PLAU, transcriptionally negatively regulated by GATA6, promotes lung squamous carcinoma cell proliferation and migration.

BACKGROUND: Lung squamous cell carcinoma (LUSC) is associated with high mortality and has limited therapeutic treatment options. Plasminogen activator urokinase (PLAU) plays important roles in tumor cell malignancy. However, the oncogenic role of PLAU in the progression of LUSC remains unknown. GATA-binding factor 6 (GATA6), a key regulator of lung development, inhibits LUSC cell proliferation and migration, but the underlying regulatory mechanism remains to be further explored. Moreover, the regulatory effect of GATA6 on PLAU expression has not been reported. The aim of this study was to identify the role of PLAU and the transcriptional inhibition mechanism of GATA6 on PLAU expression in LUSC. METHODS: To identify the potential target genes regulated by GATA6, differentially expressed genes (DEGs) obtained from GEO datasets analysis and RNA-seq experiment were subjected to Venn analysis and correlation heatmap analysis. The transcriptional regulatory effects of GATA6 on PLAU expression were detected by real-time PCR, immunoblotting, and dual-luciferase reporter assays. The oncogenic effects of PLAU on LUSC cell proliferation and migration were evaluated by EdU incorporation, Matrigel 3D culture and Transwell assays. PLAU expression was detected in tissue microarray of LUSC via immunohistochemistry (IHC) assay. To determine prognostic factors for prognosis of LUSC patients, the clinicopathological characteristics and PLAU expression were subjected to univariate Cox regression analysis. RESULTS: PLAU overexpression promoted LUSC cell proliferation and migration. PLAU is overexpressed in LUSC tissues compared with normal tissues. Consistently, high PLAU expression, which acts as an independent risk factor, is associated with poor prognosis of LUSC patients. Furthermore, the expression of PLAU is transcriptionally regulated by GATA6. CONCLUSION: In this work, it was revealed that PLAU is a novel oncogene for LUSC and a new molecular regulatory mechanism of GATA6 in LUSC was unveiled. Targeting the GATA6/PLAU pathway might help in the development of novel therapeutic treatment strategies for LUSC.

A One-Bit Programmable Multi-Functional Metasurface for Microwave Beam Shaping.

In this paper, we demonstrate a multi-functional metasurface for microwave beam-shaping application. The metasurface consists of an array of programmable unit cells, and each unit cell is integrated with one varactor diode. By turning the electrical bias on the diode on and off, the phase delay of the microwave reflected by the metasurface can be switched between 0 and π at a 6.2 GHz frequency, which makes the metasurface 1-bit-coded. By programming the 1-bit-coded metasurface, the generation of a single-focus beam, a double-focus beam and a focused vortex beam was experimentally demonstrated. Furthermore, the single-focus beam with tunable focal lengths of 54 mm, 103 mm and 152 mm was experimentally observed at 5.7 GHz. The proposed programmable metasurface manifests robust and flexible beam-shaping ability which allows its application to microwave imaging, information transmission and sensing applications.

Ruthenium-Catalyzed 1,6-Hydroalkylation of para-Quinone Methides with Ketones via the in Situ Activation of C(sp3)-H Bonds.

A simple and efficient method for the ruthenium-catalyzed 1,6-hydroalkylation of para-quinone methides (p-QMs) with ketones via the in situ activation of C(sp3)-H bonds has been disclosed. Without the need for preactivation of the substrates and oxidant, a broad range of p-QMs and ketones are well tolerated, producing the expected 1,6-hydroalkylation products with moderate to good yields. Step-by-step control experiments and DFT calculation were conducted systematically to gain insights for the plausible reaction mechanism. This finding may have potential application in the selective diarylmethylation of ketones at the α-C position in organic synthesis.

Anakinra was not associated with lower mortality in hospitalised COVID-19 patients: A systematic review and meta-analysis of randomized controlled trials.

The Coronavirus disease-2019 (COVID-19) pandemic continues, and the death toll continues to surge. This meta-analysis aimed to determine the efficacy of anakinra on mortality in patients with COVID-19. A systematic search was made of PubMed, Embase, Cochrane Library, and clinicaltrials.gov, without language restrictions. Randomized controlled trials on treatment of COVID-19 with anakinra, compared with placebo or blank, were reviewed. Studies were pooled to risk ratios (RRs), with 95% confidence intervals (CIs). Five Randomized controlled trials (enrolling 1859 participants) met the inclusion criteria. There was no statistically significant difference in 14-day mortality (RR 0.78, 95% CI 0.43-1.39; P = 0.40), 28-day mortality (RR 1.06, 95% CI 0.89-1.26; P = 0.51), and 90-day mortality (RR 1.01, 95% CI 0.73-1.39; P = 0.97) between the two groups. Sensitivity analyses further confirmed these results. Anakinra was not associated with reduced mortality in hospitalised patients with COVID-19. Anakinra probably should not be used routinely in COVID-19 patients.

Benefits of ozone on mortality in patients with COVID-19: A systematic review and meta-analysis.

BACKGROUND: The Coronavirus disease-2019 (COVID-19) pandemic continues, and the death toll continues to surge. Ozone therapy has long been used in the treatment of a variety of infectious diseases, probably through its antioxidant properties and the supply of oxygen to hypoxic tissues. This systematic review and meta-analysis aimed to determine the efficacy of ozone on mortality in patients with COVID-19. METHODS: A systematic search was made of PubMed, Embase, Cochrane Library, and clinicaltrials.gov, without language restrictions. Prospective controlled trials on treatment of COVID-19 with ozone, compared with placebo or blank, were reviewed. Studies were pooled to risk ratios (RRs) and weighted mean differences (WMDs), with 95% confidence intervals (CIs). RESULTS: Eight trials (enrolling 371 participants) met the inclusion criteria. Ozone therapy showed significant effects on mortality (RR 0.38, 95% CI 0.17-0.85; P = 0.02), length of hospital stay (WMD -1.63 days, 95% CI -3.05 to -0.22 days; P = 0.02), and polymerase chain reaction (PCR) positivity (RR 0.07, 95% CI 0.01-0.34; P = 0.001). CONCLUSIONS: Ozone therapy significantly reduced mortality, PCR positivity, and length of stay in hospitalized patients with COVID-19. Ozone therapy should be considered for COVID-19 patients.

Terahertz Metamaterials for Biosensing Applications: A Review.

In recent decades, THz metamaterials have emerged as a promising technology for biosensing by extracting useful information (composition, structure and dynamics) of biological samples from the interaction between the THz wave and the biological samples. Advantages of biosensing with THz metamaterials include label-free and non-invasive detection with high sensitivity. In this review, we first summarize different THz sensing principles modulated by the metamaterial for bio-analyte detection. Then, we compare various resonance modes induced in the THz range for biosensing enhancement. In addition, non-conventional materials used in the THz metamaterial to improve the biosensing performance are evaluated. We categorize and review different types of bio-analyte detection using THz metamaterials. Finally, we discuss the future perspective of THz metamaterial in biosensing.

Benefits of tolvaptan on early dyspnea relief in patients with acute heart failure: A meta-analysis.

Considering the prevalence of dyspnea in acute heart failure (AHF), its reduction is important to both patients and caregivers. This meta-analysis was performed to determine the efficacy and safety of tolvaptan on early dyspnea relief in patients with AHF. A systematic search was made of PubMed, Embase, Web of Science, Cochrane Library, and clinicaltrials.gov, without language restrictions. Randomized controlled trials (RCTs) on treatment of AHF with tolvaptan, compared with placebo or blank, were reviewed. Studies were pooled to relative risk (RR), with 95% confidence interval (CI). Five RCTs (enrolling 4857 participants) met the inclusion criteria. Tolvaptan presented significant effects on 12 h dyspnea relief (RR: 1.98; 95% CI: 1.24-3.15; p = .004), 24 h/day 1 dyspnea relief (RR: 1.15; 95% CI: 1.07-1.24; p = .0003), 48 h dyspnea relief (RR: 1.20; 95% CI: 1.06-1.36; p = .004), and 72 h dyspnea relief (RR: 1.18; 95% CI: 1.02-1.37; p = .03). No significant increase was noticed in the incidence of worsening renal function in tolvaptan group (RR: 1.10; 95% CI: 0.87-1.39; p = .43). Tolvaptan treatment significantly improved patient-assessed dyspnea early and persistently in patients with AHF.

Benefits of continuous positive airway pressure on blood pressure in patients with hypertension and obstructive sleep apnea: a meta-analysis.

This meta-analysis was performed to determine the effects of continuous positive airway pressure (CPAP) on blood pressure (BP) in patients with systemic hypertension and obstructive sleep apnea (OSA). A systematic search was conducted using PubMed, Embase, Web of Science, Cochrane Library, and clinicaltrials.gov, without language restrictions. Randomized controlled trials on the treatment of hypertension and OSA with CPAP, compared with sham CPAP or no CPAP, were reviewed. Studies were pooled to obtain weighted mean differences (WMDs) with 95% confidence intervals (CIs). Nineteen trials (enrolling 1904 participants) met the inclusion criteria. CPAP had significant effects on 24-h systolic blood pressure (SBP) (WMD -5.01 mmHg, 95% CI -6.94 to -3.08; P < 0.00001), 24-h diastolic blood pressure (DBP) (WMD -3.30 mmHg, 95% CI -4.32 to -2.28; P < 0.00001), daytime SBP (WMD -4.34 mmHg, 95% CI -6.27 to -2.40; P < 0.0001), daytime DBP (WMD -2.97 mmHg, 95% CI -3.99 to -1.95; P < 0.00001), nighttime SBP (WMD -3.55 mmHg, 95% CI -5.08 to -2.03; P < 0.00001), nighttime DBP (WMD -2.33 mmHg, 95% CI -3.27 to -1.40; P < 0.00001), office SBP (WMD -3.67 mmHg, 95% CI -5.76 to -1.58; P = 0.0006), office DBP (WMD -2.61 mmHg, 95% CI -4.25 to -0.97; P = 0.002), and heart rate (WMD -2.79 beats/min, 95% CI -4.88 to -0.71; P = 0.009). CPAP treatment was associated with BP reduction in patients with systemic hypertension and OSA, except when the follow-up period was shorter than 3 months.

Manipulation of Elastic Instability of Viscoelastic Fluid in a Rhombus Cross Microchannel.

This paper reports the manipulation of elastic instability of the viscoelastic fluid in a rhombus cross microchannel (RCM) structure. The bistable instability and unsteady instability of the flow is firstly demonstrated in a standard cross microchannel (SCM) for reference. We then keep the bi-stable instability over a much wider injection rate range in the RCM, which is attributed to the stabilizing effect of the rhombus structure. A semi-bistable instability was also established in the RCM at a high enough injection rate. In addition, the unsteady elastic instability is realized in the RCM through an asymmetric injection rate condition.

The safety of long-term use of inhaled corticosteroids in patients with asthma: A systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis was performed to determine the safety of long-term use of ICS in patients with asthma. METHODS: A systematic search was made of PubMed, Embase, Web of Science, Cochrane Library, and clinicaltrials.gov, without language restrictions. Randomized controlled trials (RCTs) on treatment of asthma with ICS, compared with non-ICS treatment (placebo or other active drugs), were reviewed. RESULTS: Eighty-six RCTs (enrolling 51,538 participants) met the inclusion criteria. Oral or oropharyngeal candidiasis (RR 2.58, 95% CI 2.00 to 3.33), and dysphonia/hoarseness (RR 1.56, 95% CI 1.31 to 1.85) were less frequent in the control group. There was no statistically significant difference in the risk of upper respiratory tract infection, lower respiratory tract infection, influenza, decline in bone mineral density, and fractures between the two groups. CONCLUSION: In addition to the mild local adverse events, the long-term use of ICS was safe in patients with asthma.

Benefits of continuous positive airway pressure on glycaemic control and insulin resistance in patients with type 2 diabetes and obstructive sleep apnoea: A meta-analysis.

AIM: To conduct a meta-analysis to determine the effects of continuous positive airway pressure (CPAP) treatment on glycaemic control and insulin resistance in patients with type 2 diabetes and obstructive sleep apnoea (OSA). METHODS: A systematic search was made of the MEDLINE, SCOPUS, ISI Web of Science, Cochrane databases, and clinicaltrials.gov, without language restrictions. Randomized controlled trials on treatment of type 2 diabetes and OSA with CPAP, compared with sham CPAP or no CPAP, were reviewed. Studies were pooled to obtain standardized mean differences (SMDs), with 95% confidence intervals (CIs). RESULTS: Seven trials (enrolling 691 participants) met the inclusion criteria. CPAP showed significant effects on glycated haemoglobin (HbA1c; SMD -0.32, 95% CI -0.60 to -0.03; P = 0.029), fasting glucose (SMD -0.39, 95% CI -0.76 to -0.02; P = 0.040), homeostatic model assessment of insulin resistance (HOMA-IR; SMD -1.05, 95% CI -1.91 to -0.19; P = 0.016), systolic blood pressure (SMD -1.18, 95% CI -2.29 to -0.07 mm Hg; P = 0.037), and diastolic blood pressure (SMD -1.29, 95% CI -2.48 to -0.09; P = 0.035). CONCLUSIONS: Continuous positive airway pressure treatment significantly improved glycaemic control and insulin resistance, as shown by the decreased HbA1c levels, fasting glucose levels and HOMA-IR values in patients with type 2 diabetes and OSA.

STEAP1 facilitates metastasis and epithelial-mesenchymal transition of lung adenocarcinoma via the JAK2/STAT3 signaling pathway.

Six-transmembrane epithelial antigen of prostate-1 (STEAP1) is a relatively newly identified gene target from prostate cancer, breast cancer, and gastric cancer. However, functions of STEAP1 in lung adenocarcinoma (LUAD) are still unknown. In the present study, we explored the molecular and cellular mechanisms of STEAP1 in LUAD. Western blot and Q-PCR were conducted to detect the protein and mRNA expressions respectively. The cell proliferation was tested by CCK8 assay. The effects of STEAP1 on the metastasis and epithelial-mesenchymal transition (EMT) of LUAD were evaluated by EdU assay, wound healing assay, and transwell migratory assay. H1650, H358, HCC827, H1299, H23, A549, H1693 were selected as human LUAD cell lines in the study. Results have shown that STEAP1 expression was up-regulated in LUAD cells compared with normal lung epithelial cells. Knockdowning of STEAP1 suppressed the proliferation, migration, and invasion of LUAD epithelial cells. Importantly, after comparing the proliferation, migration, and invasion of LUAD to the corresponding control groups treated in STAT3 inhibitor ADZ1480, we found that STEAP1 regulates EMT via Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway. In conclusion, STEAP1 can serve as a therapeutic target, and it may have important clinical implications for LUAD treatment.

Clinical characteristics of 194 cases of COVID-19 in Huanggang and Taian, China.

PURPOSE: We aimed to report the clinical characteristics of 194 cases coronavirus disease-19 (COVID-19) in Huanggang, Hubei and Taian, Shandong. METHODS: We retrospectively investigated the clinical, laboratory characteristics and CT imaging of confirmed cases of COVID-19 from January 22 to February 28, 2020 in Huanggang Central Hospital and The Second Affiliated Hospital of Shandong First Medical University. Real time PCR was used to detect the new coronavirus in respiratory samples. Immunohistochemical staining was used to detect the expressions of ACE2 in tissues. RESULTS: Among the 194 patients infected with COVID-19, 108 patients were male, with a median age of 48.3 years. The average preclinical period was 7.44 day. Except for 37 severe or critically ill patients, the rest of the 157 patients exhibited mild or moderate symptoms. 190 (97.94%) patients were confirmed during the three times nucleic acid test. The main clinical symptom of the patients were fever, sore throat and cough, which accounted for 146 cases (75.26%), 98 (50.52%) and 86 cases (44.33%), respectively. 30 patients (15.46%) showed liver dysfunction. Imaging examination showed that 141 patients (72.68%) showed abnormal density shadow, while 53 cases (27.32%) had no obvious abnormality in the parenchyma of both lungs. Up to now, 109 cases have been discharged from the hospital, and 9 patients died. The ACE2 expression levels were up-regulated in patients of severe type and critically ill type. CONCLUSION: Clinical symptoms, laboratory tests and CT imaging should be combined for comprehensive analysis to diagnose COVID-19. ACE2 may be the receptor of COVID-19.

Benefits of statins in chronic obstructive pulmonary disease patients with pulmonary hypertension: A meta-analysis.

PURPOSE: This meta-analysis was performed to evaluate the efficacy of statins in chronic obstructive pulmonary disease (COPD) patients with pulmonary hypertension (PH). METHODS: A systematic search was made of MEDLINE, Cochrane, ISI Web of Science and SCOPUS databases. Randomized clinical trials on treatment of COPD-PH with the statins, compared with placebo, were reviewed. Studies were pooled to weighted mean differences (WMD), with 95% confidence interval (CI). RESULTS: Five trials (enrolling 270 participants) met the inclusion criteria. Compared with placebo, the statins presented significant effects on systolic pulmonary artery pressure (WMD -4.52 mmHg; 95% CI -6.32 to -2.72 mmHg) and 6-min walk distance (6MWD) (WMD 32.46 m; 95% CI 13.63-51.29 m). CONCLUSIONS: Statins therapy significantly improves PH and 6MWD in COPD patients with PH.

Long non­coding RNA00887 reduces the invasion and metastasis of non­small cell lung cancer by causing the degradation of miRNAs.

Long non­coding RNAs (lncRNAs) can act as carcinogenic or cancer suppressive factors during the pathogenesis, invasion and metastasis of non­small cell lung cancer (NSCLC). The current study explored the role of long intergenic non­protein coding RNA 00887 (LINC00887) and competing endogenous RNAs (ceRNAs). It was revealed that LINC00887 interacts with several microRNAs (miRs), which regulates downstream genes such as fibronectin 1, MET proto­oncogene, receptor tyrosine kinase and mothers against decapentaplegic homolog 4, which are associated with the spread of lung cancer. The experimental results also suggested that LINC00887 can stimulate miR­613, miR­206 and miR­1­2 to become competing endogenous RNAs, which may regulate the epithelial­mesenchymal transition of NSCLC cells through the transforming growth factor­â signal transduction pathway, and therefore promote the migration of cells and the acquisition of stem cell characteristics. Therefore, it can be concluded that high levels of LINC00887 can accelerate the malignant transformation ability of NSCLC cells.

Ulinastatin- and thymosin α1-based immunomodulatory strategy for sepsis: A meta-analysis.

OBJECTIVE: This meta-analysis was performed to evaluate the efficacy of ulinastatin (UTI) and thymosin α1 (Tα1) based immunomodulatory strategy in sepsis patients. METHODS: A systematic search was made of MEDLINE, Cochrane, ISI Web of Science and SCOPUS databases. Randomized clinical trials on treatment of sepsis with the combination of ulinastatin and Tα1, compared with placebo, were reviewed. Studies were pooled to relative risk (RR) and weighted mean differences (WMD), with 95% confidence interval (CI). RESULTS: Six trials (enrolling 915 participants) met the inclusion criteria. Compared with placebo, the combination of ulinastatin and Tα1 presented significant effects on 28-day all-cause mortality (RR 0.67; 95% CI 0.57 to 0.80), 90-day all-cause mortality (RR 0.75; 95% CI 0.61 to 0.93), TNF-α (WMD -73.86ng/L; 95% CI -91.00 to -56.73ng/L), IL-6 (WMD -55.04ng/L; 95% CI -61.22 to -48.85ng/L), and duration of mechanical ventilation (WMD -2.26days; 95% CI -2.79 to -1.73days). CONCLUSIONS: Immunomodulatory therapy that combines ulinastatin and Tα1 significantly improves all-cause mortality, inflammatory mediators and duration of mechanical ventilation in subjects with sepsis.

Biomarker discovery and identification from non-small cell lung cancer sera.

Currently, serum biomarkers might usually be thought not to be used for early detection of lung cancer by some researchers. In this study, we used a highly optimized ClinProt-matrix-assisted laser desorption/ionization time-of flight mass spectrometer (MALDI-TOF-MS) to screen non-small cell lung carcinoma (NSCLC) markers in serum. A training set of spectra derived from 45 NSCLC patients, 24 patients with benign lung diseases (BLDs) and 21 healthy individuals, was used to develop a proteomic pattern that discriminated cancer from non-cancer effectively. A test set, including 74 cases (29 NSCLC patients and 45 controls), was used to validate this pattern. After cross-validation, the classifier showed sensitivity and specificity, 86.20% and 80.00%, respectively. Remarkably, 100% of early stage serum samples could be correctly classified as lung cancer. Furthermore, the differential peptides of 1865Da and 4209Da were identified as element of component 3 and eukaryotic peptide chain release factor GTP-binding subunit ERF, respectively. The patterns we described and peptides we identified may have clinical utility as surrogate markers for detection and classification of NSCLC.

Study of differential proteins in lung adenocarcinoma using laser capture microdissection combined with liquid chip-mass spectrometry technology.

BACKGROUND: In recent years the proportion of lung adenocarcinoma (adCA) which occurs in lung cancer patients has increased. Using laser capture microdissection (LCM) combined with liquid chip-mass spectrometry technology, we aimed to screen lung cancer biomarkers by studying the proteins in the tissues of adCA. METHODS: We used LCM and magnetic bead based weak cation exchange (MB-WCX) to separate and purify the homogeneous adCA cells and normal cells from six cases of fresh adCA and matched normal lung tissues. The proteins were analyzed and identified by matrix assisted laser desorption/ionization time-of-fight mass spectrometry (MALDI-OF-MS). We screened for the best pattern using a radial basic function neural network algorithm. RESULTS: About 2.895 × 10(6) and 1.584 × 10(6) cells were satisfactorily obtained by LCM from six cases of fresh lung adCA and matched normal lung tissues, respectively. The homogeneities of cell population were estimated to be over 95% as determined by microscopic visualization. Comparing the differentially expressed proteins between the lung adCA and the matched normal lung group, 221 and 239 protein peaks, respectively, were found in the mass-to-charge ration (M/Z) between 800 Da and 10 000 Da. According to t test, the expression of two protein peaks at 7521.5 M/Z and 5079.3 M/Z had the largest difference between tissues. They were more weakly expressed in the lung adCA compared to the matched normal group. The two protein peaks could accurately separate the lung adCA from the matched normal lung group by the sample distribution chart. A discriminatory pattern which can separate the lung adCA from the matched normal lung tissue consisting of three proteins at 3358.1 M/Z, 5079.3 M/Z and 7521.5 M/Z was established by a radial basic function neural network algorithm with a sensitivity of 100% and a specificity of 100%. CONCLUSIONS: Differential proteins in lung adCA were screened using LCM combined with liquid chip-mass spectrometry technology, and a biomarker model was established. It is possible that this technology is going to become a powerful tool in screening and early diagnosis of lung adCA.

Serum peptidome profiling in patients with lung cancer.

Serum peptide profiling is a promising approach for classification of cancer versus noncancer samples. In this study, we aimed to search for discriminating peptide patterns in serum samples between lung cancer patients and healthy controls. The magnetic beads-based weak cation-exchange chromatography followed by matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used in this study to identify patients with lung cancer. In total, serum samples from 64 lung cancer patients (32 for training set and 32 for testing set), 64 healthy controls (32 for training set and 32 for testing set), and 10 COPD patients (for disease control) were analyzed in this study. The mass spectra data analyzed with ClinProTools software was used to distinguish between cancer patients and healthy individuals based on three different algorithm models (GA, SNN, and QC). In the training set, patients with lung cancer could be identified with the mean sensitivity of 98.9% and specificity of100%. Similar results could be obtained from testing set, showing 87% sensitivity and 84.8% specificity. Screening for serum peptide patterns using MALDI-TOF MS showed high sensitivity and specificity in identifying patients with lung cancer.

Use of anchorchip-time-of-flight spectrometry technology to screen tumor biomarker proteins in serum for small cell lung cancer.

BACKGROUND: The purpose of this study is to discover potential biomarkers in serum for the detection of small cell lung cancer (SCLC). METHODS: 74 serum samples including 30 from SCLC patients and 44 from healthy controls were analyzed using ClinProt system combined with matrix-assisted laser desorption/ionization time-of-flight masss spectrometry (MALDI-TOF-MS). ClinProt software and genetic algorithm analysis selected a panel of serum markers that most efficiently predicted which patients had SCLC. RESULTS: The diagnostic pattern combined with 5 potential biomarkers could differentiate SCLC patients from healthy persons, with a sensitivity of 90%, specificity of 97.73%. Remarkably, 88.89% of stage I/II patients were accurately assigned to SCLC. CONCLUSIONS: Anchorchip-time-of-flight spectrometry technology will provide a highly accurate approach for discovering new biomarkers for the detection of SCLC.