Plin2 inhibits autophagy via activating AKT/mTOR pathway in non-small cell lung cancer.

Perilipin 2 (Plin2) is known to be dysregulated in several human malignancies, which facilitates cancer progression. Recent studies have found that the abnormal expression of Plin2 is associated with poor prognosis of non-small cell lung cancer (NSCLC). However, the specific role of Plin2 and its underlying mechanism remain unclear. This study revealed that Plin2 expression was low in NSCLC tissues, and its relatively higher expression indicated larger tumor size and poorer prognosis. In vitro experiments proved that Plin2 promoted NSCLC cellular proliferation and inhibited autophagy by activating the AKT/mTOR pathway. Meanwhile, treatment with the AKT phosphorylation promoter or inhibitor neutralized the influence of Plin2 depletion or over-expression on proliferation and autophagy, respectively. In vivo study showed that Plin2 stimulated subcutaneous tumorigenesis of NSCLC cells in nude mice. Collectively, this study clarified the carcinogenic role of Plin2 and its molecular mechanism in NSCLC progression, which may facilitate a targeted therapy in the future.

Development and validation of prognostic nomogram for T1-3N0M0 non-small cell lung cancer after curative resection.

BACKGROUND: Radical resection plus lymph node dissection is a common treatment for patients with T1-3N0M0 non-small cell lung cancer (NSCLC). Few models predicted the survival outcomes of these patients. This study aimed to developed a nomogram for predicting their overall survival (OS). MATERIALS AND METHODS: This study involved 3002 patients with T1-3N0M0 NSCLC after curative resection between January 1999 and October 2013. 1525 Patients from Sun Yat-sen University Cancer Center were randomly allocated to training cohort and internal validation cohort in a ratio of 7:3. 1477 patients from ten institutions were recruited as external validation cohort. A nomogram was constructed based on the training cohort and validated by internal and external validation cohort to predict the OS of these patients. The accuracy and practicability were tested by Harrell's C-indexes, calibration plots and decision curve analyses (DCA). RESULTS: Age, sex, histological classification, pathological T stage, and HI standard were independent factors for OS and were included in our nomogram. The C-index of the nomogram for OS estimates were 0.671 (95% CI, 0.637-0.705),0.632 (95% CI, 0.581-0.683), and 0.645 (95% CI, 0.617-0.673) in the training cohorts, internal validation cohorts, and external validation cohort, respectively. The calibration plots and DCA for predictions of OS were in excellent agreement. An online version of the nomogram was built for convenient clinical practice. CONCLUSIONS: Our nomogram can predict the OS of patients with T1-3N0M0 NSCLC after curative resection. The online version of our nomogram offer opportunities for fast personalized risk stratification and prognosis prediction in clinical practice.

The role of ERBB4 mutations in the prognosis of advanced non-small cell lung cancer treated with immune checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have witnessed the achievements of convincing clinical benefits that feature the significantly prolonged overall survival (OS) of patients suffering from advanced non-small cell lung cancer (NSCLC), according to reports recently. Sensitivity to immunotherapy is related to several biomarkers, such as PD-L1 expression, TMB level, MSI-H and MMR. However, a further investigation into the novel biomarkers of the prognosis on ICIs treatment is required. In addition, there is an urgent demand for the establishment of a systematic hazard model to assess the efficacy of ICIs therapy for advanced NSCLC patients. METHODS: In this study, the gene mutation and clinical data of NSCLC patients was obtained from the TCGA database, followed by the analysis of the detailed clinical information and mutational data relating to two advanced NSCLC cohorts receiving the ICIs treatment from the cBioPortal of Cancer Genomics. The Kaplan-Meier plot method was used to perform survival analyses, while selected variables were adopted to develop a systematic nomogram. The prognostic significance of ERBB4 in pan-cancer was analyzed by another cohort from the cBioPortal of Cancer Genomics. RESULTS: The mutation frequencies of TP53 and ERBB4 were 54% and 8% in NSCLC, respectively. The mutual exclusive analysis in cBioPortal has indicated that ERBB4 does show co-occurencing mutations with TP53. Patients with ERBB4 mutations were confirmed to have better prognosis for ICIs treatment, compared to those seeing ERBB4 wild type (PFS: exact p = 0.017; OS: exact p < 0.01) and only TP53 mutations (OS: p = 0.021). The mutation status of ERBB4 and TP53 was tightly linked to DCB of ICIs treatment, PD-L1 expression, TMB value, and TIICs. Finally, a novel nomogram was built to evaluate the efficacy of ICIs therapy. CONCLUSION: ERBB4 mutations could serve as a predictive biomarker for the prognosis of ICIs treatment. The systematic nomogram was proven to have the great potential for evaluating the efficacy of ICIs therapy for advanced NSCLC patients.

MicroRNA-638 inhibits human aortic valve interstitial cell calcification by targeting Sp7.

Calcific aortic valve disease (CAVD) is a complex heart valve disease involving a wide range of pathological changes. Emerging evidence indicates that osteogenic differentiation of human aortic valve interstitial cells (hAVICs) plays a key role in valve calcification. In this study, we aimed to investigate the function of miR-638 in hAVICs osteogenesis. Both miRNA microarray assay and qRT-PCR results demonstrating miR-638 was obviously up-regulated in calcific aortic valves compared with non-calcific valves. We also proved that miR-638 was significantly up-regulated during hAVICs osteogenic differentiation. Overexpression of miR-638 suppressed osteogenic differentiation of hAVICs in vitro, whereas down-regulation of miR-638 enhance the process. Target prediction analysis and dual-luciferase reporter assay confirmed that Sp7 transcription factor (Sp7) was a direct target of miR-638. Furthermore, knockdown of Sp7 inhibited osteogenic differentiation of hAVICs, which is similar to the results observed in up-regulation miR-638. Our data indicated that miR-638 plays an inhibitory role in hAVICs osteogenic differentiation, which may act by targeting Sp7. MiR-638 may be a potential therapeutic target for CAVD.

Identification of DNA methylation-driven genes in esophageal squamous cell carcinoma: a study based on The Cancer Genome Atlas.

BACKGROUND: Aberrant DNA methylations are significantly associated with esophageal squamous cell carcinoma (ESCC). In this study, we aimed to investigate the DNA methylation-driven genes in ESCC by integrative bioinformatics analysis. METHODS: Data of DNA methylation and transcriptome profiling were downloaded from TCGA database. DNA methylation-driven genes were obtained by methylmix R package. David database and ConsensusPathDB were used to perform gene ontology (GO) analysis and pathway analysis, respectively. Survival R package was used to analyze overall survival analysis of methylation-driven genes. RESULTS: Totally 26 DNA methylation-driven genes were identified by the methylmix, which were enriched in molecular function of DNA binding and transcription factor activity. Then, ABCD1, SLC5A10, SPIN3, ZNF69, and ZNF608 were recognized as significant independent prognostic biomarkers from 26 methylation-driven genes. Additionally, a further integrative survival analysis, which combined methylation and gene expression data, was identified that ABCD1, CCDC8, FBXO17 were significantly associated with patients' survival. Also, multiple aberrant methylation sites were found to be correlated with gene expression. CONCLUSION: In summary, we studied the DNA methylation-driven genes in ESCC by bioinformatics analysis, offering better understand of molecular mechanisms of ESCC and providing potential biomarkers precision treatment and prognosis detection.

Isolation and Characterization of a Chinese Hamster Ovary Heparan Sulfate Cell Mutant Defective in Both Met Receptor Binding and Hepatocyte Growth Factor NK1/Met Signaling.

BACKGROUND/AIMS: The up-regulation of hepatocyte growth factor/receptor, HGF/Met, signal transduction is observed in most of human cancers. Specific heparan sulfate structures enhance the HGF/Met signaling at both cell and animal-based model systems. Biochemical studies indicate that heparan sulfate interacts with HGF and a natural occurring splicing variant NK1 of HGF with similar affinity. However, it is currently unknown if cell surface heparan sulfate binds to Met at physiological conditions and if specific cell surface heparan sulfate structures are required for effective HGF/Met or NK1/Met signaling. METHODS: An established flow sorting strategy was used to isolate a soluble Met recombinant protein-binding positive or negative CHO cell clones different only in specific heparan sulfate structures. The cell surface bindings were imaged by confocal microscopy and flow cytometry analysis. Glucosamine vs. galactosamine contents from media-, cell surface-, and cell association glycosaminoglycans were quantified by HPLC. 35S-sulfate labeled glycosaminoglycans were characterized by anion exchange and size-exclusion HPLC. Heparan sulfate disaccharide compositions were determined by HPLC-MS analysis. Western blot analyses of MAPK-p42/44 were used to monitor HGF- and NK1-facillated Met signaling. RESULTS: CHO-Positive but not CHO-Negative cell surface heparan sulfate bound to Met recombinant protein and HGF/NK1 further promoted the binding. Overall glycosaminoglycan analysis results indicated that the CHO-Negative cells had reduced amount of heparan sulfate, shorter chain length, and less 6-O-sulfated disaccharides compared to that of CHO-Positive cells. Moreover, CHO-Negative cells were defective in NK1/Met but not HGF/Met signaling. CONCLUSIONS: This study demonstrated that soluble Met recombinant protein bound to cell surface HS at physiological conditions and a Met /HGF or NK1/HS ternary signaling complex might be involved in Met signaling. Shorter HS chains and reduced 6-O-sulfation might be responsible for reduced Met binding and the diminished NK1-initiated signaling in the CHO-Negative cells. The unique CHO-Positive and CHO-Negative cell clones established in current study should be effective tools for studying the role of specific glycosaminoglycan structures in regulating Met signaling. Such knowledge should be useful in developing glycosaminoglycan-based compounds that target HGF/Met signaling.

Performance differences of Rhode Island Red, Bashang Long-tail Chicken, and their reciprocal crossbreds under natural cold stress.

OBJECTIVE: The Bashang Long-tail chicken (BS), an indigenous Chinese breed, is considered cold tolerant. We selected BS, the Rhode Island Red (RIR), and their reciprocal crossbreds for the present study. The objectives were: i) to validate whether BS is cold tolerant and whether egg production and cold tolerance of crossbreds could be improved; and ii) to determine the physiological characteristics that underlie cold tolerance and favorable egg production performance in cold environments. METHODS: A total of 916 chickens were reared in warm and natural cold environments (daily mean ambient temperature varied from 7.4°C to 26.5°C in the warm environment and from -17.5°C to 27.0°C in the cold environment). To investigate their adaptability to the cold environment, the egg production performance and body weight were monitored and compared between breeds and environments. The cloacal temperature and serum biochemical parameters were monitored to reveal the physiological characteristics underlie cold tolerance and favorable egg production performance in the cold environment. RESULTS: The warm environment experiment showed that RIR had the highest egg production performance, and that the reciprocal crossbreds had a higher egg production performance than BS. While in the cold environment RIR had the lowest egg production performance, and the reciprocal crossbreds had a higher egg production performance than BS. In the cold environment BS and reciprocal crossbreds had higher triiodothyronine, tetraiodothyronine levels than RIR. At 35 and 39 wk of age, when the ambient temperature was extremely low (varied from -20°C to 0°C), serum glucose, follicle-stimulating hormone, luteinizing hormone, estradiol of BS and crossbreds were higher than RIR. CONCLUSION: Bashang Long-tail chicken has a favorable cold tolerance ability. Crossbreeding with RIR and BS is an effective way to develop cold tolerant chickens with improved egg production performance.

Pathogenic role of super-enhancers as potential therapeutic targets in lung cancer.

Lung cancer is still one of the deadliest malignancies today, and most patients with advanced lung cancer pass away from disease progression that is uncontrollable by medications. Super-enhancers (SEs) are large clusters of enhancers in the genome's non-coding sequences that actively trigger transcription. Although SEs have just been identified over the past 10 years, their intricate structure and crucial role in determining cell identity and promoting tumorigenesis and progression are increasingly coming to light. Here, we review the structural composition of SEs, the auto-regulatory circuits, the control mechanisms of downstream genes and pathways, and the characterization of subgroups classified according to SEs in lung cancer. Additionally, we discuss the therapeutic targets, several small-molecule inhibitors, and available treatment options for SEs in lung cancer. Combination therapies have demonstrated considerable advantages in preclinical models, and we anticipate that these drugs will soon enter clinical studies and benefit patients.

The predictive value of serum tumor markers for EGFR mutation in non-small cell lung cancer patients with non-stage IA.

Objective: The predictive value of serum tumor markers (STMs) in assessing epidermal growth factor receptor (EGFR) mutations among patients with non-small cell lung cancer (NSCLC), particularly those with non-stage IA, remains poorly understood. The objective of this study is to construct a predictive model comprising STMs and additional clinical characteristics, aiming to achieve precise prediction of EGFR mutations through noninvasive means. Materials and methods: We retrospectively collected 6711 NSCLC patients who underwent EGFR gene testing. Ultimately, 3221 stage IA patients and 1442 non-stage IA patients were analyzed to evaluate the potential predictive value of several clinical characteristics and STMs for EGFR mutations. Results: EGFR mutations were detected in 3866 patients (57.9 %) of all NSCLC patients. None of the STMs emerged as significant predictor for predicting EGFR mutations in stage IA patients. Patients with non-stage IA were divided into the study group (n = 1043) and validation group (n = 399). In the study group, univariate analysis revealed significant associations between EGFR mutations and the STMs (carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), and cytokeratin-19 fragment (CYFRA21-1)). The nomogram incorporating CEA, CYFRA 21-1, pathology, gender, and smoking history for predicting EGFR mutations with non-stage IA was constructed using the results of multivariate analysis. The area under the curve (AUC = 0.780) and decision curve analysis demonstrated favorable predictive performance and clinical utility of nomogram. Additionally, the Random Forest model also demonstrated the highest average C-index of 0.793 among the eight machine learning algorithms, showcasing superior predictive efficiency. Conclusion: CYFRA21-1 and CEA have been identified as crucial factors for predicting EGFR mutations in non-stage IA NSCLC patients. The nomogram and 8 machine learning models that combined STMs with other clinical factors could effectively predict the probability of EGFR mutations.

Adjuvant Therapy-Free Strategy for Stage IB to IIIA Non-Small-Cell Lung Cancer Patients After Radical Resection Based on Longitudinal Undetectable Molecular Residual Disease: Prospective, Multicenter, Single-Arm Study (CTONG 2201).

BACKGROUND: The utility of circulating tumor DNA to monitor molecular residual disease (MRD) has been clinically confirmed to predict disease recurrence in non-small cell lung cancer (NSCLC) patients after radical resection. Patients with longitudinal undetectable MRD show a favorable prognosis and might not benefit from adjuvant therapy. PATIENTS AND METHODS: The CTONG 2201 trial is a prospective, multicenter, single-arm study (ClinicalTrials.gov identifier, NCT05457049), designed to evaluate the hypothesis that no adjuvant therapy is needed for patients with longitudinal undetectable MRD. Pathologically confirmed stage IB-IIIA NSCLC patients who have undergone radical resection will be screened. Only patients with 2 consecutive rounds of undetectable MRD will be enrolled (first at days 3-10, second at days 30 ± 7 after surgery), and admitted for imaging and MRD monitoring every 3 months without adjuvant therapy. The primary endpoint is the 2-year disease-free survival rate for those with longitudinal undetectable MRD. The recruitment phase began in August 2022 and 180 patients will be enrolled. CONCLUSIONS: This prospective trial will contribute data to confirm the negative predictive value of MRD on adjuvant therapy for NSCLC patients. CLINICAL TRIAL REGISTRATION: NCT05457049 (CTONG 2201).

Identification of the intersegmental plane via electromagnetic navigation for anatomical segmentectomy.

Accurate identification of the physiological intersegmental plane is crucial for successful anatomical segmentectomy. Current techniques, such as the inflation-deflation method, may result in uncertain cutting lines, leading to unsuitable resection extents. Here, we demonstrated the successful use of electromagnetic navigation with methylene blue dye-marking to preoperatively and precisely identify the physiological intersegmental plane in two patients with small-sized peripheral non-small cell lung cancer (NSCLC). This novel technique offers the potential for precise cutting lines that align closely with the physiological intersegmental plane, thus improving the accuracy and efficacy of anatomical segmentectomy for these selected NSCLC patients.

[Development and Validation of A Prognostic Nomogram to Guide Decision-making 
in Lung Large Cell Neuroendocrine Carcinoma].

BACKGROUND: Lung large cell neuroendocrine carcinoma (LCNEC) is a rare and highly malignant lung tumor with a poor prognosis. Currently, most research on LCNEC is based on retrospective studies and lacks validation in the real world. The study aims to identify independent risk factors and establish and validate a predictive model for the prognosis of LCNEC. METHODS: Patient data were extracted from Surveillance, Epidemiology, and End Results (SEER) and our department's hospitalization records from 2010 to 2015 and 2016 to 2020, respectively. Kaplan-Meier analysis was used to evaluate overall survival (OS). OS is defined as the time from diagnosis to death or last follow-up for a patient. Univariate and multivariate Cox regression analyses were performed to identify significant prognostic factors and construct a Nomogram for predicting the prognosis of LCNEC. RESULTS: In total, 1892 LCNEC patients were included and divided into a training cohort (n=1288) and two validation cohorts (n=552, n=52). Univariate Cox regression analysis showed that age, gender, primary tumor site, laterality, T stage, N stage, M stage, surgery, and radiotherapy were factors that could affect the prognosis of LCNEC patients (P<0.05). Multivariate Cox analysis indicated that age, gender, primary tumor site, T stage, N stage, M stage, surgery, and radiotherapy were independent risk factors for the prognosis of LCNEC patients (P<0.05). Calibration curves and the concordance index (internal: 0.744±0.015; external: 0.763±0.020, 0.832±0.055) demonstrated good predictive performance of the model. CONCLUSIONS: Patients aged ≥65 years, male, with advanced tumor-node-metastasis (TNM) staging, and who have not undergone surgery or radiotherapy have a poor prognosis. Nomogram can provide a certain reference for personalized clinical decision-making for patients.

Different nodal upstaging rates and prognoses for patients with clinical T1N0M0 lung adenocarcinoma classified according to the presence of solid components in the lung and mediastinal windows.

Background: Little is known about the correlation between nodal upstaging and pulmonary nodules classified according to the presence of solid components in the lung and mediastinal windows. This study thus aimed to analyze the risk factors of nodal upstaging and prognosis based on different imaging features, clinical characteristics, and pathological results from patients with clinical stage T1N0M0 lung adenocarcinoma. Methods: A total of 340 patients between January 2016 and June 2017 were selected from the Affiliated Hospital of Qingdao University database. Imaging features, clinical characteristics, and pathological results were collected for survival and analysis of nodal upstaging risk factors. We used logistic regression models to identify important metastatic risk factors for nodal upstaging. Survival rates were calculated using Kaplan-Meier (KM) survival curves and compared with the log-rank test. Significant prognostic risk factors were identified using the Cox proportional hazards model. Results: A total of 340 patients, with an average age of 64.89 (±8.775) years, were enrolled. Among them, nonnodal upstaging occurred both in 77 (22.6%) patients with pure ground-glass nodules (pGGNs) and in 30 (8.8%) patients with heterogenous ground-glass nodules (hGGNs). Compared to the 92 (27.1%) patients with real part-solid nodules (rPSNs), the 141 (41.5%) patients with solid nodules were significantly different in terms of in nodal upstaging (P<0.001). Moreover, preoperative carcinoembryonic antigen (CEA) level >3.4 µg/L [odds ratio (OR): 2.931; 95% confidence interval (CI): 1.511-5.688; P=0.001], imaging tumor size >18.3 mm (OR, 3.482; 95% CI: 1.609-7.535; P=0.002), and consolidation tumor ratio (CTR) >0.788 (OR 8.791; 95% CI: 3.570-21.651; P<0.001) were independent risk factors for nodal upstaging. The KM survival curve results showed that patients with pGGNs and those with hGGNs had a much better 5-year disease-free survival (DFS) and 5-year overall survival (OS) than did those with rPSNs and those with solid nodules (DFS: 98.7% vs. 100% vs. 81.4% vs. 73.7%, P<0.001; OS: 97.4% vs. 100% vs. 90.2% vs. 83.7%, P=0.003). In the multivariate Cox regression analysis of patients with rPSNs and solid nodules, tumor location and pathological lymph node grade were found to be independent risk factors for DFS and OS. Conclusions: Patients with pGGNs and those with hGGNs were more likely to be free of nodal upstaging and had better prognosis than did those with clinical stage IA rPSNs and solid nodules. The patients with pGGNs or hGGNs with preoperative CEA level <3.4 µg/L, imaging tumor size <18.3 mm, and CTR <0.788 can choose systematic lymph node sampling (SLNS) or decline lymph node dissection to avoid postoperative complications.

Osimertinib as neoadjuvant therapy in patients with EGFR-mutant resectable stage II-IIIB lung adenocarcinoma (NEOS): A multicenter, single-arm, open-label phase 2b trial.

OBJECTIVES: Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has been approved for EGFR-mutant non-small-cell lung cancer (NSCLC). We aimed to evaluate the efficacy and safety of neoadjuvant osimertinib in patients with EGFR-mutant resectable locally advanced NSCLC. MATERIALS AND METHODS: This single-arm, phase 2b trial (ChiCTR1800016948) was conducted at six centers in mainland China. Patients with a measurable stage IIA-IIIB (T3-4 N2) lung adenocarcinoma and EGFR exon 19 and/or 21 mutations were enrolled. The patients were treated with osimertinib 80 mg orally once per day for six weeks, followed by surgical resection. The primary endpoint was the objective response rate (ORR) assessed according to the Response Evaluation Criteria In Solid Tumors version 1.1. RESULTS: Between October 17, 2018, and June 08, 2021, 88 patients were screened for eligibility. Forty patients were enrolled and treated with neoadjuvant osimertinib therapy. The ORR was 71.1 % (27/38) (95 % confidence interval: 55.2-83.0) in 38 patients who completed the 6-week osimertinib treatment. Thirty-two patients underwent surgery, and 30 (93.8 %) underwent successful R0 resection. Thirty (75.0 %) of 40 patients had treatment-related adverse events during neoadjuvant treatment, and three (7.5 %) had treatment-related adverse events of grade 3. The most common treatment-related adverse events were rash (n = 20 [50 %]), diarrhea (n = 12 [30 %]), and oral ulceration (n = 12 [30 %]). CONCLUSIONS: The third-generation EGFR TKI osimertinib, with satisfying efficacy and acceptable safety profile, could be a promising neoadjuvant therapy in patients with resectable EGFR-mutant NSCLC.

Randomized Trial of Modified Chest Tube Placement vs Routine Placement After Lung Resection.

BACKGROUND: Chest tube placement after pulmonary resection is usually considered a mandatory procedure. However, peritubular leakage of pleural fluid and intrathoracic air is frequent after surgery. Therefore, we separated the chest tube from the intercostal space as a modified placement strategy. METHODS: Patients undergoing robotic and video-assisted lung resection were enrolled in this study at our medical center between February 2021 and August 2021. All patients were randomly divided into either the modified group (n = 98) or the routine group (n = 101). The incidence of peritubular leakage of pleural fluid and peritubular air leaking or entering after surgery were the primary end points of the study. RESULTS: A total of 199 patients were randomized. Patients in the modified group had lower incidence of peritubular leakage of pleural fluid (after surgery, 39.6% vs 18.4% [P = .001]; after chest tube removal, 26.7% vs 11.2% [P = .005]), lower incidence of peritubular air leaking or entering (14.9% vs 5.1% [P = .022]), and fewer dressing changes (5.02 ± 2.30 vs 3.48 ± 0.94 [P < .001]). In patients undergoing lobectomy and segmentectomy, the type of chest tube placement was associated with the severity of peritubular pleural fluid leakage (P < .05). CONCLUSIONS: The modified chest tube placement was safe and had better clinical efficacy than the routine type. The reduction of postoperative peritubular leakage of pleural fluid resulted in better wound recovery. This modified strategy should be popularized, especially in patients undergoing pulmonary lobectomy or segmentectomy.

Progress in three-dimensional computed tomography reconstruction in anatomic pulmonary segmentectomy.

The number of minimally invasive surgeries, such as video-assisted thoracoscopic surgery and robot-assisted thoracoscopic surgery, has increased enormously in recent years. More and more relevant studies report that anatomic pulmonary segmentectomy has the same effect as traditional lobectomy in the surgical treatment of early stage non-small cell lung cancer (diameter less than 2.0 cm). Segmentectomy requires sufficient knowledge of the location of the pulmonary nodules, as well as the anatomy of the target segments, blood vessels, and bronchi. With the rapid development of imaging technology and three-dimensional technology, three-dimensional reconstruction has been widely used in the medical field. It can effectively assess the vascular branching patterns, discover the anatomic variations of the blood vessels and bronchi, determine the location of the lesion, and clarify the division of the segments. Therefore, it is helpful for preoperative positioning, surgical planning, preoperative simulation and intraoperative navigation, and provides a reference for formulating an individualized surgical plan. It therefore plays a positive role in anatomic pulmonary segmentectomy. This study reviews the progress made in three-dimensional computed tomography reconstruction in anatomic pulmonary segmentectomy.

[Research Progress, Benefit Groups, Treatment Cycle and Efficacy Prediction 
of Neoadjuvant Immunotherapy for Non-small Cell Lung Cancer].

The emergence of immune checkpoint inhibitors (ICIs) has dramatically changed the therapeutic outlook for patients with non-small cell lung cancer (NSCLC). Preoperative neoadjuvant immunotherapy has been paid more and more attention as an effective and safe treatment. Neoadjuvant immune therapy, however, the relevant research started late, relatively few research results and mainly focused on the small sample size of phase I and II studies, treatment itself exists many places it is not clear, also in benefit population screening, the respect such as the choice of treatment and curative effect prediction has not yet reached broad consensus. This paper reviews the important studies and recent achievements related to neoadjuvant immunotherapy, aiming to comprehensively discuss the procedures and existing problems of this kind of therapy from three aspects of beneficiary groups, treatment cycle and efficacy prediction.
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Positron emission tomography/computed tomography and endobronchial ultrasound-guided transbronchial needle aspiration to evaluate the status of N2 in preoperative non-small cell lung cancer: a diagnostic test.

Background: As a minimally invasive method, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) was more accurate than non-invasive methods such as positron emission tomography (PET) and computed tomography (CT) to evaluate the lymph nodes in preoperative non-small cell lung cancer (NSCLC). PET/CT has more anatomical advantages than PET scanning and is more accurate in lung cancer staging. However, no relevant studies have comparatively evaluated PET/CT and EBUS-TBNA for NSCLC patients. Methods: A total of 112 patients were included in this retrospective analysis. The golden diagnosis of N2 status was postoperative pathological results. In EBUS-TBNA puncture specimens, if clear malignant tumor cells could be seen, the results were taken as positive. In PET/CT image analysis, the CT values, short diameter, and maximum standardized uptake value (SUVmax) of each lymph node were recorded to evaluate N2 status. The results of PET/CT and EBUS-TBNA were compared with the final pathological results, and respective sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated. - Then, the patients were divided into adenocarcinoma group and squamous cell carcinoma group -and the results were calculated and compared with the above method. Results: The results showed that EBUS-TBNA had a higher diagnostic value for mediastinal lymph nodes than PET/CT, and the difference was statistically significant (P<0.001). In NSCLC patients, the results showed that the sensitivity (P=0.013), specificity (P<0.001), PPV (P<0.001), NPV (P<0.001), and accuracy (P<0.001) of EBUS-TBNA were higher than that of PET/CT (AUC =0.954 and 0.636, respectively). In adenocarcinoma cases, specificity (P<0.001), PPV (P<0.001), NPV (P<0.001), and accuracy (P<0.001) of EBUS-TBNA were higher than that of PET/CT (AUC =0.957 and 0.596, respectively).In cases with squamous cell carcinoma, specificity (P=0.003), PPV (P<0.001), and accuracy (P<0.001) of EBUS-TBNA were higher than PET/CT (AUC =0.952 and 0.657, respectively). Conclusions: For preoperative diagnosis of mediastinal lymph node metastases in NSCLC, EBUS-TBNA is more accurate than PET/CT. For those patients with suspected mediastinal lymph node metastasis, EBUS-TBNA should be preferred method to evaluate the status of mediastinal lymph nodes.

Single utility port approach in robot-assisted sleeve segmentectomy for bronchial carcinoid tumor.

Bronchial carcinoid tumors are low-grade malignant and lung-sparing surgery is preferred for the removal of these tumors. We describe a surgical technique of robot-assisted sleeve segmentectomy via single utility port approach with three robotic arms. This operation was performed in an aged patient with decreased pulmonary function, whose carcinoid tumor was located at the origin of the right superior segmental bronchus. A 1.5-cm incision was performed in the eighth intercostal space of the midaxillary line and another 4-cm incision was made in the fifth intercostal space of the anterior axillary line. Postoperative recovery of the patient was smooth without postoperative complications.

Development and validation of a prognostic risk signature for lung adenocarcinoma constructed by six ferroptosis, necroptosis, and pyroptosis-related lncRNAs.

Background: Identifying populations that benefit from immune checkpoint blockade (ICB) therapy remains a major challenge in the treatment of lung adenocarcinoma (LUAD). Existing programmed cell death (PCD) related prognostic models only consider a single mechanism, such as ferroptosis, necroptosis, and pyroptosis, and do not reflect the interaction of multiple mechanisms. This study aims to explore lncRNAs associated with multiple modes of PCD and reveal a risk signature to assess prognosis and treatment outcomes in LUAD patients. Methods: Based on expression data in The Cancer Genome Atlas (TCGA) database, ferroptosis, necroptosis, and pyroptosis-related lncRNAs (FNPRlncRNAs) were obtained by taking the intersection of ferroptosis-related lncRNAs (FRlncRNAs), necroptosis-related lncRNAs (NRlncRNAs), and pyroptosis-related lncRNAs (PRlncRNAs) differentially expressed in LUAD and normal tissues. Patients with complete survival information and expression data from TCGA database were randomly assigned to training and testing sets (1:1). Univariate, LASSO, and multivariate Cox regression analyses were performed on the training set, and a risk signature was established. Kaplan-Meier survival curves were used to verify the prognostic ability of risk signature, and receiver operating characteristic (ROC) curves were used to assess the predictive accuracy. We then analyzed molecular and immune profile differences between high and low-risk subgroups. T-cell dysfunction and Exclusion (TIDE) scores were used to assess the response to immunotherapy in each risk subgroup. Finally, three LUAD clusters (C1, C2, and C3) were identified according to the risk signature. Results: Patients in the low-risk subgroup had higher overall survival (OS) than that in the high-risk subgroup in the K-M survival curve. The area under ROC curves (AUC) of 1-, 3-, and 5-year ROC were 0.742, 0.762, and 0.749 in the training set, and 0.672, 0.642, and 0.563 in the testing set, respectively. Compared with the high-risk subgroup, patients in the low-risk subgroup have beneficial tumor immune microenvironment and molecular characteristics, but are less likely to benefit from immunotherapy. Finally, the three LUAD clusters (C1, C2, C3) identified by risk signature had different responses to drug treatment. Conclusions: The prognosis risk signature constructed using FNPRlncRNAs is helpful to predict the prognosis of LUAD and may contribute to its individualized treatment.