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Lung cancer is one of the most prevalent and lethal cancers worldwide (1). The traditional treatments include surgery, chemotherapy, radiotherapy and interventional therapy. The survival of lung cancer patients has dramatically been prolonged in recent years with the availability of targeted therapies, antiangiogenic agents and immune checkpoint inhibitors (ICIs). Meanwhile, technologies for the molecular detection of lung cancer have also advanced rapidly: the detection of single driver genes has evolved to cover combined multi-gene analysis, and whole exome sequencing (WES) has increasingly been applied in the clinical setting. In addition, life support technologies, including ventilators, artificial liver, and artificial kidney as well as extracorporeal membrane oxygenation (ECMO), have further matured, providing powerful forms of life support for patients with various acute and critical diseases. However, most clinical studies have only enrolled patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) scores from 0 to 1, with few patients having PS scores of 2; patients with a PS score of 3 or 4 have been typically excluded. Therefore, due to the lack of high-quality evidence, supportive care is recommended for patients with a PS score of 3 to 4 in the current guidelines. In the real-world, however, approximately 25% of lung cancer patients present with PS score of 3 or 4 (2) or attain scores between 3 and 4 during the course of treatment. Certain patients with high PS scores can benefit from individualized anti-tumor treatment plus appropriate life-support techniques. In 2017, the Lung Cancer Research Team at the First Affiliated Hospital of Guangzhou Medical College & Institute of Respiratory Diseases for the first time pioneered the concept of “advanced severe lung cancer” (3) and argued that standardized therapy for chronic obstructive pulmonary disease (COPD) plus anti-tumor therapy can improve both quality of life and prognosis in patients with lung cancer combined with COPD. The authors also found that the early detection of lung cancer driver genes and timely targeted therapy can be successful in treating patients with advanced severe lung adenocarcinoma with a PS score of 4 (4). In 2019, the concept of advanced severe lung cancer was further developed in a featured article (5) that indicated “Advanced severe lung cancer: does not refer to end-stage lung cancer but rather to stage IIIB, IIIC and IV lung cancers with a PS score of 2–4, which can result from a variety of factors related to the disease itself or anti-tumor drugs and which are highly likely to benefit from the currently available systemic anti-tumor therapies”. In recent years, with the advances in lung cancer diagnosis and treatment techniques and life support technologies, more clinical studies have enrolled patients with a PS score of 2, and some real-world studies have enrolled patients with PS scores of 3–4. Even for patients with early-stage lung cancer, studies have shown that patients with poor PS scores and co-morbidities have a reduced chance of undergoing surgery and an increased mortality rate (6); nevertheless, survival benefit may still be obtained through surgical modifications combined with individualized and multidisciplinary treatment (7). Therefore, the concept of severe lung cancer should not be limited to advanced lung cancer, but applied to all lung cancer patients. In particular, due to the increase in treatment options as well as substantially prolonged survival, the majority of patients may have a PS score between 2 and 4 for a certain period of time due to a variety of reasons. How to provide timely and reasonable treatment for these lung cancer patients has become a critically important real-world research topic. Therefore, we invited lung cancer experts at home and abroad to consider this issue, and this group has reached the following consensus.

BACKGROUND: Given the high prevalence of coronavirus disease 2019 (COVID-19) globally, and the increased number of patients being discharged, it is necessary to understand the health consequences of COVID-19 to formulate and manage public policy concerning convalescent patients. METHODS: A longitudinal follow-up investigation of 25 patients from a tertiary hospital in Henan provincial was conducted 8 weeks after discharge. Of these patients, 15 attended a second follow-up appointment 8 weeks after that. A throat swab reverse transcription-polymerase chain reaction (RT-PCR) analysis for SARS-CoV-2 and chest computerized tomography (CT) scans were implemented at the first follow-up appointment, and a total of 40 blood samples (25 from the first and 15 from the second follow-up appointment) were collected. Patients’ levels of Immunoglobulin G (IgG) antibody against S-Receptor binding domain (S-RBD) and Nucleocapsid Protein (NP) of SARS-CoV-2 and the subpopulation of lymphocytes were evaluated using an enzyme-linked immunoassay (ELISA) test and flow cytometry, respectively. RESULTS: At the first follow-up appointment, 10 of the 25 patients (40.0%) showed complete radiological resolution. Of these patients, 80.0% were classified as moderate, and 80.0% were younger (those whose age was ≤ the median age of all the patients). The predominant patterns of abnormalities included an irregular line (12/25, 48.0%), ground-glass opacity (GGO) (44.0%), and multiple GGOs (28.0%). At the first follow-up appointment, 40.0% (10/25) of patients still had lymphopenia. Of the 15 patients who were followed-up with twice, the ratio of lymphopenia was 80% (12/15), 60.0% (9/15), and 46.7% (7/15) at 0, 8, and 16 weeks after discharge, respectively. This was mainly due to a decrease in the cluster of differentiation (CD) 4+ T lymphocyte, which was observed in 60% (9/15), 60% (9/15), and 46.7% (7/15) of total patients at 0, 8, and 16 weeks after discharge, respectively. All of the patients were S-RBD and NP IgG antibody positive at the first follow-up appointment. 40.0% (6/15) and 66.7% (10/15) of patients showed a decrease over 50.0% in the level of NP and S-RBD IgG antibodies, respectively, at the second follow-up appointment. The NP and S-RBD IgG antibodies’ levels declined to 44.6% (P=0.044) and 28.1% (P=0.18), respectively. 0 and 26.7% (4/15) of patients turned from NP and S-RBD IgG antibody positive to negative, respectively. CONCLUSIONS: About half of the patients still showed at least 1 abnormality in chest CT scans 8 weeks after discharge and lymphopenia 16 weeks after discharge. The level of the IgG antibody had declined by the follow-up appointment. Notably, the S-RBD IgG antibody declined more dramatically than that of NP. These results may have implications in the making of policies related to disease prevention, the long-term management of discharged patients, and vaccines’ development.

Background: Carbapenemase-producing Klebsiella pneumoniae (CpKP) has been implicated as an increasing threat to public health. CpKP is a ubiquitous, opportunistic pathogen that causes both hospital and community acquired infections. This organism hydrolyzes carbapenems and other β-lactams and thus, leading to multiple resistance to these antibiotics. Despite the difficult to treat nature of infections caused by CpKP, little has been discussed on the mortality, clinical response and microbiological success rates associated with various antibiotic regimen against CpKP. This meta-analysis was designed to fill the paucity of information on the clinical impact of various antibiotic therapeutic regimens among patients infected with CpKP.Materials and Methods: Literature in most English databases such as Medline through PubMed, Google Scholar, Web of Science, Cochrane Library and EMBASE, were searched for most studies published between the years 2015–2020. Data were analyzed using the R studio 2.15.2 statistical software program (metaphor and meta Package, Version 2) by random-effects (DerSimonian and Laird) model.Results: Twenty-one (21) studies including 2841 patients who had been infected with CpKP were analysed. The overall mortality rate was 32.2% (95%CI = 26.23–38.87; I2 = 89%; p-value ≤ 0.01, Number of patients = 2716). Pooled clinical and microbiological success rates were 67.6% (95%CI = 58.35–75.64, I2 = 22%, p-value = 0.25, Number of patients = 171) and 74.9% (95%CI = 59.02–86.09, I2 = 53%, p-value = 0.05, Number of patients = 121), respectively. CpKP infected patients treated with combination therapy are less likely to die as compared to those treated with monotherapy (OR = 0.55, 95%CI = 0.35–0.87, p-value = 0.01, Number of patients = 1,475). No significant difference existed between the mortality rate among 60years and above patients vs below 60years (OR = 0.84, 95%CI = 0.28–2.57, p-value = 0.76, 6 studies, Number of patients = 1,688), and among patients treated with triple therapy vs. double therapy (OR = 0.50, 95%CI = 0.21–1.22, p-value = 0.13, 2 studies, Number of patients = 102). When compared with aminoglycoside-sparing therapies, aminoglycoside-containing therapies had positive significant outcomes on both mortality and microbiological success rates.Conclusion: New effective therapies are urgently needed to help fight infections caused by this organism. The effective use of various therapeutic options and the strict implementation of infection control measures are of utmost importance in order to prevent infections caused by CpKP. Strict national or international implementation of infection control measures and treatment guidelines will help improve healthcare, and equip governments and communities to respond to and prevent the spread of infectious diseases caused by CpKP.

Rapid recruitment of neutrophils to an inflamed site is one of the hallmarks of an effective host defense mechanism. The main pathway through which this happens is by the innate immune response. Neutrophils, which play an important part in innate immune defense, migrate into lungs through the modulation actions of chemokines to execute a variety of pro-inflammatory functions. Despite the importance of chemokines in host immunity, little has been discussed on their roles in host immunity. A holistic understanding of neutrophil recruitment, pattern recognition pathways, the roles of chemokines and the pathophysiological roles of neutrophils in host immunity may allow for new approaches in the treatment of infectious and inflammatory disease of the lung. Herein, this review aims at highlighting some of the developments in lung neutrophil-immunity by focusing on the functions and roles of CXC/CC chemokines and pattern recognition receptors in neutrophil immunity during pulmonary inflammations. The pathophysiological roles of neutrophils in COVID-19 and thromboembolism have also been summarized. We finally summarized various neutrophil biomarkers that can be utilized as prognostic molecules in pulmonary inflammations and discussed various neutrophil-targeted therapies for neutrophil-driven pulmonary inflammatory diseases.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) continue to wreak havoc across the globe. Higher transmissibility and immunologic resistance of VOCs bring unprecedented challenges to epidemic extinguishment. Here we describe a monoclonal antibody, 2G1, that neutralizes all current VOCs and has surprising tolerance to mutations adjacent to or within its interaction epitope. Cryo-electron microscopy structure showed that 2G1 bound to the tip of receptor binding domain (RBD) of spike protein with small contact interface but strong hydrophobic effect, which resulted in nanomolar to sub-nanomolar affinities to spike proteins. The epitope of 2G1 on RBD partially overlaps with angiotensin converting enzyme 2 (ACE2) interface, which enables 2G1 to block interaction between RBD and ACE2. The narrow binding epitope but high affinity bestow outstanding therapeutic efficacy upon 2G1 that neutralized VOCs with sub-nanomolar half maximal inhibitory concentration in vitro. In SARS-CoV-2, Beta or Delta variant-challenged transgenic mice and rhesus macaque models, 2G1 protected animals from clinical illness and eliminated viral burden, without serious impact to animal safety. Mutagenesis experiments suggest that 2G1 is potentially capable of dealing with emerging SARS-CoV-2 variants in the future. This report characterized the therapeutic antibodies specific to the tip of spike against SARS-CoV-2 variants and highlights the potential clinical applications as well as for developing vaccine and cocktail therapy.

Swine diarrhea can be caused by multiple agents, including porcine epidemic diarrhea virus (PEDV), porcine sapelovirus (PSV), and porcine sapovirus (SaV). We designed a one-step triplex reverse-transcription PCR (RT-PCR) detection method including 3 pairs of primers that focused on the S1 gene of PEDV, a conserved gene of PSV, and the VP1 gene of SaV. The optimal concentrations of upstream and downstream primers in the triplex RT-PCR were 0.24 μM for PEDV, 0.15 μM for PSV, and 0.2 μM for SaV, and the optimal annealing temperature was 55.5°C. Triplex RT-PCR assessment of 402 piglet diarrhea samples was compared with conventional individual RT-PCR. Concordance rates in both tests for individual viruses were 100%, 97.6%, and 94.4% for PEDV, PSV, and SaV, respectively. PEDV, PSV, and SaV were detected in 57.2%, 10.4%, and 9.0% of the samples, respectively. The high sensitivity and specificity of this triplex RT-PCR–based detection method for PEDV, PSV, and SaV could allow rapid detection and analysis of mixed infections by these 3 viruses.

According to multiple studies, the objective response rate of PD‐1/PD‐L1 inhibitors in the second‐line treatment of unscreened non‐small cell lung cancer (NSCLC) is only approximately 20%. Predictive biomarkers of treatment efficacies are still under investigation. In selected NSCLC patients with PD‐L1 expression ≥ 50%, the response rate of pembrolizumab in first‐line treatment can reach 44.8%. Moreover, patients with a higher tumor mutation burden (TMB) tend to achieve a better response with nivolumab. Besides PD‐L1 expression and TMB, taking all these indicators into consideration would hypothetically maximize the clinical response in a specific subgroup of patients. Our study aims to accumulate large and complete samples and clinical data to verify the biomarkers and their cutoff values related to the efficacy of PD‐1/PD‐L1 inhibitors in Chinese NSCLC patients, and to construct a comprehensive predictive model by combining multi‐omics data with contemporary machine learning techniques. NSCLC patients administered treatment of anti‐PD‐1/PD‐L1 antibodies or a combination with other drugs have been enrolled. The estimated enrollment is 250 participants. A sophisticated predictive model of immunotherapy response in the Chinese population has not yet been developed. It is clinically and practically imperative to comprehensively evaluate the possible indicators of Chinese NSCLC patients through multiple test platforms, such as next generation sequencing, PCR, or immunohistochemistry. This study is registered in the Chinese Clinical Trial Registry (ChiCTR1900021395).

Collecting duct carcinoma is a rare and highly aggressive renal tumor with a poor prognosis. The presence of metastasis is common at collecting duct carcinoma diagnosis, but widespread metastases involving multiple soft tissues are extremely unusual. Here, we describe a 65-year-old man presenting with fever and lower leg pain as the first and main manifestations. After receiving anti-infective therapy for over 6 weeks without improvement, 18F-FDG PET/CT revealed a primary renal carcinoma with widespread metastases. A biopsy from the tubercle of fascicular spinal muscle indicated a diagnosis of collecting duct carcinoma.

Objective To evaluate the efficacy of the Archimedes Navigation System (Broncus Medical, San Jose, CA, USA) for guidance during transbronchial cryobiopsy and the incidence of complications in patients with diffuse lung disease. Methods High-resolution computed tomography and transbronchial cryobiopsy were used to evaluate eight patients with diffuse lung disease. The Archimedes Navigation System was used before cryobiopsy to obtain the best path with which to avoid large vessels. Three to five cryobiopsy specimens were taken from each sampled segment. Results Preoperative planning using the Archimedes Navigation System was successfully performed on all eight patients. The probe-to-pleura distance was approximately 10 mm. No cases of pneumothorax occurred, one patient developed moderate bleeding, two developed minor bleeding, and five developed minimal bleeding that stopped spontaneously. A final diagnosis was obtained for seven patients, and ongoing follow-up was being conducted for the last patient at the time of this writing. Conclusions This is the first report of combining navigation technology with cryobiopsy to diagnose diffuse lung disease. The Archimedes Navigation System, which provides real-time guidance, is helpful in pre-cryobiopsy planning and diagnosis of diffuse lung disease. Moreover, this system can reduce the pneumothorax rate and bleeding risk by avoiding large vessels.

Background Idiopathic pulmonary fibrosis (IPF) is a genetic heterogeneous disease with high mortality and poor prognosis. Hyaluronidase 1 (HYAL1) was found to be upregulated in fibroblasts from IPF patients, and overexpression of HYAL1 could prevent human fetal lung fibroblast proliferation. However, the genetic correlation between the HYAL1 and IPF or connective tissue diseases related interstitial lung disease (CTD‐ILD) has not been determined. Methods A two‐stage study was conducted in Southern Han Chinese population. We sequenced the coding regions and flanking regulatory regions of HYAL1 in stage one (253 IPF cases and 125 controls). A statistically significant variant was further genotyped in stage two (162 IPF cases, 182 CTD‐ILD cases, and 225 controls). Results We identified a nonsynonymous polymorphism (rs117179004, T392M) significantly associated with increased IPF risk (dominant model: OR = 2.239, 95% CI = 1.212–4.137, p = 0.010 in stage one; OR = 2.383, 95% CI = 1.376–4.128, p = 0.002 in stage two). However, we did not observe this association in CTD‐ILD (OR = 1.401, 95% CI = 0.790–2.485, p = 0.248). Conclusion Our findings suggest that the nonsynonymous polymorphism (rs117179004, T392M) may confer susceptibility to IPF in Southern Han Chinese, but is not associated with susceptibility to CTD‐ILD., A nonsynonymous polymorphism (rs117179004, T392M) of hyaluronidase 1 (HYAL1) is associated with increased risk of idiopathic pulmonary fibrosis (IPF) (p = 0.002 in allele‐model) but not connective tissue diseases related interstitial lung disease (CTD‐ILD) (p = 0.181 in allele‐model) in Southern Han Chinese.

BackgroundPulmonary lymphangitic carcinomatosis (PLC) is a malignant lung disease characterized by metastatic tumor lesions in the lung lymphatic vessels with a poor prognosis. Early diagnosis is the key to improve the outcome. However, when PLC is the first manifestation of patients without a known malignancy, it often leads to delayed diagnosis and treatment, and even fatal consequences due to non-specific symptoms. Here, we describe a young male presenting PLC as the first and only manifestation followed by diagnosis of gastric adenocarcinoma and systemically summarized previously reported clinical properties of PLC cases in the literature.Case presentationA 32 years old male presented nonproductive cough for 20 days and progressive exertional dyspnea in a week. He was diagnosed with pneumonia and received antibiotics for almost 3 weeks without any improvement. Chest computed tomography showed multiple nodules and thickened interlobular septa in bilateral lung. PET/CT revealed a primary gastric tumor with PLC and the biopsy of the cervical lymph node confirmed a poorly metastatic differentiated gastric adenocarcinoma. The patient’s general condition deteriorated rapidly and he developed respiratory failure, requiring non-invasive mechanical ventilation on day 9 after admission. Chemotherapy was given to the patient on the tenth day. However, few hours after receiving the first dose, the patient died of respiratory failure. It was only one month from the onset of symptoms to death of our case.ConclusionsPatients presenting PLC as the first manifestation of an unknown malignancy carry a bleak prognosis. PLC be considered for differential diagnosis in patients who present with dyspnea, dry cough with or without loss of weight. Particular attentions need to be given to patients, especially young ones without histories of malignancy, whose chest imaging exhibits thickened interlobular septa. While the stomach, lung and prostate are the most likely origins of the primary tumors, patients with PLC derived from prostate cancer may have a better prognosis after anti-cancer treatment.

BACKGROUND: Although studies have identified hundreds of genetic variants associated with asthma risk, a large fraction of heritability remains unexplained, especially in Chinese individuals. METHODS: To identify genetic risk factors for asthma in a Han Chinese population, 211 asthma‐related genes were first selected based on database searches. The genes were then sequenced for subjects in a Discovery Cohort (284 asthma patients and 205 older healthy controls) using targeted next‐generation sequencing. Bioinformatics analysis and statistical association analyses were performed to reveal the associations between rare/common variants and asthma, respectively. The identified common risk variants underwent a validation analysis using a Replication Cohort (664 patients and 650 controls). RESULTS: First, we identified 18 potentially functional rare loss‐of‐function (LOF) variants in 21/284 (7.4%) of the asthma cases. Second, using burden tests, we found that the asthma group had nominally significant (p

Background: Peripherally inserted central catheters (PICCs) and totally implanted vascular access ports (PORTs) have been widely used for medium- to long-term chemotherapy. PICCs are associated with lower insertion cost, but higher complication rates than PORTs. However, there is a paucity of cost-effectiveness comparisons between the devices. We aimed to compare the cost-effectiveness of PICCs and PORTs for medium- to long-term chemotherapy from catheter insertion to removal. Methods: A cost-effectiveness analysis was conducted based on propensity score matching (PSM) from the hospital perspective. Data were collected from a retrospective cohort study. The total cost outcome comprised insertion, maintenance, removal and complication costs. The effectiveness outcome was the complication-free rate. The primary and supplemental outcomes were cost-effectiveness ratios (CERs) and incremental cost-effectiveness ratios (ICERs). Results: A total of 1050 patients (after PSM for 417 patients) were included. The average total cost for 3–6 month ($603.55 ± 78.68 vs $1270.21 ± 128.84), 6–9 month ($731.40 ± 42.97 vs $1414.48 ± 155.43), and 9–12 month ($966.83 ± 53.78 vs $1587.76 ± 160.56) dwell times were all significantly lower for PICCs than for PORTs ( p Conclusion: This study provided economic evidence that informs vascular access device choice for medium- to long-term chemotherapy. For 3–9 month dwell times, PICCs were more cost-effective than PORTs. Furthermore, ICERs were applied and the choice was determined by willingness-to-pay. For 9–12 month dwell times, PORTs might be more cost-effective than PICCs, and studies with larger sample size would be needed to verify this finding in the future.

Since December 2019, the novel coronavirus SARS-CoV-2 pandemic (COVID-19) outbroke in Wuhan and spread in China. Here we aimed to investigate the clinical and radiological characteristics of COVID-19 cases. We collected and analyzed the clinical data of 172 hospitalized cases of COVID-19 who were diagnosed via qRT-PCR of nasopharyngeal swabs during January 2020 and February 2020. The chest images were reviewed by radiologists and respirologists. The older patients with COVID-19 in Henan Province had more severe disease and worse prognosis. The male sex, smoking history and Wuhan exposure of patients are not related to the severity or prognosis of COVID-19. Family gatherings were showed among 26.7% of patients. A greater proportion of patients in the severe group suffer from combined chronic diseases. CT results showed that most patients had bilateral lung lesions and multiple lung lobes. The lungs of severe patients are more damaged. Both the infection range and inflammatory factor levels are related to the poor prognosis. Antiviral drugs, immunoglobulin and traditional Chinese medicine are mainly used for the treatment of COVID-19 patients. The discharge rate of COVID-19 patients was 93.0%, and the mortality rate was 2.3%. Case type, lymphocyte ratio grade, and respiratory failure at admission are risk factors for poor prognosis, except for the number of infiltrating lung lobes. The results showed that severe disease process, lymphopenia and respiratory failure are risk factors for the COVID-19. Supplementary Information The online version contains supplementary material available at 10.1007/s13577-021-00499-y.

Background In 2017, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) removed spirometry as a criterion for classifying GOLD risk groups (A-D, low-high risk). Methods In this cross-sectional observational study in China, we used the GOLD 2016 (spirometry included) and 2018 (spirometry eliminated) criteria for classifying GOLD risk groups to describe: the proportion of patients with chronic obstructive pulmonary disease (COPD) in each GOLD risk group; disease severity; demographics and comorbidities. Patients aged ≥40 years with a clinical COPD diagnosis for ≥1 year were included. During a single study visit, patients completed the COPD assessment test, modified Medical Research Council (mMRC) dyspnea scale assessment, and spirometry tests. Demographics, medical history, and treatment data were recorded. Results In total, 838 patients were included. Most patients were male (86.4%), ≥65 years old (58.6%), and current or former smokers (78.5%). By GOLD 2016, the highest proportion of patients were Group D (42.8%), followed by B (28.2%). By GOLD 2018, the highest proportion of patients were Group B (57.3%), followed by A (25.5%). A total of 296 patients (35.3%) were reclassified, either from Group C to Group A or from Group D to Group B. Overall, 36.2% of patients were receiving treatment concordant with GOLD 2016 recommendations; 34.1% were not receiving any inhaled medication. Conclusions The distribution of COPD severity shifted from a high-risk category (by GOLD 2016) to a low-risk category (by GOLD 2018). The high proportion of patients not receiving maintenance medication reflects a high level of under-treatment of the disease.

Background Despite advances in technology, the bronchoscopic diagnosis of parenchymal pulmonary lesions (PPLs) remains difficult to achieve. Transbronchial lung cryobiopsy (TLCB) offers the potential for larger samples with improved diagnostic yield; however, a paucity of data exists describing its safety and usefulness for the diagnosis of PPL. Research Question What is the safety profile of TLCB for PPL? Study Design and Methods An observational, retrospective, multicenter cohort study enrolled patients without endobronchial disease undergoing TLCB of PPL from 2015 through 2019. All procedures were performed using both rigid and flexible bronchoscopy with a flexible cryoprobe. Complication rates, including bleeding and pneumothorax rates, were collected. Bleeding was graded on a scale from 0 (trace) to 4 (requiring surgical intervention) with a grade of ≥ 3 considered clinically significant. Pneumothorax, tube thoracostomy placement, diagnostic yield, and need for subsequent interventions were recorded. Results One thousand twenty-four patients underwent TLCB. One hundred eighty-eight patients (18%) experienced bleeding; in 36 patients (3.5%), the bleeding was clinically significant. Sixty-eight patients (6.6%) demonstrated a pneumothorax and 64 patients (6.3%) required drainage with tube thoracostomy. All chest drains were removed within 4 days, and no cases of prolonged air leak occurred. A definitive diagnosis was achieved in 932 patients (91%). Adenocarcinoma (46%) and metastatic disease (21%) were the most common diagnoses. Interpretation TLCB showed an acceptable safety profile and diagnostic yield for the evaluation of PPL in this large retrospective cohort. Prospective clinical trials are underway to validate these findings further.

Background Lung nodules are a diagnostic challenge. Current clinical management of lung nodule patients is inefficient and therefore causes patient misclassification, which increases healthcare expenses. However, a precise and robust lung nodule classifier to minimize discomfort for patients and healthcare costs is still lacking. The aim of the present protocol is to evaluate the effectiveness of using a liquid biopsy classifier to diagnose nodules compared to physician estimates and whether the classifier can reduce the number of unnecessary biopsies in benign cases. Methods A prospective cohort of 10,560 patients enrolled at 23 clinical centers in China with non-calcified pulmonary nodules, ranging from 0.5 to 3 cm in diameter, indicated by LDCT or CT will be included. After signed consent forms, the participants' pulmonary nodules will be assessed using three evaluation tools: (I) physician cancer probability estimates (II) validated lung nodule risk models, including Mayo Clinic and Veteran's Affairs models (III) ctDNA methylation classifier previously established. Each patient will undergo LDCT/CT follow-ups for 2 to 3 years and their information and one blood sample will be collected at baseline, 3, 6, 12, 24 and 36 months. The primary study outcomes will be the diagnostic accuracy of the methylation classifier in the cohort. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) will be used to compare the diagnostic value of each testing tool in differentiating benign and malignant pulmonary nodules. Discussion We are conducting an observational study to explore the accuracy of using a ctDNA methylation classifier for incidental lung nodules diagnosis. Trial registration Clinicaltrials.gov NCT03651986.

Background and aims: Asthma–chronic obstructive pulmonary disease (COPD) overlap (ACO) is poorly recognized in China. Our study determined the distribution of ACO and its clinical characteristics among patients (aged ⩾40 years) with airflow limitation at Chinese tertiary hospitals. Methods: This cross-sectional, non-interventional study (NCT02600221), conducted between December 2015 and October 2016 in 20 Tier-3 Chinese hospitals, included patients aged ⩾40 years with post-bronchodilator (BD) FEV1/FVC 1/FVC) Results: In 2003 patients (mean age 62.30 ± 9.86 years), distribution of ACO, COPD and asthma were 37.40%, 48.50% and 14.10%, respectively. Proportions of patients with A, B, C and D grouping were 11.70%, 31.00%, 6.90% and 50.30% as per GOLD 2017, whereas they were 15.10%, 51.10%, 3.60% and 30.20% as per GOLD 2015. Similar clinical symptoms were reported in all three groups. A higher percentage of ACO patients presented with dyspnea, wheezing and chest tightness. Compared with the COPD group, a greater proportion of ACO patients reported wheezing (74.6% and 65.40%), while a lower proportion in the ACO group reported cough (79.40% versus 82.70%) and expectoration (76.50% versus 81.60%). Blood eosinophil count ⩾0.3 × 109/L was observed in 34.6% of ACO patients. The clinical recognition rate of ACO was 31.4%. Conclusion: Despite ACO affecting two-fifths of the study population, the initial diagnosis rate was low at 6% in China, thus warranting concerted efforts to improve ACO diagnosis. ClinicalTrials.gov: [ClinicalTrials.gov identifier: NCT02600221] registered 22 October 2015, https://clinicaltrials.gov/ct2/show/NCT02600221 The reviews of this paper are available via the supplemental material section.

Background Almost all cancer patients experience some level of distress, which has significantly reduced their quality of life. Nowadays evidence-based practice in various fields of health care is increasing, and it has played an important role. This study aimed to clarify the theme of guideline adaptation, integrate relevant clinical practice guidelines on distress management in cancer patients, and develop the Cancer-related Distress Management Guidelines. Methods A Guideline Adaptation and Implementation Planning Resource (CAN-IMPLEMENT) was used as the research framework, which include three phases. Here the Adaptation Part (Phase 1) was reported: adaptation of relevant clinical practice guidelines on the distress management in cancer patients to form the Cancer-related Distress Management Guidelines. Results The physical symptom distress score (0.61 ± 0.58) was almost equal to the psychological symptom distress score (0.61 ± 0.70) among cancer patients in Shanghai. A work plan for the adaptation of Cancer-related Distress Management Guidelines was developed. Two clinical practice guidelines related to distress management in cancer patents were included after searching, screening, assessment and selection. The domain scores of the draft the Cancer-related Distress Management Guidelines on Appraisal of Guidelines for Research and Evaluation II (AGREE II) were 80.00% (scope and purpose), 82.78% (stakeholder involvement), 87.50% (rigour of development), 73.89% (clarity and presentation), 73.75% (applicability), 87.50% (editorial independence) respectively. The scores of most recommendations on feasibility, appropriateness, meaningfulness and effectiveness were 90.0% or higher. The final guidelines included 13 recommendations. Conclusions The psychological symptoms and physical symptoms were both worthy of attention in cancer patients. The quality of the draft the Cancer-related Distress Management Guidelines was well-accepted based on two included guidelines. Most recommendations received positive and constructive feedback on feasibility, appropriateness, meaningfulness and effectiveness. The final guidelines was formed based on the revision of the first draft guidelines.

Background: Targeted therapy for lung cancer with epidermal growth factor receptor (EGFR) mutations with tyrosine kinase inhibitors (TKIs) represents one of the major breakthroughs in lung cancer management. However, gradually developed resistance to these drugs prevents sustained clinical benefits and calls for resistant mechanism research and identification of new therapeutic targets. Acquired T790M mutation accounts for the majority of resistance cases, yet transcriptome changes in these cells are less characterized, and it is not known if new treatment targets exist by available drugs. Methods: Transcriptome profiling was performed for lung cancer cell line PC9 and its resistant line PC9GR after long-term exposure to gefitinib through RNA sequencing. Differentially expressed genes and changed pathways were identified along with existing drugs targeting these upregulated genes. Using 144 lung cancer cell lines with both gene expression and drug response data from the cancer cell line encyclopedia (CCLE) and Cancer Therapeutics Response Portal (CTRP), we screened 549 drugs whose response was correlated with these upregulated genes in PC9GR cells, and top drugs were evaluated for their response in both PC9 and PC9GR cells. Results: In addition to the acquired T790M mutation, the resistant PC9GR cells had very different transcription programs from the sensitive PC9 cells. Multiple pathways were changed with the top ones including TNFA signaling, androgen/estrogen response, P53 pathway, MTORC1 signaling, hypoxia, and epithelial mesenchymal transition. Thirty-two upregulated genes had available drugs that can potentially be effective in treating the resistant cells. From the response profiles of CCLE, we found 17 drugs whose responses were associated with at least four of these upregulated genes. Among the four drugs evaluated (dasatinib, KPT-185, trametinib, and pluripotin), all except trametinib demonstrated strong inhibitory effects on the resistant PC9GR cells, among which KPT185 was the most potent. KPT-185 suppressed growth, caused apoptosis, and inhibited migration of the PC9GR cells at similar (or better) rates as the sensitive PC9 cells in a dose-dependent manner. Conclusions: Acquired TKI-resistant lung cancer cells (PC9GR) have dramatically changed transcription and pathway regulation, which expose new treatment targets. Existing drugs may be repurposed to treat those patients with developed resistance to TKIs.

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel coronavirus causing an outbreak of COVID-19 globally in the past six months. A relatively higher divergence on the spike protein of SASR-CoV-2 enables it to transmit across species efficiently. We particularly believe that the adaptive mutations of the receptor-binding domain (RBD) of spike protein in SARS-CoV-2 might be essential to its high transmissibility among humans. Thus here we collected 2,142 high-quality genome sequences of SARS-CoV-2 from 160 regions in over 50 countries and reconstructed their phylogeny, and also analyzed the interaction between the polymorphisms of spike protein and human ACE2 (hACE2). Phylogenetic analysis of SARS-CoV-2 and coronavirus in other hosts show SARS-CoV-2 is highly possible originated from Bat-CoV (RaTG13) found in horseshoe bat and a recombination event may occur on the spike protein of Pangolin-CoV to imbue it the ability to infect humans. Moreover, compared to the S gene of SARS-CoV-2, it is more conserved in the direct-binding sites of RBD and we noticed that spike protein of SARS-CoV-2 may under a consensus evolution to adapt to human hosts better. 3,860 amino acid mutations in spike protein RBD (T333-C525) of SARS-CoV-2 were simulated and their stability and affinity binding to hACE2 (S19-D615) were calculated. Our analysis indicates SARS-CoV-2 could infect humans from different populations with no preference, and a higher divergence in the spike protein of SARS-CoV-2 at the early stage of this pandemic may be a good indicator that could show the pathway of SARS-CoV-2 transmitting from the natural reservoir to human beings.

Background Limited data exist on VTE risk and prophylaxis in Chinese inpatients. The Identification of Chinese Hospitalized Patients' Risk Profile for Venous Thromboembolism-2 (DissolVE-2), a nationwide, multicenter, cross-sectional study, was therefore designed to investigate prevalence of VTE risks and evaluate VTE prophylaxis implementation compliant with the latest prophylaxis guidelines (American College of Chest Physicians [CHEST], 9th edition). Methods Adults admitted (≥ 72 h) to 60 urban, tertiary Chinese hospitals due to acute medical conditions or surgery from March to September 2016 were assessed for VTE risk. Risk assessments were made by using the Padua Prediction Scoring or Caprini Risk Assessment model, risk factors, and prophylaxis based on the CHEST guidelines, 9th edition. Results A total of 13,609 patients (6,986 surgical and 6,623 medical) were analyzed. VTE risk in surgical inpatients was categorized as low (13.9%; 95% CI, 13.1-14.7), moderate (32.7%; 95% CI, 31.6-33.8), and high (53.4%; 95% CI, 52.2-54.6); risk in medical patients was categorized as low (63.4%; 95% CI, 62.2-64.6) and high (36.6%; 95% CI, 35.4-37.8). Major risk factors in surgical and medical patients were major open surgery (52.6%) and acute infection (42.2%), respectively. Overall rate of any prophylaxis and appropriate prophylactic method was 14.3% (19.0% vs 9.3%) and 10.3% (11.8% vs 6.0%) in surgical and medical patients. Conclusions A large proportion of hospitalized patients reported VTE risk and low rate of CHEST-recommended prophylaxis. The data highlight the insufficient management of VTE risk and show the great potential for improving physicians' awareness and current practices across China. Trial Registry Chinese Clinical Trial Registry; No.: ChiCTR-OOC-16010187; URL: http://www.chictr.org.cn/showproj.aspx?proj=17077.

Introduction Tumours are more likely to metastasize after the development of resistance to EGFR-TKIs. CD146 is a multifunctional molecule and is implicated in tumour invasion and metastasis; however, its role in lung cancer has not been clearly established. Objective Here, we aimed to explore the relationship between CD146 pathway and stem cell phenotype after EGFR-TKI resistance in lung cancer. Methods EGFR-TKI-resistant cell lines were established by exposing parental cells to erlotinib/gefitinib. The CD146 level was measured by a western blot, RT-PCR and immunocytochemistry fluorescent. Cell migration was examined by the transwell assay and the scratch assay. Stemness phenotype genes were evaluated by RT-PCR and stem cell phenotype was observed by the microsphere formation assay. Results CD146 and stemness phenotype genes increased while β-catenin decreased in acquired EGFR-TKI-resistant cell lines. CD146's over-expression induced the up-regulation of stemness-related genes and was inversely correlated with the β-catenin expression, which further increased the migration capability of resistant cancer cells. CD146's knockdown suppressed cell migration and stemness phenotype. Conclusions CD146 molecule contributes to the stemness phenotype and migration in EGFR-TKI-resistant cells. CD146 might be a potential therapeutic target for EGFR-TKI-resistant lung cancer or metastasis prevention.

Introduction: Porcine epidemic diarrhea virus (PEDV) is one of the most common viral pathogens causing swine diarrhea. Methodology: We performed a genetic evolution analysis of the S1 gene of endemic PEDV strains in Eastern China. The S1 genes of 37 PEDV-positive samples were amplified and sequenced, and compared to the standard CV777 strain, 120 nucleotides were found to have mutations. Results: The nucleotide and deduced amino acid homologies between the sequences and those of the CV777 strain were 90%–91% and 88.2%–90%, respectively, and their homologies to the vaccine strain were 88.6%–89.7% and 86.2%–87.8%, respectively. Genetic evolution and variation analyses indicated that the 37 PEDV strains belonged to genogroup 2-1, while the CV777 strain, vaccine strain, and earlier Chinese strains all belonged to genogroup 1-1. Conclusions: The newly emerged clinical PEDV strains indicate that the PEDV CV777 vaccine currently used in China may not fully protect pigs from infection with recent epidemic strains, and will require the development of new vaccine strains.

Idiopathic pulmonary fibrosis (IPF) is a genetic heterogeneous disease with high mortality and poor prognosis. However, a large fraction of genetic cause remains unexplained, especially in sporadic IPF (∼80% IPF). By systemically reviewing related literature and potential pathogenic pathways, 92 potentially IPF-related genes were selected and sequenced in genomic DNAs from 253 sporadic IPF patients and 125 matched health controls using targeted massively parallel next-generation sequencing. The identified risk variants were confirmed by Sanger sequencing. We identified two pathogenic and 10 loss-of-function (LOF) candidate variants, accounting for 4.74% (12 out of 253) of all the IPF cases. In burden tests, rare missense variants in three genes (CSF3R, DSP, and LAMA3) were identified that have a statistically significant relationship with IPF. Four common SNPs (rs3737002, rs2296160, rs1800470, and rs35705950) were observed to be statistically associated with increased risk of IPF. In the cumulative risk model, high risk subjects had 3.47-fold (95%CI: 2.07-5.81, P = 2.34 × 10-6 ) risk of developing IPF compared with low risk subjects. We drafted a comprehensive map of genetic risks (including both rare and common candidate variants) in patients with IPF, which could provide insights to help in understanding mechanisms, providing genetic diagnosis, and predicting risk for IPF.

BACKGROUND: Transbronchial cryobiopsy (TBCB) has been widely used to diagnose interstitial lung disease (ILD). Existing reports on TBCB in ILD are mostly single-center prospective or retrospective studies but rarely multicenter prospective real-world studies. We explored the diagnostic efficiency and safety of TBCB in ILD in a real world setting. METHODS: A prospective, multicenter, real-world study was conducted to analyze the data of patients with unclarified ILD who underwent TBCB in 20 hospitals in China from October 2018 to October 2019. The results of the pathological and multidisciplinary discussion (MDD) diagnosis and complications related to TBCB were then analyzed. RESULTS: A total of 373 patients were enrolled in this study, including 194 males and 179 females, with an average age of 52.6±12.4 years. None of the patients had severe hemorrhaging, and the incidence of pneumothorax was 4.8%. The proportions of definitive, possible, and unclassified pathological diagnoses were 62.5%, 5.6%, and 31.9%, respectively. The overall diagnostic yield of MDD was 63.5%. There were 237 patients with a definitive diagnosis of MDD and 136 patients with an unclarified MDD diagnosis. The cooling gas pressure, freezing durations, number of specimens, maximum lengths of specimens, and specimen sizes varied significantly between the definitive and unclarified MDD diagnoses. CONCLUSIONS: In China, the application of TBCB in ILD is generally safe, and its diagnostic efficiency is acceptable. Using a 1.9-mm cryoprobe to collect five samples would achieve a better positive diagnostic rate for TBCB in ILD, without a significant increase in complication risk. TRIAL REGISTRATION: ClinicalTrials.gov; date of registration: 09/25/2018; registration number: NCT03704233; URL: clinicaltrials.gov.

BACKGROUND The authors built a model for lung cancer diagnosis previously based on the blood biomarkers progastrin-releasing peptide (ProGRP), carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), and cytokeratin 19 fragment (CYFRA21-1). In the current study, they examined whether modification of the model to include relevant clinical information, risk factors, and low-dose chest computed tomography screening would improve the performance of the biomarker panel in large cohorts of Chinese adults. METHODS The current study was a large-scale multicenter study (ClinicalTrials.gov identifier NCT01928836) performed in a Chinese population. A total of 715 participants were enrolled from 5 regional centers in Beijing, Henan, Nanjing, Shanghai, and Chongqing between October 2012 and February 2014. Serum biomarkers ProGRP, CEA, SCC, and CYFRA21-1 were analyzed on the ARCHITECT i2000SR. Relevant clinical information was collected and used to develop a patient risk model and a nodule risk model. RESULTS The resulting patient risk model had an area under the receiver operating characteristic (ROC) curve of 0.7037 in the training data set and 0.7190 in the validation data set. The resulting nodule risk model had an area under the ROC curve of 0.9151 in the training data set and 0.5836 in the validation data set. Moreover, the nodule risk model had a relatively higher area under the ROC curve (0.9151 vs 0.8360; P = 0.001) compared with the American College of Chest Physician model in patients with lung nodules. CONCLUSIONS Both the patient risk model and the nodule risk model, developed for the early diagnosis of lung cancer, demonstrated excellent discrimination, allowing for the stratification of patients with different levels of lung cancer risk. These new models are applicable in high-risk Chinese populations. Cancer 2018;124:262-70. © 2017 American Cancer Society.

// Xiaohui Wang 1,2,* , Zhengqiang Bao 1,2,* , Xiaoju Zhang 3,* , Fei Li 1 , Tianwen Lai 1 , Chao Cao 1 , Zhihua Chen 1 , Wen Li 1 , Huahao Shen 1,4 and Songmin Ying 1,2 1 Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Institute of Respiratory Diseases, Zhejiang University School of Medicine, Hangzhou, China 2 Department of Pharmacology, Zhejiang University School of Medicine, Hangzhou, China 3 Department of Respiratory Medicine, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou, China 4 State Key Laboratory of Respiratory Diseases, Guangzhou, China * These authors have contributed equally to this manuscript Correspondence to: Songmin Ying, email: // Huahao Shen, email: // Keywords : PD-1, PD-L1, nivolumab, pembrolizumab, cancer Received : August 12, 2016 Accepted : March 01, 2017 Published : May 31, 2017 Abstract Background: PD-1/PD-L1 inhibitors have been implicated as potentially effective anti-cancer therapies. Some clinical randomized controlled trials (RCTs) have been completed for a variety of PD-1/PD-L1 inhibitors to treat various malignancies, and more RCTs are still under way. We carried out this systematic meta-analysis to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors in the treatment of solid tumors. Methods: We searched PubMed, EMBASE, clinical trial registers, conference reports, and related reviews. Eligible RCTs that compared PD-1/PD-L1 inhibitors with other chemotherapy agents or placebo in solid tumor patients were included. For each RCT, progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), stable disease rate (SDR), progressive disease rate (PDR), and adverse events (AEs) were pooled for meta-analysis. Findings: Based on an analysis of 10 eligible RCTs, PD-1/PD-L1 inhibitors were found to significantly improve PFS (Hazard ratio (HR), 0.65; 95% confidence interval (CI) 0.53 to 0.79, P

Background: SARS-CoV-2 is causing a worldwide health crisis We aimed to present clinical and CT features for a cohort of patients in Henan, China with more foc

Objective The aim of this study was to synthesize qualitative research evidence on cancer survivors' experiences with financial toxicity (FT). Methods We carried out a systematic review of qualitative studies using a meta-aggregation approach. Papers published prior to 31 August 2019, were collected from electronic databases, including PubMed/MEDLINE, MEDLINE (Ovid), EMBASE (Ovid), CINAHL (EBSCO), Web of Science, ProQuest Dissertations and Theses, and Cochrane Library (Wiley). Results Six synthesized findings were derived from 14 studies covering cancer patients' awareness of FT, cancer-related expenditures, and the risk factors, impacts, coping strategies, and unmet needs related to FT. Conclusions Cancer survivors incur FT; however, their awareness of FT is limited. Cancer-related FT has multiple impacts on survivors' lives. Although cancer survivors try to cope with FT through adjustments, they still have unmet needs for the management of FT. Nurses and social workers can play a critical role in helping survivors manage FT by increasing pre-awareness of FT, strengthening emotional empowerment, and providing personalized informative support.

CD146 alternatively called melanoma cell adhesion molecule (MCAM), is a biomarker and therapeutic target of clinical significance. It is found on different cells including the endothelial cells and lymphocytes which participate in heterotypic and homotypic ligand-receptor. This review concentrated on the CD146 expression T cells (or lymphocytes) centering on Treg in lung cancer. Here, we have also considered the vigorous investigation of CD146 mainly acknowledged new roles, essential mechanisms and clinical implications of CD146 in cancer. CD146 has progressively become a significant molecule, particularly recognized as a novel biomarker, prognosis and therapy for cancer. Hence, targeting CD146 expression by utilization of methanol extracts of Calotropis procera leaf may be useful for the treatment of carcinogenesis.

Central nervous system (CNS) disorders feature the progressive and selective loss of normal brain functions. CNS disorders often include an irreversible physiological and anatomical loss of neurons that can lead to dysfunction in various parts of the brain and eventually death. Glioblastoma multiforme (GBM) and neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD) are hard to be diagnosed at an early stage for the prevention of disease propagation. Such diagnosis is vital for the timely commencement of actual treatments. Nanotechnology brings new diagnosis hope for CNS disorders as it provides ultrasensitive detection for more specific biomarkers. Herein, the recent progress in techniques development for detecting pathological biomarkers for GBM, AD, and PD is summarized, in particular, the principles that govern the design of these sensors, blood–brain barrier (BBB) dysfunction, and its integrity during disease development. Finally, a perspective on future directions to further advance and improve the early‐stage diagnosis of CNS disorders is presented.

Highlights:-Adenocarcinoma lung cancer is common but difficult to diagnose. - Little is known for its proteome when methanol extract of Calotropis procera was used for the treatment groups. -In the treatment versus control groups, about 413 proteins were upregulated while about 626 proteins were downregulated. -Some of the proteins are potential diagnostic markers. Objectives: Adenocarcinoma lung cancer is a common type of lung cancer but the therapeutic and diagnosis are problematic. We focused on the protein expression of Adenocarcinoma lung cancer using A549 cancer cells and unveiled novel diagnostic makers and mechanisms in which methanol extracts of Calotropis procera ameliorate the disease. Methods: A549 lung cancer cell lines were obtained and we have 3 control groups and 3 treatment groups. The treatment groups were treated with 80 ug/ml of methanol extracts of Calotropis procera leaf and proteins were extracted for tandem mass tag mass spectrometry. Differential protein expression was performed between treatment groups and controls and the identified proteins were analyzed for pathway enrichment. Selected proteins were further validated in another set of samples using a more quantitative method. Results: In the treatment versus control, about 413 proteins were upregulated while about 626 proteins were downregulated. Conclusion: This balanced proteomics method not only offers important understandings of protein expression and pathways but also discover potential diagnostic markers for adenocarcinoma lung cancer. It also reveals the molecular mechanisms in which the methanol extracts of Calotropis procera leaf prevent carcinogenesis. Citation Format: Ayobami Matthew Olajuyin, Adefunke Kafayat Olajuyin, Ziqi Wang, Zhiwei Xu, Hayatu M. Raji, Malachy I. Okeke, Xiaoju Zhang. Protein expression shift and potential diagnostic markers through proteomics profiling of A549 lung cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 322.

e20581 Background: Small-cell lung cancer (SCLC) is an aggressive disease with rapid progression rate and high metastatic potential that accounts for 15% of all lung cancers. Early-stage SCLC is usually asymptomatic; therefore, the majority of the SCLC patients were diagnosed in advanced stages. Although some radiological features were reported with advanced stages SCLC by CT scans, diagnosis of early stages SCLC from CT images has remained challenging since the radiological features are not distinct. Neuron-specific enolase (NSE) is commonly used in the clinical setting as a biomarker for SCLC, but the sensitivity of the test did not meet the needs. Here, we proposed a study using Circulating Genetically Abnormal Cells (CAC) to improve the diagnosis rate of SCLC in the early stages. Methods: A series of 26 stage I SCLC patients were enrolled from October 2019 to October 2020. All participants were having newly discovered pulmonary nodules ≤ 30mm when enrolled in the study, with no previous cancer history. Before the histopathological examination, 10 ml of peripheral blood were collected from each patient for CAC test, by using a 4 color FISH–based assay to detect the genetic abnormalities of 3p22.1, 3q29, 10q22.3, and CEP10 in the chromosome. Besides, NSE was performed on all participants. Both tests were intended to evaluate the malignant risk of lung nodules. Results: Confirmed by histopathological exam, 69% patients were diagnosed with SCLC located on the central part of the lung, and 31% patients were found to have peripheral-type SCLC. 88% of the patients in the overall cohort were smokers or past smokers, and only 12% participants had a family history of cancer. For Immunohistochemistry tests, the numbers of participants with positive CD56, TTF-1, CgA, CK, Syn and Ki-67 ≥ 60% are 65%, 58%, 12%, 42%, 50% and 69%, respectively. For diagnostic performance, the sensitivity of CAC in the over-all cohort is 73.08% (95%CI: 52.21%-88.43%), compared with 50.00% (95%CI: 29.93%- 70.07%) for NSE. CAC has achieved 77.78% (95%CI: 52.36% - 93.59%) and 62.5% (95%CI：24.49% - 91.48%) sensitivity in the centra and peripheral group. For NSE, the sensitivity of these two groups were 55.56% (95%CI: 30.76% - 78.47%) and 37.5% (95%CI: 8.52% - 75.51%). Conclusions: Compared with NSE, CAC is more sensitive to stage I SCLC, especially for SCLC that arising in central locations. This non-invasive method can be a complementary diagnostic tool with LDCT for smokers aged ≥65 with newly discovered pulmonary nodules. Clinical trial information: ChiCTR1900026233.