Machine learning-based models for prediction of the risk of stroke in coronary artery disease patients receiving coronary revascularization.

BACKGROUND: To construct several prediction models for the risk of stroke in coronary artery disease (CAD) patients receiving coronary revascularization based on machine learning methods. METHODS: In total, 5757 CAD patients receiving coronary revascularization admitted to ICU in Medical Information Mart for Intensive Care IV (MIMIC-IV) were included in this cohort study. All the data were randomly split into the training set (n = 4029) and testing set (n = 1728) at 7:3. Pearson correlation analysis and least absolute shrinkage and selection operator (LASSO) regression model were applied for feature screening. Variables with Pearson correlation coefficient<9 were included, and the regression coefficients were set to 0. Features more closely related to the outcome were selected from the 10-fold cross-validation, and features with non-0 Coefficent were retained and included in the final model. The predictive values of the models were evaluated by sensitivity, specificity, area under the curve (AUC), accuracy, and 95% confidence interval (CI). RESULTS: The Catboost model presented the best predictive performance with the AUC of 0.831 (95%CI: 0.811-0.851) in the training set, and 0.760 (95%CI: 0.722-0.798) in the testing set. The AUC of the logistic regression model was 0.789 (95%CI: 0.764-0.814) in the training set and 0.731 (95%CI: 0.686-0.776) in the testing set. The results of Delong test revealed that the predictive value of the Catboost model was significantly higher than the logistic regression model (P<0.05). Charlson Comorbidity Index (CCI) was the most important variable associated with the risk of stroke in CAD patients receiving coronary revascularization. CONCLUSION: The Catboost model was the optimal model for predicting the risk of stroke in CAD patients receiving coronary revascularization, which might provide a tool to quickly identify CAD patients who were at high risk of postoperative stroke.

Large-area field application confirms the effectiveness of toxicant-infused bait for managing Helicoverpa armigera (Hübner) in maize fields.

BACKGROUND: Maize is one of the world's most important crops, so its stable production and supply is crucial for food security and socioeconomic development. The cotton bollworm, Helicoverpa armigera (Hübner), is one of the major pests in maize. We evaluated the control effect of a bio-bait, an adult attractant, combined with insecticide, a 'toxicant-infused bait', on H. armigera populations in maize fields, as well as the impact on crop yield and quality through large-scale field applications in Hebei Province, China over a period spanning 2019 to 2021. RESULT: The number of male and female H. armigera adults killed by strip application ranged from 1 to 37 and 4 to 36 per strip, respectively, of which female moths were 53%. Following the application of toxicant-infused bait, we observed a significant reduction in the populations of eggs and larvae, with the average adjusted decrease range from 58% to 63% for eggs and from 34% to 62% for larvae. The application of toxicant-infused bait also resulted in a notable reduction in the proportion of damaged maize plants, with an adjusted decline rate ranging from 59% to 69%. Concurrently, we observed an increase in yield by 4% to 8%. The concentration of aflatoxin in harvested maize grains was significantly reduced from an initial level of 1.24 to 0.1 ug/kg. CONCLUSION: By applying toxicant-infused bait, there was a significant reduction in the population of H. armigera adults and their offspring, resulting in an improved yield and quality of maize. Toxicant-infused bait has great application potential in the integrated pest management of H. armigera. © 2023 Society of Chemical Industry.

Corrigendum: milR20 negatively regulates the development of fruit bodies in Pleurotus cornucopiae.

[This corrects the article DOI: 10.3389/fmicb.2023.1177820.].

Association Between Admission Hyperglycemia and Outcomes After Endovascular Treatment in Acute Basilar Artery Occlusion.

INTRODUCTION: Admission hyperglycemia and high admission blood glucose levels have been associated with poor outcomes in acute ischemic stroke. However, the relationship between admission hyperglycemia and outcomes after endovascular treatment (EVT) in acute basilar artery occlusion (ABAO) still remain unclear. This study aimed to investigate the association between admission hyperglycemia and clinical outcomes in ABAO following EVT. METHODS: Patients from the BASILAR registry with admission blood glucose levels treated with EVT were included. We defined admission hyperglycemia as blood glucose levels ≥ 7.8 mmol/L. The primary outcome was favorable outcome [defined as a modified Rankin Scale score (mRS) of 0-3] at 90 days, Secondary outcomes included other functional outcomes (mRS 0-2, mRS 0-1) at 90 days, symptomatic intracerebral hemorrhage (sICH) within 48 h, and mortality at 90 days. RESULTS: Of 545 eligible patients included, the median age was 65 (IQR, 56-73) years, and median blood glucose level was 7.36 (IQR, 6.10-9.66) mmol/L. Multivariable logistic regression analysis showed that admission hyperglycemia was associated with decreased favorable outcome (mRS 0-3) (adjusted odds ratio = 0.52; 95% CI 0.35-0.79; P = 0.001), and increased mortality (adjusted odds ratio = 2.67; 95% CI 1.82-3.91; P < 0.001). Restricted cubic spline regression analysis showed that the blood glucose level had a non-linearity association with favorable outcome and mortality, and that there was no association between admission hyperglycemia and sICH. CONCLUSIONS: Our study suggest that admission hyperglycemia is associated with an increased risk of poor functional outcomes and mortality in patients with ABAO treated with EVT. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( http://www.chictr.org.cn ), ChiCTR180001475.

milR20 negatively regulates the development of fruit bodies in Pleurotus cornucopiae.

The mechanism underlying the development of fruit bodies in edible mushroom is a widely studied topic. In this study, the role of milRNAs in the development of fruit bodies of Pleurotus cornucopiae was studied by comparative analyses of the mRNAs and milRNAs at different stages of development. The genes that play a crucial role in the expression and function of milRNAs were identified and subsequently expressed and silenced at different stages of development. The total number of differentially expressed genes (DEGs) and differentially expressed milRNAs (DEMs) at different stages of development was determined to be 7,934 and 20, respectively. Comparison of the DEGs and DEMs across the different development stages revealed that DEMs and its target DEGs involved in the mitogen-activated protein kinase (MAPK) signaling pathway, protein processing in endoplasmic reticulum, endocytosis, aminoacyl-tRNA biosynthesis, RNA transport, and other metabolism pathways, which may play important roles in the development of the fruit bodies of P. cornucopiae. The function of milR20, which targeted pheromone A receptor g8971 and was involved in the MAPK signaling pathway, was further verified by overexpression and silencing in P. cornucopiae. The results demonstrated that the overexpression of milR20 reduced the growth rate of mycelia and prolonged the development of the fruit bodies, while milR20 silencing had an opposite effect. These findings indicated that milR20 plays a negative role in the development of P. cornucopiae. This study provides novel insights into the molecular mechanism underlying the development of fruit bodies in P. cornucopiae.

Clinical and Radiological Features Between Patients with Stable COPD from Plateau and Flatlands: A Comparative Study.

Background: COPD patients living in Tibet are exposed to specific environments and different risk factors and probably have different characteristics of COPD from those living in flatlands. We aimed to describe the distinction between stable COPD patients permanently residing at the Tibet plateau and those in flatlands. Methods: We conducted an observational cross-sectional study that enrolled stable COPD patients from Tibet Autonomous Region People's Hospital (Plateau Group) and Peking University Third Hospital (Flatland Group), respectively. Their demographic information, clinical features, spirometry test, blood routine and high-resolution chest CT were collected and evaluated. Results: A total of 182 stable COPD patients (82 from plateau and 100 from flatland) were consecutively enrolled. Compared to those in flatlands, patients in plateau had a higher proportion of females, more biomass fuel use and less tobacco exposure. CAT score and frequency of exacerbation in the past year were higher in plateau patients. The blood eosinophil count was lower in plateau patients, with fewer patients having an eosinophil count ≥300/µL. On CT examination, the proportions of previous pulmonary tuberculosis and bronchiectasis were higher in plateau patients, but emphysema was less common and milder. The ratio of diameters of pulmonary artery to aorta ≥1 was more often in plateau patients. Conclusion: Patients with COPD living at Tibet Plateau had a heavier respiratory burden, lower blood eosinophil count, less emphysema but more bronchiectasis and pulmonary hypertension. Biomass exposure and previous tuberculosis were more common in these patients.

Development of an Inactivated Avian Influenza Virus Vaccine against Circulating H9N2 in Chickens and Ducks.

Avian influenza virus (AIV) subtype H9N2 is the most widespread AIV in poultry worldwide, causing great economic losses in the global poultry industry. Chickens and ducks are the major hosts and play essential roles in the transmission and evolution of H9N2 AIV. Vaccines are considered an effective strategy for fighting H9N2 infection. However, due to the differences in immune responses to infection, vaccines against H9N2 AIV suitable for use in both chickens and ducks have not been well studied. This study developed an inactivated H9N2 vaccine based on a duck-origin H9N2 AIV and assessed its effectiveness in the laboratory. The results showed that the inactivated H9N2 vaccine elicited significant haemagglutination inhibition (HI) antibodies in both chickens and ducks. Virus challenge experiments revealed that immunization with this vaccine significantly blocked virus shedding after infection by both homogenous and heterologous H9N2 viruses. The vaccine was efficacious in chicken and duck flocks under normal field conditions. We also found that egg-yolk antibodies were produced by laying birds immunized with the inactivated vaccine, and high levels of maternal antibodies were detected in the serum of the offspring. Taken together, our study showed that this inactivated H9N2 vaccine could be extremely favourable for the prevention of H9N2 in both chickens and ducks.

Preoperative and postoperative clinical signatures of postgastrectomy venous thromboembolism in patients with gastric cancer: A retrospective cohort study.

BACKGROUND: This study aimed to identify preoperative and postoperative risk factors of venous thromboembolism (VTE) after gastrectomy in gastric cancer (GC) patients. METHODS: 757 GC patients underwent gastrectomy at our institution and 246 patients with elevated postoperative D-dimer levels who received Doppler ultrasonography of lower/upper extremity veins were enrolled. Clinicopathological factors data were collected, and the differences in clinicopathological factors between postoperative VTE (+) and VTE (-) groups were analyzed. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors of postgastrectomy VTE. RESULTS: Of 246 patients with elevated postgastrectomy D-dimer concentrations, 74 patients showed thrombosis in lower/upper extremity veins. Among preoperative factors, age, WBC level, D-dimer concentration, and blood glucose level were significantly higher in the postoperative VTE (+) group. Among the postoperative factors, hemoglobin level was significantly lower in the postoperative VTE (+) group. Among the pathological factors, tumor stage, depth of invasion and TNM classification indicated higher malignancy in the postoperative VTE (+) group. Univariate logistic regression analysis indicated age, preoperative blood glucose level, postoperative hemoglobin level, tumor stage, depth of invasion, and TNM classification as the independent risk factors for postgastrectomy VTE, whereas multivariate logistic regression analysis revealed age and tumor stage as independent risk factors for postgastrectomy VTE. CONCLUSION: Our study revealed that age, preoperative blood glucose level, postoperative anemia, and tumor malignancy were independent risk factors for GC patients exhibiting postgastrectomy VTE. Therefore, the perioperative monitoring, assessment and management of risk factors are important in achieving better outcomes after gastrectomy.

An IgY Effectively Prevents Goslings from Virulent GAstV Infection.

Goose astrovirus (GAstV) leads to viscera and joints urate deposition in 1- to 20-day-old goslings, with a mortality rate of up to 50%, posing a severe threat to entire colonies; however, there is no efficient prevention and control method for GAstV infection. This study describes a prophylactic anti-GAstV strategy based on the specific immunoglobulin Y (IgY) from egg yolk. The specific IgY was produced by 22-week-old laying hens intramuscularly immunized with the inactivated GAstV three consecutive times, with 2-week intervals. The egg yolk was collected weekly after the immunization and the anti-GAstV IgY titer was monitored using an agar gel immune diffusion assay (AGID). The results revealed that the AGID titer began to increase on day 7, reached a peak on day 49, and remained at a high level until day 77 after the first immunization. The specific IgY was prepared from the combinations of egg yolk from day 49 to day 77 through PEG-6000 precipitation. Animal experiments were conducted to evaluate the effects of prevention and treatment. The result of the minimum prophylactic dose of the IgY showed that the protection rate was 90.9% when 2.5 mg was administrated. Results of the prevention and the treatment experiments showed prevention and cure rates of over 80% when yolk antibody was administered in the early stages of the GAstV infection. These results suggested that the specific IgY obtained from immunized hens with the inactivated GAstV could be a novel strategy for preventing and treating GAstV infection.

New developments in non-exosomal and exosomal ncRNAs in coronary artery disease.

Aim & methods: Non-exosomal and exosomal ncRNAs have been reported to be involved in the regulation of coronary artery disease (CAD). Therefore, to explore the biological effects of non-exosomal/exosomal ncRNAs in CAD, the authors searched for studies published in the last 3 years on these ncRNAs in CAD and summarized their functions and mechanisms. Results: The authors summarized 120 non-exosomal ncRNAs capable of regulating CAD progression. In clinical studies, 47 non-exosomal and nine exosomal ncRNAs were able to serve as biomarkers for the diagnosis of CAD. Conclusion: Non-exosomal/exosomal ncRNAs are not only able to serve as biomarkers for CAD diagnosis but can also regulate CAD progression through ceRNA mechanisms and are a potential target for early clinical intervention in CAD.

ncRNAs are increasingly found to play regulatory roles in coronary artery disease (CAD), and transcriptome studies offer greater advantages for controlling CAD at its source. Therefore, the authors conducted an accurate search and summary of studies on CAD and ncRNAs published in the past 3 years to analyze the main pathological mechanisms in CAD progression, aiming to provide a research basis for clinical treatment of CAD.

Myostatin/HIF2α-Mediated Ferroptosis is Involved in Skeletal Muscle Dysfunction in Chronic Obstructive Pulmonary Disease.

Objective: Skeletal muscle dysfunction is an important comorbidity in patients with chronic obstructive pulmonary disease (COPD), and is associated with poor quality of life and reduced survival, but the mechanisms involved remain elusive. Ferroptosis is a newly discovered type of cell death resulting from iron-dependent lipid peroxide accumulation. The purpose of this study was to examine whether ferroptosis is involved in COPD-associated skeletal muscle dysfunction. Methods: A mouse model of COPD was established after 24 weeks of cigarette smoke (CS) exposure, and mRNA sequencing, hematoxylin-eosin (H&E) staining, immunostaining (IF), RT-PCR, and Western blot were utilized to identify the changes in gastrocnemius muscles. In vitro, C2C12 myotubes were treated with CS extract (CSE) and evaluated for ferroptosis-related molecules. The pathways regulating ferroptosis were then explored in CSE-stimulated myotubes. Results: Compared with controls, COPD mice showed an enriched ferroptosis pathway. Gpx4 was decreased, while hypoxia-inducible factor (Hif) 2α was increased, at gene and protein levels. A reduced level of GSH, but increased cell death, Fe2+, lipid ROS, LPO, and 4-HNE were observed in COPD mice or in CSE-stimulated C2C12 myotubes, which could be ameliorated by ferroptosis inhibitors. The expression of myostatin (MSTN) was enhanced in COPD mice and CSE-stimulated myotubes. MSTN up-regulated HIF2α expression and led to ferroptosis in myotubes, whereas inhibition of MSTN binding to its receptor or inhibition/knockdown of HIF2α resulted in decreased cell death, and partially restored GPX4 and GSH. Conclusion: CS exposure induced ferroptosis in vivo and in vitro. Mechanistically, CS-exposure upregulated MSTN which further induced ferroptosis through HIF2α in skeletal muscles, which may contribute to muscle dysfunction through impairing metabolic capacity and decreasing muscle fiber numbers, revealing a potential novel therapeutic target for COPD-related skeletal muscle dysfunction.

Integrated bioinformatics analysis for novel miRNAs markers and ceRNA network in diabetic retinopathy.

In order to seek a more outstanding diagnosis and treatment of diabetic retinopathy (DR), we predicted the miRNA biomarkers of DR and explored the pathological mechanism of DR through bioinformatics analysis. Method: Based on public omics data and databases, we investigated ncRNA (non-coding RNA) functions based on the ceRNA hypothesis. Result: Among differentially expressed miRNAs (DE-miRNAs), hsa-miR-1179, -4797-3p and -665 may be diagnosis biomarkers of DR. Functional enrichment analysis revealed differentially expressed mRNAs (DE-mRNAs) enriched in mitochondrial transport, cellular respiration and energy derivation. 18 tissue/organ-specific expressed genes, 10 hub genes and gene cluster modules were identified. The ceRNA networks lncRNA FBXL19-AS1/miR-378f/MRPL39 and lncRNA UBL7-AS1/miR-378f/MRPL39 might be potential RNA regulatory pathways in DR. Conclusion: Differentially expressed hsa-miR-1179, -4797-3p and -665 can be used as powerful markers for DR diagnosis, and the ceRNA network: lncRNA FBXL19-AS1/UBL7-AS1-miR-378f-MRPL39 may represent an important regulatory role in DR progression.

Dysregulated myokines and signaling pathways in skeletal muscle dysfunction in a cigarette smoke-induced model of chronic obstructive pulmonary disease.

Skeletal muscle dysfunction is an important extrapulmonary comorbidity of chronic obstructive pulmonary disease (COPD). Muscle-derived cytokines (myokines) play important roles in skeletal muscle growth and function, but their contributions to skeletal muscle dysfunction in COPD have not been fully understood. In the current study, by using a well-established mouse model of COPD with skeletal muscle dysfunction, we found that the expressions of Fndc5 (fibronectin type III domain-containing protein 5, the precursor of irisin) and peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) were decreased, while myostatin (Mstn), phosphorylated extracellular regulated kinase (p-Erk1/2), and p-Smad3 expressions were upregulated in skeletal muscles from cigarette smoke-exposed mice and in cigarette smoke extract (CSE)-stimulated C2C12 myotubes. Treatment with Smad3 or Erk1/2 inhibitors partially restored the expression of Fndc5 in CSE-stimulated C2C12 myotubes. Taken together, CSE exposure, by upregulation of p-Erk1/2, promoted the expression of Mstn, which further inhibited Fndc5 expression by the p-Smad3/PGC-1α pathway, revealing a novel regulating mechanism of myokines in the pathogenesis of skeletal muscle comorbidities of COPD.

Heat shock protein 70 (HSP70) plays important role in tembusu virus infection.

Tembusu virus (TMUV) is an avian-origined flavivirus that is prevalent in ducks and geese. TMUV causes reduced egg production and neurological problems, resulting in profound economic losses to the waterfowl industry. In the viral life cycle, cellular factors are required for viral entry, replication, assembly, release and so on. Heat shock protein 70 (HSP70) is reported to be involved in the replication of multiple viruses. In this study, we explored the roles of HSP70 in the TMUV life cycle. The results showed that TMUV infection induced HSP70 expression starting 12 h post-infection. An HSP70 inhibitor reduced TMUV viral RNA production and the number of virus particles, whereas an HSP70 activator enhanced the amount of viral RNA and virions that released from the cells. Further analysis revealed that HSP70 played important roles in the postentry stages of the TMUV life cycle, including viral replication, assembly and release. We also found that inhibition of HSP70 expression significantly reduced TMUV-induced apoptosis. Additionally, incubation of TMUV particles with an anti-HSP70 antibody significantly reduced viral infectivity, suggesting an association between HSP70 and TMUV particles. These results implicate HSP70 in the life cycle of TMUV, and therefore, targeting HSP70 may be a strategy for developing an anti-TMUV therapy.

Transcriptomic and Metabolomic Analysis of Wheat Kernels in Response to the Feeding of Orange Wheat Blossom Midges (Sitodiplosis mosellana) in the Field.

The orange wheat blossom midge (Sitodiplosis mosellana Géhin) is an insect pest that feeds on wheat (Triticum aestivum L.). The resistance mechanisms of wheat to S. mosellana infestation are largely unknown. In this study, the wheat varieties LX99 and 6218 were identified as highly resistant and susceptible, respectively, via field investigations conducted over two consecutive years. Morphological and microstructural observations of mature wheat kernels following S. mosellana infestation revealed that the degree of cell structure damage in resistant LX99 grains was less than that in susceptible 6218 grains. Transcriptomic and metabolomic analyses of seeds following S. mosellana feeding showed that the differentially expressed genes and differentially accumulated metabolites from LX99 were mostly enriched in several primary and secondary metabolic pathways, including phenylpropanoid biosynthesis, flavonoid biosynthesis, and phenylalanine biosynthesis. Additionally, phenylpropanoid- and flavonoid-related gene expression was significantly upregulated following S. mosellana infestation in LX99 relative to that in 6218. Some metabolites involved in phenylpropanoid/flavonoid pathways, such as cinnamic acid, coumarin, epigallocatechin, and naringenin, were only induced in infested LX99 kernels. These results suggest that phenylpropanoid/flavonoid pathways play important roles in wheat kernel resistance to S. mosellana attack and provide useful insights for the breeding and utilization of resistant varieties.

Microbiota associations with inflammatory pathways in asthma.

BACKGROUND: The airway microbiota plays an important role in asthma pathophysiology. However, the relationship between the airway microbiota and asthma phenotypes is still poorly understood. OBJECTIVE: We aimed to characterize the airway microbiota in asthma patients and determine its correlation with airway inflammatory phenotypes and other phenotypic characteristics. METHODS: The microbial composition of induced sputum specimens collected from asthma patients was determined using 16S rDNA gene sequencing. RESULTS: Patients with asthma had a higher abundance of bacterial taxa associated with Bacteroidetes, Fusobacteria and Proteobacteria and a reduced abundance of Firmicutes and Actinobacteria compared to healthy controls. This study classified the asthma-associated lung microbiota into three community types based on DMM models, which were defined as three pulmotypes (P1, P2 and P3). The lungs of patients with pulmotype 3 (P3) were dominated by Faecalibacterium and Bacteroides, while patients with pulmotype 1 (P1) had a greater abundance of Pasteurellaceae, Streptococcus and Rothia. P1 patients were older (p = .045) and had lower blood TGF levels (p = .028). P3 patients had fewer eosinophils (p = .016) and more neutrophils (p = .039) in induced sputa than P1 patients. CONCLUSIONS: Differences in asthma-associated airway microbiota pulmotypes are associated with and might influence asthma, particularly inflammatory phenotypes.

A Two-Fold Interpenetrated Dual-Emitting Luminescent Metal-Organic Framework as a Ratiometric Sensor for Chromium(III).

A novel two-fold interpenetrated metal-organic framework, namely Co-EDDA, was synthesized by hydrothermal reaction of 5,5'-[ethane-1,2-diylbis(oxy)]diisophthalic acid (H4EDDA), Co(NO3)2·6H2O, and 1,4-di(1H-imidazol-1-yl)benzene in water in an alkaline environment and structurally characterized. Co-EDDA could display clear dual-emission signals at 350 and 430 nm, representing the charge transfer emission between metal ions and the ligand and the ligand-based emission, respectively, which represents the ratiometric luminescence response to chromium(III) with high selectivity and sensitivity (limit of detection of 0.54 µM). Comprehensive studies indicate that the detection can be attributed to the interaction between the Cr3+ ions and the O atoms on the ether bond in Co-EDDA.

The E3 Ubiquitin Ligase TRIM25 Inhibits Tembusu Virus Replication in vitro.

Duck Tembusu virus (DTMUV) is a newly emerging pathogenic flavivirus that has caused significant economic losses to the duck industry in China since 2010 due to egg production losses and neurological dysfunction. DTMUV is a public health concern because the infection spreads rapidly among birds. Retinoic acid-inducible gene-I (RIG-I)serves as an innate immune sensor and plays a key role in host antiviral defenses. Tripartite motif-containing protein 25 (TRIM25), an E3 ubiquitin ligase, is pivotal for RIG-I ubiquitination and activation. In addition, TRIM25 acts as an interferon-stimulated gene and mediates the antiviral activity. However, the effect of duck TRIM25 on DTMUV has not been assessed. Herein, we reportthe antiviral function of TRIM25 against DTMUV. First, we constructed the pcDNA3.1-c-myc-duTRIM25 plasmid. TRIM25 has a 2052 bp open reading frame that encodes a predicted 684 amino acid protein consisting of a RING finger domain, a B-box domain, a coiled-coil domain, and a PRY/SPRY domain. The protein sequence identity with chicken, mouse, and human TRIM25 is 69.7, 47.8, and 48.3%, respectively. TRIM25 was upregulated in BHK-21 cells, duck embryo fibroblasts, and 293T cellsupon DTMUV infection. The expression of viral RNA and proteins was significantly lower in cells over expressing TRIM25 than in control cells. Furthermore, siRNA-mediated silencing of TRIM25 increased the production of viral progeny. These results help elucidate the molecular mechanisms underlying the host response to DTMUV infection and suggest potential control measures for DTMUV outbreaks.

Successful treatment of refractory lung adenocarcinoma harboring a germline BRCA2 mutation with olaparib: A case report.

BACKGROUND: In recent years, targeted therapy and immunotherapy have become important treatment strategies for patients with non-small cell lung cancer (NSCLC). However, the clinical evidence for successful off-label use of targeted drugs for patients with NSCLC following progression on multiple lines of treatment is still lacking. CASE SUMMARY: We describe a 62-year-old male patient with a right lung adenocarcinoma who harbored an EGFR exon 19 deletion mutation. He received gefitinib combined with six cycles of vinorelbine, cisplatin, and recombinant human endostatin as the first-line therapy. Then gefitinib was administered in combination with recombinant human endostatin as maintenance therapy, resulting in a progression-free survival (PFS) of 14 mo. Chemoradiotherapy was added following progression (enlarged brain metastases) on maintenance treatment. Unfortunately, the brain lesions were highly refractory and progressed again after 15 mo, at which time next-generation sequencing (NGS) of 1021 cancer-related genes was performed using peripheral blood to identify potential actionable mutations. NGS revealed that the patient harbored a BRCA2 germline mutation, the EGFR exon 19 deletion mutation disappeared, and no additional targetable genetic variant was detected. Therefore, the patient received olaparib combined with gefitinib and recombinant human endostatin, with a rapid and long-lasting clinical response (PFS = 13.5 mo). CONCLUSION: This is a rare case of lung adenocarcinoma in a patient with a BRCA2 germline mutation who had long-term benefit from olaparib combination treatment, suggesting that NGS-based genetic testing may render the possibility of long-term survival in NSCLC patients after disease progression.