Small molecule inhibitor CRT0066101 inhibits cytokine storm syndrome in a mouse model of lung injury.

Pneumonia is an acute inflammation of the lungs induced by pathogenic microorganisms, immune damage, physical and chemical factors, and other factors, and the latest outbreak of novel coronavirus pneumonia is also an acute lung injury (ALI) induced by viral infection. However, there are currently no effective treatments for inflammatory cytokine storms in patients with ALI/acute respiratory distress syndrome (ARDS). Protein kinase D (PKD) is a highly active kinase that has been shown to be associated with the production of inflammatory cytokines. Therefore, small-molecule compounds that inhibit PKD may be potential drugs for the treatment of ALI/ARDS. In the present study, we evaluated the ability of the small-molecule inhibitor CRT0066101 to attenuate lipopolysaccharide (LPS)-induced inflammatory cytokine production through in vitro cell experiments and a mouse pneumonia model. We found that CRT0066101 significantly reduced the protein and mRNA levels of LPS-induced cytokines (e.g., IL-6, TNF-α, and IL-1ß). CRT0066101 inhibited MyD88 and TLR4 expression and reduced NF-κB, ERK, and JNK phosphorylation. CRT0066101 also reduced NLRP3 activation, inhibited the assembly of the inflammasome complex, and attenuated inflammatory cell infiltration and lung tissue damage. Taken together, our data indicate that CRT0066101 exerts anti-inflammatory effects on LPS-induced inflammation through the TLR4/MyD88 signaling pathway, suggesting that CRT0066101 may have therapeutic value in acute lung injury and other MyD88-dependent inflammatory diseases.

Analysis of Influencing Factors of Psychological Intervention on International Students in China after COVID-19: Hainan Province, China.

Objectives: In the post-covid-19 era, students face numerous mental health-related effects. Returning to Chinese institutions, international students in China experienced mental health issues (anxiety and stress). These overseas students' psychological issues are obstacles to their academic performance in China. Students' fear restructured their ability to think critically and execute effectively. Consequently, the framework of this study is intended to emphasize the beneficial effects of offline activities, physical activity, and classroom activities on reducing anxiety among international students in China. Methods: This study is predicated on survey data acquired using a five-point Likert scale. 317 responses were received from overseas students enrolled in Hainan universities. Results: The findings show that offline, physical, and classroom activities substantially impact the anxiety reduction of overseas students in China. The study's contribution to the literature is a fresh concept that previous research has not addressed. In addition, this research has significant theoretical and practical consequences for both knowledge and findings. Conclusion: The study has given a paradigm for relieving anxiety among overseas students in China by addressing a research gap. Meanwhile, this study's limitations provide a roadmap for researching further areas of literature in the future.

Cultivating public health youth talents with illustrious virtue and lofty aspirations to undertake glorious tasks of a new era:Minutes of the Sixteenth National Postgra duates Symposium on Environmental and Occupational Medicine

From October 22 to 23, 2021, the 16th National Postgraduates Symposium on Environmental and Occupational Medicine was successfully held in Central South University,sponsored by the Editorial Board of Journal of Environmental and Occupational Medicine and Xiangya School of Public Health of Central South University, and co-organized by School of Public Health of South China University and Shanghai Preventive Medicine Association. Keeping in view the outbreak of COVID-19, the symposium was held in the form of "offline+online". More than 100 teachers and students from more than 30 universities and research institutions across China attended the conference. A total of 114 excellent papers were submitted to this conference.Focusing on the theme of "Research and practice: Healing the schism", young scholars' forum as well as postgraduates' academic exchanges at the main venue and four parallel sessions were launched. This conference not only provided an excellent platform for postgraduate students in the field of environmental and occupational medicine nationwide to share academic trends and exchange academic research, but also expanded the influence of the Journal of Environmental and Occupational Medicine.

Malnutrition predicts poor outcomes in diabetic COVID-19 patients in Huangshi, Hubei.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread throughout the world, which becomes a global public health emergency. Undernourishment prolongs its convalescence and has an adverse effect on its prognosis, especially in diabetic patients. The purpose of this study was to evaluate the prevalence and characteristics of undernourishment and to determine how it is related to the prognostic outcomes in the diabetic patients with coronavirus disease 2019 (COVID-19). A retrospective, multicenter study was conducted in 85 diabetic COVID-19 patients from three hospitals in Hubei Province. All patients were assessed using the European Nutritional Risk Screening 2002 (NRS-2002) and other nutritional assessments when admitted. Of them, 35 (41.18%) were at risk of malnutrition (NRS score ≥3). Severe COVID-19 patients had a significantly lower level of serum albumin and prealbumin and higher NRS score than non-severe patients. Multivariate logistic regression analysis showed that serum prealbumin and NRS score increased the likelihood of progression into severe status ( P<0.05). Meanwhile, single factor and multivariate analysis determined that grade of illness severity was an independent predictor for malnutrition. Furthermore, prealbumin and NRS score could well predict severe status for COVID-19 patients. The malnutrition group (NRS score ≥3) had more severe illness than the normal nutritional (NRS score <3) group ( P<0.001), and had a longer length of in-hospital stay and higher mortality. Malnutrition is highly prevalent among COVID-19 patients with diabetes. It is associated with severely ill status and poor prognosis. Evaluation of nutritional status should be strengthened, especially the indicators of NRS-2002 and the level of serum prealbumin.

Guidelines on the treatment with integrated traditional Chinese medicine and western medicine for severe coronavirus disease 2019.

Severe Coronavirus Disease 2019 (COVID-19) is characterized by numerous complications, complex disease, and high mortality, making its treatment a top priority in the treatment of COVID-19. Integrated traditional Chinese medicine (TCM) and western medicine played an important role in the prevention, treatment, and rehabilitation of COVID-19 during the epidemic. However, currently there are no evidence-based guidelines for the integrated treatment of severe COVID-19 with TCM and western medicine. Therefore, it is important to develop an evidence-based guideline on the treatment of severe COVID-19 with integrated TCM and western medicine, in order to provide clinical guidance and decision basis for healthcare professionals, public health personnel, and scientific researchers involved in the diagnosis, treatment, and care of COVID-19 patients. We developed and completed the guideline by referring to the standardization process of the "WHO handbook for guideline development", the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, and the Reporting Items for Practice Guidelines in Healthcare (RIGHT).

Cinobufacini Improves the Respiratory Function of Severe COVID-19 Patients

Targeted therapeutics for SARS-CoV-2 virus caused COVID-19 are in urgent need. Cinobufacini has been reported to have broad-spectrum antiviral effects and widely used in Southeast Asian countries. This study aims to assess the efficacy of Cinobufacini injection in treating patients with severe COVID-19. A randomized preliminary clinical trial was conducted and eligible patients were allocated to receive general treatment plus Cinobufacini injection or only general treatment as control for 7 days. The primary outcomes of the oxygenation index PaO2/FiO2 and ROX, secondary outcomes of white blood cell count, respiratory support step-down time (RSST), safety indicators, etc were monitored. After 7 days of treatment, the oxygenation index was improved in 95.2% patients in the treatment group compared with 68.4% in the control group. The PaO2/FiO2 and ROX indices in the treatment group (mean, 226.27±67.35 and 14.01±3.99 respectively) were significantly higher than the control group (mean, 143.23±51.29 and 9.64±5.54 respectively). The RSST was 1 day shorter in the treatment group. Multivariate regression analysis suggested that Cinobufacini injection contributed the most to the outcome of PaO2/FiO2. No obvious adverse effects were observed. The preliminary data showed that Cinobufacini injection had apparent efficacy in improving the respiratory function of patients with severe COVID-19.

Rational optimization of a human neutralizing antibody of SARS-CoV-2.

SARS-CoV-2 has caused a worldwide epidemic of coronavirus disease 19 (COVID-19). Antibody drugs present an effective weapon for tens of millions of COVID-19 patients. Antibodies disrupting the interactions between the receptor-binding domain (RBD) of SARS-CoV-2 S protein and the angiotensin converting enzyme 2 (ACE2) effectively block SARS-CoV-2 cell entry into host cells. In order to rapidly develop more potent neutralizing antibodies, we utilized virtual scanning mutageneses and molecular dynamics simulations to optimize the antibody of P2B-2F6 isolated from single B cells of SARS-CoV-2 infected patients. Two potent P2B-2F6 mutants, namely H:V106R and H:V106R/H:P107Y, were found to possess higher binding affinities with the RBD domain of SARS-CoV-2 than others. Polar interactions are preferred near 106 and 107 paratope residues of the heavy chain. The mutations also increase the hydrogen-bonding network formed between the antibody and the RBD. Notably, the optimized antibodies possess potential neutralizing activity against the alarming SARS-CoV-2 variant of N501Y. This study provides insights into structure-based optimization of antibodies with higher affinity to the antigen. We hope that our proposed antibody mutants could contribute to the development of improved therapies against COVID-19.

Prevalence and Influencing Factors on Fatigue of First-line Nurses Combating with COVID-19 in China: A Descriptive Cross-Sectional Study.

Nurses' work-related fatigue has been recognized as a threat to nurse health and patient safety. The aim of this study was to assess the prevalence of fatigue among first-line nurses combating with COVID-19 in Wuhan, China, and to analyze its influencing factors on fatigue. A multi-center, descriptive, cross-sectional design with a convenience sample was used. The statistical population consisted of the first-line nurses in 7 tertiary general hospitals from March 3, 2020 to March 10, 2020 in Wuhan of China. A total of 2667 samples from 2768 contacted participants completed the investgation, with a response rate of 96.35%. Social-demographic questionnaire, work-related questionnaire, Fatigue Scale-14, Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, and Chinese Perceived Stress Scale were used to conduct online survey. The descriptive statistic of nurses' social-demographic characteristics was conducted, and the related variables of work, anxiety, depression, perceived stress and fatigue were analyzed by t-tests, nonparametric test and Pearson's correlation analysis. The significant factors which resulted in nurses' fatigue were further analyzed by multiple linear regression analysis. The median score for the first-line nurses' fatigue in Wuhan was 4 (2, 8). The median score of physical and mental fatigue of them was 3 (1, 6) and 1 (0, 3) respectively. According to the scoring criteria, 35.06% nurses (n=935) of all participants were in the fatigue status, their median score of fatigue was 10 (8, 11), and the median score of physical and mental fatigue of them was 7 (5, 8) and 3 (2, 4) respectively. Multiple linear regression analysis revealed the participants in the risk groups of anxiety, depression and perceived stress had higher scores on physical and mental fatigue and the statistically significant positive correlation was observed between the variables and nurses' fatigue, the frequency of exercise and nurses' fatigue had a statistically significant negative correlation, and average daily working hours had a significantly positive correlation with nurses' fatigue, and the frequency of weekly night shift had a low positive correlation with nurses' fatigue (P<0.01). There was a moderate level of fatigue among the first-line nurses fighting against COVID-19 pandemic in Wuhan, China. Government and health authorities need to formulate and take effective intervention strategies according to the relevant risk factors, and undertake preventive measures aimed at reducing health hazards due to increased work-related fatigue among first-line nurses, and to enhance their health status and provide a safe occupational environment worldwide. Promoting both medical and nursing safety while combating with the pandemic currently is warranted.

Potential risks of SARS-CoV-2 infection on reproductive health.

The outbreak of 2019 novel coronavirus disease (COVID-19) has become a major pandemic threat worldwide. Such a public health emergency can greatly impact various aspects of people's health and lives. This paper focuses on its potential risks for reproductive health, including the reproductive system and its functioning, as well as gamete and embryo development, which could be affected by the virus itself, drug treatments, chemical disinfectants and psychological effects related to panic during the COVID-19 outbreak.