Who are optimal candidates for primary tumor resection in patients with metastatic gastric adenocarcinoma? A population-based study.

BACKGROUND: The research aimed to construct a novel predictive nomogram to identify specific metastatic gastric adenocarcinoma (mGAC) populations who could benefit from primary tumor resection (PTR). METHOD: Patients with mGAC were included in the SEER database and divided into PTR and non-PTR groups. The Kaplan-Meier analysis, propensity score matching (PSM), least absolute shrink and selection operator (LASSO) regression, multivariable logistic regression, and multivariate Cox regression methods were then used. Finally, the prediction nomograms were built and tested. RESULTS: 3185 patients with mGAC were enrolled. Among the patients, 679 cases underwent PTR while the other 2506 patients didn't receive PTR. After PSM, the patients in the PTR group presented longer median overall survival (15.0 vs. 7.0 months, p < 0.001). Among the PTR group, 307 (72.9%) patients obtained longer overall survival than seven months (beneficial group). Then the LASSO logistic regression was performed, and gender, grade, T stage, N stage, pathology, and chemotherapy were included to construct the nomogram. In both the training and validation cohorts, the nomogram exhibited good discrimination (AUC: 0.761 and 0.753, respectively). Furthermore, the other nomogram was constructed to predict 3-, 6-, and 12-month cancer-specific survival based on the variables from the multivariate Cox analysis. The 3-, 6-, and 12-month AUC values were 0.794, 0.739, and 0.698 in the training cohort, and 0.805, 0.759, and 0.695 in the validation cohorts. The calibration curves demonstrated relatively good consistency between the predicted and observed probabilities of survival in two nomograms. The models' clinical utility was revealed through decision curve analysis. CONCLUSION: The benefit nomogram could guide surgeons in decision-making and selecting optimal candidates for PTR among mGAC patients. And the prognostic nomogram presented great prediction ability for these patients.

A novel nomogram and risk stratification system predicting the cancer-specific survival of patients with gastric neuroendocrine carcinoma: a study based on SEER database and external validation.

BACKGROUND: Gastric neuroendocrine carcinoma (GNEC) is a rare histology of gastric cancer. The retrospective study was designed to construct and validate a nomogram for predicting the cancer-specific survival (CSS) of postoperative GNEC patients. METHODS: Data for 28 patients from the Hangzhou TCM Hospital were identified as the external validation cohort. A total of 1493 patients were included in the SEER database and randomly assigned to the training group (1045 patients) and internal validation group (448 patients). The nomogram was constructed using the findings of univariate and multivariate Cox regression studies. The model was evaluated by consistency index (C-index), calibration plots, and clinical net benefit. Finally, the effect between the nomogram and AJCC staging system was compared by net reclassification index (NRI) and integrated discrimination improvement (IDI). RESULTS: Age, gender, grade, T stage, N stage, metastasis, primary site, tumor size, RNE, and chemotherapy were incorporated in the nomogram. The C-indexes were 0.792 and 0.782 in the training and internal verification sets. The 1-, 3-, and 5-year CSS predicted by the nomogram and actual measurements had good agreement in calibration plots. The 1-, 3-, and 5-year NRI were 0.21, 0.29, and 0.37, respectively. The 1-, 3-, and 5-year IDI values were 0.10, 0.12, and 0.13 (P < 0.001), respectively. In 1-, 3-, and 5-year CSS prediction using DCA curves, the nomogram outperformed the AJCC staging system. The nomogram performed well in both the internal and external validation cohorts. CONCLUSION: We developed and validated a nomogram to predict 1-, 3-, and 5-year CSS for GNEC patients after surgical resection. This well-performing model could help doctors enhance the treatment plan.

A Novel Nomogram for Identifying Candidates for Adjuvant Chemotherapy in Patients With Stage IB Non-small Cell Lung Cancer.

BACKGROUND: This study aimed to develop a novel predictive nomogram to identify specific stage IB non-small cell lung cancer (NSCLC) populations who could benefit from adjuvant chemotherapy (ACT). METHOD: Stage IB NSCLC patients were included in the Surveillance, Epidemiology, and End Results (SEER) database and divided into the ACT and non-ACT groups. Then the methods of Kaplan-Meier analysis, propensity score matching (PSM), Least absolute shrink and selection operator (LASSO) regression, and multivariate logistic regression analyses were implemented. Finally, the predictive nomogram was constructed and validated. RESULTS: 9055 stage IB NSCLC patients were enrolled from the SEER database while 47 patients from Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University were identified as the external validation cohort. Of these patients, 1334 cases underwent ACT while the other 7721 patients didn't receive ACT. After PSM, the patients in the ACT group presented longer median overall survival (100 vs 82 months, P < .001). Among the ACT group, 482 (49.6%) patients achieving more prolonged overall survival than 82 months were regarded as the beneficiary population. Then the LASSO regression and multivariate logistic regression analyses were implemented. Finally, 8 predictors were selected for model construction, including age, gender, marital status, laterality, pathology, tumor size, regional nodes examined, and tumor size. The predictive nomogram demonstrated good discrimination in the training cohort (AUC = .781), internal validation cohort (AUC = .772), and external validation cohort (AUC = .851). And calibration curves indicated ideal consistency between the predicted and observed probabilities. Decision curve analysis presented a clinically useful model. CONCLUSION: The practical nomogram could guide treatment decision-making and select optimal ACT candidates among stage IB NSCLC patients.

Neutrophil activation and NETosis are the predominant drivers of airway inflammation in an OVA/CFA/LPS induced murine model.

BACKGROUND: Asthma is one of the most common chronic diseases that affects more than 300 million people worldwide. Though most asthma can be well controlled, individuals with severe asthma experience recurrent exacerbations and impose a substantial economic burden on healthcare system. Neutrophil inflammation often occurs in patients with severe asthma who have poor response to glucocorticoids, increasing the difficulty of clinical treatment. METHODS: We established several neutrophil-dominated allergic asthma mouse models, and analyzed the airway hyperresponsiveness, airway inflammation and lung pathological changes. Neutrophil extracellular traps (NETs) formation was analyzed using confocal microscopy and western blot. RESULTS: We found that the ovalbumin (OVA)/complete Freund's adjuvant (CFA)/low-dose lipopolysaccharide (LPS)-induced mouse model best recapitulated the complex alterations in the airways of human severe asthmatic patients. We also observed OVA/CFA/LPS-exposed mice produced large quantities of neutrophil extracellular traps (NETs) in lung tissue and bone marrow neutrophils. Furthermore, we found that reducing the production of NETs or increasing the degradation of NETs can reduce airway inflammation and airway hyperresponsiveness. CONCLUSION: Our findings identify a novel mouse model of neutrophilic asthma. We have also identified NETs play a significant role in neutrophilic asthma models and contribute to neutrophilic asthma pathogenesis. NETs may serve as a promising therapeutic target for neutrophilic asthma.

Qingfei Jiedu decoction inhibits PD-L1 expression in lung adenocarcinoma based on network pharmacology analysis, molecular docking and experimental verification.

Objective: We aim at investigating the molecular mechanisms through which the Qingfei Jiedu decoction (QFJDD) regulates PD-L1 expression in lung adenocarcinoma (LUAD). Methods: Bioactive compounds and targets of QFJDD were screened from TCMSP, BATMAN-TCM, and literature. Then, GeneCard, OMIM, PharmGKB, Therapeutic Target, and DrugBank databases were used to identify LUAD-related genes. The protein-protein interaction (PPI) network was constructed using overlapping targets of bioactive compounds in LUAD with the Cytoscape software and STRING database. The potential functions and pathways in which the hub genes were enriched by GO, KEGG, and DAVID pathway analyses. Molecular docking of bioactive compounds and key genes was executed via AutoDock Vina. Qualitative and quantitative analyses of QFJDD were performed using UPLC-Q-TOF-MS and UPLC. Expressions of key genes were determined by qRT-PCR, immunoreactivity score (IRS) of PD-L1 was assessed by immunohistochemistry (IHC), while the CD8+PD-1+T% derived from spleen tissues of Lewis lung cancer (LLC) bearing-mice was calculated using flow cytometry (FCM). Results: A total of 53 bioactive compounds and 288 targets of QFJDD as well as 8151 LUAD associated genes were obtained. Further, six bioactive compounds, including quercetin, luteolin, kaempferol, wogonin, baicalein, and acacetin, and 22 hub genes were identified. The GO analysis showed that the hub genes were mainly enriched in DNA or RNA transcription. KEGG and DAVID pathway analyses revealed that 20 hub genes were primarily enriched in virus, cancer, immune, endocrine, and cardiovascular pathways. The EGFR, JUN, RELA, HIF1A, NFKBIA, AKT1, MAPK1, and MAPK14 hub genes were identified as key genes in PD-L1 expression and PD-1 checkpoint pathway. Moreover, ideal affinity and regions were identified between core compounds and key genes. Notably, QFJDD downregulated EGFR, JUN, RELA, HIF1A, NFKBIA, and CD274 expressions (p < 0.05), while it upregulated AKT1 and MAPK1 (p < 0.05) levels in A549 cells. The PD-L1 IRS of LLC tissue in the QFJDD high dose (Hd) group was lower than model group (p < 0.01). CD8+PD-1+T% was higher in the QFJDD Hd group than in normal and model groups (p < 0.05). Conclusion: QFJDD downregulates PD-L1 expression and increases CD8+PD-1+T% via regulating HIF-1, EGFR, JUN and NFκB signaling pathways. Therefore, QFJDD is a potential treatment option for LUAD.

Is lobectomy superior to sub-lobectomy in non-small cell lung cancer with pleural invasion? A population-based competing risk analysis.

BACKGROUND: Pleural invasion (PL) has been regarded as an unfavorable prognostic factor for non-small cell lung cancer (NSCLC). But there was no agreement on the optimal surgical extent in NSCLC patients with PL. We aimed to compare the survival outcomes of lobectomy and sub-lobectomy in these patients. METHOD: 2717 patients were included in the Surveillance, Epidemiology, and End Results (SEER) database and divided into the lobectomy and sub-lobectomy groups. The propensity score matching (PSM) and competing risk analysis were implemented. Then the predictive nomogram was constructed and validated. RESULTS: 2230 Patients received lobectomy while the other 487 patients underwent sub-lobectomy. After 1:1 PSM, the cumulative incidence of cancer-specific death (CSD) was lower in the lobectomy group compared with the sub-lobectomy group (1-year: 12% vs. 15%; 3-year: 30% vs. 37%, 5-year: 34% vs. 45%, P = 0.04). According to the subgroup analysis, the patients who underwent lobectomy suffered lower CSD in the N0-1 stage, adenocarcinoma, and PL-2 cohort (p < 0.05). And there was a significant relationship between the sub-lobectomy group and CSD in the multivariate competing risks regression analysis (HR, 1.26; 95%CI, 1.02-1.56; P = 0.034). Furthermore, a competing event nomogram was constructed to assess the 1-, 3-, and 5-year chances of CSD based on the variables from the multivariate analysis. The 1-, 3-, 5-year area under the receiver operating characteristic curve (AUC) values were 0.720, 0.706, and 0.708 in the training cohort, and 0.738, 0.696, 0.680 in the validation cohorts, respectively. And calibration curves demonstrated ideal consistency between the predicted and observed probabilities of CSD. CONCLUSION: Lobectomy should be considered the preferred surgery compared to sub-lobectomy for NSCLC patients with PL. The proposed nomograms presented great prediction ability for these patients.

Pneumocystis jiroveci pneumonia with cytomegalovirus infection diagnosed by metagenomic next-generation sequencing in a patient with nephrotic syndrome: A case report.

INTRODUCTION: Opportunistic infection with multiple pathogens currently has become less uncommon since the application of immunosuppressant or corticosteroid in non- Human immunodeficiency virus patients. However, the clinical diagnosis of the co-infection remains difficult since the uncertainty and deficiency of the microbiologic testing methods. PATIENT CONCERNS: A 66-year-old male patient was admitted to our hospital with chest stuffiness, shortness of breath and elevated body temperature. DIAGNOSIS: He was diagnosed with the co-infection of Pneumocystis jiroveci and cytomegalovirus by metagenomic next-generation sequencing of bronchoalveolar lavage fluid after bronchoscopy. INTERVENTIONS: The patient was empirically treated with broad-spectrum antibiotics, trimethoprim/ sulfamethoxazole and ganciclovir in the beginning of the admission. OUTCOMES: The condition of this patient was not improved even with the intervention at the early stage of the disease. His family requested discharge after 24 inpatient days. LESSONS: This case highlights the application of metagenomic next-generation sequencing in the clinical diagnosis of pulmonary co-infection. Suitable prophylaxis, necessary clinical awareness and accurate diagnosis are indispensable for immunocompromised patients with pulmonary infection.

Andrographolide Inhibition of Th17-Regulated Cytokines and JAK1/STAT3 Signaling in OVA-Stimulated Asthma in Mice.

Asthma has long been considered a disease of airway inflammation. The excessive or prolonged production of inflammatory mediators can result in airway remodeling and severe clinical syndromes such as dyspnea or even apnea. Therefore, pharmaceutical intervention is required to restrain the excessive release of such inflammatory mediators in control of asthma. Novel therapeutics and mechanistic insight are sought for the management of this chronic inflammatory disease. Andrographolide (AG) is a type of diterpenoid ester compound and is reported to demonstrate multiple properties such as antioxidation and anti-inflammation. However, the anti-inflammatory capacity of AG by regulating immunologic function in airway of asthma has not been fully studied to date. Therefore, this study investigates whether AG is capable of suppressing the inflammatory response of asthma in OVA-stimulated mice and the mechanism by which this is achieved. Animals were randomly divided into 4 groups: control group, OVA model group, OVA + AG (0.1 mg/ml) group, and OVA + dimethylsulfoxide (DMSO) group. The serum, BALF, and lung tissue of the mice were collected separately for the administration of ELISA, rt-PCR, western blot and pathological section and staining. We found that AG attenuated the OVA-induced production of IL-6, IL-17A, IL-17F, and RORγt; inhibited the OVA-mediated phosphorylation of JAK 1 and STAT3; and alleviated airway remodeling and the neutrophil infiltration of lung tissue. We conclude that AG inhibits the inflammatory response of asthma in OVA-stimulated mice by blocking the activation of Th17-regulated cytokines and the JAK1/STAT3 signaling pathway.

[The clinical significance of inspiratory capacity measurement in patients with stable chronic obstructive pulmonary disease].

OBJECTIVE: To study the clinical significance of inspiratory capacity (IC) in the evaluation of airflow obstruction and chronic dyspnea in patients with stable chronic obstruction pulmonary disease (COPD). METHODS: Sixty-one moderate COPD patients underwent pulmonary function test. Borg Scales (BS) was used for the degree of exertional dyspnea. Measurements of pulmonary function and BS were also performed after salbutamol inhalation (400 microg) in 61 COPD patients and after 6-minute walk test (6MWT) in 36 COPD patients. RESULTS: After salbutamol administration, the patients showed a significant increase in IC [(1.6+/-0.5) L vs (1.4+/-0.5) L] and in FEV1 [(1.3+/-0.4) L vs (1.1+/-0.4) L]. The reversibility in IC was significantly higher than that in FEV1 [(20+/-16)% vs (11+/-4)%]. A reversibility greater or equal to 10% in IC was found in 75.4% (46/61) of the patients, but in FEV1 was found in 39.3% (24/61); the difference was significant (chi2=16.190, P<0.01). BS was significantly decreased after salbutamol administration (3.0+/-0.7 vs 3.9+/-0.8, P<0.01). After 6MWT, the 36 COPD patients showed a significant decrease in IC [(1.1+/-0.4) L vs (1.4+/-0.5) L] and in FEV1 [(1.0+/-0.4) L vs (1.1+/-0.4) L]. The decrease in IC was significantly greater than that in FEV1 [(26+/-8)% vs (14+/-6)%]. A decrease greater or equal to 10% in IC was found in 100% (36/36) of the patients and in FEV1 was found in 72.2% (26/36); the difference was significant (chi2=11.613, P<0.01). BS was significantly higher after 6MWT (5.6+/-1.0 vs 3.9+/-0.9, P<0.01). In the multiple regression analysis, the change of IC after and before therapy (DeltaICthe) with the change of BS after and before therapy (DeltaBSthe), and the change of IC after and before exercise (DeltaICexe) with the change of BS after and before exercise (DeltaBSexe), were significantly correlated (regression coefficient was 0.314 and 0.329, respectively, all P<0.05). In Pearson correlation analysis, IC with functional residual capacity (FRC), DeltaICthe with DeltaFRCthe and DeltaIC with DeltaFRC were negatively correlated (r=-0.416 and -0.826 and -0.778, respectively, all P<0.05 or P<0.01). CONCLUSION: IC may be more sensitive than FEV1 in evaluation of change of airflow obstruction and dyspnea in stable COPD patients.