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1.
BMJ ; 377: e068714, 2022 04 19.
Article in English | MEDLINE | ID: covidwho-1807349

ABSTRACT

OBJECTIVE: To evaluate sintilimab versus placebo in combination with chemotherapy (cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil) as first line treatment of unresectable locally advanced, recurrent, or metastatic oesophageal squamous cell carcinoma. DESIGN: Multicentre, randomised, double blind, phase 3 trial. SETTING: 66 sites in China and 13 sites outside of China between 14 December 2018 and 9 April 2021. PARTICIPANTS: 659 adults (aged ≥18 years) with advanced or metastatic oesophageal squamous cell carcinoma who had not received systemic treatment. INTERVENTION: Participants were randomised 1:1 to receive sintilimab or placebo (3 mg/kg in patients weighing <60 kg or 200 mg in patients weighing ≥60 kg) in combination with cisplatin 75 mg/m2 plus paclitaxel 175 mg/m2 every three weeks. The trial was amended to allow investigators to choose the chemotherapy regimen: cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil (800 mg/m2 continuous infusion on days 1-5). MAIN OUTCOME MEASURES: Overall survival in all patients and in patients with combined positive scores of ≥10 for expression of programmed cell death ligand 1. RESULTS: 659 patients were randomly assigned to sintilimab (n=327) or placebo (n=332) with chemotherapy. 616 of 659 patients (93%) received sintilimab or placebo in combination with cisplatin plus paclitaxel and 43 of 659 patients (7%) received sintilimab or placebo in combination with cisplatin plus 5-fluorouracil. At the interim analysis, sintilimab with chemotherapy showed better overall survival compared with placebo and chemotherapy in all patients (median 16.7 v 12.5 months, hazard ratio 0.63, 95% confidence interval 0.51 to 0.78, P<0.001) and in patients with combined positive scores of ≥10 (17.2 v 13.6 months, 0.64, 0.48 to 0.85, P=0.002). Sintilimab and chemotherapy significantly improved progression free survival compared with placebo and chemotherapy in all patients (7.2 v 5.7 months, 0.56, 0.46 to 0.68, P<0.001) and in patients with combined positive scores of ≥10 (8.3 v 6.4 months, 0.58, 0.45 to 0.75, P<0.001). Adverse events related to treatment occurred in 321 of 327 patients (98%) in the sintilimab-chemotherapy group versus 326 of 332 (98%) patients in the placebo-chemotherapy group. Rates of adverse events related to treatment, grade ≥3, were 60% (196/327) and 55% (181/332) in the sintilimab-chemotherapy and placebo-chemotherapy groups, respectively. CONCLUSIONS: Compared with placebo, sintilimab in combination with cisplatin plus paclitaxel showed significant benefits in overall survival and progression free survival as first line treatment in patients with advanced or metastatic oesophageal squamous cell carcinoma. Similar benefits of sintilimab with cisplatin plus 5-fluorouracil seem promising. TRIAL REGISTRATION: ClinicalTrials.gov NCT03748134.


Subject(s)
Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Adolescent , Adult , Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cisplatin/therapeutic use , Double-Blind Method , Esophageal Neoplasms/drug therapy , Esophageal Squamous Cell Carcinoma/drug therapy , Fluorouracil/therapeutic use , Humans , Paclitaxel/therapeutic use
2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-319513

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) is currently spreading all over the world, and the prospect of a very rapid increase in COVID-19 cases prompted us to seek effective antiviral therapeutics, from the identification of possible drugs to their potential mechanisms. Purpose: The aim of this study was to explore the efficacy of the Ephedra-Glycyrrhiza (EG) drug pair on coronavirus disease 2019 (COVID-19) by network pharmacology and molecular docking. Methods: The main active compounds, target information, meridians and properties of EG were obtained through the TCMSP and ETCM databases. The targeted information of COVID-19 was acquired from the GeneCards database. EG drug pair applied diseases were analysed by DAVID and the drug-bank database, and visualized by Rstudio and Cytoscape 3.7.2. Then, we carried out targeted intersection of the EG drug pair and COVID-19 to map the compound-target-disease interactions and visualize them with Cytoscape 3.7.2 and Venny 2.1. In addition, the enrichment analysis of the GO and KEGG pathways were visualized with Rstudio and PathVisio software through the DAVID database. Finally, we carried out the molecular docking of the EG active compounds with M hydrolase (Mpro), spike protein (S protein) and angiotensin-converting enzyme 2 (ACE2), and the binding modes between GE and the protein were verified via molecular dynamics (MD) simulation. Results: : We identified 112 active EG compounds by network pharmacological analysis. Drug pair enrichment analysis demonstrated that these compounds may participate in the cAMP, PI3K-Akt, JAK-STAT and chemokine signalling pathways, which had a high correlation with respiratory system, nervous system, blood circulation system and digestive system related diseases. Pathway analysis between EG and COVID-19 showed that the key targets were TNF, IL2, FOS, ALB and PTGS2. They may regulate the PI3K-Akt signalling pathway and natural killer cell-mediated cytotoxicity to play roles in immune regulation, organ protection, antiviral, immune regulation, and organ protection as well as having antiviral effects. Molecular docking results showed that the active EG compounds bind well to Mpro, S protein and ACE2. The binding modes between the active compounds of the EG and protein were verified via MD simulation. Conclusion: The EG drug pair can treat COVID-19 through multiple targets and pathways, which can provide a theoretical basis for further study of the mechanism of action of the EG drug pair on COVID-19.

3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315939

ABSTRACT

FURIN, as a proprotein convertase, has been found to be expressed in a variety of cancers and plays an important role in cancer. In addition, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) requires FURIN to enter human cells. However, the role of FURIN in lung adenocarcinoma remains unclear. And the expression of SARS-CoV-2 related gene in lung adenocarcinoma has not been clarified. Therefore, in order to explore the prognostic value and mechanism of FURIN in lung adenocarcinoma, we performed bioinformatics analysis with Oncomine, TIMER (Tumor Immune Estimation Resource), GEPIA (Gene Expression Profiling Interactive Analysis), HPA (human protein atlas), UALCAN, PrognoScan, Kaplan-Meier plotter, cBioPortal, and LinkedOmics databases. And then We used GSE44274 in the GEO (Gene Expression Omnibus) database to analyze the expression of FURIN in LUAD patients who infected with SARS-CoV. FURIN was highly expressed in lung adenocarcinoma and was significantly associated with poor overall survival. FURIN expression was found to be correlated with six major permeable immune cells and with macrophage immune marker in LUAD patients. In addition, SARS-CoV-2 infection might affect the expression of FURIN. FURIN can be used as a promising biomarker for determining prognosis and immune infiltration in LUAD patients.

4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315937

ABSTRACT

Background: Since the outbreak of coronavirus disease 2019 (COVID-19) in January 2020, Traditional Chinese Medicine (TCM) has been fully and deeply involved in the treatment of COVID-19 in China. An increasing number of clinical trials has been registered to evaluate the effects of TCM in the prevention and therapeutic management of COVID-19. Objective: This study aims to review the existing TCM registered trials, identify promising and available TCM therapies, in order to provide reference for the global management of COVID-19. Methods: : All clinical trials on TCM for COVID-19 registered in eight registry platforms worldwide were searched up to May 14, 2020. The data of registration trend, design, objective, interventions, current status, and relevant information were reviewed and summarized. Supportive information on the progress, results and potential value of the included registered trials were searched and reviewed from databases and official websites. Results: : 161 TCM trials registered in three registries from January 26 to May 14 were included. 94 (58.4%) were randomized controlled trials, followed by controlled clinical trials (25, 15.5%), single-arm clinical studies (18, 11.2%) and others (24, 14.9%). 114 trials (70.8%) assessed therapeutic effects;while the remaining were for prevention, rehabilitation, and TCM syndrome epidemiology. The three most evaluated TCM interventions were Chinese herbal medicine (CHM) in the preparation forms of formulae decoction/granule (41.7%), Chinese patent medicine (24.8%) and Chinese herbal-derived injections (8.1%). The common outcomes in therapeutic trials were symptoms and signs (65.8%), time to viral clearance on PCR (50.9%), and improvement in CT images (43.9%). 78 trials (48.4%) had started recruiting and six trials (3.7%) had completed recruiting. Among the TCM interventions identified from the registered trials, the following are worthy of attention and may have the potential feasibility of being evaluated and then used worldwide due to their rigorous design, previous evidence and availability: for prevention in high-risk populations or suspected cases, moxibustion, Huoxiang Zhengqi pill and Jinye Baidu granule could be considered;for treatment, Qingfei Paidu decoction or granules in mild, moderate and severe cases, Huashi Baidu decoction, Lianhua Qingwen caplsule, Toujie Quwen granule and Xiyanping injection in mild and moderate cases, and Xuebijing injection in severe cases could be considered. For rehabilitation of cured patients, the effect of Tai Chi and Liuzijue on the patients’ lung function and quality of life deserves attention. Conclusion: A series of promising potentially effective TCM interventions including CHM formulae, Chinese patent medicines, herbal-derived injections and non-drug therapies have been identified in clinical practice and are being evaluated by registered clinical trials. Available and applicable interventions within relevant trials are worthy of worldwide attention and application, in order to contribute to the global management of COVID-19 epidemic.

5.
Front Public Health ; 9: 723118, 2021.
Article in English | MEDLINE | ID: covidwho-1662631

ABSTRACT

Objective: This study investigated the COVID-19-prevention knowledge and practices of healthcare workers (HCWs), their psychological states concerning the return to work, and their trust and requirements in using traditional Chinese medicine (TCM) to prevent and treat COVID-19. It is hoped that the study can serve as a reference for policy making during the resumption of work in other countries or regions experiencing similar situations. Methods: This study comprised a quantitative cross-sectional online survey design. Purposive sampling and Cluster sampling were used to recruit all HCWs working in public hospitals in Huangzhou District, Huanggang City, Hubei Province, China. From April 23 to May 14, 2020, surveys were sent electronically to all 13 public hospitals in this area. Results: In total, 2,079 responses were received and 2,050 completed forms were included. After analysis, 47.9 and 46.6% of HCWs indicated that they possessed very good knowledge or good knowledge of preventative measures, respectively. Multivariable log-binomial regression indicated that male, tertiary hospital, medical staff, and undergraduate/postgraduate qualification were associated with good knowledge. Good knowledge was also well-correlated with good practice (OR: 3.277; 95% CI: 2.734-3.928; P < 0.01). 59.8% of HCWs reported worries about resuming work; especially asymptomatic infections. The Self-Rating Anxiety Scale (SAS) indicated that 10.8% of participants had mild anxiety, 1.5% moderate anxiety, and 0.1% severe anxiety. Female, divorced/widowed, and working in a high risk hospital (the Huangzhou District People's Hospital was used for throat swab examinations of returning workers) were risk factors for concerns about resuming work and anxiety symptoms. However, good preventive knowledge was a protective factor for anxiety. HCWs' trust in using TCM to treat COVID-19 was significantly higher than their trust in using TCM for prevention (P < 0.001). Regarding preferences for preventative TCM products, oral TCM granules were the most preferred (62.4%). HCWs also indicated they wanted to know more about the clinical efficacy, applicable population, and adverse reactions of preventative TCM products (89.3, 81.1, and 81.4%, respectively). Conclusion: While HCWs had good knowledge of COVID-19 preventative measures, this did not eliminate the psychological impact of resumption of work. Promotion of COVID-19 prevention knowledge reduces the risk of infection, and alleviates the worries and anxiety symptoms of HCWs about resuming work (especially in administrative staff, those with low education, and those working in primary hospitals). Additional psychological support is required for female HCWs, divorced/widowed HCWs, and those working in high-risk hospitals. Finally, systematic trials of preventative TCM products are recommended.


Subject(s)
COVID-19 , Return to Work , China , Cross-Sectional Studies , Female , Health Personnel , Humans , Male , SARS-CoV-2
6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-294868

ABSTRACT

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel RNA virus that emerged in late 2019 and was responsible for coronavirus disease (COVID-19). The WHO has declared the COVID-19 in the world pandemic. The most exacerbations of asthma are triggered by viral infections. However, the genetic effects of COVID-19 on asthma need to be further studied. Results Eighty-eight common differentially expressed genes (cDEGs) were identified in datasets GSE147507 and GSE30326. Function analysis showed that cDEGs has antiviral activity, histone kinase activity, chemokine activity and viral protein interaction with cytokine activity. protein–protein interactions (PPIs) network revealed that the proteins encoded by CDEGs interact with each other at a high frequency. Hub genes and essential modules were detected based on the PPIs network. Transcription factors (TF) and miRNA interaction with cDEGs are identified. Drug molecules such as suloctidil HL60 UP and Yu Ping Feng San were recommended for the treatment of novel coronavirus-induced exacerbation of asthma. Conclusions COVID-19 has a genetic effect on virus-induced exacerbation of asthma, and the hub genes we screened may be a potential therapeutic target.

7.
Front Public Health ; 9: 722604, 2021.
Article in English | MEDLINE | ID: covidwho-1450847

ABSTRACT

Objective: The objective of this study was to investigate how knowledge and practice of coronavirus disease 2019 (COVID-19) prevention measures affected concerns about returning to work among supermarket staff. Attitudes about the ability of traditional Chinese medicine (TCM) to prevent COVID-19 were also assessed. Methods: A cross-sectional study was conducted in Huanggang, Hubei Province, China from April 23 to 25, 2020. Participants were invited to fill out an electronic questionnaire on their cell phones. Results: The results showed that from 2,309 valid questionnaires, 61.5% of participants were concerned about resuming work. Major concerns included asymptomatic infection (85.01%) and employees gathering in the workplace (78.96%). Multivariate logistic regression indicated that the female gender, having school-aged children and pregnancy were risk factors for being concerned about resuming work, while good knowledge and practice of preventive measures were protective factors. Knowledge and practice of preventive measures were positively correlated. Among preventive measures, the highest percentage of participants knew about wearing masks and washing hands. Meanwhile, 65.8% of participants expressed confidence in the ability of TCM to prevent COVID-19, where 74 and 51.3% thought there was a need and a strong need, respectively, for preventive TCM-based products. Among them, 71.5% preferred oral granules. Regarding TCM as a COVID-19 preventative, most were interested in information about safety and efficacy. Conclusion: These findings suggested that promoting knowledge and practices regarding COVID-19 prevention can help alleviate concerns about returning to work. Meanwhile, TCM can feasibly be accepted to diversify COVID-19 prevention methods. Clinical Trial Registration:http://www.chictr.org.cn/, identifier: ChiCTR2000031955.


Subject(s)
COVID-19 , Medicine, Chinese Traditional , Attitude , Child , China/epidemiology , Cross-Sectional Studies , Female , Humans , Return to Work , SARS-CoV-2 , Supermarkets , Surveys and Questionnaires
8.
Clin Exp Med ; 2021 Sep 12.
Article in English | MEDLINE | ID: covidwho-1401039

ABSTRACT

FURIN, as a proprotein convertase, has been found to be expressed in a variety of cancers and plays an important role in cancer. In addition, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires FURIN to enter human cells. However, the role of FURIN in lung adenocarcinoma remains unclear. And the expression of SARS-CoV-2 related gene in lung adenocarcinoma has not been clarified. Therefore, in order to explore the prognostic value and mechanism of FURIN in lung adenocarcinoma, we performed bioinformatics analysis with Oncomine, Tumor Immune Estimation Resource, Gene Expression Profiling Interactive Analysis, human protein atlas, UALCAN, PrognoScan, Kaplan-Meier plotter, cBioPortal and LinkedOmics databases. And then we used GSE44274 in the GEO (Gene Expression Omnibus) database to analyze the expression of FURIN in LUAD patients who infected with SARS-CoV. FURIN was highly expressed in lung adenocarcinoma and was significantly associated with poor overall survival. FURIN expression was found to be correlated with six major permeable immune cells and with macrophage immune marker in LUAD patients. In addition, SARS-CoV-2 infection might affect the expression of FURIN. FURIN can be used as a promising biomarker for determining prognosis and immune infiltration in LUAD patients.

9.
J Pharm Anal ; 11(6): 683-690, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1386105

ABSTRACT

Since December 2019, severe acute respiratory syndrome coronavirus 2 has been found to be the culprit in the coronavirus disease 2019 (COVID-19), causing a global pandemic. Despite the existence of many vaccine programs, the number of confirmed cases and fatalities due to COVID-19 is still increasing. Furthermore, a number of variants have been reported. Because of the absence of approved anti-coronavirus drugs, the treatment and management of COVID-19 has become a global challenge. Under these circumstances, drug repurposing is an effective method to identify candidate drugs with a shorter cycle of clinical trials. Here, we summarize the current status of the application of drug repurposing in COVID-19, including drug repurposing based on virtual computer screening, network pharmacology, and bioactivity, which may be a beneficial COVID-19 treatment.

10.
Pharmacol Res ; 158: 104929, 2020 08.
Article in English | MEDLINE | ID: covidwho-1318939

ABSTRACT

The epidemic of pneumonia (COVID-19) caused by novel coronavirus (SARS-CoV-2) infection has been listed as a public health emergency of international concern by the World Health Organization (WHO), and its harm degree is defined as a global "pandemic". At present, the efforts of various countries focus on the rapid diagnosis and isolation of patients, as well as to find a treatment that can combat the most serious impact of the disease. The number of reported COVID-19 virus infections is still increasing. Unfortunately, no drugs or vaccines have been approved for the treatment of human coronaviruses, but there is an urgent need for in-depth research on emerging human infectious coronaviruses. Clarification transmission routes and pathogenic mechanisms, and identification of potential drug treatment targets will promote the development of effective prevention and treatment measures. In the absence of confirmed effective treatments, due to public health emergencies, it is essential to study the possible effects of existing approved antivirals drugs or Chinese herbal medicines for SARS-CoV-2. This review summarizes the epidemiological characteristics, pathogenesis, virus structure and targeting strategies of COVID-19. Meanwhile, this review also focus on the re-purposing of clinically approved drugs and Chinese herbal medicines that may be used to treat COVID-19 and provide new ideas for the discovery of small molecular compounds with potential therapeutic effects on novel COVID-19.


Subject(s)
Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Drug Repositioning , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Molecular Targeted Therapy/methods , Pneumonia, Viral/drug therapy , COVID-19 , Humans , Pandemics , SARS-CoV-2
11.
Eur J Hum Genet ; 29(8): 1312-1315, 2021 08.
Article in English | MEDLINE | ID: covidwho-1191639

ABSTRACT

Critically ill coronavirus disease 2019 (COVID-19) is characterized by severe cytokine storms, a hyperinflammatory condition intimately related to the development of fatal outcomes. Why some individuals seem particularly vulnerable to severe cytokine storms is still unknown. Primary immunodeficiency (PID)-related genes are inherited factors that dysregulate host inflammatory responses to infection, especially hemophagocytic lymphohistiocytosis (HLH)-related genes, established as contributors to the development of excessive cytokine storms. We analyzed the association between PID gene variants with severe cytokine storms in COVID-19. We conducted whole-exome sequencing in 233 hospitalized COVID-19 patients and identified four PID gene (UNC13D, AP3B1, RNF168, DHX58) variants were significantly enriched in COVID-19 patients experiencing severe cytokine storms. The total percentage of COVID-19 patients with variants in UNC13D or AP3B1, two typical HLH genes, was dramatically higher in high-level cytokine group than in low-level group (33.3 vs. 5.7%, P < 0.001). Germline variants in UNC13D and AP3B1 were associated with the development of severe cytokine storms, fatal outcomes in COVID-19. These findings advance the understanding of individual susceptibility to severe cytokine storms and help optimize the current management of COVID-19.


Subject(s)
Adaptor Protein Complex 3/genetics , Adaptor Protein Complex beta Subunits/genetics , COVID-19/genetics , COVID-19/pathology , Membrane Proteins/genetics , Adaptor Protein Complex 3/metabolism , Adaptor Protein Complex beta Subunits/metabolism , Aged , COVID-19/immunology , COVID-19/metabolism , Cytokine Release Syndrome/genetics , Humans , Lymphohistiocytosis, Hemophagocytic/genetics , Membrane Proteins/metabolism , Middle Aged
12.
J Allergy Clin Immunol ; 146(6): 1453-1454, 2020 12.
Article in English | MEDLINE | ID: covidwho-783289
13.
Aging (Albany NY) ; 13(4): 4811-4830, 2021 02 13.
Article in English | MEDLINE | ID: covidwho-1082565

ABSTRACT

Traditional Chinese medicine (TCM) had demonstrated effectiveness in the prevention and control of COVID-19. Statistics showed that Ephedra and Glycyrrhiza were frequently used in the treatment of COVID-19. We hypothesized that the Ephedra-Glycyrrhiza drug pair is a potential choice for the treatment of COVID-19. Here, 112 active compounds were identified from Ephedra-Glycyrrhiza via network pharmacology approach. Ephedra-Glycyrrhiza pair enrichment analysis demonstrated that these compounds might participate in the cAMP, PI3K-Akt, JAK-STAT and chemokine signaling pathways, which had a high correlation with respiratory, nervous, blood circulation and digestive system-related diseases. Pathway analysis between Ephedra-Glycyrrhiza and COVID-19 showed that the key targets were TNF-α, IL2, FOS, ALB, and PTGS2. They might control PI3K-Akt signaling pathway to exert immune regulation, organ protection and antiviral effects. Molecular docking results showed that the active compounds from the Ephedra-Glycyrrhiza pair bound well to COVID-19 related targets, including the main protease (Mpro, also called 3CLpro), the spike protein (S protein), and the angiotensin-converting enzyme 2 (ACE2). The Molecular dynamics simulation was analyzed for the stability and flexibility of the complex. In conclusion, our study elucidated the potential pharmacological mechanism of Ephedra-Glycyrrhiza in the treatment of COVID-19 through multiple targets and pathways.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Drugs, Chinese Herbal/pharmacology , Ephedra/chemistry , Glycyrrhiza/chemistry , SARS-CoV-2/drug effects , Angiotensin-Converting Enzyme 2/metabolism , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , COVID-19/metabolism , Drug Combinations , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/therapeutic use , Humans , Molecular Docking Simulation , Protein Interaction Maps/drug effects , SARS-CoV-2/physiology , Signal Transduction/drug effects , Spike Glycoprotein, Coronavirus/metabolism
14.
Eur J Integr Med ; 41: 101251, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1065082

ABSTRACT

INTRODUCTION: Traditional Chinese medicine (TCM) has been fully committed to the treatment of coronavirus disease 2019 (COVID-19) in China. An increasing number of clinical trials have been registered to evaluate the effects of TCM for COVID-19. The aim of this study was to review the existing TCM clinical trial registrations and identify potentially promising and available TCM therapies, in order to provide a reference for the global management of COVID-19. METHODS: All clinical trials on TCM for COVID-19 registered in registry platforms worldwide were searched. The data of registration temporal trend, design, objective, interventions, and relevant information were reviewed and summarized. RESULTS: 161 TCM trials were identified from three registries (January 26 to May 14 2020,). Of these, 94 (58.4%) were randomized controlled trials and 114 trials (70.8%) assessed therapeutic effects; while the remainder focused on prevention, rehabilitation, and the epidemiology of TCM syndromes. Eight trials (5.0%) had completed their recruitment. TCM interventions with potential for further evaluation in terms of prevention were moxibustion, Huoxiang Zhengqi pill and Jinye Baidu granules. For treatment of COVID-19, Qingfei Paidu decoction, Huashi Baidu decoction, Lianhua Qingwen capsules, Toujie Quwen granules and Xiyanping injection, and Xuebijing injection were to be tested for their therapeutic effects and symptoms relief. For rehabilitation, Tai Chi and Liuzijue were to be tested for improving patients' lung function. CONCLUSION: Some potentially promising TCM interventions have been identified and deserve further evaluation to establish their evidence base, particularly on populations outside of China.

16.
Front Pharmacol ; 11: 570893, 2020.
Article in English | MEDLINE | ID: covidwho-952214

ABSTRACT

The Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 has been rapidly spreading globally and has caused worldwide social and economic disruption. Currently, no specific antiviral drugs or clinically effective vaccines are available to prevent and treat COVID-19. Traditional Chinese medicine (TCM) can facilitate syndrome differentiation and treatment according to the clinical manifestations of patients and has demonstrated effectiveness in epidemic prevention and control. In China, TCM intervention has helped to control the epidemic; however, TCM has not been fully recognized worldwide. In this review, we summarize the epidemiology and etiological characteristics of severe acute respiratory syndrome coronavirus 2 and the prevention and treatment measures of COVID-19. Additionally, we describe the application of TCM in the treatment of COVID-19 and the identification of small molecules of TCM that demonstrate anti-coronavirus activity. We also analyze the current problems associated with the recognition of TCM. We hope that, through the contribution of TCM, combined with modern technological research and the support of our international counterparts, COVID-19 can be effectively controlled and treated.

17.
Front Genet ; 11: 575770, 2020.
Article in English | MEDLINE | ID: covidwho-886162

ABSTRACT

Type 2 transmembrane serine protease (TMPRSS2) is a new member of the serine proteases, and studies have shown that TMPRSS2 plays a role in the occurrence of prostate malignancies and is closely related to the occurrence of the coronavirus disease 2019 (COVID-19). However, the role of TMPRSS2 in prostatic adenocarcinoma (PRAD) remains largely unclear. To better explore its function in PRAD, we examined the expression level of TMPRSS2 in the GEO, tumor immune assessment resource (TIMER), as well as Oncomine databases and studied the association between TMPRSS2 and overall survival (OS) rates in the UALCAN and gene expression profiling interactive analysis (GEPIA) databases. In addition, we studied the correlation of the level of immune infiltration and markers of immune cell type in the TIMER database, analyzed the prognosis based on the expression level of TMPRSS2 in the related immune cell subsets, and determined the methylation profile of TMPRSS2 promoter by UALCAN database. Subsequently, we conducted a survival analysis and gene ontology (GO) pathway analysis in the TISID database and detected the expression of TMPRSS2 in the Human Protein Atlas (HPA) database. We also studied the protein-protein interaction (PPI) network of TMPRSS2 in the GENEMANIA database. Additionally, we used the microarray GSE56677 and GSE52920 to illustrate changes in TMPRSS2 expression in vivo and in vitro after severe acute respiratory syndrome-coronavirus (SARS-COV) infection, finding that expression of TMPRSS2 decreased after SARS-COV infection in vitro. The function of TMPRSS2 in the dataset was further verified by gene set enrichment analysis (GSEA). In conclusion, the expression of TMPRSS2 is significantly increased in PRAD, elevated TMPRSS2 is associated with immune infiltration, and prognosis is positively correlated. In addition, tumor tissue from COVID-19 patients with PRAD may be more susceptible to infection with SARS-COV-2, which may render the prognosis gets worse.

18.
Drug Dev Ind Pharm ; 46(12): 1947-1959, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-861636

ABSTRACT

PURPOSE: Shenfu decoction has outstanding curative effects in the treatment of COVID-19. This study aimed to explore the material basis and molecular mechanism of Shenfu Decoction through network pharmacology and molecular mechanisms, to provide a research basis for clinical medication and clues for subsequent research. METHODS: The active components and targets of Shenfu decoction were searched in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the COVID-19-associated genes were collected using the Gene Cards platform. The target protein-protein interaction network map was constructed by mapping two genes, and the 'drug-active ingredient-target' network was constructed using Cytoscape software. The Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of the mapping targets were analyzed. RESULT: Based on Traditional Chinese medicine, Shenfu Decoction can take effect in the lung, spleen, kidney and heart. Considering oral bioavailability (OB) ≥ 30% and drug-like (DL) ≥ 0.18 as the standard, 43 active compounds were screened and 114 Shenfu decoction action targets were collected. The key targets were CASP3, MAPK8, PTGS2, IL1B, PPARG, ICAM1, IFNG, RELA, NOS2, NOS3, HMOX1, CASP8, STAT1, and TGFB1. According to the standard of p < .05, GO function was enriched in 108 biological processes, 16 cell processes and 27 molecular processes. Sixty-three signaling pathways were enriched by KEGG, which can be divided into four types: viral infection pathways, signal pathways, biological process pathways and different disease pathways. The comparison of negative and positive prescriptions further reflects the positive effect of Shenfu decoction against COVID-19. Finally, the effective ingredients with the high degree were molecular docked with Mpro, Rdrp and Spro proteins to further confirm the intervention effect of Shenfu Decoction on COVID-19. CONCLUSION: Shenfu decoction played an important role in regulating the anti-virus process, regulating immunity, inhibiting inflammation and regulating apoptosis through the interrelated regulation mechanism of multi-components and multi-targets, to treat patients with severe COVID-19.


Subject(s)
COVID-19 , Drugs, Chinese Herbal , Molecular Docking Simulation/methods , Pneumonia, Viral , SARS-CoV-2 , Signal Transduction/drug effects , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Biological Availability , COVID-19/drug therapy , COVID-19/metabolism , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Gene Ontology , Humans , Medicine, Chinese Traditional/methods , Pneumonia, Viral/drug therapy , Pneumonia, Viral/etiology , SARS-CoV-2/drug effects , SARS-CoV-2/physiology
19.
J Allergy Clin Immunol ; 146(1): 137-146.e3, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-637807

ABSTRACT

BACKGROUND: Accumulating evidence proposed Janus-associated kinase (JAK) inhibitors as therapeutic targets warranting rapid investigation. OBJECTIVE: This study evaluated the efficacy and safety of ruxolitinib, a JAK1/2 inhibitor, for coronavirus disease 2019. METHODS: We conducted a prospective, multicenter, single-blind, randomized controlled phase II trial involving patients with severe coronavirus disease 2019. RESULTS: Forty-three patients were randomly assigned (1:1) to receive ruxolitinib plus standard-of-care treatment (22 patients) or placebo based on standard-of-care treatment (21 patients). After exclusion of 2 patients (1 ineligible, 1 consent withdrawn) from the ruxolitinib group, 20 patients in the intervention group and 21 patients in the control group were included in the study. Treatment with ruxolitinib plus standard-of-care was not associated with significantly accelerated clinical improvement in severe patients with coronavirus disease 2019, although ruxolitinib recipients had a numerically faster clinical improvement. Eighteen (90%) patients from the ruxolitinib group showed computed tomography improvement at day 14 compared with 13 (61.9%) patients from the control group (P = .0495). Three patients in the control group died of respiratory failure, with 14.3% overall mortality at day 28; no patients died in the ruxolitinib group. Ruxolitinib was well tolerated with low toxicities and no new safety signals. Levels of 7 cytokines were significantly decreased in the ruxolitinib group in comparison to the control group. CONCLUSIONS: Although no statistical difference was observed, ruxolitinib recipients had a numerically faster clinical improvement. Significant chest computed tomography improvement, a faster recovery from lymphopenia, and favorable side-effect profile in the ruxolitinib group were encouraging and informative to future trials to test efficacy of ruxolitinib in a larger population.


Subject(s)
Coronavirus Infections/drug therapy , Janus Kinase Inhibitors/therapeutic use , Pneumonia, Viral/drug therapy , Pyrazoles/therapeutic use , Aged , Betacoronavirus , COVID-19 , Coronavirus Infections/mortality , Female , Humans , Male , Middle Aged , Nitriles , Pandemics , Pneumonia, Viral/mortality , Pyrimidines , SARS-CoV-2 , Single-Blind Method , Treatment Outcome
20.
Cell Mol Immunol ; 17(9): 992-994, 2020 09.
Article in English | MEDLINE | ID: covidwho-630398
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