Search

To comprehensively evaluate the effects of drying methods on the nutritional quality and antioxidant activity of Jiangyong fragrant ginger, seven different drying methods including natural drying (ND), hot air drying (HAD), infrared drying (ID), microwave drying (MD), vacuum drying (VD), hot air-microwave combined drying (HAMCD), infrared-hot air combined drying (IHACD) were used to dry Jiangyong fragrant ginger. Thirteen indexes such as total phenols, total flavonoids, gingerols, curcumin, vitamin C, starch, cellulose, free amino acids, soluble protein, soluble sugar, DPPH free radical scavenging rate, hydroxyl radical scavenging rate and total reducing capacity of the dried samples were determined, and the core indexes were screened by principal component analysis. The comprehensive evaluation model of the quality of dried ginger was constructed for comprehensive scoring. The results showed that MD had the shortest drying time and the highest drying efficiency; The determination of quality indicators found that the total phenol content of ID was the highest; The total flavonoid content of ND was the highest; The gingerol, curcumin content and vitamin C content of MD were the highest; The starch content of HAD was the highest; The soluble sugar content of HAMCD was the highest; The soluble protein and free amino acid content of IHACD was the highest; The highest cellulose content and the best antioxidant activity were VD. Through principal component analysis, 13 quality indicators were summarized into four principal component factors, with contribution rates of 34.942%, 26.725%, 17.602%, and 12.016%, respectively, and the cumulative contribution rate was 91.285%. The quality evaluation model of Jiangyong fragrant ginger was established through principal component analysis, it was concluded that VD had the highest comprehensive score. The research results can provide a reference for the deep processing of Jiangyong fragrant ginger and the development of high-value products.

Abstract Background There are some changes in the new 9th edition Tumor-Node-Metastases (TNM) staging system for lung cancer, including subdividing M1c into M1c1 and M1c2 stage. The aim of this study was to assess the prognostic performance of the updated classification system and try to provide some real-world application data among advanced lung adenocarcinoma patients with bone metastases. Methods Advanced lung adenocarcinoma patients in M1c stage with bone metastases who receiving first-line first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and T790M-guided osimertinib as the second-line therapy were retrospectively screened from December 2016 to December 2021. A total of 126 patients were enrolled in this study. 62 patients and 64 patients were subdivided into M1c1 and M1c2 groups according to the 9th edition of TNM staging system.The first-line real-world progression-free survival (1LrwPFS), the second-line real-world progression-free survival (2LrwPFS), post-progression survival (PPS) and real-world overall survival (rwOS) were analyzed. Results The overall median rwOS was 40.1 months (95% CI 35.996–44.204). 1LrwPFS was 13.9 months (95% CI 12.653–15.147) and 2LrwPFS was 14.5 months (95% CI 11.665–17.335) for all patients.Patients in M1c2 stage was inferior to M1c1 stage patients in rwOS (35.2 months vs. 42.9 months, HR = 0.512, P = 0.005). 2LrwPFS was moderately correlated with rwOS (r = 0.621, R2 = 0.568, P = 0.000). Multivariate analysis showed performance status (PS) score ≥ 2 and TP53 alteration positive were independent prognostic factors of worse rwOS. Conclusions More refined stratification of M1c according to the 9th edition of TNM staging system is conducive to the judgment of prognosis and the implementation of precision medicine for patients.

Abstract Background The initial randomized, double‐blinded, actively controlled, phase III ANEAS study (NCT03849768) demonstrated that aumolertinib showed superior efficacy relative to gefitinib as first‐line therapy in epidermal growth factor receptor (EGFR)‐mutated advanced non‐small cell lung cancer (NSCLC). Metastatic disease in the central nervous system (CNS) remains a challenge in the management of NSCLC. This study aimed to compare the efficacy of aumolertinib versus gefitinib among patients with baseline CNS metastases in the ANEAS study. Methods Eligible patients were enrolled and randomly assigned in a 1:1 ratio to orally receive either aumolertinib or gefitinib in a double‐blinded fashion. Patients with asymptomatic, stable CNS metastases were included. Follow‐up imaging of the same modality as the initial CNS imaging was performed every 6 weeks for 15 months, then every 12 weeks. CNS response was assessed by a neuroradiological blinded, independent central review (neuroradiological‐BICR). The primary endpoint for this subgroup analysis was CNS progression‐free survival (PFS). Results Of the 429 patients enrolled and randomized in the ANEAS study, 106 patients were found to have CNS metastases (CNS Full Analysis Set, cFAS) at baseline by neuroradiological‐BICR, and 60 of them had CNS target lesions (CNS Evaluable for Response, cEFR). Treatment with aumolertinib significantly prolonged median CNS PFS compared with gefitinib in both cFAS (29.0 vs. 8.3 months; hazard ratio [HR] = 0.31; 95% confidence interval [CI], 0.17‐0.56; P < 0.001) and cEFR (29.0 vs. 8.3 months; HR = 0.26; 95% CI, 0.11‐0.57; P < 0.001). The confirmed CNS overall response rate in cEFR was 85.7% and 75.0% in patients treated with aumolertinib and gefitinib, respectively. Competing risk analysis showed that the estimated probability of CNS progression without prior non‐CNS progression or death was consistently lower with aumolertinib than with gefitinib in patients with and without CNS metastases at baseline. No new safety findings were observed. Conclusions These results indicate a potential advantage of aumolertinib over gefitinib in terms of CNS PFS and the risk of CNS progression in patients with EGFR‐mutated advanced NSCLC with baseline CNS metastases. Trial registration ClinicalTrials.gov number, NCT03849768

BackgroundTelehealth has emerged as a popular channel for providing outpatient services in many countries. However, the majority of telehealth systems focus on operational functions and offer only a sectional patient journey at most. Experiences with incorporating longitudinal real-world medical record data into telehealth are valuable but have not been widely shared. The feasibility and usability of such a telehealth platform, with comprehensive, real-world data via a live feed, for cancer patient care are yet to be studied. ObjectiveThe primary purpose of this study is to understand the feasibility and usability of cancer patient care using a telehealth platform with longitudinal, real-world data via a live feed as a supplement to hospital electronic medical record systems specifically from physician’s perspective. MethodsA telehealth platform was constructed and launched for both physicians and patients. Real-world data were collected and curated using a comprehensive data model. Physician activities on the platform were recorded as system logs and analyzed. In February 2023, a survey was conducted among the platform’s registered physicians to assess the specific areas of patient care and to quantify their before and after experiences, including the number of patients managed, time spent, dropout rate, visit rate, and follow-up data. Descriptive and inferential statistical analyses were performed on the data sets. ResultsOver a period of 15 months, 16,035 unique users (13,888 patients, 1539 friends and family members, and 174 physician groups with 608 individuals) registered on the platform. More than 382,000 messages including text, reminders, and pictures were generated by physicians when communicating with patients. The survey was completed by 78 group leaders (45% of the 174 physician groups). Of the participants, 84% (65.6/78; SD 8.7) reported a positive experience, with efficient communication, remote supervision, quicker response to questions, adverse event prevention, more complete follow-up data, patient risk reduction, cross-organization collaboration, and a reduction in in-person visits. The majority of the participants (59/78, 76% to 76/78, 97.4%) estimated improvements in time spent, number of patients managed, the drop-off rate, and access to medical history, with the average ranging from 57% to 105%. When compared with prior platforms, responses from physicians indicated better experiences in terms of time spent, the drop-off rate, and medical history, while the number of patients managed did not significantly change. ConclusionsThis study suggests that a telehealth platform, equipped with comprehensive, real-world data via a live feed, is feasible and effective for cancer patient care. It enhances inpatient management by improving time efficiencies, reducing drop-off rates, and providing easy access to medical history. Moreover, it fosters a positive experience in physician-patient interactions.

Abstract This study was designed to establish the composition of wound dressing based on poly(2‐hydroxyethylmethacrylate)‐chitosan (PHEM‐CS) hydrogels‐loaded cerium oxide nanoparticle (CeONPs) composites for cutaneous wound healing on nursing care of the chronic wound. The as‐synthesised PHEM‐CS/CeONPs hydrogels nanocomposites were characterised by using UV–visible spectroscopy, scanning electron microscopy, Fourier transform infrared spectroscopy, X‐ray diffraction, and thermo gravimetric analysis. The influence of PHEM‐CS/CeONPs hydrogels nanocomposites on the gelation time, swelling ratio, in vitro degradation, and mechanical properties was investigated. The as‐prepared PHEM‐CS/CeONPs hydrogels nanocomposites dressing shows high antimicrobial activity against Staphylococcus aureus and Escherichia coli. Similar trends were observed for the treatment of biofilms where PHEM‐CS/CeONPs hydrogels nanocomposites displayed better efficiency. Furthermore, the biological properties of PHEM‐CS/CeONPs hydrogels nanocomposites had non‐toxic in cell viability and excellent cell adhesion behaviour. After 2 weeks, the wounds treated with the PHEM‐CS/CeONPs hydrogels nanocomposite wound dressing achieved a significant closure to 98.5 ± 4.95% compared with the PHEM‐CS hydrogels with nearly 71 ± 3.55% of wound closure. Hence, this study strongly supports the possibility of using this novel PHEM‐CS/CeONPs hydrogels nanocomposites wound dressing for efficient cutaneous wound healing on chronic wound infection and nursing care.

Abstract Background Lipusu is the first commercialized liposomal formulation of paclitaxel and has demonstrated promising efficacy against locally advanced lung squamous cell carcinoma (LSCC) in a small‐scale study. Here, we conducted a multicenter, randomized, phase 3 study to compare the efficacy and safety of cisplatin plus Lipusu (LP) versus cisplatin plus gemcitabine (GP) as first‐line treatment in locally advanced or metastatic LSCC. Methods Patients enrolled were aged between 18 to 75 years, had locally advanced (clinical stage IIIB, ineligible for concurrent chemoradiation or surgery) or metastatic (Stage IV) LSCC, had no previous systemic chemotherapy and at least one measurable lesion as per the Response Evaluation Criteria in Solid Tumors (version 1.1) before administration of the trial drug. The primary endpoint was progression‐free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety profiles. To explore the possible predictive value of plasma cytokines for LP treatment, plasma samples were collected from the LP group at baseline and first efficacy evaluation time and were then subjected to analysis by 45‐Plex ProcartaPlex Panel 1 to detect the presence of 45 cytokines using the Luminex xMAP technology. The correlation between treatment outcomes and dynamic changes in the levels of cytokines were evaluated in preliminary analyses. Results The median duration of follow‐up was 15.4 months. 237 patients in the LP group and 253 patients in the GP group were included in the per protocol set (PPS). In the PPS, the median PFS was 5.2 months versus 5.5 months in the LP and GP group (hazard ratio [HR]: 1.03, P = 0.742) respectively. The median OS was 14.6 months versus 12.5 months in the LP and GP group (HR: 0.83, P = 0.215). The ORR (41.8% versus 45.9%, P = 0.412) and DCR (90.3% versus 88.1%, P = 0.443) were also similar between the LP and GP group. A significantly lower proportion of patients in the LP group experienced adverse events (AEs) leading to treatment interruptions (10.9% versus 26.4%, P < 0.001) or treatment termination (14.3% versus 23.1%, P = 0.011). The analysis of cytokine levels in the LP group showed that low baseline levels of 27 cytokines were associated with an increased ORR, and 15 cytokines were associated with improved PFS, with 14 cytokines, including TNF‐α, IFN‐γ, IL‐6, and IL‐8, demonstrating an overlapping trend. Conclusion The LP regimen demonstrated similar PFS, OS, ORR and DCR as the GP regimen for patients with locally advanced or metastatic LSCC but had more favorable toxicity profiles. The study also identified a spectrum of different cytokines that could be potentially associated with the clinical benefit in patients who received the LP regimen.

Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) P. K. Hsiao (MO) and Astragalus membranaceus (Fisch.) Bug. (ME) are two primary sources of the Astragalus herb, also known as “Huangqi” in China, which is widely applied to treat hypertension, glomerulonephritis, ischemic heart disease, and diabetes mellitus. As two different sources of the Astragalus herb, the chemical profiles of MO and ME may be different. Previous studies showed abundant differences in chemical composition between MO and ME. Therefore, the by-products of MO and ME, such as Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) P. K. Hsiao flower (MOF) and Astragalus membranaceus (Fisch.) Bug. flower (MEF), may have different phytochemical profiles. In this paper, a metabolomics method combined with ultra-high-performance liquid chromatography and electrospray ionization/quadrupole time-of-flight mass spectrometry (UHPLC−Q−TOF−MS/MS) was employed to analyze the components of MOF and MEF. Consequently, the results of principal component analysis (PCA) showed that MOF and MEF could be separated clearly. In total, 31 chemical markers differentiating MOF and MEF were successfully identified, including 22 flavonoids, 8 isoflavones and 1 benzopyran. Among them, the contents of 18 components, including Calycosin, Cyanidin-3-O-glucoside, Quercetin, Rutin, Kaempferol, Formononetin, Isomucronulatol and Prim-O-glucosylcimifugin in MEF, were significantly higher than in MOF. In turn, the contents of another 13 components, covering Biochanin A, Tectoridin, Isomucronulatol-7-O-glucoside, Liquiritin, Rhamnetin, etc., were lower in the MEF group than that in the MOF group. It is worth noting that flavonoids, especially flavonoid glycosides, were the primary active chemical ingredients in MOF and MEF. The 18 ingredients in MEF with a higher level carried out diverse activities, like anti-oxidant, anti-inflammatory, anti-bacterial and anti-tumor activities, which led us to speculate that MEF may have greater pharmacological effects and potential development prospects than MOF. The present results displayed that the contents of ingredients in the two different species of plants were radically different, and there was significant uniqueness to the components of MOF and MEF. Our study not only provides helpful chemical information for further quality assessment and active mechanism research of MOF and MEF but also offers scientific support for the resource utilization of MOF and MEF.

Background: Savolitinib, a selective MET inhibitor, showed efficacy in patients with non-small cell lung cancer (NSCLC), including pulmonary sarcomatoid carcinoma (PSC), harbouring MET exon 14 skipping alteration ( MET ex14). Objective: To analyse post hoc , the association between circulating tumour DNA (ctDNA) biomarkers and clinical outcomes, including resistance, with savolitinib. Design: A multicentre, single-arm, open-label phase 2 study. Methods: All enrolled patients with baseline plasma samples were included. Outcomes were objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) by baseline MET ex14 and post-treatment clearance, coexisting gene alterations at baseline and disease progression. Results: Among 66 patients with baseline ctDNA sequencing, 46 (70%) had detectable MET ex14. Frequent coexisting baseline gene alterations included TP53 and POT1 mutations. Patients with detectable baseline MET ex14 exhibited worse PFS [hazard ratio (HR), 1.77; 95% confidence interval (CI), 0.88–3.57; p = 0.108] and OS (HR, 3.26; 95% CI, 1.35–7.89; p = 0.006) than those without, despite showing a numerically higher ORR. Among 24 patients with baseline detectable MET ex14 and evaluable postbaseline samples, 13 achieved MET ex14 clearance post-treatment. Median time to first clearance was 1.3 months (range, 0.7–1.5). MET ex14 post-treatment clearance was associated with better ORR (92.3%; 95% CI, 64.0–99.8 versus 36.4%; 95% CI, 10.9–69.2; p = 0.0078), PFS (HR, 0.44; 95% CI, 0.2–1.3; p = 0.1225) and OS (HR, 0.31; 95% CI, 0.1–1.0; p = 0.0397) versus non-clearance. Among 22 patients with disease progression, 10 acquired pathway alterations (e.g. in RAS/RAF and PI3K/PTEN) alone or with secondary MET mutations (D1228H/N and Y1230C/H/S). Conclusion: ctDNA biomarkers may allow for longitudinal monitoring of clinical outcomes with savolitinib in patients with MET ex14-positive PSC and other NSCLC subtypes. Specifically, undetectable baseline MET ex14 or post-treatment clearance may predict favourable clinical outcomes, while secondary MET mutations and other acquired gene alterations may explain resistance to savolitinib. Registration: The trial was registered with ClinicalTrials.gov (NCT02897479) on 13 September 2016.

Introduction: Savolitinib has been found to have encouraging antitumor activity and a favorable safety profile in Chinese patients with pulmonary sarcomatoid carcinoma and other NSCLCs with MET exon 14 skipping alterations (MET ex14 positive) at the primary analysis of a phase 2 study. Here, we present the long-term efficacy and safety data of savolitinib, including subgroup analyses. Methods: This multicenter, single-arm, open-label, phase 2 study in the People’s Republic of China enrolled MET inhibitor-naive adults with locally advanced or metastatic METex14-positive NSCLC (NCT02897479). Oral savolitinib at a dose of 400 or 600 mg was administered once daily (body weight dependent). The primary objectives of the final analysis were long-term overall survival (OS) and subgroup analyses by previous systemic treatment, NSCLC subtypes, and brain metastases. Results: At the final analysis cutoff date (June 28, 2021), a total of 70 patients were enrolled and receiving savolitinib, and median follow-up was 28.4 (interquartile range: 26.2–36.3) months. The median OS was 12.5 months (95% confidence interval [CI]: 10.5–21.4 [18- and 24-mo OS rates, 42.1% and 31.5%, respectively]). Median OS in pretreated or treatment-naive patients was 19.4 (95% CI: 10.5–31.3) and 10.9 (95% CI: 7.5–14.0) months, respectively; it was 10.6 months (95% CI: 4.6–14.0) in patients with pulmonary sarcomatoid carcinoma, 17.3 months (95% CI: 10.6–23.6) in other NSCLC subtypes, and 17.7 months (95% CI: 10.5–not evaluable) in patients with brain metastases. No new safety signals emerged with prolonged follow-up and exposure. Conclusions: The updated results further confirm the favorable benefit and acceptable safety of savolitinib in Chinese patients with METex14-positive NSCLC.

Abstract Background An adverse role for obstructive sleep apnea (OSA) in cancer aggressiveness and mortality has recently emerged from clinical and animal studies, and the reasons have not been fully determined. Cancer stem cells (CSCs) are regarded as the main cause of carcinoma metastasis. So far, the relationship between OSA and lung CSCs has not been explored. Method In the present study, we established an orthotopic mouse model of primary lung cancer and utilized chronic intermittent hypoxia (CIH) exposure to mimic OSA status. Results We observed that CIH endows lung cancer with greater metastatic potential, evidenced by increased tumor growth, tumor seeding, and upregulated CSC-related gene expression in the lungs. Notably, the transcription factor BTB and CNC homology 1 (Bach1), a key factor in responding to conditions of oxidative stress, is increased in lung cancer after CIH exposure in vitro and in vivo. Meanwhile, exposing lung cancer cells to CIH promoted cell proliferation, clonal diversity, induced stem-like cell marker expression, and gave rise to CSCs at a relatively higher frequency. Furthermore, the increase of mitochondrial ROS (mtROS) and CSC-marker expression induced by CIH exposure was abolished in Bach1 shRNA-treated lung cancer cells. Conclusions Our results indicated that CIH promoted lung CSC-like properties by activating mtROS, which was partially mediated by Bach1.

Circular RNAs (circRNA) is a class of non-coding RNAs that can regulate gene translation and function. Here the authors show that a circRNA, circNDUFB2, is downregulated in non-small cell lung cancer tissues, and likely contributes to anti-tumor immunity by regulating both degradation of oncoproteins and induction of innate immunity.

Abstract Background Biological role and clinical significance of circular RNAs (circRNAs) remain largely unknown. Herein, we aimed to investigate biological function, molecular mechanism, and clinical significance of a circular RNA FOXM1 (circFOXM1) in non-small cell lung cancer (NSCLC). Methods Expression of circFOXM1 was measured in 48 paired samples of NSCLC by qRT-PCR. Functional roles of circFOXM1 on tumor cells were explored by in vitro and in vivo assays. Transcriptome sequencing was employed to screen the molecules involved in circFOXM1 regulatory network. RNA immunoprecipitation, luciferase analysis, RNA pull-down, and rescue assay were used to investigate potential mechanisms of circFOXM1. Results We found that circFOXM1 was significantly upregulated in NSCLC tissues, and its upregulation was positively correlated with advanced clinical stage and poor prognosis of NSCLC patients. Gain or loss-of-function assay showed that circFOXM1 promoted cell proliferation and cell cycle progression. In vivo assays showed that silencing circFOXM1 inhibited xenograft tumor growth. Mechanically, transcriptome sequencing data indicated that silencing circFOXM1 led to the downregulation of cell cycle-related mRNAs. RNA pull-down and dual-luciferase reporter assay suggested that circFOXM1 could bind to miR-614, and FAM83D was an essential gene involved in the circFOXM1/miR-614 regulatory network. Conclusions circFOXM1promotes NSCLC progression by interacting with miR-614 and thus inactivating the function of miR-614, which will further release the suppression of FAM83D. circFOXM1/miR-614/FAM83D regulatory network may serve as a potential therapeutic target for NSCLC patients.

Background: Pulmonary rehabilitation is one meaningful way of improving exercise tolerance and pulmonary function. Thus, it may reduce the postoperative complications and mortality of pulmonary resection. Hence, we refreshed the data and conducted this systemic analysis.Method: We searched Pubmed, Web of Science, and EMBASE using “lung OR pulmonary” AND “operation OR resection OR surgery” AND “rehabilitation or exercise.” The cut-off date was September 30, 2020. The publications were filtrated, and data were extracted from all selected studies by two reviewers. Review Manger 5.1 and the fixed or random regression model were used for calculating the pooled odds ratio (OR).Result: Finally, 13 publications were enrolled in this study. Among them, five publications reported mortality, nine reported postoperative complications, and seven reported postoperative pulmonary complications. The pooled OR of mortality was 1.32 [95% confidence interval (CI): 0.54–3.23] for the pulmonary rehabilitation group, the pooled OR of postoperative complications was 0.62 (95% CI: 0.49–0.79) for the pulmonary rehabilitation group, and the pooled OR of postoperative pulmonary complications was 0.39 (95% CI: 0.27–0.56) for the pulmonary rehabilitation group. Subgroup analysis revealed the perioperative pulmonary rehabilitation was the most important part.Conclusion: Pulmonary rehabilitation may not affect the mortality of pulmonary resection patients, however, it could decrease the number of postoperative complications, especially pulmonary complications. Perioperative pulmonary rehabilitation was the most important part of the program.

Circular RNAs are known to regulate cancer. Here, the authors show that the circular RNA circTP63 promotes lung squamous cell carcinoma by competing with endogenous RNA to upregulate FOXM1.

Background: Idiopathic pulmonary arterial hypertension (IPAH) is a life-threatening disease. Owing to its high fatality rate and narrow therapeutic options, identification of the pathogenic mechanisms of IPAH is becoming increasingly important.Methods: In our research, we utilized the robust rank aggregation (RRA) method to integrate four eligible pulmonary arterial hypertension (PAH) microarray datasets and identified the significant differentially expressed genes (DEGs) between IPAH and normal samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed to analyze their functions. The interaction network of protein–protein interaction (PPI) was constructed to explore the correlation between these DEGs. The functional modules and hub genes were further identified by the weighted gene coexpression network analysis (WGCNA). Moreover, a miRNA microarray dataset was involved and analyzed to filter differentially expressed miRNAs (DE-miRNAs). Potential target genes of screened DE-miRNAs were predicted and merged with DEGs to explore a miRNA–mRNA network in IPAH. Some hub genes were selected and validated by RT-PCR in lung tissues from the PAH animal model.Results: A total of 260 DEGs, consisting of 183 upregulated and 77 downregulated significant DEGs, were identified, and some of those genes were novel. Their molecular roles in the etiology of IPAH remained vague. The most crucial functional module involved in IPAH is mainly enriched in biological processes, including leukocyte migration, cell chemotaxis, and myeloid leukocyte migration. Construction and analysis of the PPI network showed that CXCL10, CXCL9, CCR1, CX3CR1, CX3CL1, CXCR2, CXCR1, PF4, CCL4L1, and ADORA3 were recognized as top 10 hub genes with high connectivity degrees. WGCNA further identified five main functional modules involved in the pathogenesis of IPAH. Twelve upregulated DE-miRNAs and nine downregulated DE-miRNAs were identified. Among them, four downregulated DEGs and eight upregulated DEGs were supposed to be negatively regulated by three upregulated DE-miRNAs and three downregulated DE-miRNAs, respectively.Conclusions: This study identifies some key and functional coexpression modules involved in IPAH, as well as a potential IPAH-related miRNA–mRNA regulated network. It provides deepening insights into the molecular mechanisms and provides vital clues in seeking novel therapeutic targets for IPAH.

Human proximal renal tubular epithelial cells (HK-2) are constantly exposed to glyco-oxidative injury due to the diabetic nephropathy. It has been reported that nanoparticles (NPs) due to their unique properties may show outstanding antioxidant activity. The influences of high glucose (HG) treatment with a concentration of 50 mM on HK-2 cells toxicity and the protective effects of synthesized gold NPs (AuNPs) by hydrothermal method were explored in terms of free radical production and advanced glycation end products (AGEs) formation. Also, the expression of Bax, Bcl-2, Caspase-3 at both mRNA and protein levels was evaluated by qPCR and ELISA assays, respectively followed by SIRT3 and SOD2 activity assays. It was observed that AuNPs with a diameter of about 30 nm and good colloidal stability at physiological pH attenuates HG‐induced cytotoxicity in HK-2 cells through a significant increase in cell viability and the reduction of free radical production, AGEs formation, and expression of Bax/Bcl-2 and Caspase-3 at both mRNA and protein levels. However, 3-TYP, a SIRT3 inhibitor, significantly inhibited the inhibitory effects of AuNPs on HG‐induced cytotoxicity. This data revealed that HG concentrations induced glyco-oxidative stress in kidney cells and AuNPs could be used as promising candidates in reducing the risk of progression of diabetic nephropathy.

The distinct genomic and epidemiological features of Chinese lung cancer patients suggest the presence of alternative causal mechanisms. Here, the authors present the genomic landscape of 149 Chinese NSCLC patients and reveal distinct mutational signatures associated with inflammatory microenvironments.

Background and objective A survival analysis and the influencing factors for non-small cell lung cancer (NSCLC) patients with brain metastases accepting first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs) treatment have not yet been elucidated to date. In this study, we collected and analyzed the survival data of NSCLC patients with brain metastasis to obtain evidence and to provide guidance in clinical practice. Methods NSCLC patients with brain metastases who were treated with first-generation EGFR-TKIs were retrospectively collected in 2012-2013 from Shanghai Chest Hospital, Shanghai Jiao Tong University. The Kaplan-Meier method and Cox regression were performed for univariate and multivariate analyses, respectively, to explore the independent predictors influencing the survival of patients with NSCLC brain metastases. Results The median progression-free survival (PFS) and median overall survival (OS) of all patients treated with first-generation EGFR-TKIs were 10.0 months (95%CI: 8.3-11.7) and 28.0 months (95%CI: 22.9-33.1), respectively. Pathological subtypes were the independent predictors of PFS (P=0.001), and tumor differentiations were the independent predictors of OS (P=0.050). Conclusion First-generation EGFR-TKIs showed promising efficacy in NSCLC patients with brain metastases. PFS was longer in patients with adenocarcinoma than in those with a non-adenocarcinoma subtype. OS was longer in patients with differentiated tumors than in those who developed poorly differentiated tumors.

Emerging evidence shows that signal transducer and activator of transcription 6 (STAT6) plays critical roles in tumor development. We previously found high-level expression of STAT6 in human lung adenocarcinoma and squamous cell carcinoma, specifically in infiltrated immune cells located in the lung interstitium. Nevertheless, the role of STAT6 signaling in lung carcinogenesis and lung cancer proliferation and its underlying mechanisms remain unclear. This study aimed to investigate the role of STAT6 and the interaction between STAT6 and the tumor microenvironment in pulmonary tumorigenesis. We established a murine model of primary lung carcinogenesis in STAT6-deficient (STAT6−/−) and STAT6 wild-type (WT) BALB/c mice using the carcinogen urethane. Two-month-old male mice were intraperitoneally injected with urethane (1 g/kg) dissolved in phosphate buffered saline (PBS). Primary tumors were monitored in vivo by positron emission tomography scanning. At 4, 6, and 9 months after urethane injection, lung tumors were harvested from the STAT6−/− and WT mice for analysis. Small interfering RNA was used to downregulate the expression of STAT6 in tumor cells. Fluorescence activated cell sorting analysis was used to analyze fluorescence-conjugated cell markers. Transwell assays were used in coculturing experiments. STAT6 protein expression was detected by Western blotting, immunohistochemistry, and immunofluorescence. STAT6 mRNA expression was detected by quantitative real time-polymerase chain reaction. Cell Counting Kit-8 and colony formation assays were performed to evaluate cell proliferation. We detected high expression of STAT6 in CD11b+ cells of lung carcinoma. Our results indicate that STAT6 deficiency inhibits carcinogen-induced tumor growth and improves prognosis. STAT6 deficiency also decreased the mobilization and differentiation of CD11b+ cells. STAT6 deficiency in CD11b+ cells but not tumor cells decreased interleukin (IL)-4 secretion and the differentiation of CD11b+ cells into M2 macrophage cells. In conclusion, our findings indicate that IL-4/STAT6 signaling in CD11b+ cells promotes lung cancer progression by triggering an IL-4 positive feedback loop and increasing M2 myeloid cells. STAT6 may be a new therapeutic target for the prevention and treatment of lung cancer.

Background/Aims: Neovascularization and invasion coordinate cancer metastases in non-small cell lung cancer (NSCLC). However, the underlying molecular mechanisms are poorly understood. Recently, a substantial role of placental growth factor (PLGF) in cancer cell invasion has been acknowledged in several types of cancer, whereas a possible involvement of PLGF in the metastases of NSCLC has not been studied. Methods: Here, we analyzed the levels of PLGF and matrix metalloproteinase 9 (MMP9) in NSCLC specimens. We modified either PLGF or MMP9 levels in a NSCLC cell line A549, and examined the effects on the levels of MMP9 and PLGF. The cell invasiveness was quantified in a transwell cell migration assay. Pathway inhibitors were applied to determine the molecular mechanisms underlying the control of MMP9 by PLGF. Results: We found that PLGF and MMP9 levels both significantly increased in the NSCLC specimens and were strongly correlated. Overexpression of PLGF in NSCLC cells increased the levels of MMP9 and cell invasiveness, while inhibition of PLGF in NSCLC cells decreased the levels of MMP9 and cell invasiveness. However, modification of MMP9 levels in NSCLC cells did not alter the levels of PLGF. These data suggest that PLGF may regulate MMP9 in NSCLC cells, but not vice versa. Moreover, inhibition of MMP9 in PLGF-overexpressing NSCLC cells abolished the effects of PLGF on cell invasiveness, suggesting that PLGF increases cell invasion via MMP9. Furthermore, suppression of MAPK-p38, but not suppression of either MAPK-p42/p44, or PI3k, or JNK signaling, substantially abolished the effect of PLGF on MMP9, suggesting that PLGF may activate MMP9 via MAPK-p38 signaling pathway. Conclusion: PLGF-stimulated cancer invasion may be mediated through its effects on MMP9 activation in NSCLC cells.

Background and objective Most small cell lung cancer (SCLC) patients relapse or progress and have low survival rate although they have significant response to initial chemotherapy and radiotherapy. This study intends to explore the factors affecting the relapse (or progression) of nonoperative SCLC and to explore the correlations between progression-free survival (PFS) and overall survival (OS). Methods Clinical data of 182 patients diagnosed with SCLC between January 2009 and December 2011 at Shanghai Chest Hospital has been reviewed and retrospectively analyzed. All of these patients accepted chemotherapy combined (or not combined) with radiotherapy, and relapsed or progressed after first-line therapy. Univariate Kaplan-Meier survival estimates as well as multivariate Cox regression survival analysis were used to locate the potential factors affecting PFS. The correlation between PFS and OS was analyzed via Bivariate Correlation Analysis method. Results The univariate estimates showed that the TNM stage, liver metastasis or not, brain metastasis or not, first-line chemotherapy cycles, effect of initial chemotherapy, and thoracic radiotherapy combined or not were the significant contributive factors to PFS. In the subgroup of the patients without brain metastases, those received prophylactic cranial irradiation (PCI) had longer PFS. Cox regression indicated that the three independent variables of first-line chemotherapy cycles, effect of initial chemotherapy and thoracic radiotherapy combined or not were closely related to PFS. In addition, significant positive correlation between PFS and OS had been observed. Conclusion PFS could be prolonged by having more first-line chemotherapy cycles (>4 cycles), obtaining better effect of initial chemotherapy (partial response or complete response), combining with thoracic radiotherapy and implementing PCI for patients without brain metastasis.

Background/Aims: Non-small cell lung carcinoma (NSCLC) is the most common type of lung cancer and the cause of most cancer-related deaths. The molecular mechanisms that are involved in NSCLC development are currently not well understood. Accumulating evidence shows that histone demethylases play important roles in the regulation of pathological developmental processes in many diseases, including various types of cancers. Methods: Mitochondrial membrane potential assays, migration and invasion assays, caspase-3 and caspase-9 activity assays and western blot analysis were used in this research. Results: We found that overexpression of KDM6B, a demethylase that acts on histone H3 at lysine 27 (H3K27), inhibited cell growth by initiating mitochondria-dependent apoptosis and by attenuating the invasion-metastasis cascade in NSCLC cells. Moreover, our results showed that KDM6B directly interacted with FOXO1 and that overexpression of KDM6B promoted nuclear accumulation of FOXO1. The effects of KDM6B on cell apoptosis and metastasis were weakened by knockdown of FOXO1 expression. On the contrary, knocking down expression of KDM6B inhibited cell apoptosis and promoted cell growth by mitigating the nuclear translocation of FOXO1 in NSCLC cells. Conclusions: These findings suggest that KDM6B may act in a pro-apoptotic role in NSCLC by causing the nuclear translocation of FOXO1.

Background and objective The prognosis for patients with lung cancer and brain metastases remains poor, with approximately 6 months of survival, despite active measures after treatment. In this study, we determined and analyzed clinical parameters that affect the survival of patients with lung cancer and brain metastases to provide clinical guidance. Methods Lung cancer cases with brain metastases were retrospectively collected during 2002 and 2008 from Shanghai Chest Hospital, Shanghai Jiao Tong University. Kaplan-Meier method and Cox regression were performed for univariate and multivariate analyses, respectively, to explore independent predictors influencing the survival of patients with lung cancer and brain metastases. Results Age, Eastern Cooperative Oncology Group performance status (ECOG PS), metastasis interval, number of metastasis, treatment method, treatment period, symptoms of brain metastases, extracranial metastasis, and brain metastasis order were factors that affect the survival of patients with brain metastases as confirmed through the Kaplan-Meier method. Treatment periods and extracranial metastasis were independent survival predictors in patients with lung cancer and brain metastasis as indicated by Cox proportional hazard model. Conclusion Treatment periods and extracranial metastasis were independent predictors of survival of patients with lung cancer and brain metastasis. Treatment periods and extracranial metastasis were independent predictors of survival of patients with lung cancer and brain metastasis.

The combination of the ionic liquid co-lyophilized lipase and microwave irradiation was used to improve enzyme performance in enantioselective esterification of α-lipoic acid. Effects of various reaction conditions on enzyme activity and enantioselectivity were investigated. Under optimal condition, the highest enantioselectivity (E = 41.2) was observed with a high enzyme activity (178.1 μmol/h/mg) when using the ionic liquid co-lyophilized lipase with microwave assistance. Furthermore, the ionic liquid co-lyophilized lipase exhibited excellent reusability under low power microwave.

Arbutin (p-hydroxyphenyl-β-D-glucopyranoside), a well-known tyrosinase inhibitor, has been widely used as a cosmetic whitening agent. Although its natural role is to scavenge free radicals within cells, it has also exhibited useful activities for the treatment of diuresis, bacterial infections and cancer, as well as anti-inflammatory and anti-tussive activities. Because function of free radical scavenging is also related to antioxidant and the effects of arbutin on longevity and stress resistance in animals have not yet been confirmed, here the effects of arbutin on Caenorhabditis elegans were investigated. The results demonstrated that optimal concentrations of arbutin could extend lifespan and enhance resistance to oxidative stress. The underlying molecular mechanism for these effects involves decreased levels of reactive oxygen species (ROS), improvement of daf-16 nuclear localization, and up-regulated expression of daf-16 and its downstream targets, including sod-3 and hsp16.2. In this work the roles of arbutin in lifespan and health are studied and the results support that arbutin is an antioxidant for maintaining overall health.

The finding of epidermal growth factor receptor tyrosine kinase inhibitors, which reflects a classical process of translational research, is a critical milestone for non-small-cell lung cancer treatment. Currently, epidermal growth factor receptor tyrosine kinase inhibitors are recommended as first-line therapy for non-small-cell lung cancer patients harboring epidermal growth factor receptor–sensitive mutations. The status of epidermal growth factor receptor mutation is widely acknowledged as superior to other clinical factors, such as smoking, gender, and histological types for predicting the response to epidermal growth factor receptor tyrosine kinase inhibitors. However, recent studies have shown that the efficacy might differ in patients with the same epidermal growth factor receptor–sensitive mutations, highlighting the need to investigate the putative factors related to the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors. This article reviews the factors associated with clinical efficacy of first-generation epidermal growth factor receptor tyrosine kinase inhibitors, such as gefitinib and erlotinib, and analyzes their potential implications with respect to clinical application. In addition, new findings related to clinical practice with respect to epidermal growth factor receptor tyrosine kinase inhibitors efficacy were summarized in this article.

Lung cancer is the leading cause of cancer-related death worldwide. The majority of cases, the diagnosis is made at an advanced stage. The prognosis is poor with a 5-year survival rate less than 16% and the median overall survival 1 year or so. In recent years, research has focused on the potential role of new biological factors involved in the carcinogenic process. It’s well known that thyroid transcription factor 1 (TTF-1) was a special lineage-survival oncogene in lung cancer according to recent researches. It has become apparent that TTF-1 expression has biological and clinical functions in the opposite direction that act in tumor progression. Herein, we summarize the role of this transcription factor in the development, diagnosis, and prognosis of lung cancer in the hope of providing insights into the utility of TTF-1 as a novel biomarker of lung cancer.

KRAS mutations are common in non-small cell lung cancer (NSCLC) and are associated with patient prognosis; however, targeting KRAS has faced various difficulties. Currently, immunotherapy, chemotherapy, and chemoimmunotherapy play pivotal roles in the first-line treatment of KRAS-mutated NSCLC. Here, we summarize the current evidence on first-line therapies and compare the treatment outcomes and biomarkers for different regimens. KRAS inhibitors and other emerging alternative treatments are also discussed, as combining these drugs with immunotherapy may serve as a promising first-line treatment for KRAS-mutated NSCLC in the future. We hope that this review will assist in first-line treatment choices and shed light on the development of novel agents for KRAS-mutated NSCLC.

Background and objective The prognostic factors and salvage therapy after the failure of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) therapy have brought concerns. This study aims to analyze retrospectively the clinical data of patients with advanced lung adenocarcinoma and explore their prognostic factors. Methods Patients with integral clinic dates and staged IV lung adenocarcinoma with performance status (PS) scores from 0 to 2 were enrolled between January 2009 and February 2012 and followed up until death. The primary endpoint was survival time after the failure of EGFR-TKI therapy. Results A total of 81 patients were enrolled into the study, and the median overall survival time was 9.6 months (QL-QU: 5.4-19.2). Univariate analysis showed that PS score, metastatic status, and the presence of plural effusion were significantly correlated with patient survival time (P

Small cell lung cancer (SCLC) is an aggressive disease with poor survival. A few sequencing studies performed on limited number of samples have revealed potential disease-driving genes in SCLC, however, much still remains unknown, particularly in the Asian patient population. Here we conducted whole exome sequencing (WES) and transcriptomic sequencing of primary tumors from 99 Chinese SCLC patients. Dysregulation of tumor suppressor genes TP53 and RB1 was observed in 82% and 62% of SCLC patients, respectively, and more than half of the SCLC patients (62%) harbored TP53 and RB1 mutation and/or copy number loss. Additionally, Serine/Arginine Splicing Factor 1 (SRSF1) DNA copy number gain and mRNA over-expression was strongly associated with poor survival using both discovery and validation patient cohorts. Functional studies in vitro and in vivo demonstrate that SRSF1 is important for tumorigenicity of SCLC and may play a key role in DNA repair and chemo-sensitivity. These results strongly support SRSF1 as a prognostic biomarker in SCLC and provide a rationale for personalized therapy in SCLC.

Background and objective Pemetrexed and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) were used in patients with EGFR mutation to determine their effects. This study analyzed the influence of EGFR-TKIs on pemetrexed by observing the clinical efficacy and toxicity of pemetrexed following responses to EGFR-TKIs. Methods Pulmonary adenocarcinoma patients were divided into EGFR-TKIs and no-EGFR-TKI groups according to the targeted therapy. All patients received pemetrexed (500 mg/m2) as second (or higher)-line treatment. The Response Evaluation Criteria in Solid Tumors (version 1.0) were used to evaluate the response to pemetrexed. Adverse events were classified based on version 4.0 of the National Cancer Institute Common Toxicity Criteria. Results There were 57 patients in the EGFR-TKIs group and 56 in the no-EGFR-TKIs group. The disease control rates (DCRs) were 77.2% and 67.9% (P=0.367). The progression free survival (PFS) periods were 5.95 and 3.55 months (P=0.535). The overall survival (OS) periods were 10.10 and 8.24 months (P=0.432). However, these values were not statistically significant. The common toxicities of pemetrexed were hematologic and gastrointestinal (grades I and II). Two patients in the EGFR-TKIs group discontinued pemetrexed because of severe toxicities, which were not observed in the no-EGFR-TKIs group. Both groups had one patient who reduced dosage because of myelosuppression (grade IV). There were five and nine patients in the EGFR-TKIs and no-EGFR-TKIs groups, respectively, who delayed therapy not because of severe toxicities but due to subjective factors. Conclusion The DCRs, PFS periods, and OS periods of the patients administered with pemetrexed following EGFR-TKIs were better than those of the EGFR-TKIs group, but the differences were not statistically significant. Therefore, sequential pemetrexed administration caused negligible toxicities and can be used in adenocarcinoma therapy following responses to EGFR-TKIs.

Background and objective Lung cancer is one of the most common cancers worldwide. Thus far, good tumor markers for diagnosing this disease have not been found. Therefore, the discovery of novel biomarkers through the application of new methods has become a hotspot in lung cancer research. The aim of this study is to analyze low-molecular-weight metabolites in the serum and urine samples of lung cancer patients and patients with other lung diseases through metabolomics and to explore potential tumor markers further. Methods Both serum and urine samples from 19 lung cancer patients and 15 patients with other lung diseases were subjected to metabolomic analysis using gas chromatography mass spectrometry. Orthogonal to partial least squares discriminant analysis was performed for modeling. Two sample t-test was used to identify differences in metabolite concentrations. Results A total of 57 metabolites were found in the serum, and 38 metabolites were found in the urine. Multivariate statistical analysis yielded a significant distinction in the metabolic profiles between lung cancer patients and patients with other lung diseases. The t-test results indicated a total of 13 metabolites in the serum and 7 metabolites in the urine with statistically significant differences. Conclusion Metabolomics is useful in discriminating between lung cancer and other lung diseases. As a novel approach, it has potential in the diagnosis of lung cancer at molecular level.

Background and objective At present, there is no standard salvage treatment strategies for lung cancer. The aim of this study is to compare the efficacies and safeties of pemetrexed alone with pemetrexed combined with oxaliplatin as salvage therapy in stage IV lung adenocarcinoma to provide evidences for combination therapy. Methods From January 2009 to February 2011, 83 patients with stage IV lung adenocarcinoma received pemetrexed alone (single agent arm, n=47) or pemetrexed combined with oxaliplatin (combination arm, n=36) as salvage therapy. All 83 patients had performance status (PS) scores of 0-2. Results Eighty-one patients were included in the final analysis. The median progression-free survival (PFS) in the single agent arm was 3.6 months versus 4.1 months in the combination arm (P=0.268). The objective response rate (ORR) was 6.5% versus 20% (P=0.092), and the disease control rate (DCR) was 56.5% versus 65.7% (P=0.493), respectively. The response rates of the hematological and gastrointestinal toxicities in the single agent and combination arms were 33.9% versus 47.2% (P=0.460) and 21.2% versus 25.0% (P=0.213), respectively. Conclusion For salvage therapy, pemetrexed combined with oxaliplatin is tolerable in stage IV lung adenocarcinoma patients with good PS scores. Compared with pemetrexed alone, pemetrexed combined with oxaliplatin therapy showed higher response rate, but did not significantly prolong the PFS.

Background and objective Lung lymphoepithelioma-like carcinoma is a rare subtype of large cell carcinomas of the lung. The aim of this study is to retrospectively analyze the clinical characteristics, surgical methods, laboratory inspection, chemotherapy, radiotherapy and prognosis of LELC. Methods From 2004 to 2008, clinical data were collected from 21 patients who were treated in Shanghai Chest Hospital. The correlation between clinicopathological characteristics and prognosis was evaluated. Results Of the 21 patients, 15 patients had lobectomy; 4 patients had wedge resection; 1 patient had pneumonectomy and 1 patient had sleeve resection. 12 patients received chemotherapy and 3 patients received radiotherapy after operation. Until 2009-4-31, 4 patients died, and the median survival time (MST) was 49 months. Conclusion Lymphoepitheliomalike carcinoma of the lung is a very rare and unique subtype of large cell carcinomas of the lung, which has a better prognosis with surgical, chemotherapy and radiotherapy.

Background and Objective The role of Preoperative chemotherapy in patients with resected non-small-cell lung cancer (NSCLC) remains unclear, this study is aimed at evaluating the effectiveness of Preoperative chemotherapy in patients with resected non-small-cell lung cancer (NSCLC), by performing a meta-analysis of relevant trials. Methods Searching the literature from MEDLINE, pubmed, OVID, The Cochrane library, Cancerlit, Clinicaltrials.gov, ASCO, ESMO and CBM database, a meta-analysis was carried out to compare patients with NSCLC receiving chemotherapy before surgery with those undergoing surgery alone. The odds ratio (OR) was estimated to assess the survival advantage of Preoperative chemotherapy. Results Thirteen eligible randomized controlled trials (RCT) were identified, including 2561 patients, the meta-analysis showed preoperative chemotherapy improved survival with a OR of 0.80 (95% confidence interval, 0.68-0.94; P=0.008) in a subset analysis patients with IIIa stage also benefit from the preoperative chemotherapy. There was no evidence of statistical heterogeneity. Conclusion This analysis shows a significant benefit of preoperative chemotherapy and is currently the best estimate of the effectiveness of this therapy.

INTRODUCTION: Primary pulmonary mucoepidermoid carcinoma (PMEC) is an uncommon neoplasm with remarkable resemblance to mucoepidermoid carcinoma of the salivary glands. The latter has been shown to harbor t(11,19) resulting in MECT1-MAML2 fusion, which may be of diagnostic and prognostic values. However, the importance of such feature in PMEC has not been well studied. METHODS: We detected MAML2 rearrangement using fluorescence in situ hybridization (FISH) in tissue samples from 42 cases of PMEC and 40 of adenosquamous carcinoma (ASC), and the expression of potential downstream targets of MECT1-MAML2, including HES1, FLT1 and NR4A2 with immunohistochemistry (IHC). The findings were then examined regarding the clinicopathological parameters and patient outcomes. RESULTS: FISH analysis revealed MAML2 rearrangement in 50% of the PMEC cases, and such property was prominent in considerable younger patients (33 versus 60 years; p = 0.001) and restricted to cases of low and intermediate grades. IHC analysis showed that FLT1 and HES1 were expressed at lower level in MAML2 rearranged group than MAML2 non-rearranged group (p

BACKGROUND: The use of chemotherapy has been proposed to increase the effectiveness of best supportive care (BSC) in patients with non-small cell lung cancer (NSCLC). Previous trials reported inconsistent findings regarding the efficacy and safety of chemotherapy on overall survival (OS) and treatment-related mortality. We performed a systematic review and meta-analysis to evaluate the effects of chemotherapy plus BSC versus BSC alone on survival of patients with NSCLC. METHODOLOGY AND PRINCIPAL FINDINGS: We systematically searched PubMed, EmBase, and the Cochrane Central Register of Controlled Trials for relevant literature. All eligible studies included patients with NSCLC who had received chemotherapy and BSC or BSC alone. All eligible studies measured at least 1 of the following outcomes: OS or treatment-related mortality. Overall, patients that received chemotherapy plus BSC had significant longer OS than those that received BSC alone (HR, 0.76; 95%CI, 0.69-0.84; P