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Background: Early diagnosis of esophageal squamous cell carcinoma (ESCC) remains a challenge due to the lack of specific blood biomarkers. We aimed to develop a serum multi-protein signature for early detection of ESCC. Methods: We selected 70 healthy controls, 30 precancerous patients, 60 stage I patients, 70 stage II patients and 70 stage III/IV ESCC patients from a completed ESCC case-control study in a high-risk area of China. Olink Multiplex Oncology II targeted proteomics panel was used to simultaneously detect the levels of 92 cancer-related proteins in serum using proximity extension assay. Findings: We found that 10 upregulated and 13 downregulated protein biomarkers in serum could distinguish the early ESCC from healthy controls and their serum levels had significant dose-response relationships with ESCC progression. Applying least absolute shrinkage and selection operator (LASSO) regression and backward elimination algorithm, ANXA1 (annexin A1), hK8 (kallikrein-8), hK14(kallikrein-14), VIM (vimentin), and RSPO3 (R-spondin-3) were kept in final model to discriminate early ESCC cases from healthy controls with an area under curve (AUC) of 0.936 (95% confidence interval: 0.899~0.973). The average accuracy rates of the five-protein classifier were 0.861 and 0.825 in training and test data by five-fold cross-validation. Interpretation: Our study suggested that a combination of ANXA1, hK8, hK14, VIM and RSPO3 serum proteins could be considered as a potential tool for screening and early diagnosis of ESCC. Our results, however, need be confirmed in external case-control studies and prospective studies. Funding Statement: This work was supported by National Natural Science Foundation of China (81973116, 91846302, 81573229 and 81502870), National Key Research and Development program of China (2017YFC0907002 and 2017YFC0907003), International S&T Cooperation Program of China (2015DFE32790), European Research Council (682663), Medical and Health Technology Development Plan of Shandong Province (2018WS331). The funding sources had no role in the study design, interpretation of results, writing the manuscript or decision to submit the manuscript for the publication. The corresponding author has full access to all the data and assumes final responsibility for the decision to submit for publication. Declaration of Interests: The authors declare no potential conflicts of interest. Ethics Approval Statement: The study protocol was approved by the Institutional Review Boards of the School of Life Sciences, Fudan University (date: February 19, 2009), Qilu Hospital, Shandong University (date: March 8, 2010), and Stockholm Ethical Vetting Board (2018/357-31). The study was carried out in accordance with the approved protocol, and all participants provided written informed consent.

Background: Asymptomatic brain abnormalities are common incidental findings on brain MRI in the elderly population and can be regarded as imaging markers of early stroke and dementia. We initiated the Taizhou Imaging Study (TIS) to examine the prevalence and correlates of incidental findings using brain MRI among an elderly population residing in a rural area of China. Methods: A total of 562 individuals, at the age of 55 to 65 years, participated in the TIS study with a response rate of 90%. The primary findings included lacunes, white matter hyperintensity (WMH), and cerebral microbleeds (CMB), perivascular space (PVS), intracranial arterial stenosis (ICAS), and others (venous angioma, etc.). The brain parenchymal fraction and the brain gray matter fraction (BGMF) were also estimated. Findings: The prevalence of lacunes, WMH, CMB, PVS, and ICAS was 26.69%, 10.68%, 18.51%, 27.76%, and 12.81%, respectively. Age and hypertension were the major correlates of these incidental findings. Per each year increase in age, the risks of WMH and CMB increased by 15% and 14%. Compared to individuals with normal blood pressure, individuals with hypertension had an increased risk of all incidental findings, with the adjusted odds ratios of 2.28 to 5.45. Correlations of age, gender and BMI with BGMF were also observed. Interpretation: The prevalence of MRI incidental findings was high in the rural Chinese population at the age of 55-65 years. The high prevalence of these findings indicates a need of preventative strategy to help prevent future stroke and dementia in this population. Funding: The project was supported by the International Science and Technology Cooperation Program of China (grant number: 2014DFA32830), the Key Research and Development Plans of Jiangsu Province (grant number: BE2016726), the key basic research grants from Science and Technology Commission of Shanghai Municipality (grant number: 16JC1400500), the Karolinska Institutet (Senior Researcher Award and Strategic Research Area in Epidemiology), and the National Key Research and Development program of China (grant number: 2017YFC0907002, 2017YFC0907501). Declaration of interests: We declare no competing interests. Ethical Approval Statement: This study was approved by the Human Ethics Committee of School of Life Sciences of Fudan University (number of Institutional Review Board approval: 469).