Fifth Affiliated Hospital of Sun Yat-sen University

SARS-CoV-2 Viral Load in Upper Respiratory Specimens The authors report results of an analysis of nasal and throat swabs from 17 patients in Zhuhai, China, who had received a diagnosis of Covid-19....

An acute respiratory disease, caused by a novel coronavirus (SARS-CoV-2, previously known as 2019-nCoV), the coronavirus disease 2019 (COVID-19) has spread throughout China and received worldwide attention. On 30 January 2020, World Health Organization (WHO) officially declared the COVID-19 epidemic as a public health emergency of international concern. The emergence of SARS-CoV-2, since the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, marked the third introduction of a highly pathogenic and large-scale epidemic coronavirus into the human population in the twenty-first century. As of 1 March 2020, a total of 87,137 confirmed cases globally, 79,968 confirmed in China and 7169 outside of China, with 2977 deaths (3.4%) had been reported by WHO. Meanwhile, several independent research groups have identified that SARS-CoV-2 belongs to β-coronavirus, with highly identical genome to bat coronavirus, pointing to bat as the natural host. The novel coronavirus uses the same receptor, angiotensin-converting enzyme 2 (ACE2) as that for SARS-CoV, and mainly spreads through the respiratory tract. Importantly, increasingly evidence showed sustained human-to-human transmission, along with many exported cases across the globe. The clinical symptoms of COVID-19 patients include fever, cough, fatigue and a small population of patients appeared gastrointestinal infection symptoms. The elderly and people with underlying diseases are susceptible to infection and prone to serious outcomes, which may be associated with acute respiratory distress syndrome (ARDS) and cytokine storm. Currently, there are few specific antiviral strategies, but several potent candidates of antivirals and repurposed drugs are under urgent investigation. In this review, we summarized the latest research progress of the epidemiology, pathogenesis, and clinical characteristics of COVID-19, and discussed the current treatment and scientific advancements to combat the epidemic novel coronavirus.

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak is evolving rapidly worldwide. OBJECTIVE: To evaluate the risk of serious adverse outcomes in patients with COVID-19 by stratifying the comorbidity status. METHODS: We analysed data from 1590 laboratory confirmed hospitalised patients from 575 hospitals in 31 provinces/autonomous regions/provincial municipalities across mainland China between 11 December 2019 and 31 January 2020. We analysed the composite end-points, which consisted of admission to an intensive care unit, invasive ventilation or death. The risk of reaching the composite end-points was compared according to the presence and number of comorbidities. RESULTS: The mean age was 48.9 years and 686 (42.7%) patients were female. Severe cases accounted for 16.0% of the study population. 131 (8.2%) patients reached the composite end-points. 399 (25.1%) reported having at least one comorbidity. The most prevalent comorbidity was hypertension (16.9%), followed by diabetes (8.2%). 130 (8.2%) patients reported having two or more comorbidities. After adjusting for age and smoking status, COPD (HR (95% CI) 2.681 (1.424-5.048)), diabetes (1.59 (1.03-2.45)), hypertension (1.58 (1.07-2.32)) and malignancy (3.50 (1.60-7.64)) were risk factors of reaching the composite end-points. The hazard ratio (95% CI) was 1.79 (1.16-2.77) among patients with at least one comorbidity and 2.59 (1.61-4.17) among patients with two or more comorbidities. CONCLUSION: Among laboratory confirmed cases of COVID-19, patients with any comorbidity yielded poorer clinical outcomes than those without. A greater number of comorbidities also correlated with poorer clinical outcomes.

In this retrospective case series, chest CT scans of 21 symptomatic patients from China infected with the 2019 novel coronavirus (2019-nCoV) were reviewed, with emphasis on identifying and characterizing the most common findings. Typical CT findings included bilateral pulmonary parenchymal ground-glass and consolidative pulmonary opacities, sometimes with a rounded morphology and a peripheral lung distribution. Notably, lung cavitation, discrete pulmonary nodules, pleural effusions, and lymphadenopathy were absent. Follow-up imaging in a subset of patients during the study time window often demonstrated mild or moderate progression of disease, as manifested by increasing extent and density of lung opacities.

In this retrospective study, chest CTs of 121 symptomatic patients infected with coronavirus disease-19 (COVID-19) from four centers in China from January 18, 2020 to February 2, 2020 were reviewed for common CT findings in relationship to the time between symptom onset and the initial CT scan (i.e. early, 0-2 days (36 patients), intermediate 3-5 days (33 patients), late 6-12 days (25 patients)). The hallmarks of COVID-19 infection on imaging were bilateral and peripheral ground-glass and consolidative pulmonary opacities. Notably, 20/36 (56%) of early patients had a normal CT. With a longer time after the onset of symptoms, CT findings were more frequent, including consolidation, bilateral and peripheral disease, greater total lung involvement, linear opacities, "crazy-paving" pattern and the "reverse halo" sign. Bilateral lung involvement was observed in 10/36 early patients (28%), 25/33 intermediate patients (76%), and 22/25 late patients (88%).

BACKGROUND: Knee osteoarthritis (OA) is a major cause of disability in the elderly, however, there are few studies to estimate the global prevalence, incidence, and risk factors of knee OA. METHODS: For this study, we searched PUBMED, EMBASE and SCOPUS from inception to April 4, 2020, without language restriction. We identified eligible studies with information on the prevalence or incidence of knee OA in population-based observational studies and extracted data from published reports. We did random-effects meta-analysis to generate estimates. This study was registered with PROSPERO (CRD42020181035). FINDINGS: <0⋅00), respectively. INTERPRETATION: Our study provides the global prevalence (16⋅0% [95% CI, 14⋅3%-17⋅8%]) and incidence (203 per 10,000 person-years [95% CI, 106-331]) of knee OA. These findings can be used to better assess the global health burden of knee OA. Further prospective cohort studies are warranted to identify modifiable risk factors for providing effectively preventive strategies in the early stages of the disease. FUNDING: This work was supported by grants from the National Natural Science Foundation of China (nos. 81772384 and 81572174).

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 &lt;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.

OBJECTIVE: To study the GI symptoms in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients. DESIGN: We analysed epidemiological, demographic, clinical and laboratory data of 95 cases with SARS-CoV-2 caused coronavirus disease 2019. Real-time reverse transcriptase PCR was used to detect the presence of SARS-CoV-2 in faeces and GI tissues. RESULTS: Among the 95 patients, 58 cases exhibited GI symptoms of which 11 (11.6%) occurred on admission and 47 (49.5%) developed during hospitalisation. Diarrhoea (24.2%), anorexia (17.9%) and nausea (17.9%) were the main symptoms with five (5.3%), five (5.3%) and three (3.2%) cases occurred on the illness onset, respectively. A substantial proportion of patients developed diarrhoea during hospitalisation, potentially aggravated by various drugs including antibiotics. Faecal samples of 65 hospitalised patients were tested for the presence of SARS-CoV-2, including 42 with and 23 without GI symptoms, of which 22 (52.4%) and 9 (39.1%) were positive, respectively. Six patients with GI symptoms were subjected to endoscopy, revealing oesophageal bleeding with erosions and ulcers in one severe patient. SARS-CoV-2 RNA was detected in oesophagus, stomach, duodenum and rectum specimens for both two severe patients. In contrast, only duodenum was positive in one of the four non-severe patients. CONCLUSIONS: GI tract may be a potential transmission route and target organ of SARS-CoV-2.

BACKGROUND: Platinum-based concurrent chemoradiotherapy is the standard of care for patients with locoregionally advanced nasopharyngeal carcinoma. Additional gemcitabine and cisplatin induction chemotherapy has shown promising efficacy in phase 2 trials. METHODS: In a parallel-group, multicenter, randomized, controlled, phase 3 trial, we compared gemcitabine and cisplatin as induction chemotherapy plus concurrent chemoradiotherapy with concurrent chemoradiotherapy alone. Patients with locoregionally advanced nasopharyngeal carcinoma were randomly assigned in a 1:1 ratio to receive gemcitabine (at a dose of 1 g per square meter of body-surface area on days 1 and 8) plus cisplatin (80 mg per square meter on day 1), administered every 3 weeks for three cycles, plus chemoradiotherapy (concurrent cisplatin at a dose of 100 mg per square meter every 3 weeks for three cycles plus intensity-modulated radiotherapy) or chemoradiotherapy alone. The primary end point was recurrence-free survival (i.e., freedom from disease recurrence [distant metastasis or locoregional recurrence] or death from any cause) in the intention-to-treat population. Secondary end points included overall survival, treatment adherence, and safety. RESULTS: A total of 480 patients were included in the trial (242 patients in the induction chemotherapy group and 238 in the standard-therapy group). At a median follow-up of 42.7 months, the 3-year recurrence-free survival was 85.3% in the induction chemotherapy group and 76.5% in the standard-therapy group (stratified hazard ratio for recurrence or death, 0.51; 95% confidence interval [CI], 0.34 to 0.77; P = 0.001). Overall survival at 3 years was 94.6% and 90.3%, respectively (stratified hazard ratio for death, 0.43; 95% CI, 0.24 to 0.77). A total of 96.7% of the patients completed three cycles of induction chemotherapy. The incidence of acute adverse events of grade 3 or 4 was 75.7% in the induction chemotherapy group and 55.7% in the standard-therapy group, with a higher incidence of neutropenia, thrombocytopenia, anemia, nausea, and vomiting in the induction chemotherapy group. The incidence of grade 3 or 4 late toxic effects was 9.2% in the induction chemotherapy group and 11.4% in the standard-therapy group. CONCLUSIONS: Induction chemotherapy added to chemoradiotherapy significantly improved recurrence-free survival and overall survival, as compared with chemoradiotherapy alone, among patients with locoregionally advanced nasopharyngeal carcinoma. (Funded by the Innovation Team Development Plan of the Ministry of Education and others; ClinicalTrials.gov number, NCT01872962.).

The outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 virus continually lead to worldwide human infections and deaths. Currently, there is no specific viral protein-targeted therapeutics. Viral nucleocapsid protein is a potential antiviral drug target, serving multiple critical functions during the viral life cycle. However, the structural information of SARS-CoV-2 nucleocapsid protein remains unclear. Herein, we have determined the 2.7 Å crystal structure of the N-terminal RNA binding domain of SARS-CoV-2 nucleocapsid protein. Although the overall structure is similar as other reported coronavirus nucleocapsid protein N-terminal domain, the surface electrostatic potential characteristics between them are distinct. Further comparison with mild virus type HCoV-OC43 equivalent domain demonstrates a unique potential RNA binding pocket alongside the β-sheet core. Complemented by in vitro binding studies, our data provide several atomic resolution features of SARS-CoV-2 nucleocapsid protein N-terminal domain, guiding the design of novel antiviral agents specific targeting to SARS-CoV-2.

Abstract Objective To evaluate the spectrum of comorbidities and its impact on the clinical outcome in patients with coronavirus disease 2019 (COVID-19). Design Retrospective case studies Setting 575 hospitals in 31 province/autonomous regions/provincial municipalities across China Participants 1,590 laboratory-confirmed hospitalized patients. Data were collected from November 21 st , 2019 to January 31 st , 2020. Main outcomes and measures Epidemiological and clinical variables (in particular, comorbidities) were extracted from medical charts. The disease severity was categorized based on the American Thoracic Society guidelines for community-acquired pneumonia. The primary endpoint was the composite endpoints, which consisted of the admission to intensive care unit (ICU), or invasive ventilation, or death. The risk of reaching to the composite endpoints was compared among patients with COVID-19 according to the presence and number of comorbidities. Results Of the 1,590 cases, the mean age was 48.9 years. 686 patients (42.7%) were females. 647 (40.7%) patients were managed inside Hubei province, and 1,334 (83.9%) patients had a contact history of Wuhan city. Severe cases accounted for 16.0% of the study population. 131 (8.2%) patients reached to the composite endpoints. 399 (25.1%) reported having at least one comorbidity. 269 (16.9%), 59 (3.7%), 30 (1.9%), 130 (8.2%), 28 (1.8%), 24 (1.5%), 21 (1.3%), 18 (1.1%) and 3 (0.2%) patients reported having hypertension, cardiovascular diseases, cerebrovascular diseases, diabetes, hepatitis B infections, chronic obstructive pulmonary disease, chronic kidney diseases, malignancy and immunodeficiency, respectively. 130 (8.2%) patients reported having two or more comorbidities. Patients with two or more comorbidities had significantly escalated risks of reaching to the composite endpoint compared with those who had a single comorbidity, and even more so as compared with those without (all P &lt;0.05). After adjusting for age and smoking status, patients with COPD (HR 2.681, 95%CI 1.424-5.048), diabetes (HR 1.59, 95%CI 1.03-2.45), hypertension (HR 1.58, 95%CI 1.07-2.32) and malignancy (HR 3.50, 95%CI 1.60-7.64) were more likely to reach to the composite endpoints than those without. As compared with patients without comorbidity, the HR (95%CI) was 1.79 (95%CI 1.16-2.77) among patients with at least one comorbidity and 2.59 (95%CI 1.61-4.17) among patients with two or more comorbidities. Conclusion Comorbidities are present in around one fourth of patients with COVID-19 in China, and predispose to poorer clinical outcomes. Highlights What is already known on this topic - Since November 2019, the rapid outbreak of coronavirus disease 2019 (COVID-19) has recently become a public health emergency of international concern. There have been 79,331 laboratory-confirmed cases and 2,595 deaths globally as of February 25 th , 2020 - Previous studies have demonstrated the association between comorbidities and other severe acute respiratory diseases including SARS and MERS. - No study with a nationwide representative cohort has demonstrated the spectrum of comorbidities and the impact of comorbidities on the clinical outcomes in patients with COVID-19. What this study adds - In this nationwide study with 1,590 patients with COVID-19, comorbidities were identified in 399 patients. Comorbidities of COVID-19 mainly included hypertension, cardiovascular diseases, cerebrovascular diseases, diabetes, hepatitis B infections, chronic obstructive pulmonary disease, chronic kidney diseases, malignancy and immunodeficiency. - The presence of as well as the number of comorbidities predicted the poor clinical outcomes (admission to intensive care unit, invasive ventilation, or death) of COVID-19. - Comorbidities should be taken into account when estimating the clinical outcomes of patients with COVID-19 on hospital admission.

AIMS: To provide the first systematic analysis of the burden and underlying causes of heart failure (HF) in 195 countries and territories from 1990 to 2017. METHODS AND RESULTS: We collected detailed information on prevalence, years lived with disability (YLDs), and underlying causes of HF from the Global Burden of Disease study 2017. Numbers and age-standardized rates of HF prevalence and YLDs were compared by age, sex, socio-demographic index (SDI), and location. The proportions of HF age-standardized prevalence rates due to 23 underlying causes were also presented. Globally, the age-standardized prevalence and YLD rates of HF in 2017 were 831.0 and 128.2 per 100 000 people, a decrease of -7.2% and -0.9% from 1990, respectively. Nevertheless, the absolute numbers of HF prevalent cases and YLDs have increased by 91.9% and 106.0% from 1990, respectively. There is significant geographic and socio-demographic variation in the levels and trends of HF burden from 1990 to 2017. Among all causes of HF, ischaemic heart disease accounted for the highest proportion (26.5%) of age-standardized prevalence rate of HF in 2017, followed by hypertensive heart disease (26.2%), chronic obstructive pulmonary disease (23.4%). CONCLUSION: HF remains a serious public health problem worldwide, with increasing age-standardized prevalence and YLD rates in countries with relatively low SDI. More geo-specific strategies aimed at preventing underlying causes and improving medical care for HF are warranted to reduce the future burden of this condition.

OBJECTIVE: This study investigated the influence of Coronavirus Disease 2019 (COVID-19) on lung function in early convalescence phase. METHODS: A retrospective study of COVID-19 patients at the Fifth Affiliated Hospital of Sun Yat-sen University were conducted, with serial assessments including lung volumes (TLC), spirometry (FVC, FEV1), lung diffusing capacity for carbon monoxide (DLCO),respiratory muscle strength, 6-min walking distance (6MWD) and high resolution CT being collected at 30 days after discharged. RESULTS: Fifty-seven patients completed the serial assessments. There were 40 non-severe cases and 17 severe cases. Thirty-one patients (54.3%) had abnormal CT findings. Abnormalities were detected in the pulmonary function tests in 43 (75.4%) of the patients. Six (10.5%), 5(8.7%), 25(43.8%) 7(12.3%), and 30 (52.6%) patients had FVC, FEV1, FEV1/FVC ratio, TLC, and DLCO values less than 80% of predicted values, respectively. 28 (49.1%) and 13 (22.8%) patients had PImax and PEmax values less than 80% of the corresponding predicted values. Compared with non-severe cases, severe patients showed higher incidence of DLCO impairment (75.6%vs42.5%, p = 0.019), higher lung total severity score (TSS) and R20, and significantly lower percentage of predicted TLC and 6MWD. No significant correlation between TSS and pulmonary function parameters was found during follow-up visit. CONCLUSION: Impaired diffusing-capacity, lower respiratory muscle strength, and lung imaging abnormalities were detected in more than half of the COVID-19 patients in early convalescence phase. Compared with non-severe cases, severe patients had a higher incidence of DLCO impairment and encountered more TLC decrease and 6MWD decline.

Exosomes are generated within the multivesicular endosomes (MVEs) as intraluminal vesicles (ILVs) and secreted during the fusion of MVEs with the cell membrane. The mechanisms of exosome biogenesis remain poorly explored. Here we identify that RAB31 marks and controls an ESCRT-independent exosome pathway. Active RAB31, phosphorylated by epidermal growth factor receptor (EGFR), engages flotillin proteins in lipid raft microdomains to drive EGFR entry into MVEs to form ILVs, which is independent of the ESCRT (endosomal sorting complex required for transport) machinery. Active RAB31 interacts with the SPFH domain and drives ILV formation via the Flotillin domain of flotillin proteins. Meanwhile, RAB31 recruits GTPase-activating protein TBC1D2B to inactivate RAB7, thereby preventing the fusion of MVEs with lysosomes and enabling the secretion of ILVs as exosomes. These findings establish that RAB31 has dual functions in the biogenesis of exosomes: driving ILVs formation and suppressing MVEs degradation, providing an exquisite framework to better understand exosome biogenesis.

Long noncoding RNAs (lncRNAs) have emerged as critical players in cancer progression, but their functions in colorectal cancer (CRC) metastasis have not been systematically clarified. lncRNA expression profiles in matched normal and CRC tissue were checked using microarray analysis. The biological roles of a novel lncRNA, namely RP11-138 J23.1 (RP11), in development of CRC were checked both in vitro and in vivo. Its association with clinical progression of CRC was further analyzed. RP11 was highly expressed in CRC tissues, and its expression increased with CRC stage in patients. RP11 positively regulated the migration, invasion and epithelial mesenchymal transition (EMT) of CRC cells in vitro and enhanced liver metastasis in vivo. Post-translational upregulation of Zeb1, an EMT-related transcription factor, was essential for RP11-induced cell dissemination. Mechanistically, the RP11/hnRNPA2B1/mRNA complex accelerated the mRNA degradation of two E3 ligases, Siah1 and Fbxo45, and subsequently prevented the proteasomal degradation of Zeb1. m6A methylation was involved in the upregulation of RP11 by increasing its nuclear accumulation. Clinical analysis showed that m6A can regulate the expression of RP11, further, RP11 regulated Siah1-Fbxo45/Zeb1 was involved in the development of CRC. m6A-induced lncRNA RP11 can trigger the dissemination of CRC cells via post-translational upregulation of Zeb1. Considering the high and specific levels of RP11 in CRC tissues, our present study paves the way for further investigations of RP11 as a predictive biomarker or therapeutic target for CRC.

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic and has claimed over 2 million lives worldwide. Although the genetic sequences of SARS-CoV and SARS-CoV-2 have high homology, the clinical and pathological characteristics of COVID-19 differ significantly from those of SARS. How and whether SARS-CoV-2 evades (cellular) immune surveillance requires further elucidation. In this study, we show that SARS-CoV-2 infection leads to major histocompability complex class Ι (MHC-Ι) down-regulation both in vitro and in vivo. The viral protein encoded by open reading frame 8 (ORF8) of SARS-CoV-2, which shares the least homology with SARS-CoV among all viral proteins, directly interacts with MHC-Ι molecules and mediates their down-regulation. In ORF8-expressing cells, MHC-Ι molecules are selectively targeted for lysosomal degradation via autophagy. Thus, SARS-CoV-2-infected cells are much less sensitive to lysis by cytotoxic T lymphocytes. Because ORF8 protein impairs the antigen presentation system, inhibition of ORF8 could be a strategy to improve immune surveillance.

N6-methyladenosin (m6A) is one of the most pervasive modification of mRNA in eukaryotes and the m6A methyltransferases and demethylases play critical roles in many types of cancer. However the role of m6A-binding proteins in cancer remains elusive. Here we report that the down-regulation of YTHDF2 was specifically induced by hypoxia in hepatocellular carcinoma (HCC) cells, and that overexpression of YTHDF2 suppressed cell proliferation, tumor growth and activation of MEK and ERK in HCC cells. Mechanistically, YTHDF2 directly bound the m6A modification site of EGFR 3’-UTR to promote the degradation of EGFR mRNA in HCC cells. This is the first report showing that YTHDF2 may act as a tumor suppressor to repress cell proliferation and growth via destabilizing the EGFR mRNA in HCC.

We examine the embedding approach to reason new relational facts from a largescale knowledge graph and a text corpus. We propose a novel method of jointly embedding entities and words into the same continuous vector space. The embedding process attempts to preserve the relations between entities in the knowledge graph and the concurrences of words in the text corpus. Entity names and Wikipedia anchors are utilized to align the embeddings of entities and words in the same space. Large scale experiments on Freebase and a Wikipedia/NY Times corpus show that jointly embedding brings promising improvement in the accuracy of predicting facts, compared to separately embedding knowledge graphs and text. Particularly, jointly embedding enables the prediction of facts containing entities out of the knowledge graph, which cannot be handled by previous embedding methods. At the same time, concerning the quality of the word embeddings, experiments on the analogical reasoning task show that jointly embedding is comparable to or slightly better than word2vec (Skip-Gram).

// Wenfeng Fang 1,2,* , Jianwei Zhang 3,* , Shaodong Hong 1,2,* , Jianhua Zhan 1,2,* , Nan Chen 4 , Tao Qin 1,2 , Yanna Tang 4 , Yaxiong Zhang 1,2 , Shiyang Kang 1,2 , Ting Zhou 1,2 , Xuan Wu 1,2 , Wenhua Liang 1,2 , Zhihuang Hu 1,2 , Yuxiang Ma 1,2 , Yuanyuan Zhao 1,2 , Ying Tian 1,2 , Yunpeng Yang 1,2 , Cong Xue 1,2 , Yue Yan 1,2 , Xue Hou 1,2 , Peiyu Huang 1,2 , Yan Huang 1,2 , Hongyun Zhao 1,2 and Li Zhang 1,2 1 State Key laboratory of Oncology in South China, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China 2 Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China 3 Department of Oncology, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China 4 Department of Oncology, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China * These authors contributed equally to this work Correspondence: Li Zhang, email: // Keywords : Nasopharyngeal carcinoma (NPC); latent membrane protein 1 (LMP1); PD-L1; Epstein&ndash;Barr virus (EBV) Received : July 20, 2014 Accepted : October 21, 2014 Published : October 21, 2014 Abstract PD-L1 expression is a feature of Epstein-Barr virus (EBV) associated malignancies such as nasopharyngeal carcinoma (NPC). Here, we found that EBV-induced latent membrane protein 1 (LMP1) and IFN-&gamma; pathways cooperate to regulate programmed cell death protein 1 ligand (PD-L1). Expression of PD-L1 was higher in EBV positive NPC cell lines compared with EBV negative cell lines. PD-L1 expression could be increased by exogenous and endogenous induction of LMP1 induced PD-L1. In agreement, expression of PD-L1 was suppressed by knocking down LMP1 in EBV positive cell lines. We further demonstrated that LMP1 up-regulated PD-L1 through STAT3, AP-1, and NF-&kappa;B pathways. Besides, IFN-&gamma; was independent of but synergetic with LMP1 in up-regulating PD-L1 in &nbsp;NPC. Furthermore, we showed that PD-L1 was associated with worse disease-free survival in NPC patients. These results imply that blocking both the LMP1 oncogenic pathway and PD-1/PD-L1 checkpoints may be a promising therapeutic approach for EBV positive NPC patients.

BACKGROUND: A cluster of pneumonia cases were reported by Wuhan Municipal Health Commission, China in December 2019. A novel coronavirus was eventually identified, and became the COVID-19 epidemic that affected public health and life. We investigated the psychological status and behavior changes of the general public in China from January 30 to February 3, 2020. METHODS: Respondents were recruited via social media (WeChat) and completed an online questionnaire. We used the State-Trait Anxiety Inventory, Self-rating Depression Scale, and Symptom Checklist-90 to evaluate psychological status. We also investigated respondents' behavior changes. Quantitative data were analyzed by t-tests or analysis of variance, and classified data were analyzed with chi-square tests. RESULTS: In total, 608 valid questionnaires were obtained. More respondents had state anxiety than trait anxiety (15.8% vs 4.0%). Depression was found among 27.1% of respondents and 7.7% had psychological abnormalities. About 10.1% of respondents suffered from phobia. Our analysis of the relationship between subgroup characteristics and psychological status showed that age, gender, knowledge about COVID-19, degree of worry about epidemiological infection, and confidence about overcoming the outbreak significantly influenced psychological status. Around 93.3% of respondents avoided going to public places and almost all respondents reduced Spring Festival-related activities. At least 70.9% of respondents chose to take three or more preventive measures to avoid infection. The three most commonly used prevention measures were making fewer trips outside and avoiding contact (98.0%), wearing a mask (83.7%), and hand hygiene (82.4%). CONCLUSIONS: We need to pay more attention to public psychological stress, especially among young people, as they are likely to experience anxiety, depression, and psychological abnormalities. Different psychological interventions could be formulated according to the psychological characteristics of different gender and age groups. The majority of respondents followed specific behaviors required by the authorities, but it will take time to observe the effects of these behaviors on the epidemic.