Identifying optimal surgical approach among T1N2-3M0 non-small cell lung cancer patients: a population-based analysis.

Background: Whether stage T1N2-3M0 non-small cell lung cancer (NSCLC) patients could benefit from surgery and the optimal surgical procedure have remained controversial and unclear. This study aimed to investigate whether stage T1N2-3M0 NSCLC can benefit from different surgery types and develop a tool for survival prediction. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients diagnosed with stage T1N2-3M0 NSCLC between 2000 and 2015. A 1:1 propensity score-matched (PSM) analysis was used to balance the distribution of clinical characteristics. Survival analyses were performed by using the Kaplan-Meier (KM) curves and Cox proportional hazards regression. All patients were randomly split at a ratio of 7:3 into training and validation cohorts. The nomogram was constructed by integrating all independent predictors for overall survival (OS) and cancer-specific survival (CSS). The model's performance was evaluated by discrimination, calibration ability, and risk stratification ability. Results: A total of 4,671 patients were enrolled. After 1:1 PSM, the distribution proportions of clinical characteristics in 1,146 patients were balanced (all P>0.05). The non-surgical approach was associated with worse survival compared with sublobectomy and lobectomy in the unmatched and matched cohorts. The multivariate Cox analysis showed that sublobectomy and lobectomy were both related to better OS and CSS rates compared with no surgery (P<0.001). Moreover, the results of subgroup analyses based on age, N stage, and radiotherapy or chemotherapy strategy were consistent. A total of 801 patients were included in the training cohort and 345 cases constituted the validation cohort. The nomogram constructed for the 1-, 3-, and 5-year OS and CSS prediction showed good discrimination, performance, and calibration both in the training and validation sets. Significant distinctions in survival curves between different risk groups stratified by prognostic scores were also observed (all P<0.001). Conclusions: Stage T1N2-3M0 NSCLC patients could benefit from sublobectomy or lobectomy, and lobectomy provides better survival benefits. We developed and validated nomograms, which could offer clinicians instructions for strategy making.

A rare case of pheochromocytoma in a pregnant woman presenting with chest pain: extraordinary management.

BACKGROUND: Pheochromocytoma is rare in pregnant women. It presents as diverse symptoms, including hypertension and sweating. The symptoms of pregnant women with pheochromocytoma and comorbid hypertension often mimic the clinical manifestations of preeclampsia, and these women are often misdiagnosed with preeclampsia. CASE PRESENTATION: In this case, a pregnant woman presented with chest pain as the primary symptom, and a diagnosis of pheochromocytoma was considered after ruling out myocardial ischemia and aortic dissection with the relevant diagnostic tools. This patient then underwent successful surgical resection using a nontraditional management approach, which resulted in a positive clinical outcome. CONCLUSIONS: It is essential to consider pheochromocytoma as a potential cause of chest pain and myocardial infarction-like electrocardiographic changes in pregnant women, even if they do not have a history of hypertension.

Surgery for bronchiectasis-destroyed lung: feasibility of video-assisted thoracoscopic surgery, and surgical outcomes.

OBJECTIVES: To provide the experience of surgical treatment for bronchiectasis-destroyed lung (BDL) and evaluate the feasibility of video-assisted thoracoscopic surgery (VATS). METHODS: BDL patients underwent surgical treatment between January 2013 and June 2018 were included. Logistic regression was performed to assess factors for major complications, and Cox's regression was performed to assess factors affected symptomatic outcome. RESULTS: Totally, 143 patients were treated by VATS (n = 64) and thoracotomy (n = 79). Nine (14.1%) cases scheduled for VATS were converted to thoracotomy for dense adhesions (n = 6) and frozen hilum (n = 3). The VATS group had a median chest tube duration, hospitalization and a time of returning to full activity of 4 days, 5 days and 1.5 months, respectively. Major complications occurred in 28 (19.6%) of all patients, 50.0% after pneumonectomy and 13.4% after lobectomy/extensive lobectomy. Multivariable analysis identified pneumonectomy [odds ratio, 3.64; 95% confidence interval (CI), 1.18-11.21] as a significant predictor for major complications. Overall, 141 (98.6%) patients benefitted from surgery (completely asymptomatic, n = 109; acceptable alleviation, n = 32). Thirty-four patients experienced relapse of the disease, including 13 with productive cough, 11 with haemoptysis and 10 with recurrent infections. Pseudomonas aeruginosa infection [hazard ratio (HR), 3.07; 95% CI, 1.38-6.83] and extent of remanent bronchiectatic areas (HR, 1.03; 95% CI, 1.00-1.05) were independent risk factors for shorter relapse free interval. CONCLUSIONS: VATS for BDL is feasible in well-selected patients. Pneumonectomy increased the risk of postoperative major complications. Removing all BDL lesions contributed to satisfactory prognosis.

Single- versus multi-port video-assisted thoracic surgery for pulmonary aspergilloma: a propensity-matched study.

OBJECTIVES: The utilization of single-port video-assisted thoracic surgery for pulmonary aspergilloma (PA) has not been well studied. The study was performed to evaluate the safety and feasibility of it for PA compared with multi-port video thoracic-assisted surgery. METHODS: From August 2007 to December 2019, consecutive PA patients receiving surgeries at Shanghai Pulmonary Hospital were enrolled retrospectively. Propensity score matching based on preoperative clinical variables was utilized to compare perioperative and long-term outcomes. RESULTS: In all 358 patients, a total of 63 patients underwent single-port video-assisted thoracic surgery, and 63 out of 145 patients for multi-port surgeries were paired with the single-port video-assisted thoracic surgery recipients. The median follow-up period was 40 months (range, 2-140 months). Patients receiving single-port video-assisted thoracic surgery showed a similar operation time, intraoperative blood loss, drainage duration and drainage volume to those of multi-port video-assisted thoracic surgery recipients (P > 0.05). Patients undergoing lobectomy by single-port approach experienced a shorter postoperative hospital stay {4.9 [standard deviation (SD): 2.0] vs 5.9 (SD: 2.3), P = 0.014}. The average postoperative pain scores [day 0: 2.6 (SD: 0.7) vs 3.1 (SD: 0.8), day 3: 4.0 (SD: 0.9) vs 4.8 (SD: 3.9), day 7: 2.2 (SD: 0.5) vs 3.1 (SD: 0.8), P < 0.001] and the number of days that patients required analgesic agents [3.0 (SD: 2.2) vs 4.8 (SD: 2.1), P < 0.001] were also decreased in the single-port video-assisted thoracic surgery group. CONCLUSIONS: Single-port video-assisted thoracic surgery is a safe and feasible alternative to multi-port video-assisted thoracic surgery for simple PA and selected complex ones, with a potential advantage of reduced postoperative pain.

Trace elements in red swamp crayfish (Procambarus clarkii) in China: Spatiotemporal variation and human health implications.

The enrichment and health risk assessment of trace elements in crayfish on a national scale are significant for food safety due to the rapidly expanding crayfish consumption in China. In the present study, 4709 samples were extracted from databases to explore the spatiotemporal variation characteristics of trace elements in crayfish. Due to the variance in the background value of trace elements, the level of trace elements varies by region. Additionally, levels of As and Cr in crayfish increased with the promotion of intensive rice-crayfish coculture in China. Health risk assessment results revealed that trace elements may cause non-carcinogenic risk for crayfish consumption for adults and children from the mid-lower reaches of the Yangtze River, and the main risk was from As and Hg. The cancer risk values of As for children and adults in Zhejiang, Anhui, Heilongjiang, Hubei, Hunan, Jiangsu, Jiangxi and Shandong provinces were above the allowable value. There is concern about the non-carcinogenic and carcinogenic risk of consuming crayfish containing trace elements in some areas in China. Therefore, the results can serve as a critical reference for policy purposes in China. In addition, it is recommended that further research and assessment on crayfish consumption are required.

Development and validation of nomogram prognostic model for early-stage T1-2N0M0 small cell lung cancer: A population-based analysis.

Background: Survival outcomes of early-stage T1-2N0M0 small cell lung cancer (SCLC) patients differ widely, and the existing Veterans Administration Lung Study Group (VALSG) or TNM staging system is inefficient at predicting individual prognoses. In our study, we developed and validated nomograms for individually predicting overall survival (OS) and lung cancer-specific survival (LCSS) in this special subset of patients. Methods: Data on patients diagnosed with T1-2N0M0 SCLC between 2000 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. All enrolled patients were split into a training cohort and a validation cohort according to the year of diagnosis. Using multivariable Cox regression, significant prognostic factors were identified and integrated to develop nomograms for 1-, 3-, and 5-year OS and LCSS prediction. The prognostic performance of our new model was measured by the concordance index (C-index) and calibration curve. We compared our latest model and the 8th AJCC staging system using decision curve analyses (DCA). Kaplan-Meier survival analyses were applied to test the application of the risk stratification system. Results: A total of 1,147 patients diagnosed from 2000 to 2011 were assigned to the training cohort, and 498 cases that were diagnosed from 2012 to 2015 comprised the validation cohort. Age, surgery, lymph node removal (LNR), and chemotherapy were independent predictors of LCSS. The variables of sex, age, surgery, LNR, and chemotherapy were identified as independent predictors of OS. The above-mentioned prognostic factors were entered into the nomogram construction of OS and LCSS. The C-index of this model in the training cohort was 0.663, 0.702, 0.733, and 0.658, 0.702, 0.733 for predicting 1-, 3-, and 5-year OS and LCSS, respectively. Additionally, in the validation cohort, there were 0.706, 0.707, 0.718 and 0.712, 0.691, 0.692. The calibration curve showed accepted prediction accuracy between nomogram-predicted survival and actual observed survival, regardless of OS or LCSS. In addition, there were significant distinctions in the survival curves of OS and LCSS between different risk groups stratified by prognostic scores. Compared with the 8th AJCC staging system, our new model also improved net benefits. Conclusions: We developed and validated novel nomograms for individual prediction of OS and LCSS, integrating the characteristics of patients and tumors. The model showed superior reliability and may help clinicians make treatment strategies and survival predictions for early-stage T1-2N0M0 SCLC patients.

The role of surgery in older patients with T1-2N0M0 small cell lung cancer: A propensity score matching analysis.

Background: Surgical resection could improve the survival of patients with early-stage small cell lung cancer (SCLC). However, there is a lack of dedicated studies concentrating on surgical treatment in older patients with T1-2N0M0 SCLC. Thus, we performed this population-based study to investigate whether older patients with T1-2N0M0 SCLC could benefit from surgery. Methods: We collected the data of patients with SCLC between 2000 and 2015 from the Surveillance, Epidemiology, and End Results Program database. Older patients (≥ 65 years) with T1-2N0M0 SCLC were included, and we converted the staging information into those of the eighth edition. The propensity score matching (PSM) was used to balance the distribution of clinical characteristics between surgery and no-surgery groups. Results: Before PSM, the distribution proportions of clinical characteristics in 1,229 patients were unbalanced. The Kaplan-Meier curves of overall survival (OS) and cancer-specific survival (CSS) showed that the patients in the surgery group were better than those in the non-surgery group (all P < 0.001). After 1:2 PSM, the distribution proportions of clinical characteristics in 683 patients were balanced (all P > 0.05). The OS and CSS of patients in the surgery group were still better than that of patients in the no-surgery group (all P < 0.001), and subgroup analysis showed that the surgery was a protective factor for OS and CSS in all clinical characteristics subgroups (almost P < 0.001). The multivariate Cox analysis further confirmed this result (OS: HR, 0.33; 95% CI, 0.27-0.39; P < 0.001; CSS: HR, 0.29; 95% CI, 0.23-0.36; P < 0.001). The result of subgroup analysis based on age, T stage, and adjuvant therapy showed that surgery was related to better OS and CSS compared with non-surgery group (almost P < 0.001) and that lobectomy exhibited the longer survival than sublobectomy. Age, sex, and race were the independent prognostic factors for OS in patients undergoing surgery, whereas only the factor of age affects the CSS in patients with surgery. Conclusions: Older patients with T1-2N0M0 SCLC can benefit significantly from surgical treatment, and lobectomy provides better prognosis than sublobectomy.

Surgical Options for Resectable Lung Adenosquamous Carcinoma: A Propensity Score-Matched Analysis.

Background: Surgery is the primary treatment option for Lung adenosquamous carcinoma (ASC) patients. However, no study compares the benefits of lobectomy and sublobar resection in ASC patients. Methods: A total of 1379 patients in the Surveillance, epidemiology, and End Results (SEER) database and 466 patients in Shanghai Pulmonary Hospital (SPH) were enrolled. Survival benefits were evaluated after possible confounders were eliminated by propensity score matching (PSM). Results: After 1:3 PSM, 463 SEER database patients and 244 SPH patients were enrolled. Lobectomy was associated with better overall survival (OS) and disease-free survival (DFS) than sublobar resection for ASC patients (5-year OS of SEER: 46.9% vs. 33.3%, P =0.017; 5-year OS of SPH: 35.0% vs. 16.4%, P =0.002; 5-year DFS of SPH: 29.5% vs. 14.8%, P =0.002). Similar results were observed in stage I patients. Univariate and multivariate Cox regression analyses showed that sublobar resection was an adverse prognostic factor independently (SEER: HR: 1.40, 95%CI: 1.08-1.81, P =0.012; SPH: HR: 1.73, 95%CI: 1.11-2.70, P =0.015). Subgroup analysis showed that all of the ASC patient subtypes tended to benefit more from lobectomy than sublobar resection. Conclusions: Lobectomy remains the primary option for ASC patients compared to sublobar resection, including stage I.

A Multi-Medium Analysis of Human Health Risk of Toxic Elements in Rice-Crayfish System: A Case Study from Middle Reach of Yangtze River, China.

Rice-crayfish system has been extensively promoted in China in recent years. However, the presence of toxic elements in soil may threaten the quality of agricultural products. In this study, eight toxic elements were determined in multi-medium including soil, rice, and crayfish from the rice-crayfish system (RCS) and conventional rice culture (CRC) area. Crayfish obtained a low level of toxic element content, and mercury (Hg) in rice from RCS showed the highest bioavailability and mobility. Health risk assessment, coupled with Monte Carlo simulation, revealed that the dietary exposure to arsenic (As) and Hg from rice and crayfish consumption was the primary factor for non-carcinogenic risk, while Cd and As were the dominant contributors to the high carcinogenic risk of rice intake for adults and children, respectively. Based on the estimated probability distribution, the probabilities of the total cancer risk (TCR) of rice intake for children from RCS were lower than that from CRC.

A fundamental study on selective extraction of Li+ with dibenzo-14-crown-4 ether: Toward new technology development for lithium recovery from brines.

The present study has proposed a selective Li+ extraction process using a novel extractant of dibenzo-14-crown-4 ether functionalized with an alkyl C16 chain (DB14C4-C16) synthesized based on the ion imprinting technology (IIT). Theoretical analysis of the possible complexes formed by DB14C4-C16 with Li+ and the competing ions of Na+, K+, Ca2+ and Mg2+ was performed through density functional theory (DFT) modeling. The Gibbs free energy change of the complexes of metal ions with DB14C4-C16 and water molecules were calculated to be -125.81 and -166.01 kJ/mol for lithium, -55.73 and -117.77 kJ/mol for sodium, and -196.02 and -291.52 kJ/mol for magnesium, respectively. Furthermore, the solvent extraction experiments were carried out in both single Li+ and multi-ions containing solutions, and the results delivered a good selectivity of DB14C4-C16 towards Li+ over the competing ions, showing separation coefficients of 68.09 for Ca2+-Li+, 24.53 for K+-Li+, 16.32 for Na+-Li+, and 3.99 for Mg2+-Li+ under the optimal conditions. The experimental results are generally in agreement with the theoretical calculations.

Towards subpercentage uncertainty proton stopping-power mapping via dual-energy CT: Direct experimental validation and uncertainty analysis of a statistical iterative image reconstruction method.

PURPOSE: To assess the potential of a joint dual-energy computerized tomography (CT) reconstruction process (statistical image reconstruction method built on a basis vector model (JSIR-BVM)) implemented on a 16-slice commercial CT scanner to measure high spatial resolution stopping-power ratio (SPR) maps with uncertainties of less than 1%. METHODS: JSIR-BVM was used to reconstruct images of effective electron density and mean excitation energy from dual-energy CT (DECT) sinograms for 10 high-purity samples of known density and atomic composition inserted into head and body phantoms. The measured DECT data consisted of 90 and 140 kVp axial sinograms serially acquired on a Philips Brilliance Big Bore CT scanner without beam-hardening corrections. The corresponding SPRs were subsequently measured directly via ion chamber measurements on a MEVION S250 superconducting synchrocyclotron and evaluated theoretically from the known sample compositions and densities. Deviations of JSIR-BVM SPR values from their theoretically calculated and directly measured ground-truth values were evaluated for our JSIR-BVM method and our implementation of the Hünemohr-Saito (H-S) DECT image-domain decomposition technique for SPR imaging. A thorough uncertainty analysis was then performed for five different scenarios (comparison of JSIR-BVM stopping-power ratio/stopping power (SPR/SP) to International Commission on Radiation Measurements and Units benchmarks; comparison of JSIR-BVM SPR to measured benchmarks; and uncertainties in JSIR-BVM SPR/SP maps for patients of unknown composition) per the Joint Committee for Guides in Metrology and the Guide to Expression of Uncertainty in Measurement, including the impact of uncertainties in measured photon spectra, sample composition and density, photon cross section and I-value models, and random measurement uncertainty. Estimated SPR uncertainty for three main tissue groups in patients of unknown composition and the weighted proportion of each tissue type for three proton treatment sites were then used to derive a composite range uncertainty for our method. RESULTS: Mean JSIR-BVM SPR estimates deviated by less than 1% from their theoretical and directly measured ground-truth values for most inserts and phantom geometries except for high-density Delrin and Teflon samples with SPR error relative to proton measurements of 1.1% and -1.0% (head phantom) and 1.1% and -1.1% (body phantom). The overall root-mean-square (RMS) deviations over all samples were 0.39% and 0.52% (head phantom) and 0.43% and 0.57% (body phantom) relative to theoretical and directly measured ground-truth SPRs, respectively. The corresponding RMS (maximum) errors for the image-domain decomposition method were 2.68% and 2.73% (4.68% and 4.99%) for the head phantom and 0.71% and 0.87% (1.37% and 1.66%) for the body phantom. Compared to H-S SPR maps, JSIR-BVM yielded 30% sharper and twofold sharper images for soft tissues and bone-like surrogates, respectively, while reducing noise by factors of 6 and 3, respectively. The uncertainty (coverage factor k = 1) of the DECT-to-benchmark values comparison ranged from 0.5% to 1.5% and is dominated by scanning-beam photon-spectra uncertainties. An analysis of the SPR uncertainty for patients of unknown composition showed a JSIR-BVM uncertainty of 0.65%, 1.21%, and 0.77% for soft-, lung-, and bony-tissue groups which led to a composite range uncertainty of 0.6-0.9%. CONCLUSIONS: Observed JSIR-BVM SPR estimation errors were all less than 50% of the estimated k = 1 total uncertainty of our benchmarking experiment, demonstrating that JSIR-BVM high spatial resolution, low-noise SPR mapping is feasible and is robust to variations in the geometry of the scanned object. In contrast, the much larger H-S SPR estimation errors are dominated by imaging noise and residual beam-hardening artifacts. While the uncertainties characteristic of our current JSIR-BVM implementation can be as large as 1.5%, achieving < 1% total uncertainty is feasible by improving the accuracy of scanner-specific scatter-profile and photon-spectrum estimates. With its robustness to beam-hardening artifact, image noise, and variations in phantom size and geometry, JSIR-BVM has the potential to achieve high spatial-resolution SPR mapping with subpercentage accuracy and estimated uncertainty in the clinical setting.

Prognostic value of surgical intervention in advanced lung adenocarcinoma: a population-based study.

BACKGROUND: Surgical intervention is generally not considered as a treatment option in patients with advanced non-small cell lung cancer (NSCLC). Accumulating data suggest that surgery may have beneficial effects for these advanced patients. However, no evidence supports the significance of primary tumor resection (PTR) and metastatic tumor resection (MTR) in patients with stage IV lung adenocarcinoma (LUAD). METHODS: A total of 32,497 patients diagnosed with primary stage IV LUAD were selected through the Surveillance, Epidemiology, and End Results (SEER) database. Possible confounders were eliminated by propensity score matching (PSM). The overall survival (OS) and lung cancer-specific survival (LCSS) were estimated as the primary endpoints. Furthermore, the independent prognostic factors of patients with the surgical intervention were retrospectively analyzed. RESULTS: Patients underwent surgical intervention had better OS and LCSS than those who did not (P=0.001 for OS; P<0.001 for LCSS). Meanwhile, patients who underwent surgery combined with lymph node dissection had better survival outcomes (P<0.001 for OS and LCSS) in the K-M analysis. For different metastatic sites, PTR was beneficial to the survival of patients with isolated lung metastases (LUM) and multiple organ metastases (MOM) (LUM: P=0.041; MOM: P=0.003). As for metastatic surgery, no patients were found to benefit from resection of metastatic tumor [bone metastasis (BOM): P=0.696; brain metastasis (BRM): P=0.951; LUM: P=0.402; MOM: P=0.365]. CONCLUSIONS: Surgical intervention strategies can prolong survival to some extent, depending on different sites of metastasis and highly selected patients.

Comprehensive genomic profiling of combined small cell lung cancer.

BACKGROUND: Combined small cell lung cancer (CSCLC) is an uncommon and heterogeneous subtype of small cell lung cancer (SCLC). However, there is limited data concerning the different molecular changes and clinical features in CSCLC compared to pure SCLC. METHODS: The clinical and pathological characteristics of pure SCLC and CSCLC patients were analyzed. Immunohistochemistry and microdissection were performed to isolate the CSCLC components. Further molecular analysis was carried out by next-generation sequencing (NGS) in 12 CSCLC and 30 pure SCLC. RESULTS: There were no significant differences in clinical features between CSCLC and pure SCLC. Overall survival (OS) of CSCLC patients was worse than pure SCLC (P=0.005). NGS results indicated that TP53 and RB1 were the most frequently mutated genes in both CSCLC (83.33% and 66.67%) and pure SCLC (80.00% and 63.33%) groups. However, less than 10% common mutations were found in both CSCLC and pure SCLC. When analyzing the data of SCLC and non-small cell lung cancer (NSCLC) components of CSCLC, more than 50% common mutations, and identical genes with mutations were detected. Moreover, there were also common biological processes and signaling pathways identified in CSCLC and pure SCLC, in addition to SCLC and NSCLC components. CONCLUSIONS: There were no significant differences in terms of clinical features between CSCLC and pure SCLC. However, the prognosis for CSCLC was worse than pure SCLC. NGS analysis suggested that CSCLC components might derive from the same pluripotent single clone with common initial molecular alterations and subsequent acquisitions of other genetic mutations.

Early diagnosis of lung cancer: which is the optimal choice?

The prognosis of lung cancer patients with different clinical stages is significantly different. The 5-year survival of stage IA groups can exceed 90%, while patients with stage IV can be less than 10%. Therefore, early diagnosis is extremely important for lung cancer patients. This research focused on various diagnosis methods of early lung cancer, including imaging screening, bronchoscopy, and emerging potential liquid biopsies, as well as volatile organic compounds, autoantibodies, aiming to improve the early diagnosis rate and explore feasible and effective early diagnosis strategies.

Single-cell transcriptome and antigen-immunoglobin analysis reveals the diversity of B cells in non-small cell lung cancer.

BACKGROUND: Malignant transformation and progression of cancer are driven by the co-evolution of cancer cells and their dysregulated tumor microenvironment (TME). Recent studies on immunotherapy demonstrate the efficacy in reverting the anti-tumoral function of T cells, highlighting the therapeutic potential in targeting certain cell types in TME. However, the functions of other immune cell types remain largely unexplored. RESULTS: We conduct a single-cell RNA-seq analysis of cells isolated from tumor tissue samples of non-small cell lung cancer (NSCLC) patients, and identify subtypes of tumor-infiltrated B cells and their diverse functions in the progression of NSCLC. Flow cytometry and immunohistochemistry experiments on two independent cohorts confirm the co-existence of the two major subtypes of B cells, namely the naïve-like and plasma-like B cells. The naïve-like B cells are decreased in advanced NSCLC, and their lower level is associated with poor prognosis. Co-culture of isolated naïve-like B cells from NSCLC patients with two lung cancer cell lines demonstrate that the naïve-like B cells suppress the growth of lung cancer cells by secreting four factors negatively regulating the cell growth. We also demonstrate that the plasma-like B cells inhibit cancer cell growth in the early stage of NSCLC, but promote cell growth in the advanced stage of NSCLC. The roles of the plasma-like B cell produced immunoglobulins, and their interacting proteins in the progression of NSCLC are further validated by proteomics data. CONCLUSION: Our analysis reveals versatile functions of tumor-infiltrating B cells and their potential clinical implications in NSCLC.

SNHG20 serves as a predictor for prognosis and promotes cell growth in oral squamous cell carcinoma.

Accumulating evidence indicates that long non-coding RNAs (lncRNAs) serve important roles in various tumor types, including colorectal cancer and gastric cancer. The present study aimed to investigate the contribution of the lncRNA small nucleolar RNA host gene 20 (SNHG20) in oral squamous cell carcinoma (OSCC) progression. It was demonstrated that SNHG20 expression was significantly increased in OSCC tissue specimens, compared with in adjacent non-tumor tissue specimens. The increased SNHG20 expression in OSCC tissue specimens was associated with tumor differentiation and Tumor-Node-Metastasis stage. Kaplan-Meier analysis and log-rank tests indicated that Higher SNHG20 expression predicted a poor overall survival (OS) rate in patients with OSCC. Multivariate Cox proportional hazards regression analysis demonstrated that increased SNHG20 expression was an independent predictor for the OS of patients with OSCC. Knockdown of SNHG20 expression in OSCC cells suppressed proliferation. The cell proliferation-associated proteins proliferating cell nuclear antigen and Ki67 expression levels were reduced when SNHG20 was knocked down in OSCC cells; thus, the results indicated that SHNG20 may serve as a predictor and potential target for OSCC treatment.

The secondary surgery provides significant benefits to recurrent thymoma: a retrospective analysis based on Surveillance, Epidemiology and End Results database.

BACKGROUND: Recurrent thymoma (RT) with appropriate therapies has acceptable survival. The role of secondary surgery for RT remains controversial. METHODS: Surgical treated thymoma patients were reviewed from Surveillance, Epidemiology and End Results database (SEER). Propensity score matching (PSM) was utilized to match baseline factors to balance secondary surgical treated RT and thymoma without recurrence (NRT). Univariate and multivariate analyses were performed to evaluate the role of secondary surgery for RT. RESULTS: According to analysis, 815 patients were NRT, and 185 were RT. Surgical treated RT had significantly better overall survival (OS) than conservative treated RT (P<0.001). Survival between surgical treated RT and NRT had no significant difference. Focused on surgical treated RT and NRT, after PSM, elder diagnostic age, advanced clinical stage, upgraded pathologic grade predicted worse OS (P<0.01, for all), whereas, secondary surgery for RT provided comparable outcomes to NRT. CONCLUSIONS: Masaoka stage I-III RT with secondary surgery causes acceptable outcomes compared to NRT. In addition, elder patients, advanced Masaoka stage, upgraded pathologic grade, and without PORT indicate significantly worse OS in thymoma.

PEGylated liposomes as delivery systems for Gambogenic acid: Characterization and in vitro/in vivo evaluation.

Gambogenic acid (GNA), which possesses diverse anti-tumor activities both in vitro and in vivo, is regarded as a potential anticancer compound. However, the excessive irritation to the blood vessel, short elimination half-life and poor aqueous solubility restricted its clinical application. In this study, Gambogenic acid-loaded PEGylated liposomes (GNA-PEG-LPs) were developed to reduce toxicity, prolong the half-life and enhance anticancer efficacy both in vitro and in vivo. The average particle size of GNA-PEG-LPs was 90.13 ± 0.16 nm and their polydispersity index (PDI) was 0.092 ± 0.003. The encapsulation efficiency, drug loading and zeta potential of GNA-PEG-LPs were 88.13 ± 1.31%, 3.72 ± 0.04%, -22.10 ± 0.20 mV, respectively. Compared to free GNA, GNA-PEG-LPs showed enhanced cytotoxicity and apoptosis induction effect against A549, SGC-7901 and HepG2 cells. Mechanistically, western blot analysis revealed that up-regulation of Bax, down-regulation of Bcl-2 and activation of caspase-3 contributed to apoptosis. In addition, the blood vessel irritation test showed that the vascular irritation of GNA could be reduced by liposomal encapsulation. The hemolysis assay revealed that good hemocompatibility of the liposomes. Furthermore, pharmacokinetic study showed that the t1/2 and the AUC of GNA-PEG-LPs were higher than GNA solution approximately 2.84-fold and 2.97-fold, respectively. In vivo antitumor efficacy demonstrated that GNA-PEG-LPs significantly inhibited the tumor growth in LLC tumor-bearing C57BL/6 mouse model. Results of Immunohistochemistry indicated that GNA-PEG-LPs significantly suppressed the expression of Bcl-2 and increased the expression of Bax and caspase-3 compared with free GNA. Collectively, PEGylated liposomes could be a potential nanocarrier to prolong half-life, reduce toxicity and enhance anticancer efficacy both in vitro and in vivo.

Effect of Gambogenic Acid on Cytochrome P450 1A2, 2B1 and 2E1, and Constitutive Androstane Receptor in Rats.

BACKGROUND AND OBJECTIVES: Gambogenic acid (GNA), which possesses diverse antitumor activities both in vitro and in vivo, is regarded as a potential anticancer compound. Cytochrome P450 (CYP) enzymes play an important role in the metabolism of most xenobiotics; constitutive androstane receptor (CAR), a nuclear receptor that might be activated by xenobiotics and associated with the expression of some CYPs. In this study, we determined the effect of GNA on multiple rat liver CYP isoforms (CYP1A2, 2B1, and 2E1) and CAR as well as the potential of GNA to interact with co-administered drugs. METHODS: Male SD rats were randomly divided into the control, and the low (5 mg/kg)-, medium (25 mg/kg)-, and high- (100 mg/kg) dose GNA groups. After the intragastric administration of GNA for 14 consecutive days, a cocktail method was adopted to evaluate the activities of CYP1A2, 2B1, and 2E1. The liver expression of CYP1A2, 2B1, and 2E1 and CAR was analyzed by Western blotting (WB) and quantitative real-time reverse-transcription polymerase chain reaction (RT-qPCR). RESULTS: The 14-day administration of GNA significantly increased both the mRNA and protein expressions and the activity of CYP2E1. Additionally, the mRNA and protein expressions of CYP1A2 were clearly induced, while only the high GNA dose increased the activity of liver CYP1A2. Moreover, the mRNA expression levels of CYP2B1 and CAR were increased, but their protein levels and the activity parameters of CYP2B1 did not show significant changes. CONCLUSIONS: The obtained results suggest that the CYP1A2 and CYP2E1 enzymes could be induced in rats after treatment with GNA. Therefore, when GNA is administrated with other drugs, potential drug-drug interactions (DDI) mediated by CYP1A2 and CYP2E1 induction should be taken into consideration.

PEGylated niosomes-mediated drug delivery systems for Paeonol: preparation, pharmacokinetics studies and synergistic anti-tumor effects with 5-FU.

This work describes the preparation of a PEGylated niosomes-mediated drug delivery systems for Paeonol, thereby improving the bioavailability and chemical stability of Paeonol, prolonging its cellular uptake and enhancing its synergistic anti-cancer effects with 5-Fu. PEGylated niosomes, which are prepared from biocompatible nonionic surfactant of Spans 60 and cholesterol, and modified with PEG-SA. Pae-PEG-NISVs were evaluated in vitro and in vivo. The cytotoxicity of Pae-PEG-NISVs was investigated against HepG2 cells. Fluorescence microscope was used to detect the apoptotic morphological changes. Growth inhibition assays were carried out to investigate whether Pae-PEG-NISVs could enhance the antiproliferative effects of Pae co-treated with 5-FU on HepG2 cells. The optimized Pae-PEG-NISVs had mean diameters of approximately 166 nm and entrapment efficiency (EE) of 61.8%. Furthermore, the in vitro release study of Paeonol from PEGylated niosomes exhibited a relatively prolonged release profile for 12 h. Pharmacokinetic studies in rats after i.v. injection showed that Pae-PEG-NISVs had increased elimination half-lives (t1/2, 87.5 versus 17.0 min) and increased area under the concentration-time curve (AUC0-t, 38.0 versus 19.48 µg/ml*min) compared to Paeonol solution. Formulated Paeonol had superior cytotoxicity versus the free drug with IC50 values of 22.47 and 85.16 µg/mL at 24 h on HepG2 cells, respectively, and we found that low concentration of Pae-PEG-NISVs and 5-Fu in conjunction had obviously synergistic effect. Our results indicate that the PEG-NISVs system has the potential to serve as an efficient carrier for Paeonol by effectively solubilizing, stabilizing and delivering the drug to the cancer cells.