Background: Programmed cell death 1 (PD-1) blockade induces tumor regression in patients with advanced esophageal squamous cell carcinoma (ESCC); however, little is known about the efficacy of PD-1 blockade as neoadjuvant therapy in resectable ESCC. We aim to assess the safety and feasibility of using the combination of neoadjuvant PD-1 blockade with chemotherapy in patients with ESCC. Methods: Patients with previously untreated, resectable (stage II or III) ESCC were enrolled. Each patient received two 21-day cycles of neoadjuvant treatment with camrelizumab, nab-paclitaxel, and carboplatin before undergoing surgical resection approximately 6–9 weeks after the first cycle. Results: Between January 2020 and September 2020, 37 patients were screened, of whom 23 were enrolled. The neoadjuvant therapeutic regimen had an acceptable side effect profile, and no delays in surgery were observed. Severe (grade 3–4) treatment-related adverse events included neutropenia (9 of 23, 39.1%) and leukopenia (2 of 23, 8.7%). The objective response and disease control rates were 90.5% and 100%, respectively. Twenty patients received surgery, and R0 resection was achieved in all cases. Five (25%) patients had a pathological complete response (PCR) and 10 (50%) patients had a major pathological response. The proportion of patients with a high tumor mutation burden and a high expression of programmed death-ligand 1 (PD-L1) in primary tumor was significantly higher in the PCR group than in the non-PCR group (p=0.044). The number of infiltrating PD-L1⁺ CD163⁺ cells was significantly lower in the PCR group than in the non-PCR group after treatment (p=0.017). Conclusions: Neoadjuvant camrelizumab plus carboplatin and nab-paclitaxel had manageable treatment-related adverse effects and induced an objective response in 90.5% of patients, demonstrating its antitumor efficacy in resectable ESCC. Trial registration number: ChiCTR2000028900.

Background: People undergoing mass home- and community-based quarantine are vulnerable to mental health disorders during outbreaks of coronavirus disease (COVID-19), but few studies have evaluated the associated psychosocial factors. Objective: This study aimed to estimate the prevalence of anxiety and depressive symptoms and identify associated demographic and psychosocial factors in the general Chinese population during the COVID-19 pandemic quarantine period. Methods: Participants aged 18 years or above were recruited in a cross-sectional online survey using snowball sampling from February 26-29, 2020. The survey included questions on demographics, family relationships, chronic diseases, quarantine conditions, lifestyle, COVID-19 infection, and anxiety and depressive symptoms. Logistic regression analyses were conducted to identify factors associated with elevated anxiety or depressive symptoms. Results: Out of 2331 participants, 762 (32.7%) experienced elevated anxiety or depressive symptoms. Nine risk factors associated with anxiety or depressive symptoms included younger age, reduced income, having cancer or other chronic diseases, having family members living with cancer, concerns related to COVID-19 infection for themselves or family members, living alone, having family conflicts, having 8 hours of sedentary time per day, and worsened sleep quality. Conclusions: The findings highlight an urgent need for psychological support for populations at high risk for elevated anxiety or depressive symptoms during the COVID-19 pandemic.

BACKGROUND. Current clinical management of patients with pulmonary nodules involves either repeated low-dose CT (LDCT)/CT scans or invasive procedures, yet causes significant patient misclassification. An accurate noninvasive test is needed to identify malignant nodules and reduce unnecessary invasive tests. METHOD. We developed a diagnostic model based on targeted DNA methylation sequencing of 389 pulmonary nodule patients’ plasma samples and then validation in 140 plasma samples independently. We tested the model in different stages and subtypes of pulmonary nodules. RESULTS. A 100-feature model was developed and validated for pulmonary nodule diagnosis; the model achieved a receiver operating characteristic curve–AUC (ROC-AUC) of 0.843 on 140 independent validation samples, with an accuracy of 0.800. The performance was well maintained in (a) a 6 to 20 mm size subgroup (n = 100), with a sensitivity of 1.000 and adjusted negative predictive value (NPV) of 1.000 at 10% prevalence; (b) stage I malignancy (n = 90), with a sensitivity of 0.971; (c) different nodule types: solid nodules (n = 78) with a sensitivity of 1.000 and adjusted NPV of 1.000, part-solid nodules (n = 75) with a sensitivity of 0.947 and adjusted NPV of 0.983, and ground-glass nodules (n = 67) with a sensitivity of 0.964 and adjusted NPV of 0.989 at 10% prevalence. This methylation test, called PulmoSeek, outperformed PET-CT and 2 clinical prediction models (Mayo Clinic and Veterans Affairs) in discriminating malignant pulmonary nodules from benign ones. CONCLUSION. This study suggests that the blood-based DNA methylation model may provide a better test for classifying pulmonary nodules, which could help facilitate the accurate diagnosis of early stage lung cancer from pulmonary nodule patients and guide clinical decisions. FUNDING. The National Key Research and Development Program of China; Science and Technology Planning Project of Guangdong Province; The National Natural Science Foundation of China National.

Important evidence indicates the microbiota plays a key role in esophageal squamous cell carcinoma (ESCC). The esophageal microbiota was prospectively investigated in 18 patients with ESCC and 11 patients with physiological normal (PN) esophagus by 16S rRNA gene profiling, using next-generation sequencing. The microbiota composition in tumor tissues of ESCC patients were significantly different from that of patients with PN tissues. The ESCC microbiota was characterized by reduced microbial diversity, by decreased abundance of Bacteroidetes, Fusobacteria, and Spirochaetes. Employing these taxa into a microbial dysbiosis index demonstrated that dysbiosis microbiota had good capacity to discriminate between ESCC and PN esophagus. Functional analysis characterized that ESCC microbiota had altered nitrate reductase and nitrite reductase functions compared with PN group. These results suggest that specific microbes and the microbiota may drive or mitigate ESCC carcinogenesis, and this study will facilitate assigning causal roles in ESCC development to certain microbes and microbiota.

Comprehensive N6-methyladenosine (m6A) epitranscriptomic profiling of primary tumors remains largely uncharted. Here, we profiled the m6A epitranscriptome of 10 nonneoplastic lung tissues and 51 lung adenocarcinoma (LUAD) tumors, integrating the corresponding transcriptomic, proteomic, and extensive clinical annotations. We identified distinct clusters and genes that were exclusively linked to disease progression through m6A modifications. In comparison with nonneoplastic lung tissues, we identified 430 transcripts to be hypo-methylated and 222 to be hyper-methylated in tumors. Among these genes, EML4 emerged as a novel metastatic driver, displaying significant hypermethylation in tumors. m6A modification promoted the translation of EML4, leading to its widespread overexpression in primary tumors. Functionally, EML4 modulated cytoskeleton dynamics by interacting with ARPC1A, enhancing lamellipodia formation, cellular motility, local invasion, and metastasis. Clinically, high EML4 protein abundance correlated with features of metastasis. METTL3 small-molecule inhibitor markedly diminished both EML4 m6A and protein abundance and efficiently suppressed lung metastases in vivo. Significance: Our study reveals a dynamic and functional epitranscriptomic landscape in LUAD, offering a valuable resource for further research in the field. We identified EML4 hypermethylation as a key driver of tumor metastasis, highlighting a novel therapeutic strategy of targeting EML4 to prevent LUAD metastasis.