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.
.
Extracellular Traps/immunology* ; Humans ; Lung Neoplasms/metabolism* ; Neutrophils/metabolism* ; Animals ; Tumor Microenvironment

Objective To investigate the pathogenesis of high-altitude cerebral edema(HACE)and develop new therapeutic strategies.Methods Male Sprague-Dawley(SD)rats of 6 weeks old were selected and placed in a hypobaric chamber.The rats were exposed to the high-altitude environment of 7000 m above sea level for 3 days for HACE modeling.Whether the HACE model was successfully established in the rats was evaluated by measuring brain water content,the degree of disruption to the blood-brain barrier(BBB),and brain tissue Nissl staining.The experimental animals were divided into four groups,with 28 rats in each group.The blank control group was exposed to a normobaric and normoxic environment simulating the conditions at 500 m above sea level for 3 d.The other groups,including a model group(the HACE group),a bumetanide group(the positive control group),and a XH-6003 treatment group,were placed at an altitude of 7 000 m above sea level and were injected with normal saline,bumetanide,and XH-6003,a new type of Na-K-2C1 cotransporter 1(NKCC1)inhibitor,via the tail vein,respectively,twice daily for 3 d.The experimental animals were taken out of the hypobaric chamber for testing after 3 d.The primary outcome measures included brain water content,BBB permeability,changes in brain tissue morphology,and the expression levels of aquaporin-4(AQP4)and NKCC1.The secondary outcome measures included behavioral changes,apoptosis,and oxidative stress markers.Results The HACE rat model was successfully established.The model group exhibited increased brain water content(P＜0.0001),BBB disruption(P＜0.0001),impairment in learning skills and memory(P＜0.001),and anxiety/depression-like behaviors(P＜0.01).qPCR results showed significantly increased expression of NKCC1 and AQP4 in the brain tissue of the model group(P＜0.01).Pathology examination revealed neuronal and glial cell damage in the hippocampus of the model group(P＜0.01).Treatment with XH-6003,the NKCC1 inhibitor,reversed brain water content,BBB disruption,and neuronal and glial cell damage to a certain degree(P＜0.05),decreased the expression of NKCC1 and AQP4 in the brain tissue(P＜0.01),and inhibited apoptosis-related proteins.Among the oxidative stress indices,only glutathione(GSH)showed improvement(P＜0.001).Rats treated with XH-6003 showed functional improvement only in the time spent exploring novel objects,while other behavioral outcomes remained unchanged.Conclusion HACE is associated with the activation of the NKCC1/AQP4 pathway.Inhibition of this pathway alleviates brain edema,BBB disruption,and neuronal and glial cell damage.These findings suggest that XH-6003 holds potential as a therapeutic strategy for HACE at the cellular and molecular levels,but its effects in improving HACE-related behavioral disorders warrant further investigation.

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 investigate the level of injury first aid skills and its influencing factors among parents of preschool children in Dongxihu District, Wuhan City, so as to provide insights into carrying out targeted health education work. Methods: Parents of preschool children from kindergarten in Dongxihu District were selected using multi-stage stratified cluster sampling method. Basic information of preschool children, parents' demographic information, and parents' knowledge of injury first aid skills were collected through questionnaires. The level of injury first aid skills among parents was analyzed and its influencing factors were identified using a multivariable logistic regression model. Results: A total of 1 148 questionnaires were allocated and 1 131 valid questionnaires were recovered, with an effective recovery rate of 98.52%. The respondents included 242 men (21.40%) and 889 women (78.60%). The parents surveyed were mainly mothers, with 862 accounting for 76.22%. The level of injury first aid skills was 39.43%. Among the individual injury first aid skills, the proportions of mastering the treatment of cardiac arrest and arm fracture were relatively high, which were 94.69% and 94.16%, respectively, while the proportion of mastering the correct steps of cardiopulmonary resuscitation was the lowest, at 31.21%. Multivariable logistic regression analysis showed that the grade of children (middle class, OR=1.374, 95%CI: 1.021-1.847; senior class, OR=1.561, 95%CI: 1.147-2.125), age (30 to 34 years old, OR=1.712, 95%CI: 1.170-2.505), education level (high school/technical secondary school and below, OR=0.664, 95%CI: 0.515-0.857), and having learned injury first aid skills (OR=1.653, 95%CI: 1.284-2.129) were influencing factors of injury first aid skills among parents of preschool children. Conclusions The level of injury first aid skills among parents of preschool children is relatively low. The first aid ability of parents whose children are in small classes, older, less educated, and have not learned injury first aid skills should be specifically improved.

Objective To assess the reinforcing effect and operability of DNV-1929 in canine lungs so as to provide scientific basis for its clinical application by observing its characterisation during surgical resection.Methods Fifteen Beagles of 10-to 15-month-old,randomly assigned to three experimental groups,were used in this study for implantation experiments with DNV-1929 and negative control material.The experimental animals were housed in a defined environment and detailed clinical observations were made before and after the experiments.By using specific surgical techniques,the materials were implanted into different parts of the left lung of the dogs and their pressure resistance was assessed by airway pressure tests.The handling properties of the implanted materials were also evaluated.At weeks 2 and 4 after implantation,macroscopic visual observations and pathological examinations were performed on three sites of the canine left lung,the posterior anterior anterior lobe,the anterior posterior lobe,and and the posterior posterior lobe,in order to compare the tissue response of DNV-1929 with that of the negative control material.In addition,all experimental animals were evaluated for safety,including monitoring of clinical signs,food intake,and body weight.Results At airway pressure levels up to 35 hPa,both DNV-1929 and the negative control material showed similar pressure resistance with no gas leakage at the implantation site.During the procedure,DNV-1929 showed similar manoeuvrability to the negative control material,with no significant abnormalities observed.As seen by visual pathological observation after 2 and 4 weeks of implantation,both materials formed an encapsulation around the implantation site and underwent different degrees of adhesion with the thoracic organs,but the difference was not statistically significant(P＞0.05).There were more residual implants in the DNV-1929 group at 2 weeks and almost disappeared at 4 weeks of implantation,whereas a small amount of implanted material was still present in the negative control group,but residual material did not differ significantly between the two groups(P＞0.05).Histological evaluation showed that the subtotal score of inflammatory condition of DNV-1929 in the 2-week implantation group was slightly higher than that of the negative control substance(P=0.016),while the subtotal score of inflammatory condition in the 4-week implantation group was not statistically different compared with that of the negative control substance(P＞0.05).In terms of safety evaluation,the experimental dogs did not show any clinical abnormality or reduction in food intake during the study period,and there was no death on the day of implantation of DNV-1929 and the negative control substance.There was no significant change in body weight of the experimental dogs during the study cycle(P＞0.05).Conclusion DNV-1929 demonstrated a strengthening effect and good manoeuvrability in canine lungs with no toxic effects on surrounding tissues.This provides preliminary evidence for the use of DNV-1929 in surgical treatment of the lung,establishes scientific basis for its use in clinical practice,and demonstrates its potential value.

Objective:To investigate the predictive value of a clinical imaging model based on multi-slice helical computer tomography (MSCT) examination in predicting prognosis of advanced gastric adenocarcinoma.Methods:The retrospective cohort study was conducted. The clinicopatho-logical data of 88 patients with advanced gastric adenocarcinoma who were admitted to the Ningbo Yinzhou No.2 Hospital from January 2019 to January 2021 were collected. There were 62 males and 26 females, aged (60±15)years. All patients underwent preoperative MSCT examination. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were expressed as absolute numbers. Univariate and multivariate analyses were conducted using the Logistic regression model. The receiver opera-ting characteristic curve was used to analyze the predictive efficacy of prognosis, and the area under the curve (AUC), sensitivity, and specificity were calculated. Results:(1) Surgical situations and follow-up. All 88 patients underwent radical gastrectomy for gastric cancer and were diagnosed with advanced gastric adenocarcinoma through postoperative pathological examination. All 88 patients were followed up after surgery for 41(range, 36?48)months, with a 3-year overall survival rate of 69.32%. (2) Analysis of factors affecting the prognosis of advanced gastric adenocarcinoma after radical surgery. Results of multivariate analysis showed that preoperative carcinoembryonic antigen (CEA) and extramural venous invasion (EMVI) were independent factors affecting the prognosis of advanced gastric adenocarcinoma after radical surgery ( odds ratio=1.10, 7.72, 95% confidence interval as 1.01?3.82, 1.42?15.42, P<0.05). (3) Construction and evaluation of predictive model. The AUC of predictive efficacy of prognosis for advanced gastric adenocarcinoma of preoperative CEA and EMVI were 0.90 (95% confidence interval as 0.82?0.97) and 0.80 (95% confidence intervalas 0.71?0.89), respectively, with sensitivity of 85.25% and 78.69% and specificity of 100.00% and 81.48%, respec-tively. A predictive model was constructed by combining preoperative CEA and EMVI based on the results of multivariate analysis, and the AUC of the predictive model was 0.93 (95% confidence interval as 0.87?0.98), with sensitivity and specificity of 86.89% and 96.30%. Conclusions:CEA and EMVI are independent factors affecting the prognosis of advanced gastric adenocarcinoma after radical surgery. The predictive model constructed by combining preoperative CEA and EMVI has good predictive efficacy for patient prognosis.

Klebsiella pneumoniae(KPn),as a conditioned pathogen that causes calf pneumonia,has caused serious harm to cattle industry,but the harm of Klebsiella pneumoniae to calves in Xin-jiang region is still unclear.In this study,to investigate the prevalence of KPn,its harm and some biological characteristics of pneumonia calves in Xinjiang,nasal swabs of pneumonia calves in some areas were collected aseptically,KPn isolation and identification were performed by routine meth-od,and 16S rDNA sequence evolutionary tree analysis was performed.The drug resistance was de-tected by K-B method,and a strain carrying multiple virulence was selected for mice median lethal dose test.The serotype,virulence gene and drug resistance gene of the strain were detected by PCR.The results showed that the detection rate of Klebsiella pneumoniae in nasal swabs of 218 pneumonia calves from Aksu,Changji and Yili regions of Xinjiang was as follows:14.68％(32/218),including 28.33％(17/60)in Aksu Prefecture,24.00％(6/25)in Changji Prefecture and 6.77％(9/133)in Yili Prefecture,they were divided into two serotypes,namely K1(7/32)and K5(5/32).A total of 13 KPn virulence genes were detected,mainly mrkD,ureA,wabG,uge and en-tB.LD50 was 2.38X 107cfu/mL.Drug susceptibility test and drug resistance gene detection showed that the isolated strain showed multiple drug resistance,and the resistance genes mainly carried blasHv and floR.16S rDNA sequence evolutionary tree results showed that the isolated strain had high homology with the isolates from Italy,Beijing and Shanghai of China.The detection rate of KPn in nasal swabs of pneumonia calves in Xinjiang region is high.The dominant serotypes are K1 and K5.The isolates carry a variety of virulence genes and have strong virulence.All of them are KPn strains producing ESBLs,suggesting that Klebsiella pneumoniae in Xinjiang region of China have a certain potential harm to calves.

Pregnant women account for 40% of all epilepsy patients, and the economic burden of pregnant women with epilepsy is 5 times higher than that of non-pregnant patients. Additionally, the rates of stillbirth and congenital malformations in pregnant women with epilepsy are 5 times greater than those in normal pregnant women. Therefore, it is crucial to comprehensively review and summarize the management of pregnant women with epilepsy to reduce the burden of the disease. This study provides a thorough review on teratogenic effects of anti-seizure medications (ASMs) used during pregnancy, and summarizes the effects of ASMs on health of offspring and offers clinical management recommendations for pregnant women with epilepsy, aiming to provide guidance for safe use of medications during pregnancy.

Objective Alzheimer disease(AD),a continuous disease spectrum,includes the symptomatic stages of the period of mild cognitive impairment(MCI)and the dementia period,also known as AD dementia.Focusing on MCI and AD dementia screening,i.e.,AD spectrum screening,we analyzed the value of plasma biomarkers for diagnosing cognitive dysfunction in the local populations of Deyang City,Sichuan Province,China to provide evidence for the early screening and diagnosis of cognitive dysfunction.Methods A questionnaire survey was conducted between August 2023 and October 2023 among people aged 50 years or older in Deyang City,Sichuan Province.The survey covered demographic information,information on medical history,and cognitive function assessment.Subjects with MCI were included in the MCI group,those with AD dementia were included in the AD group,and the others were included in the healthy controls(HC)group.A partial sample,including all patients with AD dementia and a randomized sample of MCI patients and HC,was drawn.Then,the plasma levels of four cognition-related biomarkers,including phosphorylated tau217(p-tau217),were measured using an ultrasensitive digital chip immunoassay technology independently developed in China.Amyloid beta(Aβ)deposition was determined by positron emission tomography(PET)using Aβ molecular probes in all AD dementia patients and some of the MCI patients.The diagnostic value of the plasma biomarkers for cognitive dysfunction was assessed.Results A total of 2833 subjects were investigated,including 30(1.1％)with AD dementia,437(15.4％)with MCI,and 2366(83.5％)with HC.We measured the plasma levels of 4 biomarkers of 30 AD dementia patients,50 MCI patients,and 35 HC.Plasma p-tau217 performed best in differentiating AD dementia from HC and MCI,with the area under the curve(AUC)of receiver operator characteristic curves being 0.96(95％CI:0.91-1.00)and 0.93(95％CI:0.87-0.98),respectively.Plasma p-tau217 levels in the AD dementia,MCI,and HC groups were(2.32±1.27),(0.54±0.45),and(0.42±0.19)pg/mL,respectively,and the difference was statistically significant(P＜0.000 1).A total of 36 patients underwent Aβ PET examination.Plasma p-tau217 showed the best performance in the diagnosis of Aβ deposition(AUC:0.99,95％CI:0.96-1.00).Plasma p-tau217 levels were higher in Aβ-deposition-positive patients([2.52±1.17]pg/mL)than those in Aβ-deposition-negative patients([0.53±0.19]pg/mL),and the difference was statistically significant(P＜0.000 1).Plasma p-tau217 levels were significantly and positively correlated with Aβ PET uptake values in multiple brain regions of the frontal,temporal,and occipital lobes(r＞0.70,P＜0.000 1).Conclusion Plasma biomarkers measured with a technology independently developed in China demonstrate good performance in diagnosing AD dementia.Plasma p-tau217,in particular,demonstrates the highest diagnostic value and can be used for AD dementia screening of large populations.