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= .002); scans obtained in stage 3 (9-13 days) showed consolidation (19 of 21 scans [91%]) and a peak in the total CT score (mean, 7 ± 4); and scans obtained in stage 4 (≥14 days) showed gradual resolution of consolidation (15 of 20 scans [75%]) and a decrease in the total CT score (mean, 6 ± 4) without crazy-paving pattern. Conclusion In patients recovering from coronavirus disease 2019 (without severe respiratory distress during the disease course), lung abnormalities on chest CT scans showed greatest severity approximately 10 days after initial onset of symptoms. © RSNA, 2020.

autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

BackgroundThe dynamic changes of lymphocyte subsets and cytokines profiles of patients with novel coronavirus disease (COVID-19) and their correlation with the disease severity remain unclear.MethodsPeripheral blood samples were longitudinally collected from 40 confirmed COVID-19 patients and examined for lymphocyte subsets by flow cytometry and cytokine profiles by specific immunoassays.FindingsOf the 40 COVID-19 patients enrolled, 13 severe cases showed significant and sustained decreases in lymphocyte counts [0·6 (0·6-0·8)] but increases in neutrophil counts [4·7 (3·6-5·8)] than 27 mild cases [1.1 (0·8-1·4); 2·0 (1·5-2·9)]. Further analysis demonstrated significant decreases in the counts of T cells, especially CD8+ T cells, as well as increases in IL-6, IL-10, IL-2 and IFN-γ levels in the peripheral blood in the severe cases compared to those in the mild cases. T cell counts and cytokine levels in severe COVID-19 patients who survived the disease gradually recovered at later time points to levels that were comparable to those of the mild cases. Moreover, the neutrophil-to-lymphocyte ratio (NLR) (AUC=0·93) and neutrophil-to-CD8+ T cell ratio (N8R) (AUC =0·94) were identified as powerful prognostic factors affecting the prognosis for severe COVID-19.InterpretationThe degree of lymphopenia and a proinflammatory cytokine storm is higher in severe COVID-19 patients than in mild cases, and is associated with the disease severity. N8R and NLR may serve as a useful prognostic factor for early identification of severe COVID-19 cases.FundingThe National Natural Science Foundation of China, the National Science and Technology Major Project, the Health Commission of Hubei Province, Huazhong University of Science and Technology, and the Medical Faculty of the University of Duisburg-Essen and Stiftung Universitaetsmedizin, Hospital Essen, Germany.

Abstract The novel COVID-19 outbreak has affected more than 200 countries and territories as of March 2020. Given that patients with cancer are generally more vulnerable to infections, systematic analysis of diverse cohorts of patients with cancer affected by COVID-19 is needed. We performed a multicenter study including 105 patients with cancer and 536 age-matched noncancer patients confirmed with COVID-19. Our results showed COVID-19 patients with cancer had higher risks in all severe outcomes. Patients with hematologic cancer, lung cancer, or with metastatic cancer (stage IV) had the highest frequency of severe events. Patients with nonmetastatic cancer experienced similar frequencies of severe conditions to those observed in patients without cancer. Patients who received surgery had higher risks of having severe events, whereas patients who underwent only radiotherapy did not demonstrate significant differences in severe events when compared with patients without cancer. These findings indicate that patients with cancer appear more vulnerable to SARS-CoV-2 outbreak. Significance: Because this is the first large cohort study on this topic, our report will provide much-needed information that will benefit patients with cancer globally. As such, we believe it is extremely important that our study be disseminated widely to alert clinicians and patients. This article is highlighted in the In This Issue feature, p. 747

Abstract Objective To assess the prevalence of diabetes and its risk factors. Design Population based, cross sectional study. Setting 31 provinces in mainland China with nationally representative cross sectional data from 2015 to 2017. Participants 75 880 participants aged 18 and older—a nationally representative sample of the mainland Chinese population. Main outcome measures Prevalence of diabetes among adults living in China, and the prevalence by sex, regions, and ethnic groups, estimated by the 2018 American Diabetes Association (ADA) and the World Health Organization diagnostic criteria. Demographic characteristics, lifestyle, and history of disease were recorded by participants on a questionnaire. Anthropometric and clinical assessments were made of serum concentrations of fasting plasma glucose (one measurement), two hour plasma glucose, and glycated haemoglobin (HbA 1c ). Results The weighted prevalence of total diabetes (n=9772), self-reported diabetes (n=4464), newly diagnosed diabetes (n=5308), and prediabetes (n=27 230) diagnosed by the ADA criteria were 12.8% (95% confidence interval 12.0% to 13.6%), 6.0% (5.4% to 6.7%), 6.8% (6.1% to 7.4%), and 35.2% (33.5% to 37.0%), respectively, among adults living in China. The weighted prevalence of total diabetes was higher among adults aged 50 and older and among men. The prevalence of total diabetes in 31 provinces ranged from 6.2% in Guizhou to 19.9% in Inner Mongolia. Han ethnicity had the highest prevalence of diabetes (12.8%) and Hui ethnicity had the lowest (6.3%) among five investigated ethnicities. The weighted prevalence of total diabetes (n=8385) using the WHO criteria was 11.2% (95% confidence interval 10.5% to 11.9%). Conclusion The prevalence of diabetes has increased slightly from 2007 to 2017 among adults living in China. The findings indicate that diabetes is an important public health problem in China.

Abstract By 27 February 2020, the outbreak of coronavirus disease 2019 (COVID‐19) caused 82 623 confirmed cases and 2858 deaths globally, more than severe acute respiratory syndrome (SARS) (8273 cases, 775 deaths) and Middle East respiratory syndrome (MERS) (1139 cases, 431 deaths) caused in 2003 and 2013, respectively. COVID‐19 has spread to 46 countries internationally. Total fatality rate of COVID‐19 is estimated at 3.46% by far based on published data from the Chinese Center for Disease Control and Prevention (China CDC). Average incubation period of COVID‐19 is around 6.4 days, ranges from 0 to 24 days. The basic reproductive number ( R 0 ) of COVID‐19 ranges from 2 to 3.5 at the early phase regardless of different prediction models, which is higher than SARS and MERS. A study from China CDC showed majority of patients (80.9%) were considered asymptomatic or mild pneumonia but released large amounts of viruses at the early phase of infection, which posed enormous challenges for containing the spread of COVID‐19. Nosocomial transmission was another severe problem. A total of 3019 health workers were infected by 12 February 2020, which accounted for 3.83% of total number of infections, and extremely burdened the health system, especially in Wuhan. Limited epidemiological and clinical data suggest that the disease spectrum of COVID‐19 may differ from SARS or MERS. We summarize latest literatures on genetic, epidemiological, and clinical features of COVID‐19 in comparison to SARS and MERS and emphasize special measures on diagnosis and potential interventions. This review will improve our understanding of the unique features of COVID‐19 and enhance our control measures in the future.

Abstract Background Since December 2019, acute respiratory disease (ARD) due to 2019 novel coronavirus (2019-nCoV) emerged in Wuhan city and rapidly spread throughout China. We sought to delineate the clinical characteristics of these cases. Methods We extracted the data on 1,099 patients with laboratory-confirmed 2019-nCoV ARD from 552 hospitals in 31 provinces/provincial municipalities through January 29 th , 2020. Results The median age was 47.0 years, and 41.90% were females. Only 1.18% of patients had a direct contact with wildlife, whereas 31.30% had been to Wuhan and 71.80% had contacted with people from Wuhan. Fever (87.9%) and cough (67.7%) were the most common symptoms. Diarrhea is uncommon. The median incubation period was 3.0 days (range, 0 to 24.0 days). On admission, ground-glass opacity was the typical radiological finding on chest computed tomography (50.00%). Significantly more severe cases were diagnosed by symptoms plus reverse-transcriptase polymerase-chain-reaction without abnormal radiological findings than non-severe cases (23.87% vs. 5.20%, P <0.001). Lymphopenia was observed in 82.1% of patients. 55 patients (5.00%) were admitted to intensive care unit and 15 (1.36%) succumbed. Severe pneumonia was independently associated with either the admission to intensive care unit, mechanical ventilation, or death in multivariate competing-risk model (sub-distribution hazards ratio, 9.80; 95% confidence interval, 4.06 to 23.67). Conclusions The 2019-nCoV epidemic spreads rapidly by human-to-human transmission. Normal radiologic findings are present among some patients with 2019-nCoV infection. The disease severity (including oxygen saturation, respiratory rate, blood leukocyte/lymphocyte count and chest X-ray/CT manifestations) predict poor clinical outcomes.

Abstract Antibody–drug conjugate (ADC) is typically composed of a monoclonal antibody (mAbs) covalently attached to a cytotoxic drug via a chemical linker. It combines both the advantages of highly specific targeting ability and highly potent killing effect to achieve accurate and efficient elimination of cancer cells, which has become one of the hotspots for the research and development of anticancer drugs. Since the first ADC, Mylotarg ® (gemtuzumab ozogamicin), was approved in 2000 by the US Food and Drug Administration (FDA), there have been 14 ADCs received market approval so far worldwide. Moreover, over 100 ADC candidates have been investigated in clinical stages at present. This kind of new anti-cancer drugs, known as “biological missiles”, is leading a new era of targeted cancer therapy. Herein, we conducted a review of the history and general mechanism of action of ADCs, and then briefly discussed the molecular aspects of key components of ADCs and the mechanisms by which these key factors influence the activities of ADCs. Moreover, we also reviewed the approved ADCs and other promising candidates in phase-3 clinical trials and discuss the current challenges and future perspectives for the development of next generations, which provide insights for the research and development of novel cancer therapeutics using ADCs.

BACKGOUND: To figure out whether diabetes is a risk factor influencing the progression and prognosis of 2019 novel coronavirus disease (COVID-19). METHODS: A total of 174 consecutive patients confirmed with COVID-19 were studied. Demographic data, medical history, symptoms and signs, laboratory findings, chest computed tomography (CT) as well the treatment measures were collected and analysed. RESULTS: We found that COVID-19 patients without other comorbidities but with diabetes (n = 24) were at higher risk of severe pneumonia, release of tissue injury-related enzymes, excessive uncontrolled inflammation responses and hypercoagulable state associated with dysregulation of glucose metabolism. Furthermore, serum levels of inflammation-related biomarkers such as IL-6, C-reactive protein, serum ferritin and coagulation index, D-dimer, were significantly higher (P < .01) in diabetic patients compared with those without, suggesting that patients with diabetes are more susceptible to an inflammatory storm eventually leading to rapid deterioration of COVID-19. CONCLUSIONS: Our data support the notion that diabetes should be considered as a risk factor for a rapid progression and bad prognosis of COVID-19. More intensive attention should be paid to patients with diabetes, in case of rapid deterioration.

OBJECTIVE. The objective of our study was to determine the misdiagnosis rate of radiologists for coronavirus disease 2019 (COVID-19) and evaluate the performance of chest CT in the diagnosis and management of COVID-19. The CT features of COVID-19 are reported and compared with the CT features of other viruses to familiarize radiologists with possible CT patterns.

The emergence of immune checkpoint inhibitors (ICIs), mainly including anti-programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) and anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) monoclonal antibodies (mAbs), has shaped therapeutic landscape of some type of cancers. Despite some ICIs have manifested compelling clinical effectiveness in certain tumor types, the majority of patients still showed de novo or adaptive resistance. At present, the overall efficiency of immune checkpoint therapy remains unsatisfactory. Exploring additional immune checkpoint molecules is a hot research topic. Recent studies have identified several new immune checkpoint targets, like lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin and mucin-domain containing-3 (TIM-3), T cell immunoglobulin and ITIM domain (TIGIT), V-domain Ig suppressor of T cell activation (VISTA), and so on. The investigations about these molecules have generated promising results in preclinical studies and/or clinical trials. In this review, we discussed the structure and expression of these newly-characterized immune checkpoints molecules, presented the current progress and understanding of them. Moreover, we summarized the clinical data pertinent to these recent immune checkpoint molecules as well as their application prospects.

Background CT may play a central role in the diagnosis and management of coronavirus disease 2019 (COVID-19) pneumonia. Purpose To perform a longitudinal study to analyze the serial CT findings over time in patients with COVID-19 pneumonia. Materials and Methods During January 16 to February 17, 2020, 90 patients (33 men, 57 women; mean age, 45 years) with COVID-19 pneumonia were prospectively enrolled and followed up until being discharged, death, or the end of the study. A total of 366 CT scans were acquired and reviewed by two groups of radiologists for the patterns and distribution of lung abnormalities, total CT scores, and number of zones involved. Those features were analyzed for temporal change. Results CT scores and number of zones involved progressed rapidly, peaked during illness days 6-11 (median CT score, 5; median number of zones involved, five), and were followed by persistence of high levels. The predominant pattern of abnormalities after symptom onset was ground-glass opacity (35 of 78 scans [45%] to 49 of 79 scans [62%] in different periods). The percentage of mixed pattern peaked on illness days 12-17 (30 of 78 scans [38%]) and became the second most predominant pattern thereafter. Pure ground-glass opacity was the most prevalent subtype of ground-glass opacity after symptom onset (20 of 50 scans [40%] to 20 of 28 scans [71%]). The percentage of ground-glass opacity with irregular linear opacity peaked on illness days 6-11 (14 of 50 scans [28%]) and became the second most prevalent subtype thereafter. The distribution of lesions was predominantly bilateral and subpleural. Sixty-six of the 70 patients discharged (94%) had residual disease on final CT scans (median CT score, 4; median number of zones involved, four), with ground-glass opacity (42 of 70 patients [60%]) and pure ground-glass opacity (31 of 42 patients [74%]) the most common pattern and subtype. Conclusion The extent of lung abnormalities at CT peaked during illness days 6-11. The temporal changes of the diverse CT manifestations followed a specific pattern, which might indicate the progression and recovery of the illness. © RSNA, 2020

Gastric cancer is one of the most common malignant tumors in the digestive system. Surgery is currently considered to be the only radical treatment. As surgical techniques improve and progress is made in traditional radiotherapy, chemotherapy, and the implementation of neoadjuvant therapy, the 5-year survival rate of early gastric cancer can reach >95%. However, the low rate of early diagnosis means that most patients have advanced-stage disease at diagnosis and so the best surgical window is missed. Therefore, the main treatment for advanced gastric cancer is the combination of neoadjuvant chemoradiotherapy, molecular-targeted therapy, and immunotherapy. In this article, we summarize several common methods used to treat advanced gastric cancer and discuss the progress made in the treatment of gastric cancer in detail. Only clinical practice and clinical research will allow us to prolong the survival time of patients and allow the patients to truly benefit by paying attention to the individual patient characteristics, drug choice, and developing a reasonable and comprehensive treatment plan.

BACKGROUND: The role of endovascular therapy for acute stroke with a large infarction has not been extensively studied in differing populations. METHODS: We conducted a multicenter, prospective, open-label, randomized trial in China involving patients with acute large-vessel occlusion in the anterior circulation and an Alberta Stroke Program Early Computed Tomography Score of 3 to 5 (range, 0 to 10, with lower values indicating larger infarction) or an infarct-core volume of 70 to 100 ml. Patients were randomly assigned in a 1:1 ratio within 24 hours from the time they were last known to be well to undergo endovascular therapy and receive medical management or to receive medical management alone. The primary outcome was the score on the modified Rankin scale at 90 days (scores range from 0 to 6, with higher scores indicating greater disability), and the primary objective was to determine whether a shift in the distribution of the scores on the modified Rankin scale at 90 days had occurred between the two groups. Secondary outcomes included scores of 0 to 2 and 0 to 3 on the modified Rankin scale. The primary safety outcome was symptomatic intracranial hemorrhage within 48 hours after randomization. RESULTS: A total of 456 patients were enrolled; 231 were assigned to the endovascular-therapy group and 225 to the medical-management group. Approximately 28% of the patients in both groups received intravenous thrombolysis. The trial was stopped early owing to the efficacy of endovascular therapy after the second interim analysis. At 90 days, a shift in the distribution of scores on the modified Rankin scale toward better outcomes was observed in favor of endovascular therapy over medical management alone (generalized odds ratio, 1.37; 95% confidence interval, 1.11 to 1.69; P = 0.004). Symptomatic intracranial hemorrhage occurred in 14 of 230 patients (6.1%) in the endovascular-therapy group and in 6 of 225 patients (2.7%) in the medical-management group; any intracranial hemorrhage occurred in 113 (49.1%) and 39 (17.3%), respectively. Results for the secondary outcomes generally supported those of the primary analysis. CONCLUSIONS: In a trial conducted in China, patients with large cerebral infarctions had better outcomes with endovascular therapy administered within 24 hours than with medical management alone but had more intracranial hemorrhages. (Funded by Covidien Healthcare International Trading [Shanghai] and others; ANGEL-ASPECT ClinicalTrials.gov number, NCT04551664.).

CT examination of patients with COVID-19 pneumonia showed a mixed and diverse pattern with both lung parenchyma and the interstitium involved. Identification of GGO and a single lesion on the initial CT scan suggested early-phase disease. CT signs of aggravation and repair coexisted in advanced-phase disease. Lesions presented with a characteristic multifocal distribution in the middle and lower lung regions and in the posterior lung area. A decreased lymphocyte count and an increased high-sensitivity C-reactive protein level were the most common laboratory findings.

Although substantial progress has been made in cancer biology and treatment, clinical outcomes of bladder carcinoma (BC) patients are still not satisfactory. The tumor microenvironment (TME) is a potential target. Here, by single-cell RNA sequencing on 8 BC tumor samples and 3 para tumor samples, we identify 19 different cell types in the BC microenvironment, indicating high intra-tumoral heterogeneity. We find that tumor cells down regulated MHC-II molecules, suggesting that the downregulated immunogenicity of cancer cells may contribute to the formation of an immunosuppressive microenvironment. We also find that monocytes undergo M2 polarization in the tumor region and differentiate. Furthermore, the LAMP3 + DC subgroup may be able to recruit regulatory T cells, potentially taking part in the formation of an immunosuppressive TME. Through correlation analysis using public datasets containing over 3000 BC samples, we identify a role for inflammatory cancer-associated fibroblasts (iCAFs) in tumor progression, which is significantly related to poor prognosis. Additionally, we characterize a regulatory network depending on iCAFs. These results could help elucidate the protumor mechanisms of iCAFs. Our results provide deep insight into cancer immunology and provide an essential resource for drug discovery in the future.

Importance: Laparoscopic distal gastrectomy is accepted as a more effective approach to conventional open distal gastrectomy for early-stage gastric cancer. However, efficacy for locally advanced gastric cancer remains uncertain. Objective: To compare 3-year disease-free survival for patients with locally advanced gastric cancer after laparoscopic distal gastrectomy or open distal gastrectomy. Design, Setting, and Patients: The study was a noninferiority, open-label, randomized clinical trial at 14 centers in China. A total of 1056 eligible patients with clinical stage T2, T3, or T4a gastric cancer without bulky nodes or distant metastases were enrolled from September 2012 to December 2014. Final follow-up was on December 31, 2017. Interventions: Participants were randomized in a 1:1 ratio after stratification by site, age, cancer stage, and histology to undergo either laparoscopic distal gastrectomy (n = 528) or open distal gastrectomy (n = 528) with D2 lymphadenectomy. Main Outcomes and Measures: The primary end point was 3-year disease-free survival with a noninferiority margin of -10% to compare laparoscopic distal gastrectomy with open distal gastrectomy. Secondary end points of 3-year overall survival and recurrence patterns were tested for superiority. Results: Among 1056 patients, 1039 (98.4%; mean age, 56.2 years; 313 [30.1%] women) had surgery (laparoscopic distal gastrectomy [n=519] vs open distal gastrectomy [n=520]), and 999 (94.6%) completed the study. Three-year disease-free survival rate was 76.5% in the laparoscopic distal gastrectomy group and 77.8% in the open distal gastrectomy group, absolute difference of -1.3% and a 1-sided 97.5% CI of -6.5% to ∞, not crossing the prespecified noninferiority margin. Three-year overall survival rate (laparoscopic distal gastrectomy vs open distal gastrectomy: 83.1% vs 85.2%; adjusted hazard ratio, 1.19; 95% CI, 0.87 to 1.64; P = .28) and cumulative incidence of recurrence over the 3-year period (laparoscopic distal gastrectomy vs open distal gastrectomy: 18.8% vs 16.5%; subhazard ratio, 1.15; 95% CI, 0.86 to 1.54; P = .35) did not significantly differ between laparoscopic distal gastrectomy and open distal gastrectomy groups. Conclusions and Relevance: Among patients with a preoperative clinical stage indicating locally advanced gastric cancer, laparoscopic distal gastrectomy, compared with open distal gastrectomy, did not result in inferior disease-free survival at 3 years. Trial Registration: ClinicalTrials.gov Identifier: NCT01609309.

With the development of information technology, the concept of smart healthcare has gradually come to the fore. Smart healthcare uses a new generation of information technologies, such as the internet of things (loT), big data, cloud computing, and artificial intelligence, to transform the traditional medical system in an all-round way, making healthcare more efficient, more convenient, and more personalized. With the aim of introducing the concept of smart healthcare, in this review, we first list the key technologies that support smart healthcare and introduce the current status of smart healthcare in several important fields. Then we expound the existing problems with smart healthcare and try to propose solutions to them. Finally, we look ahead and evaluate the future prospects of smart healthcare.

Mitochondria are indispensable for energy metabolism, apoptosis regulation, and cell signaling. Mitochondria in malignant cells differ structurally and functionally from those in normal cells and participate actively in metabolic reprogramming. Mitochondria in cancer cells are characterized by reactive oxygen species (ROS) overproduction, which promotes cancer development by inducing genomic instability, modifying gene expression, and participating in signaling pathways. Mitochondrial and nuclear DNA mutations caused by oxidative damage that impair the oxidative phosphorylation process will result in further mitochondrial ROS production, completing the "vicious cycle" between mitochondria, ROS, genomic instability, and cancer development. The multiple essential roles of mitochondria have been utilized for designing novel mitochondria-targeted anticancer agents. Selective drug delivery to mitochondria helps to increase specificity and reduce toxicity of these agents. In order to reduce mitochondrial ROS production, mitochondria-targeted antioxidants can specifically accumulate in mitochondria by affiliating to a lipophilic penetrating cation and prevent mitochondria from oxidative damage. In consistence with the oncogenic role of ROS, mitochondria-targeted antioxidants are found to be effective in cancer prevention and anticancer therapy. A better understanding of the role played by mitochondria in cancer development will help to reveal more therapeutic targets, and will help to increase the activity and selectivity of mitochondria-targeted anticancer drugs. In this review we summarized the impact of mitochondria on cancer and gave summary about the possibilities to target mitochondria for anticancer therapies. J. Cell. Physiol. 231: 2570-2581, 2016. © 2016 Wiley Periodicals, Inc.