A screening tool was devised to aid the diagnosis and treatment of ground-glass nodules (GGNs).
The current ambispective cohort study included retrospective collation of 20 variables synthesizing a patient's clinical characteristics, serum tumor markers, and CT results, which allowed division into noninvasive (benign, atypical adenomatous hyperplasia, and adenocarcinoma in situ) and invasive (minimally invasive and invasive adenocarcinomas) tumors to build a prediction nomogram and GGN screening scale. The model was verified internally. A prospective cohort of patients was randomly divided by envelope method into those assessed by the GGN screening scale and those assessed via CT values. The diagnostic efficiencies were compared to allow external verification of the model.
A total of 223 patients with 225 GGNs were recruited into the retrospective cohort between January 2021 and December 2022. Multivariable analysis showed sex, diameter, air bronchogram, and vessel convergence sign to be independent factors for prediction of noninvasive and invasive GGNs. Internal verification showed the model had a sensitivity of 70.7% and specificity of 75.0% with the Youden index at 0.457 and area under the curve (AUC) of 0.793 (95% CI: 0.734–0.852). Calibration curves indicated good internal stability (p = 0.357). Between January 2023 and March 2023, 147 patients with 148 GGNs were recruited into the prospective cohort. External verification showed the model had a sensitivity of 92.4% and specificity of 40.0% with the Youden index at 0.324 and AUC of 0.678 (95% CI: 0.509–0.847). Calibration curves indicated good external stability (p = 0.088). The scale was shown to have a sensitivity of 75.00%, specificity of 37.50%, positive predictive value of 91.53%, negative predictive value of 14.29%, and accuracy of 71.25%.
The GGN screening scale has high sensitivity and accuracy, making it suitable for diagnosis of GGNs.
The incidence of small cell lung cancer (SCLC) among Asian patients is on the rise. Nevertheless, there remains a deficiency in precise prognostic models tailored to the specific needs of this patient population. It is imperative to develop a novel nomogram aimed at forecasting the prognosis of Asian SCLC patients.
The SEER database supplied data on 661 Asian SCLC patients, who were then divided into training and internal validation sets through a random selection process. In addition, we identified 212 patients from a Chinese medical institution for the purpose of creating an external validation cohort. To forecast survival, we employed both univariate and multivariate analyses. The performance of our nomogram was assessed through calibration plots, the concordance index (C-index), and decision curve analysis (DCA).
Five independent prognostic factors were determined and integrated into the nomogram. C-index values for the training and internal validation cohorts were 0.774 (95% confidence interval [CI] = 0.751–0.797) and 0.731 (95%CI = 0.690–0.772), respectively. In the external validation cohort, the C-index is 0.712 (95% CI = 0.655–0.7692). Calibration curves demonstrated highly accurate predictions. When compared to the AJCC staging system, our model exhibited improved net benefits in DCA. Furthermore, the risk stratification system effectively differentiated patients with varying survival risks.
We have created a novel nomogram for predicting the survival of Asian patients with SCLC. This nomogram has been subjected to external validation and has shown its superiority over the conventional TNM staging system. It offers a more precise and reliable means of forecasting the prognosis of Asian SCLC patients.
Kinesin family member 5A (KIF5A) has been reported to be closely related to cancer progression. The aim of this study was to investigate the effect of KIF5A on lung adenocarcinoma (LUAD) and its potential molecular mechanisms.
Using bioinformatics analysis methods and molecular experiments, the expression of KIF5A in LUAD was analyzed, with its expression in attached and detached tumor cells assessed. Gene set enrichment analysis (GSEA) of KIF5A was carried out. The small molecular drug with the highest affinity for KIF5A was screened out through molecular docking experiments, which was validated through cellular thermal shift assay (CETSA). Quantitative polymerase chain reaction (qPCR) was employed to measure the expression levels of anoikis-repressing genes (BCL2, CAV1), as well as anoikis-inducing gene (PDCD4). CCK-8 assay was applied to examine cell viability. Cell colony formation experiments were utilized to evaluate cell proliferation ability.
We observed that KIF5A was highly upregulated in LUAD tissues and cells, with a higher level detected in detached LUAD cells. By resorting to bioinformatics analysis, we discovered that KIF5A was abundant in the anoikis pathway. Knocking down KIF5A reinforced anoikis in LUAD. Further screening identified Ergotamine as the small molecular drug with the highest affinity for KIF5A. The CETSA confirmed the binding relationship between the two. In addition, Ergotamine has a promoting effect on the anoikis of LUAD, while overexpression of KIF5A reversed the effects of Ergotamine on LUAD cells.
This project uncovered that the small molecular drug Ergotamine targets and inhibits the expression of KIF5A. Downregulated KIF5A can enhance the anoikis of LUAD. Our results supported the inhibition of KIF5A as an attractive therapeutic strategy for LUAD. This finding provides a new innovative pathway for the treatment of LUAD and offers a strong theoretical basis for the development of therapeutic drugs targeting KIF5A.
Sirtuin 3 (SIRT3) is located in the mitochondrial matrix, regulating acetylation levels of metabolic enzymes. As an oncogene or a tumor suppressor gene, SIRT3 plays an important role in the commencement and progression of certain cancers. In this research, we investigated the role of SIRT3 in the progression of nonsmall cell lung carcinoma (NSCLC).
In this study, bioinformatics was used to analyze the differential expression of SIRT3 in NSCLC tissue and normal tissues, prognosis, single-cell analysis, and related signaling pathways. The Lentiviral overexpressing SIRT3 was constructed, and CCK8 and colony formation assay were used to evaluate the NSCLC cells proliferation, ROS production was detected by flow cytometry, and the sea-horse test was used to measure cellular oxygen consumption (OCR).
SIRT3 expression was significantly decreased in NSCLC, and low expression of SIRT3 was closely related to the poor prognosis. Besides, on the whole, upregulation of SIRT3 suppressed cell proliferation in A549 and SK-MES-1 cells via increasing oxidative phosphorylation (OXPHOS) and ROS production.
Overall, our findings suggested that SIRT3 functions as a tumor suppressor that can suppress the progression of NSCLC via stimulating ROS production.
Small cell lung cancer (SCLC) is one of the most lethal malignancies worldwide. This study aimed to examine the clinical benefits of new systemic therapies derived from randomized controlled trials (RCTs) published from 2002 to 2023 based on the magnitude of clinical benefit scale developed by the European Society for Medical Oncology (ESMO-MCBS).
We searched PubMed for Phase 3 RCTs on systemic therapy for SCLC published between January 2002 and December 2023. Therapeutic benefit was graded from 5 to 1 according to the ESMO-MCBS framework, with a score of 4 or 5 representing a meaningful clinical benefit. The statistical power of the trial design was also assessed using ESMO-MCBS.
Sixty-four RCTs with 23 683 participants were eligible for inclusion. The number of RCTs related to molecular targeted therapy or immunotherapy has increased over the years. Among the 62 RCTs for which statistical power could be evaluated, 38 (61.3%) were designed to identify an effect size that would meet the ESMO-MCBS benefit threshold and were less likely to investigate second- or subsequent-line treatment (15.8% vs. 50.0%, p = 0.004), have noninferiority design (0% vs. 25.0%, p = 0.002) and set PFS (0% vs. 16.7%) or response rate (0% vs. 16.7%) as the only primary endpoint (p = 0.002). The ESMO-MCBS framework was applied in 29 RCTs reporting positive results, and only 8 (27.6%) met the threshold for a clinical benefit. The RCTs designed to detect differences that would meet the thresholds were more likely to demonstrate meaningful clinical benefit (87.5% vs. 50.0%, p = 0.099).
Most positive SCLC-RCTs did not meet the ESMO-MCBS threshold for meaningful clinical benefits. Strict power calculations should be adopted in the design of future RCTs.
Dynamic hyperinflation in chronic obstructive pulmonary disease (COPD) results in intrinsic positive end-expiratory pressure (auto-PEEP). Automatic tube compensation (ATC) is used to increase airway pressure in COPD and overcome endotracheal tube (ETT)–imposed respiratory workload. We aim to investigate effects of ATC activation on auto-PEEP decrease in COPD.
ATC was activated three times a day (1 min duration) in the morning, evening, and night shift. Auto-PEEP was measured for the 1 min period (every 6 s) following ATC activation. Linear mixed model (LMM) was used to measure changes in auto-PEEP and compare with baseline value. Age, gender, and COPD types were inserted in model as covariates and analyzed using SPSS.
A total of 60 patients including COPD (n = 40) and COPD with exacerbation (n = 20) were included. Compared with exacerbated COPD, baseline auto-PEEP in COPD was significantly lower in morning (p = 0.011), evening (p = 0.043), and night shift (p = 0.007). After ATC activation, auto-PEEP decreased significantly in COPD in morning, evening, and night (p = 0.001), but magnitude of this decrease was notably larger in COPD than in exacerbated COPD (p = 0.001). Moreover, there was a significant relationship between COPD exacerbation and changes in auto-PEEP in morning (β = −0.27, p = 0.001), evening (β = −0.16, p = 0.001), and night (β = −0.26, p = 0.001).
The activation of ATC mode in COPD patients under mechanical ventilation could decrease the value of auto-PEEP. Nevertheless, COPD patients with an exacerbation appear to benefit less from ATC activation.
This study aimed to identify a specific SCLC population that would benefit from surgery.
This study utilized patient data retrieved from the Surveillance, Epidemiology, and End Results (SEER) database spanning 2010 to 2017. To mitigate clinical biases, the propensity score matching (PSM) technique was employed. Separate cohorts were aligned using PSM according to the AJCC 8th edition TNM classification. The Kaplan–Meier method and a competing risk model were applied to evaluate overall survival (OS) and lung cancer–specific survival (LCSS), respectively.
Among the 3394 patients with potentially resectable SCLC included in the study, 3062 underwent chemoradiotherapy and 332 underwent surgical treatment with adjuvant chemotherapy. Surgery was associated with better OS (median OS: 49 months; 95% CI: 35–63 months vs. 27 months; 95% CI: 21–33 months, p < 0.001) and LCSS (SHR, 0.578; 95% CI: 0.411–0.815, p < 0.001) in stage I patients after PSM. However, there was no significant difference in OS and LCSS between the surgery and nonsurgery groups in stage II and III patients after PSM. In the entire cohort, lobectomy was associated with improved OS (median OS: 48.6 vs. 28.7 months, p < 0.0001), but not LCSS (SHR, 0.696; 95% CI: 0.466–1.040, p = 0.078) compared with sublobar resection after PSM.
Surgery with adjuvant chemotherapy significantly improved the survival prognosis of patients with early-stage SCLC. However, surgical treatment should be carefully considered in patients with stage II/III disease. Lobectomy is oncologically equal to sublobar resection.
This study systematically analyzes the relationship of vitamin A on the neonatal respiratory diseases. An extensive literature search for relevant studies was conducted on PubMed, Web of Science, and so on. After screening in strict accordance with the inclusion and exclusion criteria, 12 articles on vitamin A deficiency and 12 articles on vitamin A supplementation were included. Stata 17.0 software was used to perform meta-analysis, heterogeneity test, and sensitivity analysis, and the corresponding mathematical model was used to merge the data. The meta-analysis results of the relationship between vitamin A deficiency and neonatal respiratory diseases indicated that compared with the neonates with normal vitamin A, the neonates with vitamin A deficiency had adverse health outcomes of neonatal respiratory diseases (OR = 4.86, 95% CI: 2.68–8.84), of which neonatal respiratory distress syndrome (NRDS) (OR = 4.10, 95% CI: 2.32–7.23) and neonatal pneumonia (OR = 3.22, 95% CI: 2.18–4.77) were analyzed by subgroup analysis. The meta-analysis of the relationship between vitamin A supplementation therapy and neonatal respiratory diseases showed that vitamin A supplementation was an effective therapeutic measure for neonatal respiratory diseases (RR = 1.06, 95% CI: 1.04–1.07): NRDS (RR = 1.03, 95% CI: 1.02–1.05) and NBPD (RR = 1.08, 95% CI: 1.01–1.15). The funnel chart method results show that there was publication bias in studies on vitamin A deficiency induced to and vitamin A supplementation therapy for neonatal respiratory diseases. The sensitivity analysis results showed that excluding some special article had some effect on the final pooled effect. But generally speaking, the result of meta-analysis was stable. There is a statistical correlation of vitamin A on the neonatal respiratory diseases from two aspects of etiological exploration and effect evaluation of treatment.
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