and miRNA sequencing technique was used to identify differentially expressed miRNAs between the two groups.Three miRNAs with significant differential expression between the two groups,whose high expression was associated with VM,were selected for verification with RT-qPCR.Dual luciferase reporter assays were used to verify the regulatory effect of miR-122-5p on its predicted target genes AKT3 and CCDC88C.Gene ontology(GO)and KEGG pathway analyses were performed to explore the possible roles of the top 40 significant differential miRNAs in the pathophysiology of VM.Results We identified a total of 272 differentially expressed miRNAs in VM cases,including 43 up-regulated and 229 down-regulated miRNAs.The target genes of these differential miRNAs were associated with DNA and transcription factor binding,transmembrane transporter and nucleic acid binding transcription factor activity,and cell developmental process.These miRNAs were mostly enriched in the MAPK,cGMP-PKG and Wnt signaling pathways.Verification with RT-qPCR showed that miR-122-5p expression level was significantly lower in VM group than in the control group(P<0.05),which was consistent with miRNA sequencing results;let-7b-5p expression level was significantly lower in VM group,which was contrary to miRNA sequencing result.Dual luciferase reporter assays showed that miR-122-5p was not capable of regulating AKT3 or CCDC88C expressions.Conclusions The highly abundant differentially expressed miRNAs in maternal amniotic fluid exosomes play important roles in the occurrence of fetal VM possibly by regulating the MAPK,PI3K-Akt,Wnt and cGMP-PKG signaling pathways.

Objective To investigate the role of miRNAs in maternal amniotic fluid exosomes in development of isolated ventriculomegaly(VM)in fetuses.Methods Amniotic fluid samples were collected from 9 cases of moderate isolated VM and 8 normal control cases to extract exosomal miRNA,and miRNA sequencing technique was used to identify differentially expressed miRNAs between the two groups.Three miRNAs with significant differential expression between the two groups,whose high expression was associated with VM,were selected for verification with RT-qPCR.Dual luciferase reporter assays were used to verify the regulatory effect of miR-122-5p on its predicted target genes AKT3 and CCDC88C.Gene ontology(GO)and KEGG pathway analyses were performed to explore the possible roles of the top 40 significant differential miRNAs in the pathophysiology of VM.Results We identified a total of 272 differentially expressed miRNAs in VM cases,including 43 up-regulated and 229 down-regulated miRNAs.The target genes of these differential miRNAs were associated with DNA and transcription factor binding,transmembrane transporter and nucleic acid binding transcription factor activity,and cell developmental process.These miRNAs were mostly enriched in the MAPK,cGMP-PKG and Wnt signaling pathways.Verification with RT-qPCR showed that miR-122-5p expression level was significantly lower in VM group than in the control group(P<0.05),which was consistent with miRNA sequencing results;let-7b-5p expression level was significantly lower in VM group,which was contrary to miRNA sequencing result.Dual luciferase reporter assays showed that miR-122-5p was not capable of regulating AKT3 or CCDC88C expressions.Conclusions The highly abundant differentially expressed miRNAs in maternal amniotic fluid exosomes play important roles in the occurrence of fetal VM possibly by regulating the MAPK,PI3K-Akt,Wnt and cGMP-PKG signaling pathways.

Objective To summarize the clinical characteristics of delayed diagnosis of tuberculosis in children,analyze the risk factors of delayed diagnosis,and support early diagnosis of tuberculosis in children.Methods This is a retrospective analysis based on the clinical data of tuberculosis patients admitted to the Children's Hospital Affiliated to Zhengzhou University from January 2015 to February 2023.The clinical characteristics of children were analyzed in terms of age group.According to the definition of diagnosis delay,the patients were assigned to delayed group and non-delayed group.Univariate analysis and multivariate logistic regression were used to analyze the risk factors for diagnosis delay.Results A total of 82 children with tuberculosis were included(46 cases in delayed diagnosis group and 36 cases in non-delayed diagnosis group).The rate of diagnosis delay was 56.1％.The incidence of acute miliary pulmonary tuberculosis and tuberculous meningitis was significantly higher in children ≤5 years old than that in children＞5 years old(P＜0.05).Diagnosis delay was associated with significantly higher prevalence of chronic fever,cough＞2 weeks,growth retardation and significantly longer duration of empirical antibiotic use compared to the children without diagnosis delay(P＜0.05).Univariate analysis showed that patient origin,contact history,mixed infection,tuberculosis type,molecular biological assay and severe disease were related to the delay of TB diagnosis(P＜0.05).Multivariate logistic regression analysis showed that patient origin[≥3 clinic visits(OR=7.064,95％CI:1.677-29.754)],mixed infection(OR=3.812,95％CI:1.185-12.260),severe disease(OR=3.697,95％CI:1.081-12.646)]were risk factors for diagnosis delay in children.Molecular biological assay(OR=4.642,95％CI:1.318-16.345)was a protective factor.Conclusions The clinical symptoms of tuberculosis in children are atypical.Delayed diagnosis of tuberculosis is common.Multiple clinic visits,mixed infection,and severe disease are the risk factors for diagnosis delay.Tuberculosis should be taken into account for the children with chronic fever,cough and growth retardation who have failed to respond to adequate therapy with third-generation cephalosporin and carbapenems.Molecular biological assay is helpful for early diagnosis of tuberculosis in children with negative sputum smear.

Objective To summarize the clinical characteristics of delayed diagnosis of tuberculosis in children,analyze the risk factors of delayed diagnosis,and support early diagnosis of tuberculosis in children.Methods This is a retrospective analysis based on the clinical data of tuberculosis patients admitted to the Children's Hospital Affiliated to Zhengzhou University from January 2015 to February 2023.The clinical characteristics of children were analyzed in terms of age group.According to the definition of diagnosis delay,the patients were assigned to delayed group and non-delayed group.Univariate analysis and multivariate logistic regression were used to analyze the risk factors for diagnosis delay.Results A total of 82 children with tuberculosis were included(46 cases in delayed diagnosis group and 36 cases in non-delayed diagnosis group).The rate of diagnosis delay was 56.1％.The incidence of acute miliary pulmonary tuberculosis and tuberculous meningitis was significantly higher in children ≤5 years old than that in children＞5 years old(P＜0.05).Diagnosis delay was associated with significantly higher prevalence of chronic fever,cough＞2 weeks,growth retardation and significantly longer duration of empirical antibiotic use compared to the children without diagnosis delay(P＜0.05).Univariate analysis showed that patient origin,contact history,mixed infection,tuberculosis type,molecular biological assay and severe disease were related to the delay of TB diagnosis(P＜0.05).Multivariate logistic regression analysis showed that patient origin[≥3 clinic visits(OR=7.064,95％CI:1.677-29.754)],mixed infection(OR=3.812,95％CI:1.185-12.260),severe disease(OR=3.697,95％CI:1.081-12.646)]were risk factors for diagnosis delay in children.Molecular biological assay(OR=4.642,95％CI:1.318-16.345)was a protective factor.Conclusions The clinical symptoms of tuberculosis in children are atypical.Delayed diagnosis of tuberculosis is common.Multiple clinic visits,mixed infection,and severe disease are the risk factors for diagnosis delay.Tuberculosis should be taken into account for the children with chronic fever,cough and growth retardation who have failed to respond to adequate therapy with third-generation cephalosporin and carbapenems.Molecular biological assay is helpful for early diagnosis of tuberculosis in children with negative sputum smear.

Objective To summarize the clinical characteristics of delayed diagnosis of tuberculosis in children,analyze the risk factors of delayed diagnosis,and support early diagnosis of tuberculosis in children.Methods This is a retrospective analysis based on the clinical data of tuberculosis patients admitted to the Children's Hospital Affiliated to Zhengzhou University from January 2015 to February 2023.The clinical characteristics of children were analyzed in terms of age group.According to the definition of diagnosis delay,the patients were assigned to delayed group and non-delayed group.Univariate analysis and multivariate logistic regression were used to analyze the risk factors for diagnosis delay.Results A total of 82 children with tuberculosis were included(46 cases in delayed diagnosis group and 36 cases in non-delayed diagnosis group).The rate of diagnosis delay was 56.1％.The incidence of acute miliary pulmonary tuberculosis and tuberculous meningitis was significantly higher in children ≤5 years old than that in children＞5 years old(P＜0.05).Diagnosis delay was associated with significantly higher prevalence of chronic fever,cough＞2 weeks,growth retardation and significantly longer duration of empirical antibiotic use compared to the children without diagnosis delay(P＜0.05).Univariate analysis showed that patient origin,contact history,mixed infection,tuberculosis type,molecular biological assay and severe disease were related to the delay of TB diagnosis(P＜0.05).Multivariate logistic regression analysis showed that patient origin[≥3 clinic visits(OR=7.064,95％CI:1.677-29.754)],mixed infection(OR=3.812,95％CI:1.185-12.260),severe disease(OR=3.697,95％CI:1.081-12.646)]were risk factors for diagnosis delay in children.Molecular biological assay(OR=4.642,95％CI:1.318-16.345)was a protective factor.Conclusions The clinical symptoms of tuberculosis in children are atypical.Delayed diagnosis of tuberculosis is common.Multiple clinic visits,mixed infection,and severe disease are the risk factors for diagnosis delay.Tuberculosis should be taken into account for the children with chronic fever,cough and growth retardation who have failed to respond to adequate therapy with third-generation cephalosporin and carbapenems.Molecular biological assay is helpful for early diagnosis of tuberculosis in children with negative sputum smear.

ObjectiveTo investigate the effects of Bushen Huoxue prescription on the cardiac function， inflammation， and quality of life of the patients with chronic heart failure resistant to diuretics. MethodA total of 78 patients who met the inclusion criteria were randomized into observation and control groups （39 cases）. Both groups received standardized treatment for diuretic resistance in accordance with the guidelines. In addition， the observation group received Bushen Huoxue prescription. The cardiac function indicators， total response rate regarding symptom alleviation， exercise endurance， urine volume， body mass， quality of life， and levels of inflammatory cytokines were compared between the two groups before and after treatment. ResultBefore treatment， the two groups of patients showed no significant differences in terms of 24 h urine volume， body mass， 6 minute walk test （6MWT）， Minnesota Living with Heart Failure Questionnaire （MLHFQ） score， N-terminal pro-B-type natriuretic peptide （NT-proBNP） level， left ventricular ejection fraction （LVEF）， stroke volume （SV）， and serum levels of interleukin-6 （IL-6）， interleukin-4 （IL-4）， and tumor necrosis factor-alpha （TNF-α）. After treatment， the observation group outperformed the control group in terms of the response rates regarding traditional Chinese medicine symptom scores and New York Heart Association （NYHA） grading of cardiac function （P<0.05）. After treatment， the body mass， MLHFQ score， and IL-6， TNF-α， and NT-proBNP levels decreased in both groups （P<0.05， P<0.01）， and the observation group showed more significant decreases than the control group （P<0.05， P<0.01）. Both groups showed increases in 24-h urine volume， 6MWT， LVEF， SV， and IL-4 after treatment （P<0.05， P<0.01）， and the observation group showed more significant increases than the control group （P<0.05， P<0.01）. ConclusionThe combination of Bushen Huoxue prescription with standardized treatment is effective in ameliorating the clinical symptoms of the patients with chronic heart failure resistant to diuretics. Moreover， it alleviates diuretic resistance and improves the cardiac function without causing obvious adverse reactions.