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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Evaluation of the significance of subcarinal lymph node dissection in stage IB non­small cell lung cancer.

Lymph node dissection is used to treat early-stage lung cancer. The present study aimed to investigate if resecting the subcarinal lymph nodes affects prognosis of patients with stage IB non-small cell lung cancer (NSCLC). A total of 597 patients with stage IB NSCLC who underwent lung cancer surgery at Sun Yat-Sen University Cancer Center from January 1999 to December 2009 were included in the present study. The potential prognostic factors were evaluated using the Cox proportional hazard regression model. A total of 252 cases were obtained following propensity score matching (PSM). To compare overall survival (OS) and recurrence-free survival (RFS), Kaplan-Meier method and log-rank test were used. Among the 597 cases included, 185 did not undergo subcarinal lymph node resection, whereas 412 did. There were statistically significant differences between the two groups in terms of bronchial invasion, number of resected lymph node stations and resected lymph node numbers (P<0.05). Age, family history of cancer and the number of resected lymph nodes were prognostic factors for OS, whereas age and the number of resected lymph nodes were prognostic factors for RFS (P<0.05). Resection of subcarinal lymph nodes was not associated with OS and RFS. After PSM, survival analysis was recalculated using the Kaplan-Meier method and log-rank test; subcarinal lymph node resection was not statistically associated with OS and RFS. (P>0.05). For stage IB NSCLC, there was no statistically significant association between subcarinal lymph node resection and OS and RFS. Subcarinal lymph node resection in surgery of stage IB NSCLC may be considered optional.

Reconsidering N component of cancer staging for T1-2N0-2M0 small-cell lung cancer: a retrospective study based on multicenter cohort.

BACKGROUND: The current nodal (pN) classification still has limitations in stratifying the prognosis of small cell lung cancer (SCLC) patients with pathological classifications T1-2N0-2M0. Thus. This study aimed to develop and validate a modified nodal classification based on a multicenter cohort. MATERIALS AND METHODS: We collected 1156 SCLC patients with pathological classifications T1-2N0-2M0 from the Surveillance, Epidemiology, and End Results database and a multicenter database in China. The X-tile software was conducted to determine the optimal cutoff points of the number of examined lymph nodes (ELNs) and lymph node ratio (LNR). The Kaplan-Meier method, the Log-rank test, and the Cox regression method were used in this study. We classified patients into three pathological N modification categories, new pN#1 (pN0-#ELNs > 3), new pN#2 (pN0-#ELNs ≤ 3 or pN1-2-#LNR ≤ 0.14), and new pN#3 (N1-2-#LNR > 0.14). The Akaike information criterion (AIC), Bayesian Information Criterion, and Concordance index (C-index) were used to compare the prognostic, predictive ability between the current pN classification and the new pN component. RESULTS: The new pN classification had a satisfactory effect on survival curves (Log-rank P < 0.001). After adjusting for other confounders, the new pN classification could be an independent prognostic indicator. Besides, the new pN component had a much more accurate predictive ability in the prognostic assessment for SCLC patients of pathological classifications T1-2N0-2M0 compared with the current pN classification in the SEER database (AIC: 4705.544 vs. 4731.775; C-index: 0.654 vs. 0.617, P < 0.001). Those results were validated in the MCDB from China. CONCLUSIONS: The multicenter cohort developed and validated a modified nodal classification for SCLC patients with pathological category T1-2N0-2M0 after surgery. Besides, we propose that an adequate lymph node dissection is essential; surgeons should perform and consider the situation of ELNs and LNR when they evaluate postoperative prognoses of SCLC patients.

Diterpenoids with an unusual tricyclo[10.3.0.02,9]pentadecane skeleton from Pedilanthus tithymaloides as multidrug resistance modulators.

Three new diterpenoids with an unusual carbon skeleton, pedilanins A-C (1-3), and nine new jatrophane diterpenoids, pedilanins D-L (4-12), along with five known ones (13-17), were isolated from Pedilanthus tithymaloides. Compounds 1-3 characterize an unprecedented tricyclo[10.3.0.02,9]pentadecane skeleton. Compounds 4-8 are rare examples of the jatrophanes bearing a cyclic hemiketal substructure. Their structures were determined by an extensive analysis of HRESIMS, NMR, quantum-chemical calculation, DP4+ probability, and X-ray crystallographic data. In the bioassay, compounds 1-12 dramatically reversed multidrug resistance in cancer cells with the fold-reversals ranging from 17.9 to 396.8 at the noncytotoxic concentration of 10 µM. The mechanism results indicated that compounds 2 and 3 inhibited the P-glycoprotein (Pgp) transporter function, thus reversing the drug resistance.

Ten-year trends of the clinicopathological characteristics, surgical treatments and survival outcomes of operable lung cancer patients in monocenter: a retrospective cohort study.

Background: Lung cancer is one of the cancers with the highest morbidity and mortality. During the last decade, the trends of clinical characteristics, surgical treatments and survival of lung cancer patients in China have remained unclear. Methods: All lung cancer patients operated on from 2011 to 2020 were identified in a prospectively maintained database of Sun Yat-sen University Cancer Center. Results: A total of 7,800 lung cancer patients were included in this study. Within the past 10 years, the average age at diagnosis of the patients remained stable, the proportion of asymptomatic, female and nonsmoking patients increased, and the average tumor size decreased from 3.766 to 2.300 cm. In addition, the proportion of early stage and adenocarcinoma increased, while that of squamous cell carcinoma decreased. Among the patients, the proportion of patients having video-assisted thoracic surgery increased. More than 80% of the patients underwent lobectomy and systematic nodal dissection over the 10 years. Additionally, both the average postoperative length of stay and 1-, 3-, and 6-month postoperative mortality decreased. Moreover, the 1-, 3-, and 5-year overall survival (OS) rates of all the operable patients increased from 89.8, 73.9, and 63.8% to 99.6, 90.7, and 80.8%, respectively. The 5-year OS rates of the patients with stage I, II, and III lung cancer were 87.6, 79.9, and 59.9%, respectively, which were higher than those in other published data. Conclusion: There were significant changes in the clinicopathological characteristics, surgical treatments and survival outcomes of the patients with operable lung cancer from 2011 to 2020.

Prognostic value of L4 lymph node dissection during video-assisted thoracoscopic surgery in patients with left-sided non-small cell lung cancer: a single-center, retrospective cohort study.

Background: Lymph node dissection (LND) is crucial procedure during radical resection of non-small cell lung cancer (NSCLC), but the prognostic value of L4 LND remains elusive. To investigate the prognostic value of L4 LND in patients with left-side NSCLC who underwent video-assisted thoracoscopic surgery (VATS). Methods: Three hundred twelve patients who underwent VATS between Jan. 2007 and Dec. 2016 were reviewed. Of those, 119 underwent L4 LND (L4D+), whereas the other 193 patients did not (L4D-). The inclusion criteria were as follows: patients diagnosed with primary left-sided NSCLC who underwent VATS lobectomy combined with LND; patients subjected to R0 resection and tumor pathological stage T1-4N0-2M0. The primary endpoint was overall survival (OS). OS was calculated from the operation date to the date of death. The chi-square test was used for categorical variables, and a t test was used for continuous variables. Results: A total of 119 patients underwent L4 LND, and the procedure was more likely to be performed on upper lobe tumors (P=0.019). Patient distributions with respect to age, gender, smoking history, clinical stage, adjuvant therapy, tumor differentiation and tumor size were well balanced between two groups. More lymph nodes (LNs) were dissected in the L4D+ group than in the L4D- group (P<0.001). The rate of metastasis to L4 lymph nodes was 9.2%, which was comparable between patients with upper and lower lobe tumors (8.9% vs. 10.0%, P=1.000). The L4D+ group exhibited a significantly better OS than the L4D- group (median OS: undefined vs. 130 months, HR 0.47; 95% CI: 0.31-0.72; P=0.002). Multivariate analysis showed that L4 LND was an independent factor for OS. However, OS did not significantly differ between the two groups of cT1aN0 and cT1bN0 patients (OS: HR 0.44; 95% CI: 0.18-1.06; P=0.12). Conclusions: L4 LND is recommended for patients with left-sided NSCLC as an essential component of radical resection. The role of L4 LND in cT1a-bN0 disease warrants further study.

Comparison of Short-Term Outcomes Between Robot-Assisted and Video-Assisted Segmentectomy for Small Pulmonary Nodules: A Propensity Score-Matching Study.

BACKGROUND: Our study aimed to compare the short-term outcomes between robot-assisted segmentectomy (RAS) and video-assisted segmentectomy (VAS) for small pulmonary nodules. METHODS: The study included of 299 segmentectomies (132 RAS and 167 VAS procedures) for small pulmonary nodules between June 2018 and November 2021. The patients were divided into two groups: the RAS group and the VAS group. Propensity score-matching (PSM) analysis was performed to minimize bias. A logistic regression model was performed to identify the independent risk factors associated with complications. RESULTS: Before PSM, the following clinical variables were not balanced: age (P = 0.004), tumor size (P < 0.001), forced expiratory volume for 1 s (FEV1), and FEV1 percentage (P < 0.001). The patients with RAS had a shorter operative time (P = 0.014), less blood loss, a shorter postoperative hospital stay, less use of strong opioids, less drainage on postoperative day 1, and less postoperative total drainage, but more cost (all P < 0.001). Conversion to open surgery was performed for two patients in the VAS group but none in the RAS group. After PSM, 53 pairs were successfully matched. The data again suggested that the patients with RAS had less blood loss, a shorter postoperative hospital stay, and less use of strong opioids, but more cost (all P < 0.001). The operation time also was shorter in the RAS group, with a borderline statistically significant P value (0.053). CONCLUSIONS: In our study, RAS had better short-term outcomes than VAS, indicating a safer and more efficient technique than VAS.