BACKGROUND: Previous studies have shown that the levels of 15‐lipoxygenase 1 (15‐LOX‐1) and 15‐LOX‐2 as well as their metabolites 13‐S‐hydroxyoctadecadienoic acid (13(S)‐HODE) and 15(S)‐hydroxyeicosatetraenoic acid (15(S)‐HETE) are significantly reduced in smokers with non–small cell lung carcinoma (NSCLC). Furthermore, animal model experiments have indicated that the reduction of these molecules occurs before the establishment of cigarette smoking carcinogen–induced lung tumors, and this suggests roles in lung tumorigenesis. However, the functions of these molecules remain unknown in NSCLC.METHODS: NSCLC cells were treated with exogenous 13(S)‐HODE and 15(S)‐HETE, and then the ways in which they affected cell function were examined. 15‐LOX‐1 and 15‐LOX‐2 were also overexpressed in tumor cells to restore these 2 enzymes to generate endogenous 13(S)‐HODE and 15(S)‐HETE before cell function was assessed.RESULTS: The application of exogenous 13(S)‐HODE and 15(S)‐HETE significantly enhanced the activity of peroxisome proliferator‐activated receptor γ (PPARγ), inhibited cell proliferation, induced apoptosis, and activated caspases 9 and 3. The overexpression of 15‐LOX‐1 and 15‐LOX‐2 obviously promoted the endogenous levels of 13(S)‐HODE and 15(S)‐HETE, which were demonstrated to be more effective in the inhibition of NSCLC.CONCLUSIONS: This study has demonstrated that exogenous or endogenous 13(S)‐HODE and 15(S)‐HETE can functionally inhibit NSCLC, likely by activating PPARγ. The restoration of 15‐LOX activity to increase the production of endogenous 15(S)‐HETE and 13(S)‐HODE may offer a novel research direction for molecular targeting treatment of smoking‐related NSCLC. This strategy can potentially avoid side effects associated with the application of synthetic PPARγ ligands. Cancer 2015;121:3130‐45. © 2015 American Cancer Society.

Patients with non-small-cell lung cancer (NSCLC) and primary or acquired resistance do not respond to targeted drugs. We explored whether cancer cells can be cultured from liquid biopsies from patients with primary resistance to tyrosine kinase inhibitors (TKIs). We aimed to predict patients’ responses to drugs according to in vitro drug testing results. Cancer cell cultures were established from the pleural effusion of a patient with TKI-resistant NSCLC using a conditional reprogramming technique. Phenotypic drug sensitivity tests were performed using the Cell Counting Kit-8 assay. We tested individual drugs and compared the synergistic and inhibitory effects of drug combinations. The results of our in vitro sensitivity test using the combination of cisplatin and pemetrexed were correlated with the patient’s response. This represents the first successful report of predictive testing for combination therapy in patients with epidermal growth factor receptor-mutant NSCLC and primary TKI resistance. This strategy should be applicable to both chemotherapies and targeted therapies, and it will significantly improve the clinical treatment and management of patients with NSCLC and primary or acquired resistance to targeted therapies, as well as patients lacking targetable mutations.

Background: There is an increasing demand for minimally invasive myxoma resection. This study aimed to investigate the safety and feasibility of minimally invasive myxoma resection. Methods: In this retrospective study, we collected information from 95 patients who underwent myxoma resection between January 2016 and December 2020. Based on the operative approach, the patients were divided into the minimally invasive myxoma resection (Mini-MR) group (N = 30) and the sternotomy myxoma resection (SMR) group (N = 65). Intraoperative and postoperative data were compared between the two groups. Results: The postoperative ventilator-assisted time, CSICU time, and postoperative hospital stay were shorter in the Mini-MR group than in the SMR (13.05 ± 4.98 vs. 17.07 ± 9.52 h; 1.73 ± 0.29 vs. 2.27 ± 1.53 d; 6.20 ± 1.50 vs. 9.48 ± 3.37 d, respectively), and the difference was statistically significant (P < 0.05). Mini-MR had lower postoperative drainage and blood transfusion rate in the first 24 h compared with SMR (38.93 ± 69.62 vs. 178.25 ± 153.06 ml; 26.6% vs. 63.1%), and the differences were statistically significant (P < 0.05). Conclusion: Mini-MR has the advantages of less CSICU stay time, less ventilator time, less postoperative drainage in the first 24h, less blood transfusion, fewer postoperative hospital stays, and faster recovery. Mini-MR is a safe and feasible surgical procedure for myxoma resection.

Background. The need for minimally invasive Bentall surgery for the treatment of aortic lesions with aortic insufficiency is increasing; however, comparative studies on the safety of the minimally invasive Bentall procedure and sternotomy Bentall procedure are lacking. Methods. Clinical data of 56 patients who underwent the Bentall procedure performed by the same surgical team at our center between December 2018 and December 2021 were retrospectively analyzed and followed up for 6 months after discharge. After dividing the patients into a right anterior chest minimally invasive Bentall surgery (RAT-Bentall) group (n = 13) and a conventional sternotomy Bentall surgery (C-Bentall) group (n = 43), intraoperative and early postoperative clinical data and echocardiography at 6 months after discharge were compared. Results. Compared with the C-Bentall group, the RAT-Bentall group had a lower postoperative visual analogue scale (VAS) pain score [(3.00 ± 2.08) VS (5.77 ± 1.84), ] and a shorter CSICU hospital stay [(1.90 ± 0.52) VS (2.51 ± 1.58) d, ] and postoperative hospital stay [(7.62 ± 1.81) VS (10.42 ± 2.45) d, ]. The incidence of postoperative complications and echocardiographic at 6-month follow-up after discharge was not statistically different between the two groups. Conclusion. The RAT-Bentall procedure is safe and effective. Compared with the sternotomy Bentall procedure, it can reduce postoperative pain as well as patients’ CSICU and postoperative hospital stay. Therefore, this technology is worth promoting and applying.

BackgroundIncreasing demand for minimally invasive myxoma resection. This study aimed to investigate the safety and feasibility of minimally invasive myxoma resection. MethodsThis is a retrospective study, we collected information on 95 patients who underwent myxoma resection from January 2016 to December 2020. According to the operative approach, they were divided into a minimally invasive myxoma resection(Mini-MR) group (n=30) and a sternotomy myxoma resection(SMR) group (n=65), we compared the intraoperative and postoperative data between the two groups. ResultsPostoperative ventilator assisted time, CSICU time and postoperative hospital stay of Mini-AVR were shorter than SAVR [(13.05 ± 4.98) VS (17.07 ± 9.52)h ;(1.73 ± 0.29) VS (2.27 ± 1.53)d; (6.20 ± 1.50) VS (9.48 ± 3.37)d], the difference was statistically significant (P <0.05). Mini-AVR has lower postoperative drainage and blood transfusion rate of the first 24 h compared with SAVR [(38.93 ± 69.62) VS (178.25 ± 153.06)ml; 26.6% VS 63.1%], the differences were statistically significant (P <0.05). ConclusionMini-MR has the advantages of less CSICU stay time, less ventilator time, less postoperative drainage the first 24h, less blood transfusion, fewer postoperative hospital stays, and faster recovery. Mini-MR is a safe and feasible surgical procedure for the resection of myxoma.

Background: Sepsis-induced cardiomyopathy (SICM) is a life-threatening complication driven by inflammatory cascades. Current genetic studies are restricted to single-trait analyses that cannot capture the shared genetic architecture spanning from immune dysregulation to structural myocardial damage. Methods: We applied genomic structural equation modeling to integrate genome-wide association study (GWAS) summary statistics for six phenotypes—sepsis, cardiac troponin I, left ventricular ejection fraction (LVEF), left ventricular diastolic strain rate, right ventricular peak ejection rate, and heart failure—constructing a latent factor for the shared genetic basis of SICM-related phenotypes. Downstream analyses included multivariate GWAS, fine-mapping (SuSiE/FINEMAP), sparse canonical correlation analysis-based transcriptome-wide association study (sCCA-TWAS) with FOCUS prioritization, MAGMA gene-set enrichment, cell-type enrichment (CELLECT), spatial transcriptomic mapping (gsMap), and stratified LD score regression (S-LDSC). Results: The model showed adequate fit (CFI = 0.936), with left ventricular diastolic strain rate and LVEF anchoring the factor most strongly (λ = 0.811 and 0.636, respectively). Multivariate GWAS identified 4220 lead variants, of which 4197 did not reach genome-wide significance in any constituent single-trait GWAS. Cross-referencing sCCA-TWAS with FOCUS fine-mapping prioritized 39 genes spanning inflammatory transduction, gap junction remodeling, proteostatic defense, and energy sensing. AMPK signaling was recurrently captured across fine-mapping and transcriptome-wide analyses. CELLECT identified cardiac muscle cells as the sole significant cell type. Conclusions: This study provides the first integrative multi-trait genetic framework for the shared genetic basis of SICM-related phenotypes, identifying AMPK as a recurrently captured pleiotropic hub at the inflammation–metabolism intersection and providing a foundation for future biomarker and mechanistic investigations.