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1.
Aust N Z J Obstet Gynaecol ; 2023 May 18.
Article in English | MEDLINE | ID: covidwho-2323222

ABSTRACT

Uterine transplantation (UT) is an emerging medical treatment for women affected by absolute uterine factor infertility (AUFI). To date there have been over 90 documented cases of UT performed worldwide, with over 50 live births. UT allows women affected by AUFI the opportunity to carry and deliver a childd. The Royal Prince Alfred Hospital (RPAH) introduced a UT study in 2019; however, due to the impacts of the COVID pandemic the study was placed on hold for two years. In February 2023, RPAH performed the centre's first UT from a living unrelated donor to a 25-year-old woman with Mayer-Rokitansky-Küster-Hauser syndrome. The donor and recipient surgeries were uncomplicated and both are recovering well in the early post-operative period.

2.
Euro Surveill ; 25(15)2020 04.
Article in English | MEDLINE | ID: covidwho-2316774

ABSTRACT

BackgroundIn December 2019, a pneumonia caused by a novel coronavirus (SARS-CoV-2) emerged in Wuhan, China and has rapidly spread around the world since then.AimThis study aims to understand the research gaps related to COVID-19 and propose recommendations for future research.MethodsWe undertook a scoping review of COVID-19, comprehensively searching databases and other sources to identify literature on COVID-19 between 1 December 2019 and 6 February 2020. We analysed the sources, publication date, type and topic of the retrieved articles/studies.ResultsWe included 249 articles in this scoping review. More than half (59.0%) were conducted in China. Guidance/guidelines and consensuses statements (n = 56; 22.5%) were the most common. Most (n = 192; 77.1%) articles were published in peer-reviewed journals, 35 (14.1%) on preprint servers and 22 (8.8%) posted online. Ten genetic studies (4.0%) focused on the origin of SARS-CoV-2 while the topics of molecular studies varied. Nine of 22 epidemiological studies focused on estimating the basic reproduction number of COVID-19 infection (R0). Of all identified guidance/guidelines (n = 35), only ten fulfilled the strict principles of evidence-based practice. The number of articles published per day increased rapidly until the end of January.ConclusionThe number of articles on COVID-19 steadily increased before 6 February 2020. However, they lack diversity and are almost non-existent in some study fields, such as clinical research. The findings suggest that evidence for the development of clinical practice guidelines and public health policies will be improved when more results from clinical research becomes available.


Subject(s)
Coronavirus Infections , Pandemics , Pneumonia, Viral , COVID-19 , Humans , Randomized Controlled Trials as Topic
3.
Front Psychol ; 13: 969087, 2022.
Article in English | MEDLINE | ID: covidwho-2242564

ABSTRACT

Objectives: The pandemic has greatly impacted people's lives and mental health. Therefore, it is now especially important to help people maintain good mental health. The positive effects of mindfulness-based practices on mental health have been demonstrated previously. However, no consensus has yet been reached on the potential mechanisms of mindfulness. This study adopted the two-component model of mindfulness to explain the relationships between fear of COVID-19, and mental health. We proposed the following hypothetical model: (1) fear of COVID-19 could affect orientation to experience; (2) orientation to experience could affect mental health. Directly; (3) fear of COVID-19 could mental health directly; (4) orientation to experience could be a mediator between fear of COVID-19 and mental health. Methods: We conducted an online survey in the present study. Three hundred and forty-four respondents were recruited to participate in the present study. After informed consent, they completed the questionnaires on the websites. The participants were asked to complete a questionnaire including the Beck Depression Inventory-II, Beck Anxiety Inventory, the Taiwan version of the Five Facet Mindfulness Questionnaire, and the Fear of COVID-19 Scale. Descriptive analysis and structural equation modeling were used to analyze the data and examine the goodness-of-fit indices. Results: Our results not only showed orientation to experience playing as a mediator between fear of COVID-19 and mental health; but also confirmed the roles of nonjudgment and nonreactivity in regulating emotions. Conclusion: Experimentation and longitudinal study could be applied to examine the roles of nonjudgment and nonreactivity in the future.

4.
Front Pharmacol ; 13: 950012, 2022.
Article in English | MEDLINE | ID: covidwho-2199104

ABSTRACT

Background/Aim: Since 2019, the COVID-19 pandemic has been a devastating disease affecting global health to a great extent. Some countries have added on herbal medicines as a complementary treatment for combating COVID-19 due to the urgency of stopping the spread of this viral disease. However, whether these herbal medicines are effective is uncertain. This systematic review and meta-analysis aimed to evaluate the effects of herbal medicine combined therapy in the treatment of COVID-19. Methods: A literature search was performed following the PRISMA Statement and without language restrictions. Seven databases were searched from inception through December 2021. All selected studies were randomized clinical trials (RCTs). Comparing the effects of herbal medicine combined therapy with conventional western medicine, including improvement of clinical symptoms, chest CT images, viral conversion rate, C-reactive protein (CRP) and interleukin 6. Cochrane criteria were applied to examine the methodological quality of the enrolled trials; and meta-analysis software (RevMan 5.4.1) was used for data analysis. Results: In total, the data of 5,417 participants from 40 trials were included in this systematic review; and 28 trials were qualified for meta-analysis. The trials had medium-to-high quality based on GRADE system. Meta-analysis showed that combining herbal medicine vs conventional treatment in 1) coughing (1.43 95% CI:1.21, 1.71, p = 0.0001), 2) fever (1.09 95% CI:1.00, 1.19, p = 0.06), 3) fatigue (1.21 95% CI:1.10, 1.33, p = 0.0001); 4) CT images (1.26 95% CI:1.19, 1.34, P ≤ 0.00001), 5) viral conversion rates (1.22 95% CI:1.06, 1.40, p = 0.005) and 6) viral conversion times (-3.72 95% CI: -6.05, -1.40, p = 0.002), 7) IL6 change (1.97 95% CI: -0.72, 4.66, p = 0.15) and 8) CRP change (-7.92 95% CI: -11.30, -4.53, P ≤ 0.00001). Conclusion: Herbal medicine combined therapy significantly reduces COVID-19 clinical symptoms, improving CT images and viral conversion rates. Reported adverse events are mild. However, for certain biases in the included studies, and the need for further study on effective components of herbal medicine. Further large trials with better randomized design are warranted to definite a more definite role of herbal medicine.

5.
BMC Med Imaging ; 22(1): 209, 2022 Nov 29.
Article in English | MEDLINE | ID: covidwho-2139182

ABSTRACT

OBJECTIVE: To explore the characteristics of peripheral blood, high resolution computed tomography (HRCT) imaging and the radiomics signature (RadScore) in patients infected with delta variant virus under different coronavirus disease (COVID-19) vaccination status. METHODS: 123 patients with delta variant virus infection collected from November 1, 2021 to March 1, 2022 were analyzed retrospectively. According to COVID-19 vaccination Status, they were divided into three groups: Unvaccinated group, partially vaccinated group and full vaccination group. The peripheral blood, chest HRCT manifestations and RadScore of each group were analyzed and compared. RESULTS: The mean lymphocyte count 1.22 ± 0.49 × 10^9/L, CT score 7.29 ± 3.48, RadScore 0.75 ± 0.63 in the unvaccinated group; The mean lymphocyte count 1.55 ± 0.70 × 10^9/L, CT score 5.27 ± 2.72, RadScore 1.03 ± 0.46 in the partially vaccinated group; The mean lymphocyte count 1.87 ± 0.70 × 10^9/L, CT score 3.59 ± 3.14, RadScore 1.23 ± 0.29 in the fully vaccinated group. There were significant differences in lymphocyte count, CT score and RadScore among the three groups (all p < 0.05); Compared with the other two groups, the lung lesions in the unvaccinated group were more involved in multiple lobes, of which 26 cases involved the whole lung. CONCLUSIONS: Through the analysis of clinical features, pulmonary imaging features and radiomics, we confirmed the positive effect of COVID-19 vaccine on pulmonary inflammatory symptoms and lymphocyte count (immune system) during delta mutant infection.


Subject(s)
COVID-19 Vaccines , COVID-19 , Humans , COVID-19/prevention & control , Retrospective Studies , SARS-CoV-2 , Tomography, X-Ray Computed , Vaccination
6.
Front Public Health ; 10: 1038017, 2022.
Article in English | MEDLINE | ID: covidwho-2109888

ABSTRACT

COVID-19, referred to as new coronary pneumonia, is an acute infectious disease caused by a new type of coronavirus SARS-CoV-2. To evaluate the effect of integrated Chinese medicine and Western medicine in patients with COVID-19 from overseas. Data were collected from 178 COVID-19 patients overseas at First Affiliated Hospital of Xiamen University from April 1, 2021 to July 31, 2021. These patients received therapy of integrated Chinese medicine and western medicine. Demographic data and clinical characteristics were extracted and analyzed. In addition, the prescription which induced less length of PCR positive days and hospitalization days than the median value was obtained. The top 4 frequently used Chinese medicine and virus-related genes were analyzed by network pharmacology and bioinformatics analysis. According to the chest computed tomography (CT) measurement, abnormal lung findings were observed in 145 subjects. The median length of positive PCR/hospitalization days was 7/7 days for asymptomatic subjects, 14/24 days for mild subjects, 10/15 days for moderate subjects, and 14/20 days for severe subjects. The most frequently used Chinese medicine were Scutellaria baicalensis (Huangqin), Glycyrrhiza uralensis (Gancao), Bupleurum chinense (Chaihu), and Pinellia ternata (Banxia). The putative active ingredients were baicalin, stigmasterol, sigmoidin-B, cubebin, and troxerutin. ACE, SARS-CoV-2 3CL, SARS-CoV-2 Spike, SARS-CoV-2 ORF7a, and caspase-6 showed good binding properties to active ingredients. In conclusion, the clinical results showed that integrated Chinese medicine and Western medicine are effective in treating COVID-19 patients from overseas. Based on the clinical outcomes, the putative ingredients from Chinese medicine and the potential targets of SARS-CoV-2 were provided, which could provide a reference for the clinical application of Chinese medicine in treating COVID-19 worldwide.


Subject(s)
COVID-19 , Humans , SARS-CoV-2 , Retrospective Studies , Medicine, Chinese Traditional , Hospitalization
8.
Frontiers in pharmacology ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-2033837

ABSTRACT

Background/Aim: Since 2019, the COVID-19 pandemic has been a devastating disease affecting global health to a great extent. Some countries have added on herbal medicines as a complementary treatment for combating COVID-19 due to the urgency of stopping the spread of this viral disease. However, whether these herbal medicines are effective is uncertain. This systematic review and meta-analysis aimed to evaluate the effects of herbal medicine combined therapy in the treatment of COVID-19. Methods: A literature search was performed following the PRISMA Statement and without language restrictions. Seven databases were searched from inception through December 2021. All selected studies were randomized clinical trials (RCTs). Comparing the effects of herbal medicine combined therapy with conventional western medicine, including improvement of clinical symptoms, chest CT images, viral conversion rate, C-reactive protein (CRP) and interleukin 6. Cochrane criteria were applied to examine the methodological quality of the enrolled trials;and meta-analysis software (RevMan 5.4.1) was used for data analysis. Results: In total, the data of 5,417 participants from 40 trials were included in this systematic review;and 28 trials were qualified for meta-analysis. The trials had medium-to-high quality based on GRADE system. Meta-analysis showed that combining herbal medicine vs conventional treatment in 1) coughing (1.43 95% CI:1.21, 1.71, p = 0.0001), 2) fever (1.09 95% CI:1.00, 1.19, p = 0.06), 3) fatigue (1.21 95% CI:1.10, 1.33, p = 0.0001);4) CT images (1.26 95% CI:1.19, 1.34, P ≤ 0.00001), 5) viral conversion rates (1.22 95% CI:1.06, 1.40, p = 0.005) and 6) viral conversion times (−3.72 95% CI: −6.05, −1.40, p = 0.002), 7) IL6 change (1.97 95% CI: −0.72, 4.66, p = 0.15) and 8) CRP change (−7.92 95% CI: −11.30, −4.53, P ≤ 0.00001). Conclusion: Herbal medicine combined therapy significantly reduces COVID-19 clinical symptoms, improving CT images and viral conversion rates. Reported adverse events are mild. However, for certain biases in the included studies, and the need for further study on effective components of herbal medicine. Further large trials with better randomized design are warranted to definite a more definite role of herbal medicine.

9.
International Journal of Manpower ; 43(4):982-1000, 2022.
Article in English | ProQuest Central | ID: covidwho-1948673

ABSTRACT

Purpose>Based on path–goal theory and social learning theory, this research is aimed at investigating how authentic leadership can influence team performance in virtual teams, specifically the mechanisms through the mediator of high-quality interpersonal relationships and the moderator of task interdependence.Design/methodology/approach>The valid data of this research were collected from 90 virtual teams including 388 team members and their 90 leaders with a time-lag in China, and then the data were mainly analyzed by the hierarchical multiple regression and bootstrapping method to test the hypotheses.Findings>The research results reveal that authentic leadership can positively influence virtual team performance. High-quality interpersonal relationships mediate the relationship between authentic leadership and virtual team performance. Furthermore, the indirect relationship between authentic leadership and virtual team performance via high-quality interpersonal relationships is moderated by task interdependence.Originality/value>Team performance as an important kind of team effectiveness is crucial to the virtual team's advantage and success. This research enriches the knowledge on the relationship between authentic leadership and virtual team performance, which contributes to the virtual leadership effectiveness and virtual team management.

10.
Theranostics ; 12(10): 4606-4628, 2022.
Article in English | MEDLINE | ID: covidwho-1897098

ABSTRACT

Rationale: Evident immunosuppression has been commonly seen among septic patients, and it is demonstrated to be a major driver of morbidity. Nevertheless, a comprehensive view of the host immune response to sepsis is lacking as the majority of studies on immunosuppression have focused on a specific type of immune cells. Methods: We applied multi-compartment, single-cell RNA sequencing (scRNA-seq) to dissect heterogeneity within immune cell subsets during sepsis progression on cecal ligation and puncture (CLP) mouse model. Flow cytometry and multiplex immunofluorescence tissue staining were adopted to identify the presence of 'mature DCs enriched in immunoregulatory molecules' (mregDC) upon septic challenge. To explore the function of mregDC, sorted mregDC were co-cultured with naïve CD4+ T cells. Intracellular signaling pathways that drove mregDC program were determined by integrating scRNA-seq and bulk-seq data, combined with inhibitory experiments. Results: ScRNA-seq analysis revealed that sepsis induction was associated with substantial alterations and heterogeneity of canonical immune cell types, including T, B, natural killer (NK), and myeloid cells, across three immune-relevant tissue sites. We found a unique subcluster of conventional dendritic cells (cDCs) that was characterized by specific expression of maturation- and migration-related genes, along with upregulation of immunoregulatory molecules, corresponding to the previously described 'mregDCs' in cancer. Flow cytometry and in stiu immunofluorescence staining confirmed the presence of sepsis-induced mregDC at protein level. Functional experiments showed that sepsis-induced mregDCs potently activated naive CD4+ T cells, while promoted CD4+ T cell conversion to regulatory T cells. Further observations indicated that the mregDC program was initiated via TNFRSF-NF-κB- and IFNGR2-JAK-STAT3-dependent pathways within 24 h of septic challenge. Additionally, we confirmed the detection of mregDC in human sepsis using publicly available data from a recently published single-cell study of COVID-19 patients. Conclusions: Our study generates a comprehensive single-cell immune landscape for polymicrobial sepsis, in which we identify the significant alterations and heterogeneity in immune cell subsets that take place during sepsis. Moreover, we find a conserved and potentially targetable immunoregulatory program within DCs that associates with hyperinflammation and organ dysfunction early following sepsis induction.


Subject(s)
COVID-19 , Sepsis , Animals , Dendritic Cells , Gene Expression Profiling , Humans , Mice , T-Lymphocytes, Regulatory
11.
Front Public Health ; 10: 776850, 2022.
Article in English | MEDLINE | ID: covidwho-1775980

ABSTRACT

Objective: The purpose of this study is to empirically examine the impact of environmental information disclosure on the health of middle-aged and old residents and investigate whether such disclosure can improve the health of middle-aged and old residents. Methods: This study matches the data of the Pollution Information Transparency Index (PITI) and China Health and Retirement Longitudinal Study in 2018 and uses the ordered logistic regression model to assess the impact of environmental information disclosure on the health of middle-aged and old residents. Furthermore, stepwise regression, ordinary least square, and ordered probit regression models are used for robustness tests. The IV-Ordered probit regression model solves the endogenous problem. Results: Environmental information disclosure has a significant positive correlation with the health level of middle-aged and old residents. After the robustness test and endogenous problem handling, this conclusion still holds. Estimation results show that when PITI increases by 1 unit, the probability of improving the self-reported health level and actual health level of middle-aged and old residents increases by 1 and 0.87%, respectively. The impact of environmental information disclosure on the health of middle-aged and old residents also has significant regional heterogeneity. Specifically, the impact is mainly reflected in the central region of China. Conclusion: Environmental information disclosure can improve the health of middle-aged and old residents. To improve the health of middle-aged and old residents, it is necessary to implement and enhance the environmental information disclosure system continuously. The anti-driving effect of environmental information disclosure on the treatment of environmental pollution must be intensified further, particularly focusing on the central region of China, where is more polluted and more concentrated than other regions.


Subject(s)
Disclosure , Environmental Pollution , Health Status , Aged , China , Humans , Longitudinal Studies , Middle Aged
12.
Medicine (Baltimore) ; 101(9): e28976, 2022 Mar 04.
Article in English | MEDLINE | ID: covidwho-1730760

ABSTRACT

ABSTRACT: The Corona Virus Disease 2019 (COVID-19) pandemic has huge impacts on the world, including human health and economic decline. The COVID-19 has severe infectivity, especially the elderly with chronic diseases will cause various complications after infection and accelerate the disease process. In addition, COVID-19 will also affect their mental health. Therefore, the mental health of elderly patients with chronic diseases cannot be ignored. The aim of this study was to investigate the well-being level of elderly people with chronic disease during COVID-19 postpandemic period in Beijing and analysis related influencing factors, so as to provide a basis for improving the well-being level of elderly chronic patients during the postpandemic period.Elderly patients with chronic diseases who met the inclusion criteria in 5 different administrative regions in Beijing were selected to carry out a questionnaire survey. The contents of the questionnaire included general data, the Memorial University of Newfoundland Happiness scale and the awareness situation of the COVID-19 pandemic. A total of 500 questionnaires were distributed by WeChat and 486 valid questionnaires were collected. The t test and one-way analysis of variance were used to compare Memorial University of Newfoundland Happiness scores between 2 or more groups, multiple linear regression analysis was used to conduct multiple factor analysis to explore the related factors about well-being level of elderly chronic patients.A total of 109 cases (22.43%) were evaluated high well-being level, 319 cases (65.64%) were evaluated moderate well-being level and 58 cases (11.93%) were evaluated low well-being according to the Memorial University of Newfoundland Happiness (MUNSH) scores rating. The multiple linear regression indicated that the education level, number of chronic diseases, medical expenses, frequency of children's visits, taking care of grandchildren or not, and group activity frequency significantly affected the well-being of patients with chronic diseases during COVID-19 postpandemic period in Beijing (P < .05).Most elderly patients with chronic diseases had moderate or above sense of well-being during postpandemic period, but we should still pay attention to the mental health of those elderly chronic patients with low education level, much comorbidity, more medical expenses, less visits by children, not take care of grandchildren and never participate in group activities.


Subject(s)
COVID-19/epidemiology , Chronic Disease/epidemiology , Aged , Aged, 80 and over , Child , China/epidemiology , Health Status , Humans , Pandemics , SARS-CoV-2 , Surveys and Questionnaires
13.
Int J Mol Sci ; 22(20)2021 Oct 14.
Article in English | MEDLINE | ID: covidwho-1470889

ABSTRACT

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection; the pathophysiology of sepsis is complex. The incidence of sepsis is steadily increasing, with worldwide mortality ranging between 30% and 50%. Current treatment approaches mainly rely on the timely and appropriate administration of antimicrobials and supportive therapies, but the search for pharmacotherapies modulating the host response has been unsuccessful. Chinese herbal medicines, i.e., Chinese patent medicines, Chinese herbal prescriptions, and single Chinese herbs, play an important role in the treatment of sepsis through multicomponent, multipathway, and multitargeting abilities and have been officially recommended for the management of COVID-19. Chinese herbal medicines have therapeutic actions promising for the treatment of sepsis; basic scientific research on these medicines is increasing. However, the material bases of most Chinese herbal medicines and their underlying mechanisms of action have not yet been fully elucidated. This review summarizes the current studies of Chinese herbal medicines used for the treatment of sepsis in terms of clinical efficacy and safety, pharmacological activity, phytochemistry, bioactive constituents, mechanisms of action, and pharmacokinetics, to provide an important foundation for clarifying the pathogenesis of sepsis and developing novel antisepsis drugs based on Chinese herbal medicines.


Subject(s)
Drugs, Chinese Herbal/therapeutic use , Sepsis/drug therapy , COVID-19/virology , Drug Combinations , Humans , Medicine, Chinese Traditional , SARS-CoV-2/isolation & purification , COVID-19 Drug Treatment
14.
Signal Transduct Target Ther ; 6(1): 337, 2021 09 06.
Article in English | MEDLINE | ID: covidwho-1402050

ABSTRACT

SARS-CoV-2 has been reported to show a capacity for invading the brains of humans and model animals. However, it remains unclear whether and how SARS-CoV-2 crosses the blood-brain barrier (BBB). Herein, SARS-CoV-2 RNA was occasionally detected in the vascular wall and perivascular space, as well as in brain microvascular endothelial cells (BMECs) in the infected K18-hACE2 transgenic mice. Moreover, the permeability of the infected vessel was increased. Furthermore, disintegrity of BBB was discovered in the infected hamsters by administration of Evans blue. Interestingly, the expression of claudin5, ZO-1, occludin and the ultrastructure of tight junctions (TJs) showed unchanged, whereas, the basement membrane was disrupted in the infected animals. Using an in vitro BBB model that comprises primary BMECs with astrocytes, SARS-CoV-2 was found to infect and cross through the BMECs. Consistent with in vivo experiments, the expression of MMP9 was increased and collagen IV was decreased while the markers for TJs were not altered in the SARS-CoV-2-infected BMECs. Besides, inflammatory responses including vasculitis, glial activation, and upregulated inflammatory factors occurred after SARS-CoV-2 infection. Overall, our results provide evidence supporting that SARS-CoV-2 can cross the BBB in a transcellular pathway accompanied with basement membrane disrupted without obvious alteration of TJs.


Subject(s)
Basement Membrane/metabolism , Blood-Brain Barrier/metabolism , COVID-19/metabolism , SARS-CoV-2/metabolism , Tight Junctions/metabolism , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , Basement Membrane/pathology , Basement Membrane/virology , Blood-Brain Barrier/pathology , Blood-Brain Barrier/virology , COVID-19/genetics , COVID-19/pathology , Chlorocebus aethiops , Disease Models, Animal , Humans , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/metabolism , Mice , Mice, Transgenic , SARS-CoV-2/genetics , Tight Junctions/genetics , Tight Junctions/pathology , Tight Junctions/virology , Vero Cells
15.
Front Med (Lausanne) ; 8: 591830, 2021.
Article in English | MEDLINE | ID: covidwho-1302113

ABSTRACT

At the time of the prevalence of coronavirus disease 2019 (COVID-19), pulmonary fibrosis (PF) related to COVID-19 has become the main sequela. However, the mechanism of PF related to COVID (COVID-PF) is unknown. This study aimed to explore the key targets in the development of COVID-PF and the mechanism of d-limonene in the COVID-PF treatment. The differentially expressed genes of COVID-PF were downloaded from the GeneCards database, and their pathways were analyzed. d-Limonene was molecularly docked with related proteins to screen its pharmacological targets, and a rat lung fibrosis model was established to verify d-limonene's effect on COVID-PF-related targets. The results showed that the imbalance between collagen breakdown and metabolism, inflammatory response, and angiogenesis are the core processes of COVID-PF; and PI3K/AKT signaling pathways are the key targets of the treatment of COVID-PF. The ability of d-limonene to protect against PF induced by bleomycin in rats was reported. The mechanism is related to the binding of PI3K and NF-κB p65, and the inhibition of PI3K/Akt/IKK-α/NF-κB p65 signaling pathway expression and phosphorylation. These results confirmed the relationship between the PI3K-Akt signaling pathway and COVID-PF, showing that d-limonene has a potential therapeutic value for COVID-PF.

16.
Jiegou Huaxue ; 40(4):431-442, 2021.
Article in English | Scopus | ID: covidwho-1268426

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) gained tremendous attention due to its high infectivity and pathogenicity. The 3-chymotrypsin-like hydrolase protease (Mpro) of SARS-CoV-2 has been proven to be an important target for anti-SARS-CoV-2 activity. To better identify the drugs with potential in treating coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 and according to the crystal structure of Mpro, we conducted a virtual screening of FDA-approved drugs and chemical agents that have entered clinical trials. As a result, 9 drug candidates with therapeutic potential for the treatment of COVID-19 and with good docking scores were identified to target SARS-CoV-2. Consequently, molecular dynamics (MD) simulation was performed to explore the dynamic interactions between the predicted drugs and Mpro. The binding mode during MD simulation showed that hydrogen bonding and hydrophobic interactions played an important role in the binding processes. Based on the binding free energy calculated by using MM/PBSA, Lopiravir, an inhibitor of human immunodeficiency virus (HIV) protease, is under investigation for the treatment of COVID-19 in combination with ritionavir, and it might inhibit Mpro effectively. Moreover, Ombitasvir, an inhibitor for non-structural protein 5A of hepatitis C virus (HCV), has good inhibitory potency for Mpro. It is notable that the GS-6620 has a binding free energy, with respect to binding Mpro, comparable to that of ombitasvir. Our study suggests that ombitasvir and lopinavir are good drug candidates for the treatment of COVID-19, and that GS-6620 has good anti-SARS-CoV-2 activity. © 2021 Fujian Institute of Research of the Structure of Matter. All rights reserved.

17.
Acta Pharmacol Sin ; 42(12): 2155-2172, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1209738

ABSTRACT

LianhuaQingwen capsule, prepared from an herbal combination, is officially recommended as treatment for COVID-19 in China. Of the serial pharmacokinetic investigations we designed to facilitate identifying LianhuaQingwen compounds that are likely to be therapeutically important, the current investigation focused on the component Glycyrrhiza uralensis roots (Gancao). Besides its function in COVID-19 treatment, Gancao is able to induce pseudoaldosteronism by inhibiting renal 11ß-HSD2. Systemic and colon-luminal exposure to Gancao compounds were characterized in volunteers receiving LianhuaQingwen and by in vitro metabolism studies. Access of Gancao compounds to 11ß-HSD2 was characterized using human/rat, in vitro transport, and plasma protein binding studies, while 11ß-HSD2 inhibition was assessed using human kidney microsomes. LianhuaQingwen contained a total of 41 Gancao constituents (0.01-8.56 µmol/day). Although glycyrrhizin (1), licorice saponin G2 (2), and liquiritin/liquiritin apioside (21/22) were the major Gancao constituents in LianhuaQingwen, their poor intestinal absorption and access to colonic microbiota resulted in significant levels of their respective deglycosylated metabolites glycyrrhetic acid (8), 24-hydroxyglycyrrhetic acid (M2D; a new Gancao metabolite), and liquiritigenin (27) in human plasma and feces after dosing. These circulating metabolites were glucuronized/sulfated in the liver and then excreted into bile. Hepatic oxidation of 8 also yielded M2D. Circulating 8 and M2D, having good membrane permeability, could access (via passive tubular reabsorption) and inhibit renal 11ß-HSD2. Collectively, 1 and 2 were metabolically activated to the pseudoaldosterogenic compounds 8 and M2D. This investigation, together with such investigations of other components, has implications for precisely defining therapeutic benefit of LianhuaQingwen and conditions for its safe use.


Subject(s)
Antiviral Agents/pharmacokinetics , COVID-19 Drug Treatment , Drugs, Chinese Herbal/pharmacokinetics , Phytochemicals/pharmacokinetics , 11-beta-Hydroxysteroid Dehydrogenase Type 2/antagonists & inhibitors , 11-beta-Hydroxysteroid Dehydrogenase Type 2/metabolism , Administration, Oral , Animals , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , Biological Availability , Biotransformation , Capsules , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/adverse effects , Female , Glycyrrhiza/adverse effects , HEK293 Cells , Humans , Liddle Syndrome/chemically induced , Liddle Syndrome/enzymology , Male , Patient Safety , Phytochemicals/administration & dosage , Phytochemicals/adverse effects , Rats, Sprague-Dawley , Risk Assessment
18.
Ann Transl Med ; 9(5): 395, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1176211

ABSTRACT

BACKGROUND: Hand hygiene is one of the ways to prevent the spread of diseases. Our aim was to explore the relationship between hand washing frequency and the impact on disease, and give recommendations on the number of times to wash hands. METHODS: We searched seven electronic databases from their inception to April 11, 2020, and reference lists of related reviews for all studies on hand washing frequency and disease prevention. The Review Manager 5.3. software was used to conduct a meta-analysis. We assessed the risk of bias of included studies, and quality of evidence of the main findings. RESULTS: A total of eight studies were included. The results of the meta-analysis showed that there was no statistical significance between the effect of disease prevention and washing more than 4 times/day compared to not [odds ratio (OR) =0.61, 95% confidence interval (CI): 0.37 to 1.01]. The results of a case-control study showed that compared with hand washing ≤4 times/day, hand washing 5-10 times/day (OR =0.75, 95% CI: 0.63 to 0.91) and hand washing >10 times/day (OR =0.65, 95% CI 0.53 to 0.80) could reduce the risk of disease infection. There was no statistical significance advantage to hand washing more than 10 times/day compared to 5-10 times/day (OR =0.86, 95% CI: 0.70 to 1.06). Comparing hand washing ≤10 times/day with hand washing >10 times/day, increased hand washing was a protective factor against infection (OR =0.59, 95% CI: 0.36 to 0.97). CONCLUSIONS: The more frequently hands were washed, the lower risk of disease. So far however, there is no high-quality evidence indicating the best range of hand washing frequency for disease prevention.

19.
Taiwan Gong Gong Wei Sheng Za Zhi ; 39(4):397-410, 2020.
Article in Chinese | ProQuest Central | ID: covidwho-1150915

ABSTRACT

Objectives: This study aims to compare the resources invested during the SARS and COVID-19 epidemics, analyze and compare resources invested by a medical center and a regional hospital during SARS, and estimate the possible investment of resources (including expenses and costs) by the hospitals in different stages of epidemic development. Methods: Compare the different epidemics and hospitals at different levels based on retrospective data, and estimate the investment of resources. Results: A medical center invested NT$ 70.34 million worth of resources during SARS, mainly for setting up negative-pressure isolation rooms and a fever clinic (accounting for about 50% of the total investment), whereas the investment during COVID-19 is mainly on anti-epidemic supplies and special allowances for healthcare workers. There is a high level of correlation between investment in anti-epidemic resources by a medical center/regional hospital and the scale of a hospital. Moreover, a medical center estimates that when COVID-19 develops to the most severe stage, the investment will be around NT$ 43.04 million (excluding cost allocation), that is about 61% of the expenditure during SARS, and around NT$ 53.34 million (including cost allocation), about 76% of the SARS expenditure, at Purple Level 2 status. At the time of SARS, with no similar experience before, hospitals were caught unprepared upon the sudden outbreak, with no negative-pressure isolation facilities. Immense investment had to be made in this resource to accommodate confirmed cases. Although the COVID-19 epidemic is severe, with the negative-pressure isolation facilities already established and the advance deployment already adopted by both the government and the medical center, the epidemic has been kept in control to date. Conclusions: Due to the unpredictability of the epidemic, the time when the epidemic will end is unpredictable, and this will constrain the hospitals' ability to estimate the investment in anti-epidemic resources. The length of a certain stage of epidemic, the severity of the epidemic, the government's anti-epidemic policy, and the result of the hospitals' implementation of anti-epidemic measures all affect the amount of investment in resources. When combating the epidemic, hospitals will have reduced income, and hospitals may face cash flow problem if no government funding is provided. To give back up for the hospitals' anti-epidemic efforts, the government should provide timely financial support for the hospitals to help them overcome the challenge. (Taiwan J Public Health. 2020;39(4):397-410)

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