Mechanism of low-intensity pulse ultrasound combined with Rhodiola to promote bone formation in spinal fusion.

This study aimed to explore the influence and mechanism of low-intensity pulsed ultrasound (LIPUS) combined with Rhodiola bone penetration on the formation of spinal fusion bone. Sixty clean-grade New Zealand white rabbits were selected for randomization and divided into combined group and Rhodiola group, with 30 rabbits in each group to construct a rabbit lumbar intervertebral fusion model, using Rhodiola intervention and Rhodiola combined with LIPUS intervention protocol, respectively. The axial strength, axial stiffness, maximum compressive load, vascular endothelial growth factor (VEGF), cycloxygenase-2 (COX-2), prostaglandin E2 (PGE2) and transforming growth factor-ß (TGF-ß) were compared after HE staining, immunohistochemistry and biomechanical detection. Spine fusion rate was 100.00%; the combined bone graft tissue had implanted bone cell degeneration, cell necrosis and cell hyperplasia, chondrocytes differentiated into trabecular bone and some hematopoietic cells, severe cell necrosis and fiber cell proliferation and late bone formation in the Rhodiola group, VEGF, COX-2, PGE2, TGF-ß, axial strength, axial stiffness, and maximum compression load in the combined group significantly increased (P<0.05). Spinal fusion using LIPUS combined with Rhodiola can enhance biomechanical properties and promote the role of PGE2, COX-2, VEGF, TGF-ß expression and bone formation, and this protocol is worthy of clinical application.

Stereotactic body radiotherapy with sequential tislelizumab and chemotherapy as neoadjuvant therapy in patients with resectable non-small-cell lung cancer in China (SACTION01): a single-arm, single-centre, phase 2 trial.

BACKGROUND: Neoadjuvant immunotherapy with chemotherapy improves outcomes in patients with resectable non-small-cell lung cancer (NSCLC). Given its immunomodulating effect, we investigated whether stereotactic body radiotherapy (SBRT) enhances the effect of immunochemotherapy. METHODS: The SACTION01 study was a single-arm, open-label, phase 2 trial that recruited patients who were 18 years or older and had resectable stage IIA-IIIB NSCLC from the Sun Yat-sen University Cancer Center, Guangzhou, China. Eligible patients received SBRT (24 Gy in three fractions) to the primary tumour followed by two cycles of 200 mg intravenous PD-1 inhibitor, tislelizumab, plus platinum-based chemotherapy. Surgical resection was performed 4-6 weeks after neoadjuvant treatment. The primary endpoint was major pathological response (MPR), defined as no more than 10% residual viable tumour in the resected tumour. All analyses were conducted on an intention-to-treat basis, including all patients who were scheduled for neoadjuvant treatment. The trial was registered with ClinicalTrials.gov (NCT05319574) and is ongoing but closed to recruitment. FINDINGS: Between May 18, 2022, and June 20, 2023, 46 patients (42 men and four women) were enrolled and scheduled for neoadjuvant treatment. MPR was observed in 35 (76%, 95% CI 61-87) of 46 patients. The second cycle of immunochemotherapy was withheld in four (9%) patients due to pneumonia (n=2), colitis (n=1), and increased creatinine (n=1). Grade 3 or worse adverse events related to neoadjuvant treatment occurred in 12 (26%, 95% CI 14-41) patients. The most frequent treatment-related adverse event (TRAE) was alopecia (16 [35%] patients), and the most frequent grade 3 or worse TRAE was neutropenia (six [13%]). There was one treatment-related death, caused by neutropenia. No deaths within 90 days of surgery were reported. INTERPRETATION: Preoperative SBRT followed by immunochemotherapy is well tolerated, feasible, and leads to a clinically significant MPR rate. Future randomised trials are warranted to support these findings. FUNDING: BeiGene.

Expert consensus on the multidisciplinary diagnosis and treatment of multiple ground glass nodule-like lung cancer (2024 Edition).

ABSTRACT: This expert consensus reviews current literature and provides clinical practice guidelines for the diagnosis and treatment of multiple ground glass nodule-like lung cancer. The main contents of this review include the following: ① follow-up strategies, ② differential diagnosis, ③ diagnosis and staging, ④ treatment methods, and ⑤ post-treatment follow-up.

Polysaccharides Analysis of Cell Wall Using Carbohydrate Gel Electrophoresis.

The plant cell wall is rich in polysaccharides with high heterogeneity. Investigating the composition and structure of cell wall polysaccharides is crucial for understanding the functionalities of plant cell walls. Carbohydrate electrophoresis is a sensitive and rapid method to analyze polysaccharides qualitatively and quantitatively. The process includes digesting the polysaccharides with appropriate cleavage enzymes, labeling the reducing ends of the released oligosaccharides with a highly charged fluorophore, and separating the labeled oligosaccharides in a polyacrylamide gel via high-voltage electrophoresis. The generated fluorescence can be calculated as compared to that of oligosaccharide standards. Therefore, this is a convenient method for polysaccharide characterization that can be performed in most laboratories. Here, we introduce the detailed operational steps and precautions, which are helpful for researchers to quickly obtain the structural information of polysaccharides.

Prevalence and quantity of lymph nodes at mediastinal stations in patients with lung cancer: lessons from 181 bilateral mediastinal lymphadenectomies.

BACKGROUND: This study evaluated the prevalence and quantity of lymph nodes at particular stations of the mediastinum in patients with lung cancer. These data are important to radiologists, pathologists, and thoracic surgeons because they can serve as a benchmark when assessing the completeness of lymph node dissection. However, relevant data in the literature are scarce. METHODS: Data regarding the number of lymph nodes derived from two randomised trials of bilateral mediastinal lymph node dissection, the BML-1 and BML-2 study, were included in this analysis. Detectable nodes at particular stations of the mediastinum and the number of nodes at these stations were analysed. RESULTS: The mean number of removed nodes was 28.67 (range, 4-88). Detectable lymph nodes were present at stations 2R, 4R, and 7 in 93%, 98%, and 99% of patients, respectively. Nodes were rarely present at stations 9 L (33%), and 3 (35%). The largest number of nodes was observed at stations 7 and 4R (mean, 5 nodes). CONCLUSION: The number of mediastinal lymph nodes in patients with lung cancer may be greater than that in healthy individuals. Lymph nodes were observed at stations 2R, 4R, and 7 in more than 90% of patients with lung cancer. The largest number of nodes was observed at stations 4R and 7. Detectable nodes were rarely observed at stations 3 and 9 L. TRIAL REGISTRATION: ISRCTN 86,637,908.

Preparation and application of alkali-activated cementitious materials in solidification/stabilization of chromite ore processing residue.

Chromite ore processing residue (COPR) is a typical hazardous waste, which contains Cr(vi) and poses a great threat to the ecological environment and human health. In this study, solidification/stabilization (S/S) of COPR was carried out by using blast furnace slag (BFS) and fly ash (FA) to prepare alkali-activated cementitious materials (AACM). The influence of different factors (water glass modulus, liquid-solid ratio, alkali-solid content and curing temperature) on compressive strength was investigated by single-factor experiment. Additionally, solidification effect of AACM was determined according to the compressive strength and the leaching concentration of chromium (Cr(vi) and total Cr). According to the optimal conditions of the single-factor experiment, the highest compressive strength of 147.6 MPa was obtained after using the water glass modulus 1.0, liquid-solid ratio 0.28, alkali-solid content 8%, curing temperature 45 °C. The COPR was solidified in the AACM sample having highest compressive strength. The solidified body still has a good mechanical property (38.2 MPa) with 60% addition COPR. According to leaching tests, the leaching of Cr(vi) and total Cr of solidified body with 50% COPR was far lower than the limit value, which met the purpose of construction and landfill disposal. X-ray diffraction (XRD) analysis, Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) analysis proved that heavy metal chromium was solidified in AACM by physical and chemical means.

Diagnostic yield using electromagnetic navigation bronchoscopy for peripheral pulmonary nodules <2 cm.

BACKGROUND: Although electromagnetic navigation bronchoscopy (ENB) is highly sensitive in the diagnosis of peripheral pulmonary nodules (PPNs), its diagnostic yield for subgroups of smaller PPNs is under evaluation. OBJECTIVES: Diagnostic yield evaluation of biopsy using ENB for PPNs <2 cm. DESIGN: The diagnostic yield, sensitivity, specificity, positive predictive value, and negative predictive value of the ENB-mediated biopsy for PPNs were evaluated. METHODS: Patients who had PPNs with diameters <2 cm and underwent ENB-mediated biopsy between May 2015 and February 2020 were consecutively enrolled. The final diagnosis was made via pathological examination after surgery. RESULTS: A total of 82 lesions from 65 patients were analyzed. The median tumor size was 11 mm. All lesions were subjected to ENB-mediated biopsy, of which 29 and 53 were classified as malignant and benign, respectively. Subsequent segmentectomy, lobectomy, or wedge resection, following pathological examinations were performed on 64 nodules from 57 patients. The overall sensitivity, specificity, positive predictive value, and negative predictive value for nodules <2 cm were 53.3%, 91.7%, 92.3%, and 51.2%, respectively. The receiver operating curve showed an area under the curve of 0.721 (p < 0.001). Additionally, the sensitivity, specificity, positive predictive value, and negative predictive value were 62.5%, 100%, 100%, and 42.9%, respectively, for nodules with diameters equal to or larger than 1 cm; and 30.8%, 86.7%, 66.7%, and 59.1%, respectively, for nodules less than 1 cm. In the subgroup analysis, neither the lobar location nor the distance of the PPNs to the pleura affected the accuracy of the ENB diagnosis. However, the spiculated sign had a negative impact on the accuracy of the ENB biopsy (p = 0.010). CONCLUSION: ENB has good specificity and positive predictive value for diagnosing PPNs <2 cm; however, the spiculated sign may negatively affect ENB diagnostic accuracy. In addition, the diagnostic reliability may only be limited to PPNs equal to or larger than 1 cm.

Catalytic pyrolysis and in situ carbonization of walnut shells: poly-generation and enhanced electrochemical performance of carbons.

In this study, walnut shell (WS) was used as feedstock, incorporating lithium carbonate (LC), sodium carbonate (SC), potassium carbonate (PC), and potassium hydroxide (PH) as pyrolysis catalysts and carbonization activators. A one-step method that allows catalytic pyrolysis and carbonization to be carried out consecutively under their respective optimal conditions is employed, enabling the concurrent production of high-quality pyrolysis oil, pyrolysis gas, and carbon materials from biomass conversion. The effects of LC, SC, PC, and PH on the yield and properties of products derived from WS pyrolysis as well as on the properties and performance of the resulting carbon materials were examined. The results indicated that the addition of LC, SC, PC, and PH enhanced the secondary cracking of tar, leading to increased solid and gas yields from WS. Additionally, it increased the production of phenolic compounds in bio-oil and H2 in syngas, concurrently yielding a walnut shell-based carbon material exhibiting excellent electrochemical performance. Specifically, when PC was used as an additive, the phenolic content in the pyrolysis oil increased by 27.64% compared to that without PC, reaching 74.9%, but the content of ketones, acids, aldehydes, and amines decreased. The hydrogen content increased from 2.5% (without the addition of PC) to 12.75%. The resulting carbon (WSC-PC) displayed a specific surface area of 598.6 m2 g-1 and achieved a specific capacitance of 245.18 F g-1 at a current density of 0.5 A g-1. Even after 5000 charge and discharge cycles at a current density of 2 A g-1, the capacitance retention rate remained at 98.16%. This method effectively enhances the quality of the biomass pyrolysis oil, gas, and char, contributing to the efficient and clean utilization of biomass in industrial applications.

Tumor-derived apoptotic extracellular vesicle-mediated intercellular communication promotes metastasis and stemness of lung adenocarcinoma.

Apoptosis has long been recognized as a significant mechanism for inhibiting tumor formation, and a plethora of stimuli can induce apoptosis during the progression and treatment of tumors. Moreover, tumor-derived apoptotic extracellular vesicles (apoEVs) are inevitably phagocytosed by live tumor cells, promoting tumor heterogeneity. Understanding the mechanism by which apoEVs regulate tumor cells is imperative for enhancing our knowledge of tumor metastasis and recurrence. Herein, we conducted a series of in vivo and in vitro experiments, and we report that tumor-derived apoEVs promoted lung adenocarcinoma (LUAD) metastasis, self-renewal and chemoresistance. Mechanistically, we demonstrated that apoEVs facilitated tumor metastasis and stemness by initiating the epithelial-mesenchymal transition program and upregulating the transcription of the stem cell factor SOX2. In addition, we found that ALDH1A1, which was transported by apoEVs, activated the NF-κB signaling pathway by increasing aldehyde dehydrogenase enzyme activity in recipient tumor cells. Furthermore, targeting apoEVs-ALDH1A1 significantly abrogated these effects. Collectively, our findings elucidate a novel mechanism of apoEV-dependent intercellular communication between apoptotic tumor cells and live tumor cells that promotes the formation of cancer stem cell-like populations, and these findings reveal that apoEVs-ALDH1A1 may be a potential therapeutic target and biomarker for LUAD metastasis and recurrence.

The molecular characteristics could supplement the staging system of pT2/T3N0M0 esophageal squamous cell carcinoma: a translational study based on a cohort with over 20 years of follow-up.

OBJECTIVE: This study aimed to construct a model based on 23 enrolled molecules to evaluate prognoses of pT2/3N0M0 esophageal squamous cell carcinoma (ESCC) patients with up to 20 years of follow-up. METHODS: The lasso-Cox model was used to identify the candidate molecule. A nomogram was conducted to develop the survival model (molecular score, MS) based on the molecular features. Cox regression and Kaplan-Meier analysis were used in this study. The concordance index (C-index) was measured to compare the predicted ability between different models. The primary endpoint was overall survival (OS). RESULTS: A total of 226 patients and 23 proteins were enrolled in this study. Patients were classified into high-risk (MS-H) and low-risk (MS-L) groups based on the MS score of 227. The survival curves showed that the MS-L cohort had better 5-year and 10-year survival rates than the MS-H group (5-year OS: 51.0% vs. 8.0%; 10-year OS: 45.0% vs. 5.0%, all p < 0.001). Furthermore, multivariable analysis confirmed MS as an independent prognostic factor after eliminating the confounding factors (Hazard ratio 3.220, p < 0.001). The pT classification was confirmed to differentiate ESCC patients' prognosis (Log-rank: p = 0.029). However, the combination of pT and MS could classify survival curves evidently (overall p < 0.001), which showed that the prognostic prediction efficiency was improved significantly by the combination of the pT and MS than by the classical pT classification (C-index: 0.656 vs. 0.539, p < 0.001). CONCLUSIONS: Our study suggested an MS for significant clinical stratification of T2/3N0M0 ESCC patients to screen out subgroups with poor prognoses. Besides, the combination of pT staging and MS could predict survival more accurately for this cohort than the pT staging system alone.

Xylan-directed cell wall assembly in grasses.

Xylan is the most abundant hemicellulosic polysaccharide in the cell walls of grasses and is pivotal for the assembly of distinct cell wall structures that govern various cellular functions. Xylan also plays a crucial role in regulating biomass recalcitrance, ultimately affecting the utilization potential of lignocellulosic materials. Over the past decades, our understanding of the xylan biosynthetic machinery and cell wall organization has substantially improved due to the innovative application of multiple state-of-the-art techniques. Notably, novel xylan-based nanostructures have been revealed in the cell walls of xylem vessels, promoting a more extensive exploration of the role of xylan in the formation of cell wall structures. This Update summarizes recent achievements in understanding xylan biosynthesis, modification, modeling, and compartmentalization in grasses, providing a brief overview of cell wall assembly regarding xylan. We also discuss the potential for tailoring xylan to facilitate the breeding of elite energy and feed crops.

Woody plant cell walls: Fundamentals and utilization.

Cell walls in plants, particularly forest trees, are the major carbon sink of the terrestrial ecosystem. Chemical and biosynthetic features of plant cell walls were revealed early on, focusing mostly on herbaceous model species. Recent developments in genomics, transcriptomics, epigenomics, transgenesis, and associated analytical techniques are enabling novel insights into formation of woody cell walls. Here, we review multilevel regulation of cell wall biosynthesis in forest tree species. We highlight current approaches to engineering cell walls as potential feedstock for materials and energy and survey reported field tests of such engineered transgenic trees. We outline opportunities and challenges in future research to better understand cell type biogenesis for more efficient wood cell wall modification and utilization for biomaterials or for enhanced carbon capture and storage.

Effect of low-intensity pulsed ultrasound combined with Rhodiola rosea on proliferation and differentiation of osteoblasts.

Osteoblasts (OB), as the mesenchymal progenitor cells differentiated from the inner and outer periosteum and the stroma in bone marrow, can specifically secrete a variety of bioactive substances, thereby regulating and influencing the process of bone formation and reconstruction. Therefore, promoting the proliferation and differentiation of OB plays an important role in promoting bone formation. Based on this, this study studied the proliferation and differentiation of OB by low-intensity pulsed ultrasound (LIPUS) combined with Rhodiola rosea to provide a reliable theoretical basis for bone repair. In this study, rat OB was used as the research material and divided into groups A, B, C and D according to different intervention methods after osteogenic culture. Joint Salvia miltiorrhiza LIPUS ever seen from the results of the study promotes the strongest OB proliferation, at the same time, effectively reduces the apoptosis rate of the OB and apoptosis-related proteins expression, and promotes the OCN and ALO protein expression, indicated by LIPUS Salvia miltiorrhiza can effectively promote the osteoblast proliferation, differentiation, in order to promote cartilage repair and bone strengthen provides an effective means.

SUMOylation-triggered ALIX activation modulates extracellular vesicles circTLCD4-RWDD3 to promote lymphatic metastasis of non-small cell lung cancer.

Lymph node (LN) metastasis is one of the predominant metastatic routes of non-small cell lung cancer (NSCLC) and is considered as a leading cause for the unsatisfactory prognosis of patients. Although lymphangiogenesis is well-recognized as a crucial process in mediating LN metastasis, the regulatory mechanism involving lymphangiogenesis and LN metastasis in NSCLC remains unclear. In this study, we employed high-throughput sequencing to identify a novel circular RNA (circRNA), circTLCD4-RWDD3, which was significantly upregulated in extracellular vesicles (EVs) from LN metastatic NSCLC and was positively associated with deteriorated OS and DFS of patients with NSCLC from multicenter clinical cohort. Downregulating the expression of EV-packaged circTLCD4-RWDD3 inhibited lymphangiogenesis and LN metastasis of NSCLC both in vitro and in vivo. Mechanically, circTLCD4-RWDD3 physically interacted with hnRNPA2B1 and mediated the SUMO2 modification at K108 residue of hnRNPA2B1 by upregulating UBC9. Subsequently, circTLCD4-RWDD3-induced SUMOylated hnRNPA2B1 was recognized by the SUMO interaction motif (SIM) of ALIX and activated ALIX to recruit ESCRT-III, thereby facilitating the sorting of circTLCD4-RWDD3 into NSCLC cell-derived EVs. Moreover, EV-packaged circTLCD4-RWDD3 was internalized by lymphatic endothelial cells to activate the transcription of PROX1, resulting in the lymphangiogenesis and LN metastasis of NSCLC. Importantly, blocking EV-mediated transmission of circTLCD4-RWDD3 via mutating SIM in ALIX or K108 residue of hnRNPA2B1 inhibited the lymphangiogenesis and LN metastasis of NSCLC in vivo. Our findings reveal a precise mechanism underlying SUMOylated hnRNPA2B1-induced EV packaging of circTLCD4-RWDD3 in facilitating LN metastasis of NSCLC, suggesting that EV-packaged circTLCD4-RWDD3 could be a potential therapeutic target against LN metastatic NSCLC.

Abietane diterpenoids with anti-inflammatory activities from Callicarpa bodinieri.

Nine undescribed abietane diterpenoids (1-9) and eleven known abietane analogs (10-20) were isolated from Callicarpa bodinieri. Their structures were characterized by interpreting spectroscopic data, X-ray crystallography, and ECD analysis. The anti-inflammatory activities of these compounds were tested by evaluation of their inhibitory effect on NO production by lipopolysaccharide in RAW 264.7 macrophages, and compounds 3 and 8 exhibited potent anti-inflammatory activities with IC50 values of 36.35 ± 1.12 and 37.21 ± 0.92 µM. The western blotting studies demonstrated that compound 3 inhibited the expression of nitric oxide synthase and p65 that involved in the NF-κB pathway.

Development and validation of web-based dynamic nomograms predictive of disease-free and overall survival in patients who underwent pneumonectomy for primary lung cancer.

Background: The tumour-node-metastasis (TNM) staging system is insufficient to precisely distinguish the long-term survival of patients who underwent pneumonectomy for primary lung cancer. Therefore, this study sought to identify determinants of disease-free (DFS) and overall survival (OS) for incorporation into web-based dynamic nomograms. Methods: The clinicopathological variables, surgical methods and follow-up information of 1,261 consecutive patients who underwent pneumonectomy for primary lung cancer between January 2008 and December 2018 at Sun Yat-sen University Cancer Center were collected. Nomograms for predicting DFS and OS were built based on the significantly independent predictors identified in the training cohort (n = 1,009) and then were tested on the validation cohort (n = 252). The concordance index (C-index) and time-independent area under the receiver-operator characteristic curve (AUC) assessed the nomogram's discrimination accuracy. Decision curve analysis (DCA) was applied to evaluate the clinical utility. Results: During a median follow-up time of 40.5 months, disease recurrence and death were observed in 446 (35.4%) and 665 (52.7%) patients in the whole cohort, respectively. In the training cohort, a higher C-reactive protein to albumin ratio, intrapericardial pulmonary artery ligation, lymph node metastasis, and adjuvant therapy were significantly correlated with a higher risk for disease recurrence; similarly, the independent predictors for worse OS were intrapericardial pulmonary artery and vein ligation, higher T stage, lymph node metastasis, and no adjuvant therapy. In the validation cohort, the integrated DFS and OS nomograms showed well-fitted calibration curves and yielded good discrimination powers with C-index of 0.667 (95% confidence intervals CIs [0.610-0.724]) and 0.697 (95% CIs [0.649-0.745]), respectively. Moreover, the AUCs for 1-year, 3-year, and 5-year DFS were 0.655, 0.726, and 0.735, respectively, and those for 3-year, 5-year, and 10-year OS were 0.741, 0.765, and 0.709, respectively. DCA demonstrated that our nomograms could bring more net benefit than the TNM staging system. Conclusions: Although pneumonectomy for primary lung cancer has brought encouraging long-term outcomes, the constructed prediction models could assist in precisely identifying patients at high risk and developing personalized treatment strategies to further improve survival.

SERPINB5 is a prognostic biomarker and promotes proliferation, metastasis and epithelial-mesenchymal transition (EMT) in lung adenocarcinoma.

BACKGROUND: Serine protease inhibitors clade B serpins (SERPINBs) are the largest subclass of protease inhibitors, once thought of as a tumor suppressor gene family. However, some SERPINBs exhibit functions unrelated to the inhibition of catalytic activity. METHODS: The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Gene Set Cancer Analysis (GSCA), and cBioPortal databases were utilized to investigate SERPINBs expression, prognostic correlation, and genomic variation in 33 cancer types. We also conducted a comprehensive transcriptome analysis in multiple lung adenocarcinoma (LUAD) cohorts to reveal the molecular mechanism of SERPINB5 in LUAD. Then, qPCR and immunohistochemistry were used to verify the expression and prognostic value of SERPINB5 in LUAD patients. Furthermore, knockdown and overexpression of SERPINB5 in LUAD cell lines were performed to evaluate cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). RESULTS: The expression of SERPINB5 was upregulated and demethylated in LUAD, and its abnormally high expression was significantly correlated with poor overall survival (OS). In addition, the expression of SERPINB5 was analyzed to determine its prognostic value in LUAD and confirmed that SERPINB5 was an independent predictor of LUAD in TCGA and GEO cohorts and qPCR validation with 106 clinical samples. At last, A knockdown of SERPINB5 in LUAD cells reduced proliferation, migration, and EMT. Proliferation, migration, and invasion are promoted by the overexpression of SERPINB5. CONCLUSION: Therefore, SERPINB5 has shown potential as a prognostic biomarker for LUAD, and it may become a potential therapeutic target for lung adenocarcinoma.

Impact of the Number of Harvested Lymph Nodes on Long-Term Survival in Node-Negative Non-Small-Cell Lung Cancer: Based on Clinical Stage But Not Pathological Stage.

BACKGROUND: We aimed to investigate the impact of the number of harvested lymph nodes (LNs) on the overall survival (OS) and disease-free survival (DFS) of patients with clinical node-negative (cN0) non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 2247 patients with cN0 NSCLC between 2001 and 2014 were included. Scatter plots of hazard ratios from Cox proportional hazards models against the number of harvested LNs were created, and curves were fitted using a LOWESS smoother. Chow test was used to determine the cut-off points for the optimal number of harvested LNs. Long-term survival was compared between groups divided by the cut-off points. RESULTS: The increasing numbers of harvested LNs and N2 level LNs were independent factors favoring OS and DFS. Seventeen LNs and 10 N2 level LNs were determined as the optimal cut-off points. The patients with ≥17 harvested LNs had a better OS (P = .001) and DFS (P = .002), while the patients with ≥10 harvested N2 level LNs also had a better OS (P < .001) and DFS (P = .001). The increasing numbers of harvested LNs and N2 level LNs were independent prognostic factors associated with prolonged OS and DFS only in patients with clinical T2 (cT2) NSCLC. CONCLUSIONS: The increasing numbers of harvested LNs and N2 level LNs were associated with better OS and DFS in cN0 NSCLC patients that were suitable for lobectomies. At least 17 LNs and 10 N2 level LNs were required to be harvested, especially in cT2 patients.

The independent prognostic effect of marital status on non-small cell lung cancer patients: a population-based study.

Background: Previous studies had demonstrated that marital status was an independent prognostic factor in multiple cancers. However, the impact of marital status on non-small cell lung cancer (NSCLC) patients was still highly controversial. Method: All NSCLC patients diagnosed between 2010-2016 were selected from the Surveillance, Epidemiology and End Results (SEER) database. To control the confounding effect of related clinicopathological characteristics, propensity score matching (PSM) was conducted between married and unmarried groups. In addition, independent prognostic clinicopathological factors were evaluated via Cox proportional hazard regression. Moreover, nomograms were established based on the clinicopathological characteristics, and the predictive accuracy was assessed by calibration curves. Furthermore, decision curve analysis (DCA) was used to determine the clinical benefits. Results: In total, 58,424 NSCLC patients were enrolled according to the selection criteria. After PSM, 20,148 patients were selected into each group for further analysis. The married group consistently demonstrated significantly better OS and CSS compared to unmarried group [OS median survival (95% CI): 25 (24-26) vs. 22 (21-23) months, p < 0.001; CSS median survival (95% CI): 31 (30-32) vs. 27 (26-28) months, p < 0.001]. Moreover, single patients were associated with the worst OS [median survival (95% CI): 20 (19-22) months] and CSS [median survival (95%CI): 24 (23-25) months] among unmarried subgroups. Besides, unmarried patients had a significantly worse prognosis compared to married patients in both univariate and multivariate Cox proportional hazard regressions. Furthermore, married group was associated with better survival in most subgroups. To predict the 1-, 3- and 5-year OS and CSS probabilities, nomograms were established based on age, race, sex, gender, marital status, histology, grade, TNM stage. The C-index for OS and CSS were 0.759 and 0.779. And the calibration curves showed significant agreement between predictive risk and the observed probability. DCA indicated nomograms had consistently better predict performance. Conclusion: This study demonstrated that unmarried NSCLC patients were associated with significantly worse OS and CSS compared to married NSCLC patients. Therefore, unmarried patients need not only closer surveillance, but also more social and family support, which may improve patients' adherence and compliance, and eventually improve the survival.

Intrinsic Immunogenic Tumor Cell Death Subtypes Delineate Prognosis and Responsiveness to Immunotherapy in Lung Adenocarcinoma.

Recent studies have highlighted the combination of activation of host immunogenic cell death (ICD) and tumor-directed cytotoxic strategies. However, overall multiomic analysis of the intrinsic ICD property in lung adenocarcinoma (LUAD) has not been performed. Therefore, the aim of this study was to develop an ICD-based risk scoring system to predict overall survival (OS) and immunotherapeutic efficacy in patients. In our study, both weighted gene co-expression network analysis (WGCNA) and LASSO-Cox analysis were utilized to identify ICDrisk subtypes (ICDrisk). Moreover, we identify genomic alterations and differences in biological processes, analyze the immune microenvironment, and predict the response to immunotherapy in patients with pan-cancer. Importantly, immunogenicity subgroup typing was performed based on the immune score (IS) and microenvironmental tumor neoantigens (meTNAs). Our results demonstrate that ICDrisk subtypes were identified based on 16 genes. Furthermore, high ICDrisk was proved to be a poor prognostic factor in LUAD patients and indicated poor efficacy of immune checkpoint inhibitor (ICI) treatment in patients with pan-cancer. The two ICDrisk subtypes displayed distinct clinicopathologic features, tumor-infiltrating immune cell patterns, and biological processes. The ISlowmeTNAhigh subtype showed low intratumoral heterogeneity (ITH) and immune-activated phenotypes and correlated with better survival than the other subtypes within the high ICDrisk group. This study suggests effective biomarkers for the prediction of OS in LUAD patients and immunotherapeutic response across Pan-cancer and contributes to enhancing our understanding of intrinsic immunogenic tumor cell death.