Effectiveness of Xiangsha Liujun pills on decreased digestive function in convalescent patients of coronavirus disease 2019: a randomized, double blind, placebo controlled clinical trial.

OBJECTIVE: To evaluate the effectiveness and safety of Xiangsha Liujun pills on the decreased digestive function in patients in the recovery phase of the Coronavirus disease 2019 (COVID-19). METHODS: A randomized, double blind, placebo controlled clinical trial was conducted. A total of 200 COVID-19 patients in the recovery phase were included in our study in Ezhou Hospital of Traditional Chinese Medicine. Totally 200 subjects were randomly divided into a treatment group (Xiangsha Liujun pills) and a control group (placebo), with 100 in each group. Subjects took Xiangsha Liujun pills or placebo orally three times a day for two weeks. Three visits were scheduled at week 0 (baseline), week 1 (the middle of the intervention) and week 2 (the end of the intervention) for each eligible patient. The total efficacy rates for improving the Traditional Chinese Medicine (TCM) symptoms (fatigue, poor appetite, abdominal distension and loose stools) and the disappearance rates of symptoms were observed and compared in the treatment and control groups. Adverse events were recorded during the study period. SAS 9.4 was used to analyze the data. RESULTS: A total of 200 patients were included in this study, among which 4 participants withdrew because the drugs did not work. Three patients were excluded for age. Before the treatment, there was no significant difference between the TCM symptoms scores of subjects. After 1 week of treatment, the full analysis set (FAS) showed that the efficacy rates for abdominal distension and loose stools in the treatment group were significantly higher than the control group ( 0.05). There were no significant differences in the efficacy rates for fatigue and poor appetite between the two groups (0.05). In addition, the disappearance rate of fatigue in the treatment group was significantly higher than the control group (0.05); there were no significant differences between the two groups after treatment in the rates of poor appetite, abdominal distension, and loose stools (>0.05). After 2 weeks of treatment, the efficacy rates for fatigue, poor appetite, abdominal distension, and loose stools in the treatment group were significantly higher than the control group (0.05). The disappearance rate of loose stools in the treatment group was significantly higher than the control group ( 0.05). However, there were no significant differences in the disappearance rates of fatigue, poor appetite, and abdominal distension between the two groups ( 0.05). No severe adverse events were reported by subjects during the study. CONCLUSIONS: This clinical study confirmed that Xiangsha Liujun pills can effectively improve the symptoms related to the decreased digestive function in COVID-19 convalescent patients.

ZBP1-Mediated Necroptosis: Mechanisms and Therapeutic Implications.

Cell death is a fundamental pathophysiological process in human disease. The discovery of necroptosis, a form of regulated necrosis that is induced by the activation of death receptors and formation of necrosome, represents a major breakthrough in the field of cell death in the past decade. Z-DNA-binding protein (ZBP1) is an interferon (IFN)-inducing protein, initially reported as a double-stranded DNA (dsDNA) sensor, which induces an innate inflammatory response. Recently, ZBP1 was identified as an important sensor of necroptosis during virus infection. It connects viral nucleic acid and receptor-interacting protein kinase 3 (RIPK3) via two domains and induces the formation of a necrosome. Recent studies have also reported that ZBP1 induces necroptosis in non-viral infections and mediates necrotic signal transduction by a unique mechanism. This review highlights the discovery of ZBP1 and its novel findings in necroptosis and provides an insight into its critical role in the crosstalk between different types of cell death, which may represent a new therapeutic option.

Markers of Fungal Translocation Are Elevated During Post-Acute Sequelae of SARS-CoV-2 Infection and Induce NF-κB Triggered Inflammation. (preprint)

Long COVID, a type of Post-Acute Sequelae of SARS CoV-2 infection (PASC), has been associated with sustained elevated levels of immune activation and inflammation. However, the pathophysiological mechanisms that drive this inflammation remain unknown. Inflammation during acute Coronavirus Disease 2019 (COVID-19) could be exacerbated by microbial translocation (from the gut and/or lung) to the blood. Whether microbial translocation contributes to inflammation during PASC is unknown. We found higher levels of fungal translocation - measured as beta-glucan, a fungal cell wall polysaccharide - in the plasma of individuals experiencing PASC compared to those without PASC or SARS-CoV-2 negative controls. The higher beta-glucan correlated with higher levels of markers of inflammation and elevated levels of host metabolites involved in activating N-Methyl-D-aspartate receptors (such as metabolites within the tryptophan catabolism pathway) with established neuro-toxic properties. Mechanistically, beta-glucan can directly induce inflammation by binding to myeloid cells (via the Dectin-1 receptor) and activating Syk/NF-kB signaling. Using an in vitro Dectin-1/NF-kB reporter model, we found that plasma from individuals experiencing PASC induced higher NF-kB signaling compared to plasma from SARS-CoV-2 negative controls. This higher NF-kB signaling was abrogated by the Syk inhibitor Piceatannol. These data suggest a potential targetable mechanism linking fungal translocation and inflammation during PASC.

Effects of medical insurance system on the hospitalization cost of acute myocardial infarction patients.

BACKGROUND: Acute myocardial infarction is still a burden on Chinese patients. Whether different medical insurance system have any influence on the hospitalization cost and therapeutic effect of acute myocardial infarction patient needs further investigation. METHOD: In this study, 600 patients were stratified by health insurance status to investigate the cost effectiveness. RESULT: Compared with free medical care, patients with other health insurance status have a significantly lower age (P Ë‚ 0.05-0.001), the youngest of which is new rural cooperative medical system. The hospital expense, nursing fee, length of stay, daily hospitalization cost, daily drug cost, daily nursing cost and percent of nursing cost of different health insurance status were statistically significant. ANCOVA analyses controlling for age showed that the differences of hospital expenses, nursing fee, length of stay and daily hospitalization cost were still statistically significant. Further studies found that health insurance status was the leading factors influencing length of stay (ß = - 0.305, P = 0.0000001), nursing costs (ß = - 0.319, P = 0.004), daily hospitalization costs (ß = 0.296, P = 0.0001) and occurrence of clinical events (ß = - 0.186, OR = 0.830, 95% CI 0.694-0.993, P = 0.041). CONCLUSIONS: The hospitalization cost, length of stay, nursing work and therapeutic effect of acute myocardial infarction patients are affected by different health insurance status and age.

Discovery and evolution of 12N-substituted aloperine derivatives as anti-SARS-CoV-2 agents through targeting late entry stage.

So far, there is still no specific drug against COVID-19. Taking compound 1 with anti-EBOV activity as the lead, fifty-four 12N-substituted aloperine derivatives were synthesized and evaluated for the anti-SARS-CoV-2 activities using pseudotyped virus model. Among them, 8a exhibited the most potential effects against both pseudotyped and authentic SARS-CoV-2, as well as SARS-CoV and MERS-CoV, indicating a broad-spectrum anti-coronavirus profile. The mechanism study disclosed that 8a might block a late stage of viral entry, mainly via inhibiting host cathepsin B activity rather than directly targeting cathepsin B protein. Also, 8a could significantly reduce the release of multiple inflammatory cytokines in a time- and dose-dependent manner, such as IL-6, IL-1ß, IL-8 and MCP-1, the major contributors to cytokine storm. Therefore, 8a is a promising agent with the advantages of broad-spectrum anti-coronavirus and anti-cytokine effects, thus worthy of further investigation.

Anti-SARS-CoV-2 Repurposing Drug Database: Clinical Pharmacology Considerations.

A critical step to evaluate the potential in vivo antiviral activity of a drug is to connect the in vivo exposure to its in vitro antiviral activity. The Anti-SARS-CoV-2 Repurposing Drug Database is a database that includes both in vitro anti-SARS-CoV-2 activity and in vivo pharmacokinetic data to facilitate the extrapolation from in vitro antiviral activity to potential in vivo antiviral activity for a large set of drugs/compounds. In addition to serving as a data source for in vitro anti-SARS-CoV-2 activity and in vivo pharmacokinetic information, the database is also a calculation tool that can be used to compare the in vitro antiviral activity with in vivo drug exposure to identify potential anti-SARS-CoV-2 drugs. Continuous development and expansion are feasible with the public availability of this database.

Modifying reusable elastomeric respirators to utilise breathing system filters with 3D printed adapters, a safe alternative to N95 during COVID-19 (preprint)

The COVID-19 pandemic has caused a worldwide shortage of personal protective equipment including N95 and FFP3 respirators. Reusable elastomeric respirators are suitable alternatives when used with compatible filters. These filters may be difficult to source and elastomeric respirators are not recommended for surgical use as the exhaled air is not filtered. Breathing system filters are routinely used in anaesthetic circuits to filter virus and bacteria. In this study, we designed 3D printed adapters that allowed elastomeric respirators to utilise breathing system filters and made simple modifications to the respirators to filter exhaled breaths. We then evaluated the performance and safety of our modified elastomeric respirators with quantitative fit tests. We recruited 8 volunteers to perform quantitative fit tests. Fit factors, respiratory rate and end-tidal carbon dioxide were recorded before and after wearing the modified respirators for 1 hour. All 8 volunteers obtained fit factors of 200+, the maximum achievable, for all tests exercises in all fit tests. The mean (range) end-tidal carbon dioxide was 4.5 (3.9-5.5) kPa and 4.6 (range 4.1-5.3) kPa before and after 1 hour of usage. The mean (range) respiratory rate was 16.5 (11-24) min-1 and 17.4 (15-22) min-1 before and after 1 hour of usage. Four (50%) did not experience any subjective discomfort while 2 (25%) reported pressure on the face, 1 (12.5%) reported exhalation resistance and 1 (12.5%) reported transient dizziness with exertion. Breathing system filters combined with properly fitted reusable elastomeric respirators is a safe alternative to N95 during the COVID-19 pandemic.