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1.
Applied Sciences ; 12(10):5122, 2022.
Article in English | ProQuest Central | ID: covidwho-1870863

ABSTRACT

This study took food-grade polypropylene packaging products as the research project and discussed how to control the polypropylene extrusion sheet thickness and vacuum thermoforming quality and weight. The research objective was to find the key factors for reducing costs and energy consumption. The key aspects that may influence the polypropylene extrusion molding quality control were analyzed using literature and in-depth interviews with scholars and experts. These four main aspects are (1) key factors of polypropylene extrusion sheet production, (2) key factors of the extrusion line design, (3) key factors of polypropylene forming and mold manufacturing, and (4) key factors of mold and thermoforming line equipment design. These were revised and complemented by the scholar and expert group. There are 49 subitems for discussion. Thirteen scholars and experts were invited to use qualitative and quantitative research methods. A Delphi questionnaire survey team was organized to perform three Delphi questionnaire interviews. The statistical analyses of encoded data such as the mean (M), mode (Mo), and standard deviation (SD) of various survey options were calculated. Seeking a more cautious research theory and result, the K-S simple sample test was used to review the fitness and consistency of the scholars’ and experts’ opinions on key subitem factors. There are ten key factors in the production quality, including “A. Main screw pressure”, “B. Polymer temperature”, “C. T-die lips adjustment thickness”, “D. Cooling rolls pressing stability”, “E. Cooling rolls temperature stability”, “F. Extruder main screw geometric design”, “G. Heating controller is stable”, “H. Thermostatic control”, “I. Vacuum pressure”, and “J. Mold forming area design”. The key factors are not just applicable to classical polypropylene extrusion sheet and thermoforming production but also to related process of extrusion and thermoforming techniques in expanded polypropylene (EPP) sheets and polylactic acid (PLA). This study aims to provide a key technical reference for enterprises to improve quality to enhance the competitiveness of products, reduce production costs, and achieve sustainable development, energy savings, and carbon reductions.

2.
Healthcare Analytics ; 2022.
Article in English | EuropePMC | ID: covidwho-1837923

ABSTRACT

In the later stages of the COVID-19 pandemic, hotels are taking various measures to balance pandemic prevention and business operations. Some hotels require travelers to be fully vaccinated prior to check-in, while others do not. In the latter type of hotels, fully vaccinated travelers may encounter others who are not vaccinated. All of these have created constraints for travelers to choose suitable hotel accommodation during this time. To address this issue, a fuzzy multi-criteria decision-making approach is proposed in this study to help traveler choose suitable hotel accommodation. In the proposed methodology, firstly, hotels are divided into two types considering their requirements for COVID-19 vaccination. Travelers are then asked to list the key factors to consider when choosing between these two types of hotels. To derive the priorities of these key factors, the proportionally calibrated fuzzy geometric mean (pcFGM) method is proposed. Subsequently, the fuzzy VIšekriterijumskoKOmpromisnoRangiranje (fuzzy VIKOR) method is applied to evaluate and compare the overall performances of different types of hotels for recommendations to travelers. The applicability of the proposed methodology is illustrated by a real case study. According to the experimental results, most hotels did not request travelers to be full vaccinated. Nevertheless, the hotels recommended to travelers covered both hotel types.

3.
Frontiers in cardiovascular medicine ; 9, 2022.
Article in English | EuropePMC | ID: covidwho-1837494

ABSTRACT

Background The COVID-19 pandemic has led to concerns around its subsequent impact on global health. Objective To investigate the health-seeking behavior, reflected by ECG utilization patterns, of patients with non-COVID-19 diseases during and after COVID-19 epidemic. Methods Taking advantage of the remote ECG system covering 278 medical institutions throughout Shanghai, the numbers of medical visits with ECG examinations during the lockdown (between January 23 and April 7, 2020), post-lockdown (between April 8 and December 31, 2020) and post-SARS-CoV-2 (between January 23 and April 7, 2021) periods were analyzed and compared against those during the same periods of the preceding years (2018 and 2019). Results Compared with the same period during pre-COVID years, the number of medical visits decreased during the lockdown (a 38% reduction), followed by a rebound post-lockdown (a 17% increase) and a fall to the baseline level in post-SARS-CoV-2 period. The number of new COVID-19 cases announced on a given day significantly correlated negatively with the numbers of medical visits during the following 7 days. Medical visit dynamics differed for various arrhythmias. Whereas medical visits for sinus bradycardia exhibited a typical decrease-rebound-fallback pattern, medical visits for atrial fibrillation did not fall during the lockdown but did exhibit a subsequent increase during the post-lockdown period. By comparison, the volume for ventricular tachycardia remained constant throughout this entire period. Conclusion The ECG utilization patterns of patients with arrhythmias exhibited a decrease-rebound-fallback pattern following the COVID-19 lockdowns. Medical visits for diseases with more severe symptoms were less influenced by the lockdowns, showing a resilient demand for healthcare.

4.
Eur J Med Chem ; 238: 114426, 2022 May 07.
Article in English | MEDLINE | ID: covidwho-1821218

ABSTRACT

The COVID-19 pandemic generates a global threat to public health and continuously emerging SARS-CoV-2 variants bring a great challenge to the development of both vaccines and antiviral agents. In this study, we identified UA-18 and its optimized analog UA-30 via the hit-to-lead strategy as novel SARS-CoV-2 fusion inhibitors. The lead compound UA-30 showed potent antiviral activity against infectious SARS-CoV-2 (wuhan-HU-1 variant) in Vero-E6 cells and was also effective against infection of diverse pseudotyped SARS-CoV-2 variants with mutations in the S protein including the Omicron and Delta variants. More importantly, UA-30 might target the cavity between S1 and S2 subunits to stabilize the prefusion state of the SARS-CoV-2 S protein, thus leading to interfering with virus-cell membrane fusion. This study offers a set of novel SARS-CoV-2 fusion inhibitors against SARS-CoV-2 and its variants based on the 3-O-ß-chacotriosyl UA skeleton.

5.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-331890

ABSTRACT

After the adoption of a dynamic zero-COVID strategy in China for nearly two years, whether and for how long this policy can remain in place is unclear. The debate has thus shifted towards the identification of mitigation strategies capable to prevent the disruption of the healthcare system, should a nationwide epidemic caused by the SARS-CoV-2 Omicron variant start to unfold. To this aim, we developed a mathematical model of SARS-CoV-2 transmission tailored to the unique immunization and epidemiological situation of China. We find that the level of immunity induced by the current vaccination campaign would be insufficient to prevent overwhelming the healthcare system and major losses of human lives. Instead, a synergetic strategy would be needed and based on 1) a heterologous booster vaccination campaign, 2) treating 50% of symptomatic cases with an antiviral with an 80% efficacy in preventing severe outcomes, and 3) the adoption of non-pharmaceutical interventions (NPIs) capable of reducing Rt to ≤2. Protecting vulnerable individuals by ensuring accessibility to vaccines and antivirals, and maintaining a certain degree of NPIs should be emphasised in a future mitigation policy, possibly supported by strengthening critical care capacity and the development of highly efficacious vaccines with long-lasting immunity.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315481

ABSTRACT

In this paper, we firstly propose SQIARD and SIARD models to investigate the transmission of COVID-19 with quarantine, infected and asymptomatic infected, and discuss the relation between the respective basic reproduction number $R_0, R_Q$ and the stability of the equilibrium points of model. Secondly, after training the related data parameters, in our numerical simulations, we respectively conduct the forecast of the data of US, South Korea, Brazil, India, Russia and Italy, and the effect of prediction of the epidemic situation in each country. Furthermore, we apply US data to compare SQIARD with SIARD, and display the effects of predictions.

7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315157

ABSTRACT

Background: The COVID-19 pandemic has led to concerns around its subsequent impact on patients with non-COVID-19 diseases, and the health-seeking behavior of such patients must be investigated.Methods: Taking advantage of the remote ECG system covering 278 medical institutions throughout Shanghai, the numbers of hospital visits with ECG examinations during the lockdown (between January 23 and April 7, 2020), post-lockdown (between April 8 and December 31, 2020) and post-epidemic (between January 23 and April 7, 2021) periods were analyzed and compared against those during the same periods of the preceding years (2018 and 2019).Findings: Compared with those of the same period during pre-COVID years, the number of hospital visits decreased during the lockdown (a 38% reduction), followed by a rebound post-lockdown (a 17% increase) and a fall to the baseline level of the post-epidemic period. This decrease-rebound-fallback pattern was largely attributed to the dynamics of visits to community clinics rather than academic hospitals. The number of new COVID-19 cases or deaths announced on a given day correlated negatively with hospital visits during the same day and for the following 42 days, with the correlation at its most prominent at seven days. Hospital visit dynamics differed for various cardiovascular diseases. Whereas hospital visits for sinus bradycardia exhibited a typical decrease-rebound-fallback pattern, hospital visits for ST-segment elevated myocardial infarction did not fall during the lockdown period but did exhibit a subsequent increase during the post-lockdown period. By comparison, the volume for ventricular tachycardia remained constant throughout this entire period.Interpretation: The health-seeking behavior of patients with cardiovascular diseases exhibited a decrease-rebound-fallback pattern following the COVID-19 lockdowns. Hospital visits for diseases with more severe symptoms were less influenced by the lockdowns, showing a resilient demand for healthcare.Funding: Shanghai Hospital Development Center, National Natural Science Foundation of China, Shanghai Municipal Science and Technology Commission, and Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. Declaration of Interest: All authors declare no conflicts of interest.Ethical Approval: This study was approved by the ethics committee at Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine.

8.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-313451

ABSTRACT

Background: Transarterial chemoembolization (TACE) may not be repeated “on-demand” timely for hepatocellular carcinoma (HCC) patients in the era of the novel coronavirus disease (COVID-19). We aim to evaluate the impact of the COVID-19 pandemic on the intervals and outcomes of TACE in HCC patients. Methods: This retrospective study included HCC patients who underwent TACE from Jan 1, 2020 to March 31, 2020 (study group) and Jan 1, 2019 to Mar 31, 2019 (control group) at two institutions in China. The endpoints included the TACE interval and the overall response rate (ORR). Uni- and multivariate logistic analyses were performed to identify independent risk factors associated with a worse ORR. The cut-off point was determined to divide repeated TACE time into long- and short- intervals. Findings: 154 patients (71 in the study group, 83 in the control group) were enrolled. The median TACE interval in the study group was 82·0 days (IQR, 61–109), longer than 66·0 days (IQR, 51–94) in the control group (p=0·004). The ORR was 23·9% in the study group, while 39·8% in the control group (p=0·037). The cut-off value was 95 days. The group (OR, 2·402;95% CI, 1·040–5·546;p=0·040), the long interval (OR, 2·573;95% CI, 1·022–6·478;p=0·045), and the stage system (OR, 2·500;95% CI, 1·797–3·480;p<0·001) were independent predictors. Interpretation: For HCC patients, the COVID-19 pandemic results in a longer re-TACE schedule, which may further lead to a lower ORR. Patients with a TACE interval of more than 95 days may have a worse prognosis. Funding: This study was supported by the National Key Research and Development Project of China (2018YFA0704100), the National Natural Science Foundation of China (Major Scientific Research Instrument Development Program 81827805, 81441054, 81520108015, 81671796, 81901847), Jiangsu Provincial Medical Youth Talent Program (ZDRCA2016078), the Key Research and Development Project of Jiangsu Province (BE2019750), the Natural Science Foundation of Jiangsu Province (BK20190177), Innovation Platform of Jiangsu Provincial Medical Center (YXZXA2016005), and the Suzhou Science and Technology Youth Plan (KJXW2018003).Declaration of Interests: All authors declare no competing interests.Ethics Approval Statement: The study was approved by the institutional ethics review boards in two participating institutions and the requirement for written informed consent was waived due to its retrospective nature.

9.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324643

ABSTRACT

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection swept through Wuhan and spread across China and overseas beginning in December 2019. To identify predictors associated with disease progression, we evaluated clinical risk factors for exacerbation of SARS-CoV-2 infection. Methods: A retrospective analysis was used for PCR-confirmed COVID-19 (coronavirus disease 2019)-diagnosed hospitalized cases between January 19, 2020, and February 19, 2020, in Zhejiang, China. We systematically analysed the clinical characteristics of the patients and predictors of clinical deterioration. Results: One hundred patients with COVID-19, with a median age of 54 years, were included. Among them, 49 patients (49%) had severe and critical disease. Age ([36-58] vs [51-70], P=0.0001);sex (49% vs 77.6%, P=0.0031);Body Mass Index (BMI ) ([21.53-25.51] vs [23.28-27.01], P=0.0339);hypertension (17.6% vs 57.1%, P<0.0001);IL-6 ([6.42-30.46] vs [16.2-81.71], P=0.0001);IL-10 ([2.16-5.82] vs [4.35-9.63], P<0.0001);T lymphocyte count ([305- 1178] vs [167.5-440], P=0.0001);B lymphocyte count ([91-213] vs [54.5-163.5], P=0.0001);white blood cell count ([3.9-7.6] vs [5.5-13.6], P=0.0002);D2 dimer ([172-836] vs [408-953], P=0.005), PCT ([0.03-0.07] vs [0.04-0.15], P=0.0039);CRP ([3.8-27.9] vs [17.3-58.9], P<0.0001);AST ([16, 29] vs [18, 42], P=0.0484);artificial liver therapy (2% vs 16.3%, P=0.0148);and glucocorticoid therapy (64.7% vs 98%, P<0.0001) were associated with the severity of the disease. Age and weight were independent risk factors for disease severity. Conclusion: Deterioration among COVID-19-infected patients occurred rapidly after hospital admission. In our cohort, we found that multiple factors were associated with the severity of COVID19. Early detection and monitoring of these indicators may reduce the progression of the disease. Removing these factors may halt the progression of the disease. In addition, Oxygen support, early treatment with low doses of glucocorticoids and liver therapy, when necessary, may help reduce mortality in critically ill patients.

10.
Agriculture ; 12(1):111, 2022.
Article in English | MDPI | ID: covidwho-1625916

ABSTRACT

With the widespread vaccination against COVID-19, people began to resume regional tourism. Outdoor attractions, such as leisure agricultural parks, are particularly attractive because they are well ventilated and can prevent the spread of COVID-19. However, during the COVID-19 pandemic, the considerations around choosing a leisure agricultural park are different from usual, and will be affected by uncertainty. Therefore, this research proposes a fuzzy collaborative intelligence (FCI) approach to help select leisure agricultural parks suitable for traveler groups during the COVID-19 pandemic. The proposed FCI approach combines asymmetrically calibrated fuzzy geometric mean (acFGM), fuzzy weighted intersection (FWI), and fuzzy Vise Kriterijumska Optimizacija I Kompromisno Resenje (fuzzy VIKOR), which is a novel attempt in this field. The effectiveness of the proposed FCI approach has been verified by a case study in Taichung City, Taiwan. The results of the case study showed that during the COVID-19 pandemic, travelers (especially traveler groups) were very willing to go to leisure agricultural parks. In addition, the most important criterion for choosing a suitable leisure agricultural park was the ease of maintaining social distance, while the least important criterion was the distance from a leisure agricultural park. Further, the successful recommendation rate using the proposed methodology was as high as 90%.

11.
Clin Infect Dis ; 73(11): e3949-e3955, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1561940

ABSTRACT

BACKGROUND: We evaluated an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine for immunogenicity and safety in adults aged 18-59 years. METHODS: In this randomized, double-blinded, controlled trial, healthy adults received a medium dose (MD) or a high dose (HD) of the vaccine at an interval of either 14 days or 28 days. Neutralizing antibody (NAb) and anti-S and anti-N antibodies were detected at different times, and adverse reactions were monitored for 28 days after full immunization. RESULTS: A total of 742 adults were enrolled in the immunogenicity and safety analysis. Among subjects in the 0, 14 procedure, the seroconversion rates of NAb in MD and HD groups were 89% and 96% with geometric mean titers (GMTs) of 23 and 30, respectively, at day 14 and 92% and 96% with GMTs of 19 and 21, respectively, at day 28 after immunization. Anti-S antibodies had GMTs of 1883 and 2370 in the MD group and 2295 and 2432 in the HD group. Anti-N antibodies had GMTs of 387 and 434 in the MD group and 342 and 380 in the HD group. Among subjects in the 0, 28 procedure, seroconversion rates for NAb at both doses were both 95% with GMTs of 19 at day 28 after immunization. Anti-S antibodies had GMTs of 937 and 929 for the MD and HD groups, and anti-N antibodies had GMTs of 570 and 494 for the MD and HD groups, respectively. No serious adverse events were observed during the study period. CONCLUSIONS: Adults vaccinated with inactivated SARS-CoV-2 vaccine had NAb as well as anti-S/N antibody and had a low rate of adverse reactions. CLINICAL TRIALS REGISTRATION: NCT04412538.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , Double-Blind Method , Humans , Immunogenicity, Vaccine
12.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-295323

ABSTRACT

Background To allow a return to a pre-COVID-19 lifestyle, virtually every country has initiated a vaccination program to mitigate severe disease burden and control transmission. However, it remains to be seen whether herd immunity will be within reach of these programs. Methods We developed a data-driven model of SARS-CoV-2 transmission for China, a population with low prior immunity from natural infection. The model is calibrated considering COVID-19 natural history and the estimated transmissibility of the Delta variant. Three vaccination programs are tested, including the one currently enacted in China and model-based estimates of the herd immunity level are provided. Results We found that it is unlike to reach herd immunity for the Delta variant given the relatively low efficacy of the vaccines used in China throughout 2021, the exclusion of underage individuals from the targeted population, and the lack of prior natural immunity. We estimate that, assuming a vaccine efficacy of 90% against the infection, vaccine-induced herd immunity would require a coverage of 93% or higher of the Chinese population. However, even when vaccine-induced herd immunity is not reached, we estimated that vaccination programs can reduce SARS-CoV-2 infections by 53-58% in case of an epidemic starts to unfold in the fall of 2021. Conclusions Efforts should be taken to increase population’s confidence and willingness to be vaccinated and to guarantee highly efficacious vaccines for a wider age range.

13.
Sustainability ; 13(23):13449, 2021.
Article in English | MDPI | ID: covidwho-1554819

ABSTRACT

The machine tool industry is an economically important industry in Taiwan. However, due to the limited natural resources in Taiwan, many of the raw materials required for production must be imported. In 2020, COVID-19, the most serious infectious disease in modern times, broke out across the globe. This has had a great impact on the economic and industrial development of various countries and indirectly affected the development of the machine tool industry. The machine tool industry generally is facing shocks and crises. Therefore, this research article mainly discusses a sustainable operation strategy for the machine tool industry during the COVID-19 epidemic period in Taiwan. Firstly, through the literature on dynamic capability theory (DCT) and expert interviews, the relevant dimensions and criteria are summarized. Then, the fuzzy Delphi method (FDM) and the analytic network process (ANP) are integrated to confirm the relevant dimensions and criteria and to sort the criteria. The five dimensions, in order, are integration ability, learning ability, quality improvement, environmental adaptation, and marketing ability. The ten criteria are diversified learning and innovation ability, integration of multiple sources of knowledge, the ability to learn across departments, the ability to adapt to the external environment, marketing strategy ability, organizational learning ability, integration of resources, improved management efficiency, market research ability, and backward integration. Finally, we put forward business strategies for the ranking results and provide relevant research and industry references.

14.
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/drug therapy , COVID-19/virology , Drug Combinations , Humans , Medicine, Chinese Traditional , SARS-CoV-2/isolation & purification
15.
Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi ; 2021.
Article in English | EuropePMC | ID: covidwho-1451502

ABSTRACT

<h4>Background</h4> Respiratory tract infections (RTIs) represent a major cause of clinical visits worldwide. Viral epidemiology of RTIs in adults has been less studied compared to children. FilmArray respiratory panel (FA-RP), a multiplex, real time polymerase chain reaction method can simultaneously detect the nucleic acids of multiple pathogens. The purpose of this study is to analyze the epidemiology and clinical presentations of an RTI cohort. <h4>Methods</h4> This retrospective cohort study was conducted at China Medical University Hospital (CMUH) and China Medical University Children’s Hospital (CMUCH), from January 2020 to June 2020. The FA-RP results were collected and analyzed according to upper versus lower RTIs. <h4>Results</h4> Among 253 respiratory samples tested, 135 (53.4%) were from adults and 118 (46.6%) from children. A total positive rate of 33.9% (86/253) was found, with 21.48% (29/135) in adults and 48.31% (57/118) in children. Human rhinovirus/Enterovirus (HRV/EV) was detected in most of the age groups and was more common in URIs. HRV/EV was found as a frequent co-detection virus. Among children, HRV/EV was the most detected pathogen of URIs, while the most predominant pathogen in LRIs was M. pneumoniae. <h4>Conclusions</h4> FA-RP has the potential to improve the detection rate of respiratory pathogens. The positive rate of FA-RP was higher in children compared to adults, which likely corresponds to the higher incidence of viral RTIs in children. Different pathogens may lead to different types of respiratory infections.

16.
Advanced Materials Technologies ; n/a(n/a):2100842, 2021.
Article in English | Wiley | ID: covidwho-1408260

ABSTRACT

Abstract In light of the swift outspread and considerable mortality, coronavirus disease 2019 (COVID-19) necessitates a rapid screening tool and a precise diagnosis. Saliva is considered as an alternative specimen to detect the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) since the viral load is comparable to what are found in a throat and a nasal cavity. The electrical double layer (EDL)-gated field-effect transistor-based biosensor (BioFET) emerges as a promising candidate for salivary COVID-19 tests due to a high sensitivity, a portable configuration, a label-free operation, and a matrix insensitivity. In this work, the authors utilize EDL-gated BioFETs to detect complementary DNAs (cDNAs) and viral RNAs with various testing conditions such as switches of probes, temperature treatments, and matrices. The selectivity is confirmed with cDNA and noncomplementary DNA (ncDNA), exhibiting an eightfold difference in electrical signals. The matrix insensitivity is evaluated, and BioFETs successfully validate the detection of SARS-CoV-2 N-gene RNA down to 1 fm in diluted human saliva with a 95°C- and a 25°C-treatment, respectively. This proposed system has a high potential to be deployed for an on-site COVID-19 screening, improving the disease control and benefitting frontline healthcare system.

17.
Signal Transduct Target Ther ; 5(1): 220, 2020 10 06.
Article in English | MEDLINE | ID: covidwho-1387194
18.
Mol Ther Methods Clin Dev ; 23: 108-118, 2021 Dec 10.
Article in English | MEDLINE | ID: covidwho-1379195

ABSTRACT

Because of the relatively limited understanding of coronavirus disease 2019 (COVID-19) pathogenesis, immunological analysis for vaccine development is needed. Mice and macaques were immunized with an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine prepared by two inactivators. Various immunological indexes were tested, and viral challenges were performed on day 7 or 150 after booster immunization in monkeys. This inactivated SARS-CoV-2 vaccine was produced by sequential inactivation with formaldehyde followed by propiolactone. The various antibody responses and specific T cell responses to different viral antigens elicited in immunized animals were maintained for longer than 150 days. This comprehensive immune response could effectively protect vaccinated macaques by inhibiting viral replication in macaques and substantially alleviating immunopathological damage, and no clinical manifestation of immunopathogenicity was observed in immunized individuals during viral challenge. This candidate inactivated vaccine was identified as being effective against SARS-CoV-2 challenge in rhesus macaques.

19.
Soft Computing Letters ; : 100016, 2021.
Article in English | ScienceDirect | ID: covidwho-1356444

ABSTRACT

A decision maker may hold multiple viewpoints regarding the relative priorities of criteria simultaneously, but this has rarely been considered in past studies. Therefore, this study proposes a bi-objective analytic hierarchy process (AHP)–mixed integer nonlinear programming (MINLP)–genetic algorithm (GA) approach. First, AHP is applied to decompose the decision maker's judgment matrix into several sub-judgment matrices. Each sub-judgment matrix represents a single viewpoint and generates a priority set. To generate diversified priority sets, a bi-objective MINLP problem is solved using a GA, and multiple alternatives can be selected based on these priority sets. The proposed approach has been applied to the real case of choosing diversified alternative suppliers amid the COVID-19 pandemic to assess its effectiveness. Several existing methods were also applied to this case for comparison. Experimental results showed that only the proposed approach was able to diversify the recommended alternative suppliers that were simultaneously optimal, thereby enhancing decision-making flexibility. In addition, the application of GA increased the solution efficiency by up to 75%.

20.
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 therapy , 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
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