Application of network composite module analysis and verification to explore the bidirectional immunomodulatory effect of Zukamu granules on Th1 / Th2 cytokines in lung injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Zukamu granules (ZKMG), as the preferred drug for the treatment of colds in Uygur medical theory, has been used for 1500 years. It is also widely used in China and included in the National Essential Drugs List (2018 edition). It has unique anti-inflammatory, antitussive and analgesic effects. AIM OF THE STUDY: Aiming at the research of traditional Chinese medicine (TCM) with the characteristics of overall regulation of body diseases and the immune regulation mechanism with the concept of integrity, this paper put forward the integrated application of network composite module analysis and animal experiment verification to study the immune regulation mechanism of TCM. MATERIALS AND METHODS: The active components and targets of ZKMG were predicted, and network module analysis was performed to explore their potential immunomodulatory mechanisms. Then acute lung injury (ALI) mice and idiopathic pulmonary fibrosis (IPF) rats were used as pathological models to observe the effects of ZKMG on the pathological conditions of infected ALI and IPF rats, determine the contents of Th1, Th2 characteristic cytokines and immunoglobulins, and study the intervention of GATA3/STAT6 signal pathway. RESULTS: The results of network composite module analysis showed that ZKMG contained 173 pharmacodynamic components and 249 potential targets, and four key modules were obtained. The immunomodulatory effects of ZKMG were related to T cell receptor signaling pathway. The validation results of bioeffects that ZKMG could carry out bidirectional immune regulation on Th1/Th2 cytokines in the stage of ALI and IPF, so as to play the role of regulating immune homeostasis and organ protection. CONCLUSIONS: The network composite module analysis and verification method is an exploration to study the immune regulation mechanism of TCM by combining the network module prediction analysis with animal experiments, which provides a reference for subsequent research.

2D Zn‐Porphyrin‐Based Co(II)‐MOF with 2‐Methylimidazole Sitting Axially on the Paddle–Wheel Units: An Efficient Electrochemiluminescence Bioassay for SARS‐CoV‐2

High electrocatalytic activity with tunable luminescence is crucial for the development of electrochemiluminescence (ECL) luminophores. In this study, a porphyrin‐based heterobimetallic 2D metal organic framework (MOF), [(ZnTCPP)Co2(MeIm)] (1), is successfully self‐assembled from the zinc(II) tetrakis(4‐carboxyphenyl)porphine (ZnTCPP) linker and cobalt(II) ions in the presence of 2‐methylimidazole (MeIm) by a facile one‐pot reaction in methanol at room temperature. On the basis of the experimental results and the theoretical calculations, the MOF 1 contains paddle–wheel [Co2(‐CO2)4] secondary building units (SBUs) axially coordinated by a MeIm ligand, which is very beneficial to the electron transfer between the Co(II) ions and oxygen. Combining the photosensitizers ZnTCPP and the electroactive [Co2(‐CO2)4] SBUs, the 2D MOF 1 possesses an excellent ECL performance, and can be used as a novel ECL probe for rapid nonamplified detection of the RdRp gene of SARS‐CoV‐2 with an extremely low limit of detection (≈30 aM). A novel porphyrin‐based heterobimetallic 2D MOF, [(ZnTCPP)Co2(MeIm)] (1) is constructed to act as an excellent electrochemiluminescence probe for rapid nonamplified detection of SARS‐CoV‐2.

The perceived work environment and well-being: A survey of emergency health care workers during the COVID-19 pandemic.

BACKGROUND: During the COVID-19 pandemic, health care provider well-being was affected by various challenges in the work environment. The purpose of this study was to evaluate the relationship between the perceived work environment and mental well-being of a sample of emergency physicians (EPs), emergency medicine (EM) nurses, and emergency medical services (EMS) providers during the pandemic. METHODS: We surveyed attending EPs, resident EPs, EM nurses, and EMS providers from 10 academic sites across the United States. We used latent class analysis (LCA) to estimate the effect of the perceived work environment on screening positive for depression/anxiety and burnout controlling for respondent characteristics. We tested possible predictors in the multivariate regression models and included the predictors that were significant in the final model. RESULTS: Our final sample included 701 emergency health care workers. Almost 23% of respondents screened positive for depression/anxiety and 39.7% for burnout. Nurses were significantly more likely to screen positive for depression/anxiety (adjusted odds ratio [aOR] 2.04, 95% confidence interval [CI] 1.11-3.86) and burnout (aOR 2.05, 95% CI 1.22-3.49) compared to attendings. The LCA analysis identified four subgroups of our respondents that differed in their responses to the work environment questions. These groups were identified as Work Environment Risk Group 1, an overall good work environment; Risk Group 2, inadequate resources; Risk Group 3, lack of perceived organizational support; and Risk Group 4, an overall poor work environment. Participants in the two groups who perceived their work conditions as most adverse were significantly more likely to screen positive for depression/anxiety (aOR 1.89, 95% CI 1.05-3.42; and aOR 2.04, 95% CI 1.14-3.66) compared to participants working in environments perceived as less adverse. CONCLUSIONS: We found a strong association between a perceived adverse working environment and poor mental health, particularly when organizational support was deemed inadequate. Targeted strategies to promote better perceptions of the workplace are needed.

To Adopt CCU Technology or Not? An Evolutionary Game between Local Governments and Coal-Fired Power Plants

Carbon dioxide capture and utilization (CCU) technology is a significant means by which China can achieve its ambitious carbon neutrality goal. It is necessary to explore the behavioral strategies of relevant companies in adopting CCU technology. In this paper, an evolutionary game model is established in order to analyze the interaction process and evolution direction of local governments and coal-fired power plants. We develop a replicator dynamic system and analyze the stability of the system under different conditions. Based on numerical simulation, we analyze the impact of key parameters on the strategies of stakeholders. The simulation results show that the unit prices of hydrogen and carbon dioxide derivatives have the most significant impact: when the unit price of hydrogen decreases to 15.9 RMB/kg or the unit price of carbon dioxide derivatives increases to 3.4 RMB/kg, the evolutionary stabilization strategy of the system changes and power plants shift to adopt CCU technology. The results of this paper suggest that local governments should provide relevant support policies and incentives for CCU technology deployment, as well as focusing on the synergistic development of CCU technology and renewable energy hydrogen production technology.

Xuanfei Baidu Decoction reduces acute lung injury by regulating infiltration of neutrophils and macrophages via PD-1/IL17A pathway.

The pathogenic hyper-inflammatory response has been revealed as the major cause of the severity and death of the Corona Virus Disease 2019 (COVID-19). Xuanfei Baidu Decoction (XFBD) as one of the "three medicines and three prescriptions" for the clinically effective treatment of COVID-19 in China, shows unique advantages in the control of symptomatic transition from moderate to severe disease states. However, the roles of XFBD to against hyper-inflammatory response and its mechanism remain unclear. Here, we established acute lung injury (ALI) model induced by lipopolysaccharide (LPS), presenting a hyperinflammatory process to explore the pharmacodynamic effect and molecular mechanism of XFBD on ALI. The in vitro experiments demonstrated that XFBD inhibited the secretion of IL-6 and TNF-α and iNOS activity in LPS-stimulated RAW264.7 macrophages. In vivo, we confirmed that XFBD improved pulmonary injury via down-regulating the expression of proinflammatory cytokines such as IL-6, TNF-α and IL1-ß as well as macrophages and neutrophils infiltration in LPS-induced ALI mice. Mechanically, we revealed that XFBD treated LPS-induced acute lung injury through PD-1/IL17A pathway which regulates the infiltration of neutrophils and macrophages. Additionally, one major compound from XFBD, i.e. glycyrrhizic acid, shows a high binding affinity with IL17A. In conclusion, we demonstrated the therapeutic effects of XFBD, which provides the immune foundations of XFBD and fatherly support its clinical applications.

Prevalence of mental health problems among children and adolescents during the COVID-19 pandemic: A systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis examined the prevalence of depression, anxiety, sleep disorders, and posttraumatic stress symptoms among children and adolescents during global COVID-19 pandemic in 2019 to 2020, and the potential modifying effects of age and gender. METHODS: A literature search was conducted in PubMed, Web of Science, PsycINFO, and two Chinese academic databases (China National Knowledge Infrastructure and Wanfang) for studies published from December 2019 to September 2020 that reported the prevalence of above mental health problems among children and adolescents. Random-effects meta-analyses were used to estimate the pooled prevalence. RESULTS: Twenty-three studies (21 cross-sectional studies and 2 longitudinal studies) from two countries (i.e., China and Turkey) with 57,927 children and adolescents were identified. Depression, anxiety, sleep disorders, and posttraumatic stress symptoms were assessed in 12, 13, 2, and 2 studies, respectively. Meta-analysis of results from these studies showed that the pooled prevalence of depression, anxiety, sleep disorders, and posttraumatic stress symptoms were 29% (95%CI: 17%, 40%), 26% (95%CI: 16%, 35%), 44% (95%CI: 21%, 68%), and 48% (95%CI: -0.25, 1.21), respectively. The subgroup meta-analysis revealed that adolescents and females exhibited higher prevalence of depression and anxiety compared to children and males, respectively. LIMITATIONS: All studies in meta-analysis were from China limited the generalizability of our findings. CONCLUSIONS: Early evidence highlights the high prevalence of mental health problems among children and adolescents during the COVID-19 pandemic, especially among female and adolescents. Studies investigating the mental health of children and adolescents from countries other than China are urgently needed.

Improving Stem Cell Clinical Trial Design and Conduct: Development of a Quality Assessment Tool for Stem Cell Clinical Trials.

BACKGROUND: Clinical trials are at the cornerstone of evidence-based stem cell therapies, but the quality assessment for designing and conduct these sometimes-complex studies are scarce of evidence. This study is aimed at developing a handy quality assessment tool for stem cell clinical trials, enhancing capacity of the self-regulate overall quality, and participating protection. METHODS: The framework of quality assessment tool was based on the PQRS (progress-quality-regulation-scientific) quality assessment tool, and detailed quality indicators were developed by leader group discussion, expert consulting, and literature review. Stem cell clinical trials were retrieved from the International Clinical Trials Registry Platform, and corresponding quality indicators were assessed and extracted. The validity and feasibility of conceptual quality assessment tool were further evaluated by using structural equation modeling. RESULTS: The quality assessment tool for stem cell clinical trials contains four critical quality attributes, including participant protection, scientific value, quality control, and stem cell products, and 9 observed quality indicators. From 11 primary clinical trial registries in the International Clinical Trials Registry Platform, 9410 stem cell trial registrations were identified, and 1036 studies were eligible for publications and protocols screening. After reviewed full text, 37 studies were included in the validity and feasibility evaluation: 32 studies were completed, and 3 studies terminated early. Most of the studies (83.79%) were in the early phase, and 63.16% of the studies were investigator-initiated trial. To further tested for validity, the critical quality attributes and quality indicators (QIs) between expertise further validated by the SEM method, which showed a good fit for the model (chi - square = 26.008; P = 0.353; TLI = 0.967; CFI = 0.978; RMSEA = 0.048). Compared with exploratory trials, evaluating using the quality assessment tool, confirmatory trials performed similarly in participant protection, scientific value, and quality control, but lower in stem cell products. CONCLUSIONS: The results of critical quality attributes and quality indicators between expertise and confirmatory validation analysis are basically consistent, indicating the feasibility and validity of applying this quality assessment tool for overall quality evaluation of stem cell trials.