Hematologic health services and practical characteristics: report of a nationwide survey among Chinese hematologists (preprint)

Background: In the past 40 years, China has experienced tremendous economic development, but the current situation of hematologists has rarely been reported. A landscape survey of human resources is essential for healthcare development and policy formulation in the future. Methods: The Chinese Society of Hematology initiated a survey of Chinese hematologists in mainland China for evaluating demographic and practice characteristics. Respondents were anonymous, and there were no limitations regarding their age, sex, etc. Results: Totally 2032 hematologists responded, with a median age bracket of 36-45 years. Respondents were well engaged into subspecialties, and 28.1% acquired doctorates of philosophy. Hematopoietic cell transplantation (HCT) centers have been established all over China. Higher-GDP regions reported more advantages, including bigger scale of transplant centers (P < 0.001), younger age structure (P = 0.039), better education qualifications (P = 0.001) and less turnover intentions (P = 0.004), despite of increased risk of medical disputes (P = 0.028). Although females accounted for 65.5% of hematologists, males were older (P < 0.001), and had more senior professional titles (P < 0.001), academic positions (P < 0.001), opportunities for continuing education (P < 0.001), and paper publishing in the recent two years (P = 0.001). For turnover intention, the higher GDP regions led to an independently reduced risk (HR = 0.673, 95%CI [0.482-0.940], P = 0.020), whereas medical disputes resulted in an increased the risk (HR = 2.037, 95%CI [1.513-2.743], P < 0.001). Considering the impact of the COVID-19 pandemic, majority of respondents believed that the decline in patient visits and delay in treatment was within 30%. 67.9% of respondents reported a decrease of the use of bone marrow as grafts but 18.8% reported an increase of cord blood units. 35.0% of the respondents switched their daily work to support the anti-epidemic medical activities. Conclusions: We concluded the discipline of hematology in China has flourished in recent years with a young workforce, while regional economic and gender disparities warrant further continuous optimization. Joint efforts against the impact of COVID-19 are needed in the post-pandemic era.

Anxiety, depression, psychological stress and coping style in medical postgraduates in southeastern China when restricted to commuting between the campus and hospital during the COVID-19 pandemic

Background As the COVID-19 epidemic was gradually brought under control, a new autumn semester began in 2020. How was the mental health of postgraduates as they experienced quarantine at home, only commuting between the school and hospital? Methods The research was conducted in a cross-sectional online survey in October 2020. The data were collected from 1,645 medical postgraduates (master's and doctoral students) by using the demographic information questionnaire, the Self-rating Depression Scale (SDS), the Self-rating Anxiety Scale (SAS), the Questionnaire on Psychological Stressors of Postgraduates (QPSP), the Simplified Coping Style Questionnaire (SCSQ) and the Social Support Rate Scale (SSRS). One-way ANOVA and Pearson correlation were used to explore the relationships among anxiety, depression, psychological stressors, social support and coping style. Structural equation modeling (SEM) was conducted to assess the mediation model. Results Among the total of 1,645 medical postgraduates, 21.6% (n = 356) had self-rated depression symptoms, and 9.4% (n = 155) had self-rated anxiety symptoms. The main disturbances they experienced were employment, academic and interpersonal pressure. The master of third grade students had the highest employment pressure, and the master of second grade students had the highest academic and interpersonal pressure. Negative coping played a negative mediating role and social support played a positive mediating role in the relationships between perceived stress and anxiety (β = 0.027, P < 0.01;β = 0.124, P < 0.01) and depression (β = 0.016, P < 0.01;β = 0.193, P < 0.01). Conclusion Medical postgraduates in China restricted to studies on campus and in the hospital experienced psychological distress. Our results suggest that providing employment and learning guidance, while strengthening social support and guiding positive coping may be effective at improving the mental health of the medical graduate students, mediating their perceived stress and negative emotions.

Synergistic relationship or not? Understanding the resilience and efficiency of the tourism economy: evidence from Hainan Province, China.

The COVID-19 pandemic has dealt a serious blow to the global tourism industry, causing a fracturing of and decline in tourism development efficiency and even a stagnation of tourism development in some regions. To solve the contradiction between efficiency and quality, it is necessary to ensure the endogenous power of tourism resilience while pursuing the efficiency of tourism development. This study assumes that Hainan Province follows a tourism development path led by resilience. The improved weighting method, EBM model and Haken model are used to evaluate the level of resilience, the level of efficiency and their co-evolution. The findings indicate that the core tourism cities represented by Sanya and Haikou have a high level in the individual fields of tourism development efficiency and tourism economic resilience but have limited performance in the synergistic relationship between tourism development efficiency and tourism economic resilience. In contrast, the marginal tourism cities represented by Tunchang County and Ledong County have low tourism development efficiency and resilience, but their synergistic development level is high. This result proves that co-evolution plays a dual forward and reverse driving role. Based on the identification of the order parameters, it is concluded that Hainan Province is characterized by a synergistic evolutionary synergy dominated by resilience, which is in line with the trend of social development and the sustainable development of tourism. While reasonably pursuing the tourism economy and development efficiency, we should pay attention to strengthening resilience construction based on multiple aspects, such as tourists, enterprises, organizations, governments and destinations.

Improving the Deeplabv3+ Model with Attention Mechanisms Applied to Eye Detection and Segmentation

Research on eye detection and segmentation is even more important with mask-wearing measures implemented during the COVID-19 pandemic. Thus, it is necessary to build an eye image detection and segmentation dataset (EIMDSD), including labels for detecting and segmenting. In this study, we established a dataset to reduce elaboration for chipping eye images and denoting labels. An improved DeepLabv3+ network architecture (IDLN) was also proposed for applying it to the benchmark segmentation datasets. The IDLN was modified by cascading convolutional block attention modules (CBAM) with MobileNetV2. Experiments were carried out to verify the effectiveness of the EIMDSD dataset in human eye image detection and segmentation with different deep learning models. The result shows that the IDLN model achieves the appropriate segmentation accuracy for both eye images, while the UNet and ISANet models show the best results for the left eye data and the right eye data among the tested models.

2019冠状病毒病(COVID-19)诊疗浙江经验 Management of COVID-19: the Zhejiang experience

当前2019冠状病毒病（COVID-19）疫情仍处于胶着状态。浙江大学医学院附属第一医院是国家感染性疾病临床医学中心，浙江省COVID-19患者救治中心。疫情一线的专家集智攻关，以国家卫生健康委员会和国家中医药管理局发布的COVID-19诊治指南为依据，以抗病毒、抗休克、抗低氧血症、抗继发感染、维持水电解质和酸碱平衡、维持微生态平衡的“四抗二平衡”救治策略为核心，总结完善诊治方案，聚焦临床实践的一些具体问题，为COVID-19患者临床诊治提供借鉴。推荐以多学科协作诊治个性化治疗提高COVID-19患者救治质量。建议病原学检测、炎症指标监测和肺部影像学动态观察指导临床诊治。痰液的病毒核酸检测阳性率最高，约10%的急性期患者血液中检测到病毒核酸，50%的患者粪便中检测到病毒核酸，粪便中可分离出活病毒，须警惕粪便是否具有传染性；开展细胞因子等炎症指标监测有助于发现是否出现细胞因子风暴，判断是否需要人工肝血液净化治疗。通过以“四抗二平衡”为核心的综合治疗提高治愈率、降低病死率；早期抗病毒治疗能减少重症、危重症发生，前期使用阿比多尔联合洛匹那韦/利托那韦抗病毒显示出一定效果。休克和低氧血症多为细胞因子风暴所致，人工肝血液净化治疗能迅速清除炎症介质，阻断细胞因子风暴，对维持水电解质酸碱平衡也有很好的作用，可以提高危重型患者的疗效。重型病例疾病早期可适量、短程应用糖皮质激素。氧疗过程中，患者氧合指数小于200 mmHg时应及时转入重症医学科治疗；采用保守氧疗策略，不推荐常规进行无创通气；机械通气患者应严格执行集束化呼吸机相关性肺炎预防管理策略；氧合指数大于150 mmHg时，及早减、停镇静剂并撤机拔管。不推荐预防性使用抗菌药物，对于病程长，体温反复升高和血降钙素原水平升高的患者可酌情使用抗菌药物；要关注COVID-19患者继发真菌感染的诊治。COVID-19患者有肠道微生态紊乱，肠道乳酸杆菌、双歧杆菌等有益菌减少，推荐对所有患者进行营养和胃肠道功能评估，以营养支持和补充大剂量肠道微生态调节剂，纠正肠道微生态失衡，减少细菌移位和继发感染。COVID-19患者普遍存在焦虑和恐惧心理，应建立动态心理危机干预和处理。提倡中西医结合辨证施治；优化重型患者护理促进康复。严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染后病毒清除规律仍不明了，出院后仍须居家隔离2周，并定期随访。以上经验和建议在本中心实行，取得较好效果，但COVID-19是一种新的疾病，其诊治方案及策略仍有待进一步探索与完善。

Bearing Fault Reconstruction Diagnosis Method Based on ResNet-152 with Multi-Scale Stacked Receptive Field.

The axle box in the bogie system of subway trains is a key component connecting primary damper and the axle. In order to extract deep features and large-scale fault features for rapid diagnosis, a novel fault reconstruction characteristics classification method based on deep residual network with a multi-scale stacked receptive field for rolling bearings of a subway train axle box is proposed. Firstly, multi-layer stacked convolutional kernels and methods to insert them into ultra-deep residual networks are developed. Then, the original vibration signals of four fault characteristics acquired are reconstructed with a Gramian angular summation field and trainable large-scale 2D time-series images are obtained. In the end, the experimental results show that ResNet-152-MSRF has a low complexity of network structure, less trainable parameters than general convolutional neural networks, and no significant increase in network parameters and calculation time after embedding multi-layer stacked convolutional kernels. Moreover, there is a significant improvement in accuracy compared to lower depths, and a slight improvement in accuracy compared to networks than unembedded multi-layer stacked convolutional kernels.

Structure and computation-guided design of a mutation-integrated trimeric RBD candidate vaccine with broad neutralization against SARS-CoV-2 (preprint)

The spike (S) protein receptor-binding domain (RBD) of SARS-CoV-2 is an attractive target for COVID-19 vaccine developments, which naturally exists in a trimeric form. Here, guided by structural and computational analyses, we present a mutation-integrated trimeric form of RBD (mutI tri-RBD) as a broadly protective vaccine candidate, in which three RBDs were individually grafted from three different circulating SARS-CoV-2 strains including the prototype, Beta (B.1.351) and Kappa (B.1.617). The three RBDs were then connected end-to-end and co-assembled to possibly mimic the native trimeric arrangements in the natural S protein trimer. The recombinant expression of the mutI tri-RBD, as well as the homo-tri-RBD where the three RBDs were all truncated from the prototype strain, by mammalian cell exhibited correct folding, strong bio-activities, and high stability. The immunization of both the mutI tri-RBD and homo-tri-RBD plus aluminum adjuvant induced high levels of specific IgG and neutralizing antibodies against the SARS-CoV-2 prototype strain in mice. Notably, regarding to the immune-escape Beta (B.1.351) variant, mutI tri-RBD elicited significantly higher neutralizing antibody titers than homo-tri-RBD. Furthermore, due to harboring the immune-resistant mutations as well as the evolutionarily convergent hotspots, the designed mutI tri-RBD also induced strong broadly neutralizing activities against various SARS-CoV-2 variants, especially the variants partially resistant to homo-tri-RBD. Homo-tri-RBD has been approved by the China National Medical Products Administration to enter clinical trial (No. NCT04869592), and the superior broad neutralization performances against SARS-CoV-2 support the mutI tri-RBD as a more promising vaccine candidate for further clinical developments.

Dynamics of SARS-CoV-2 and host immunity in infection and vaccine protection (preprint)

Once challenged by the SARS-CoV-2 virus, the human host immune system triggers a dynamic process against infection. We constructed a simplistic mathematical model to describe host innate and adaptive immune response to viral challenge. Based on the dynamic properties of viral load and immune response, we classified the resulting dynamics into four modes, corresponding to the increasing severity of COVID-19 disease. We found immune efficacy against viral attack, clearance of infected cells, and IL-6 levels to be prognostic determinants, especially for severe and critical patients. We also investigated vaccine-induced protection against SARS-CoV-2 infection. Results strongly suggested that immune efficacy based on memory T cells, as well as neutralizing antibody titers, could be true indicators of vaccine protection rates. Finally, we analyzed infection dynamics of SARS-CoV-2 variants within the construct of our mathematical model. Overall, our results provide a systematic framework for understanding the dynamics of host response upon challenge by SARS-CoV-2 infection, and this framework can be used to predict vaccine protection and perform clinical diagnosis.

Immunological profiling of COVID-19 patients with pulmonary sequelae (preprint)

Cellular immunity may be involved in organ damage and rehabilitation in patients with coronavirus disease 2019 (COVID-19). We aimed to delineate immunological features of COVID-19 patients with pulmonary sequelae (PS) one year after discharge. 50 COVID-19 survivors were recruited and classified according to radiological characteristics: 24 patients with PS and 26 patients without PS. Phenotypic and functional characteristics of immune cells were evaluated by multiparametric flow cytometry. Patients with PS had an increased proportion of natural killer (NK) cells and lower percentage of B cells compared to patients without PS. Phenotypic and functional features of T cells in patients with PS were predominated by the accumulation of CD4+ T cells secreting IL-17A, short-lived effector-like CD8+ T cells (CD27-CD62L-) and senescent T cells with excessive secretion of granzyme-B/perforin/IFN-{gamma}. NK cells were characterized by the excessive secretion of granzyme-B and perforin and the downregulation of NKP30 and NKP46; highly activated NKT and {gamma}{delta} T cells exhibited NKP30 and TIM-3 upregulation and NKB1 downregulation in patients with PS. However, immunosuppressive cells were comparable between the two groups. The interrelation of immune cells in COVID-19 was intrinsically identified, whereby T cells secreting IL-2, IL-4 and IL-17A were enriched among CD28+ and CD57- cells and cells secreting perforin/granzyme-B/IFN-{gamma}/TNF- expressed markers of terminal differentiation. CD57+NK cells, CD4+perforin+ T cells and CD8+CD27+CD62L+ T cells were identified as the independent predictors for residual lesions. Overall, our findings unveil the profound imbalance of immune landscape that may correlate with organ damage and rehabilitation in COVID-19.

Application of SARS-CoV-2 antibody sample panel in quality evaluation of test cassettes for colloidal gold lateral flow assay

Objective: To establish a SARS-CoV-2 antibody sample panel and apply to the quality evaluation of test cassettes for colloidal gold lateral flow assay.

Psychological and occupational impact on healthcare workers and its associated factors during the COVID-19 outbreak in China.

PURPOSE: China was affected by an outbreak of coronavirus disease 2019 (COVID-19) in 2019-2020. Research data are needed to develop evidence-driven strategies to reduce the adverse psychological and occupational impacts on healthcare workers (HCWs). METHODS: From March 1, 2020, to March 8, 2020, 946 HCWs in China completed a survey consist of sociodemographic data, precautionary measures against COVID-19, and concerns about COVID-19. Self-administered questionnaire were collected to assess psychological and occupational adverse outcomes of HCWs. Multivariable logistic regression analysis was performed to identify factors associated with the outcomes. RESULTS: A total of 55.0%, 56.0% and 48.3% of the HCWs experienced burnout, psychological distress and posttraumatic stress, respectively. A total of seven factors were independently associated with burnout: good health status (OR 0.51, 95% CI 0.36-0.71), fear of contagion (OR 1.31, 95% CI 1.003-1.79), avoiding contact with children (OR 1.40, 95% CI 1.03-1.91), enough staff support at the workplace (OR 0.59, 95% CI 0.38-0.92), having to work overtime (OR 1.37, 95% CI 1.03-1.83), maladaptive coping (OR 3.28, 95% CI 2.42-4.45) and adaptive coping (OR 0.47, 95% CI 0.35-0.62). A total of 11 factors were independently associated with high psychological distress: having one child (OR 0.54, 95% CI 0.38-0.77), good health status (OR 0.57, 95% CI 0.39-0.83), alcohol abuse (OR 1.51, 95% CI 1.02-2.25), thinking the epidemic would continue for quite a long time (OR 1.59, 95% CI 1.08-2.34), wearing extra-work clothes (OR 1.51, 95% CI 1.06-2.15),effective protective equipment (OR 0.45, 95% CI 0.22-0.90), enough staff support at the workplace (OR 0.55, 95% CI 0.34-0.89), unable to take care of families (OR 1.99, 95% CI 1.42-2.78), economic losses (OR 1.62, 95% CI 1.14-2.31), maladaptive coping (OR 6.88, 95% CI 4.75-9.97),and adaptive coping (OR 0.29, 95% CI 0.21-0.41). These factors were independently associated with posttraumatic stress: living with the elderly (OR 1.46, 95% CI 1.04-2.05), alcohol abuse (OR 1.41, 95% CI 1.002-1.98), working at a 3A hospital(OR 0.66, 95% CI 0.49-0.88), acquaintances confirmed COVID-19 (OR 2.14, 95% CI 1.20-3.84), fear of contagion (OR 1.87, 95% CI 1.40-2.50), believing they would survive if infected (OR 0.63, 95% CI 0.46-0.86), self-disinfected after arriving home (OR 1.43, 95% CI 1.01-2.02), interpersonal isolation (OR 1.65, 95% CI 1.21-2.26), unable to take care of families (OR 1.41, 95% CI 1.05-1.88) and maladaptive coping (OR 3.09, 95% CI 2.32-4.11). CONCLUSION: The variance in adverse outcomes was explained by the effect of various factors, which will help policymakers better prepare for subsequent potential outbreaks of COVID-19.

Short Selling Bans and Limits to Regulatory Arbitrage in a Multi-Market Setting (preprint)

We evaluate the role of foreign short-sale restrictions in muting the full return-response following negative earnings surprises for stocks cross-listed in unbanned markets. We update the global timeline of short-sale restrictions until the COVID-19 crisis period. Instead of regulatory price arbitrage, we surprisingly observe cross-border reach of bans manifested in a delayed price response, accompanied by a reduction in short interest and failures to deliver. Nonetheless, large profit opportunities result in price arbitrage and full return-response. Analysis of earnings management practices and CEO compensation structure reinforces the role of the profit opportunity in moderating the effects of short-sale restrictions.

Model-based cellular kinetic analysis of SARS-CoV-2 infection: different immune response modes and treatment strategies (preprint)

Increasing number in global COVID-19 cases demands for mathematical model to analyze the interaction between the virus dynamics and the response of innate and adaptive immunity. Here, based on the assumption of a weak and delayed response of the innate and adaptive immunity in SARS-CoV-2 infection, we constructed a mathematical model to describe the dynamic processes of immune system. Integrating theoretical results with clinical COVID-19 patients data, we classified the COVID-19 development processes into three typical modes of immune responses, correlated with the clinical classification of mild & moderate, severe and critical patients. We found that the immune efficacy (the ability of host to clear virus and kill infected cells) and the lymphocyte supply (the abundance and pool of naive T and B cell) play important roles in the dynamic process and determine the clinical outcome, especially for the severe and critical patients. Furthermore, we put forward possible treatment strategies for the three typical modes of immune response. We hope our results can help to understand the dynamical mechanism of the immune response against SARS-CoV-2 infection, and to be useful for the treatment strategies and vaccine design.

Model-based cellular kinetic analysis of SARS-CoV-2 infection: different immune response modes and treatment strategies (preprint)

Increasing number in global COVID-19 cases demands for mathematical model to analyze the interaction between the virus dynamics and the response of innate and adaptive immunity. Here, based on the assumption of a weak and delayed response of the innate and adaptive immunity in SARS-CoV-2 infection, we constructed a mathematical model to describe the dynamic processes of immune system. Integrating theoretical results with clinical COVID-19 patients' data, we classified the COVID-19 development processes into three typical modes of immune responses, correlated with the clinical classification of mild & moderate, severe and critical patients. We found that the immune efficacy (the ability of host to clear virus and kill infected cells) and the lymphocyte supply (the abundance and pool of na\"ive T and B cell) play important roles in the dynamic process and determine the clinical outcome, especially for the severe and critical patients. Furthermore, we put forward possible treatment strategies for the three typical modes of immune response. We hope our results can help to understand the dynamical mechanism of the immune response against SARS-CoV-2 infection, and to be useful for the treatment strategies and vaccine design.

Incidence and Impact of Disseminated Intravascular Coagulation in COVID-19 (preprint)

Background: Coronavirus disease 2019 (COVID-19) is a novel infectious disease, with significant morbidity and mortality. This meta-analysis is to evaluate the prevalence of disseminated intravascular coagulation (DIC) in COVID-19 patients and to determine the association of DIC with the severity and prognosis of COVID-19.Methods: We searched the PubMed, EMBASE, and China National Knowledge Infrastructure (CNKI) database until August 12, 2020. The meta-analysis was performed using Stata 16.0 software.Results: 15 studies were included in our meta-analysis. The pooled analysis revealed that the incidence of COVID-19 patients developing DIC was 4% (95%: 2%-5%, P<0.001). In addition, DIC was more likely to occur in the death group (Log OR = 2.4, 95% CI: 1.58-3.21, P<0.001) with statistical significance.Conclusions: DIC is associated with the severity and poor prognosis of COVID-19 patients. Therefore, attention should be paid to coagulation dysfunction in COVID-19 patients. Monitoring of coagulation indicators may improve the prognosis of COVID-19 inpatients.