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1.
Scientific Reports ; 12(1):7402-7402, 2022.
Article in English | PMC | ID: covidwho-1821612

ABSTRACT

We evaluated pulmonary sequelae in COVID-19 survivors by quantitative inspiratory–expiratory chest CT (QCT) and explored abnormal pulmonary diffusion risk factors at the 6-month follow-up. This retrospective study enrolled 205 COVID-19 survivors with baseline CT data and QCT scans at 6-month follow-up. Patients without follow-up pulmonary function tests were excluded. All subjects were divided into group 1 (carbon monoxide diffusion capacity [DL CO ] < 80% predicted, n = 88) and group 2 (DL CO  ≥ 80% predicted, n = 117). Clinical characteristics and lung radiological changes were recorded. Semiquantitative total CT score (0–25) was calculated by adding five lobes scores (0–5) according to the range of lesion involvement (0: no involvement;1: < 5%;2: 5–25%;3: 26–50%;4: 51–75%;5: > 75%). Data was analyzed by two-sample t-test, Spearman test, etc. 29% survivors showed air trapping by follow-up QCT. Semiquantitative CT score and QCT parameter of air trapping in group 1 were significantly greater than group 2 ( p  < 0.001). Decreased DL CO was negatively correlated with the follow-up CT score for ground-glass opacity (r = − 0.246, p  = 0.003), reticulation (r = − 0.206, p  = 0.002), air trapping (r = − 0.220, p  = 0.002) and relative lung volume changes (r = − 0.265, p  = 0.001). COVID-19 survivors with lung diffusion deficits at 6-month follow-up tended to develop air trapping, possibly due to small-airway impairment.

2.
Social Science & Medicine ; 302:114988, 2022.
Article in English | ScienceDirect | ID: covidwho-1815178

ABSTRACT

Investigating the spatial epidemic dynamics of COVID-19 is crucial in understanding the routine of spatial diffusion and in surveillance, prediction, identification and prevention of another potential outbreak. However, previous studies attempting to evaluate these spatial diffusion dynamics are limited. Using city as the research unit and spatial association analysis as the primary strategy, this study explored the changing primary risk factors impacting the spatial spread of COVID-19 across Chinese cities under various diffusion assumptions and throughout the epidemic stage. Moreover, this study investigated the characteristics and geographical distributions of high-risk areas in different epidemic stages. The results empirically indicated rapid intercity diffusion at the early stage and primarily intracity diffusion thereafter. Before countermeasures took effect, proximity, GDP per capita, medical resources, outflows from Wuhan and intercity mobility significantly affected early diffusion. With speedily effective countermeasures, outflows from the epicenter, proximity, and intracity outflows played an important role. At the early stage, high-risk areas were mainly cities adjacent to the epicenter, with higher GDP per capita, or a combination of higher GDP per capita and better medical resources, with more outflow from the epicenter, or more intercity mobility. After countermeasures were effected, cities adjacent to the epicenter, or with more outflow from the epicenter or more intracity mobility became high-risk areas. This study provides an insightful understanding of the spatial diffusion of COVID-19 across cities. The findings are informative for effectively handling the potential recurrence of COVID-19 in various settings.

3.
Chest ; 2022.
Article in English | ScienceDirect | ID: covidwho-1814242

ABSTRACT

Mortality has historically been the primary outcome of choice for acute and critical care clinical trials. However, undue reliance on mortality can limit the scope of trials that can be performed. Large sample sizes are usually needed for trials powered for a mortality outcome and focusing solely on mortality fails to recognize the importance that reducing morbidity can have patients’ lives. The coronavirus disease 2019 (COVID-19) pandemic has highlighted the need for rapid, efficient trials to rigorously evaluate new therapies for hospitalized patients with acute lung injury. Oxygen-free days (OFDs) is a novel outcome for clinical trials that is a composite of mortality and duration of new supplemental oxygen use. It is designed to characterize recovery from acute lung injury in populations with a high prevalence of new hypoxemia and supplemental oxygen use. In these populations, OFDs captures two patient-centered consequences of acute lung injury, including mortality and hypoxemic lung dysfunction. Power to detect differences in OFDs is typically greater than that for other clinical trial outcomes such as mortality and ventilator-free days. OFDs is the primary outcome for the ACTIV-4 Host Tissue platform, which evaluates novel therapies targeting the host response to COVID-19 among adults hospitalized with COVID-19 and new hypoxemia. This manuscript outlines the rationale for use of OFDs as an outcome for clinical trials, proposes a standardized method for defining and analyzing OFDs, and provides a framework for sample size calculations using the OFD outcome.

4.
Environmental Research ; 212:113297, 2022.
Article in English | ScienceDirect | ID: covidwho-1796872

ABSTRACT

Meteorological factors have been confirmed to affect the COVID-19 transmission, but current studied conclusions varied greatly. The underlying causes of the variance remain unclear. Here, we proposed two scientific questions: (1) whether meteorological factors have a consistent influence on virus transmission after combining all the data from the studies;(2) whether the impact of meteorological factors on the COVID-19 transmission can be influenced by season, geospatial scale and latitude. We employed a meta-analysis to address these two questions using results from 2813 published articles. Our results showed that, the influence of meteorological factors on the newly-confirmed COVID-19 cases varied greatly among existing studies, and no consistent conclusion can be drawn. After grouping outbreak time into cold and warm seasons, we found daily maximum and daily minimum temperatures have significant positive influences on the newly-confirmed COVID-19 cases in cold season, while significant negative influences in warm season. After dividing the scope of the outbreak into national and urban scales, relative humidity significantly inhibited the COVID-19 transmission at the national scale, but no effect on the urban scale. The negative impact of relative humidity, and the positive impacts of maximum temperatures and wind speed on the newly-confirmed COVID-19 cases increased with latitude. The relationship of maximum and minimum temperatures with the newly-confirmed COVID-19 cases were more susceptible to season, while relative humidity's relationship was more affected by latitude and geospatial scale. Our results suggested that relationship between meteorological factors and the COVID-19 transmission can be affected by season, geospatial scale and latitude. A rise in temperature would promote virus transmission in cold seasons. We suggested that the formulation and implementation of epidemic prevention and control should mainly refer to studies at the urban scale. The control measures should be developed according to local meteorological properties for individual city.

5.
BMC Genom Data ; 23(1): 22, 2022 Mar 28.
Article in English | MEDLINE | ID: covidwho-1793989

ABSTRACT

OBJECTIVES: American shad (Alosa sapidissima) is an important migratory fish under Alosinae and has long been valued for its economic, nutritional and cultural attributes. Overfishing and barriers across the passage made it vulnerable to sustain. To protect this valuable species, aquaculture action plans have been taken though there are no published genetic resources prevailing yet. Here, we reported the first de novo assembled and annotated transcriptome of A. sapidissima using blood and brain tissues. DATA DESCRIPTION: We generated 160,481 and 129,040 non-redundant transcripts from brain and blood tissues. The entire work strategy involved RNA extraction, library preparation, sequencing, de novo assembly, filtering, annotation and validation. Both coding and non-coding transcripts were annotated against Swissprot and Pfam datasets. Nearly, 83% coding transcripts were functionally assigned. Protein clustering with clupeiform and non-clupeiform taxa revealed ~ 82% coding transcripts retained the orthologue relationship which improved confidence over annotation procedure. This study will serve as a useful resource in future for the research community to elucidate molecular mechanisms for several key traits like migration which is fascinating in clupeiform shads.


Subject(s)
Conservation of Natural Resources , Transcriptome , Animals , Brain , Fisheries , Fishes/genetics , Transcriptome/genetics
6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(2): 645-648, 2022 Apr.
Article in Chinese | MEDLINE | ID: covidwho-1786420

ABSTRACT

Coronavirus disease 2019 (COVID-19) has spread rapidly worldwide since outbreak in December 2019, and become a global public health crisis. Patients with hematological malignancy concurrently infected with COVID-19 are often associated with severe even fatal complications, due to low basic immune function, high intensity of chemotherapy and radiotherapy, and slow immune reconstruction post hematopoietic stem cell transplantation, and their treatment strategies, such as anti-infective therapy, blood transfusion, and the use of granulocyte colony stimulating factor need to be adjusted. The characteristics of patients, chemotherapy, hematopoietic stem cell transplantation, and other clinical factors may affect the prognosis of patients with hematological malignancy concurrently infected with COVID-19. Herein, the latest research progress is reviewed.


Subject(s)
COVID-19 , Hematologic Neoplasms , Hematopoietic Stem Cell Transplantation , Granulocyte Colony-Stimulating Factor/therapeutic use , Hematologic Neoplasms/drug therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Prognosis
7.
Vet Microbiol ; 267: 109391, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1778497

ABSTRACT

Protein tyrosine phosphatase non-receptor type 14 (PTPN14) is a member of the protein tyrosine phosphatase (PTP) family which is a potential tumor suppressor. PTPs modulate the cellular level of tyrosine phosphorylation under normal and pathological conditions. Porcine epidemic diarrhea virus (PEDV) is one of the most important pathogens in the swine industry. Our previous membrane proteomics results showed that PTPN14 was markedly upregulated in PEDV-infected Vero cells. However, its biological roles in PEDV infection have not yet been investigated. In this study, we reported PTPN14 functions as a novel regulator of signal transducer and activator of transcription 3 (STAT3) phosphorylation during PEDV infection. Firstly, PTPN14 was markedly upregulated in PEDV-infected Vero cells with the decrease of STAT3 phosphorylation. Knockdown of PTPN14 or phosphatase inhibitor treatment promoted PEDV proliferation and increased the phosphorylation of STAT3 in Vero cells. On the contrary, overexpression of PTPN14 inhibits viral infection in Vero cells. Moreover, dephosphorylation of STAT3 by PTPN14 might occur in the cytoplasm but not in nucleus. Collectively, our results indicate that PTPN14 plays a negative role in regulating STAT3 activation in PEDV infected Vero cells and demonstrate another layer of regulation in PEDV infection.


Subject(s)
Coronavirus Infections , Porcine epidemic diarrhea virus , Animals , Chlorocebus aethiops , Coronavirus Infections/pathology , Coronavirus Infections/veterinary , Porcine epidemic diarrhea virus/physiology , Protein Tyrosine Phosphatases/metabolism , STAT3 Transcription Factor/genetics , STAT3 Transcription Factor/metabolism , Swine , Tyrosine/metabolism , Vero Cells
8.
Contemp Clin Trials ; : 106758, 2022 Apr 06.
Article in English | MEDLINE | ID: covidwho-1773152

ABSTRACT

In clinical trials with the objective to evaluate the treatment effect on time to recovery, such as investigational trials on therapies for COVID-19 hospitalized patients, the patients may face a mortality risk that competes with the opportunity to recover (e.g., be discharged from the hospital). Therefore, an appropriate analytical strategy to account for death is particularly important due to its potential impact on the estimation of the treatment effect. To address this challenge, we conducted a thorough evaluation and comparison of nine survival analysis methods with different strategies to account for death, including standard survival analysis methods with different censoring strategies and competing risk analysis methods. We report results of a comprehensive simulation study that employed design parameters commonly seen in COVID-19 trials and case studies using reconstructed data from a published COVID-19 clinical trial. Our research results demonstrate that, when there is a moderate to large proportion of patients who died before observing their recovery, competing risk analyses and survival analyses with the strategy to censor death at the maximum follow-up timepoint would be able to better detect a treatment effect on recovery than the standard survival analysis that treat death as a non-informative censoring event. The aim of this research is to raise awareness of the importance of handling death appropriately in the time-to-recovery analysis when planning current and future COVID-19 treatment trials.

9.
Chinese Journal of Animal Nutrition ; 34(1):159-176, 2022.
Article in Chinese | CAB Abstracts | ID: covidwho-1771309

ABSTRACT

This experiment was conducted to investigate the effects of recombinant porcine Lactobacillus reuteri secreting bovine lactoferrin peptide (LFCA) on growth performance of newborn piglets and the protective effect on porcine transmissible gastroenteritis virus (TGEV)infection which caused piglet diarrhea. Experiment 1:thirty-six one-day-old newborn piglets with an average body weight of about 1.5 kg were randomly divided into 3 groups, which were pPG-LFCA/LR-CO21 group, pPG/LR-CO21 group and control group, each group with 12 piglets. Piglets in each group were orally administered recombinant porcine Lactobacillus reuteri expressing LFCA pPG-LFCA/LR-CO21, containing empty vector plasmid PPG/LR-CO21 and equal volume phosphate buffer (PBS);oral administration continued for 3 days, and the observation time after oral administration was 14 d. During the period, piglets were fed freely, and the changes of body weight and diarrhea were recorded. Experiment 2:thirty one-day-old newborn piglets with an average body weight of about 1.5 kg were randomly divided into 5 groups and given TGEV with a half tissue culture infection dose (TCID50) of 10-7.50/mL by oral administration of 1, 3, 6, 9 and 12 mL, respectively. The observation period of 7 d was set to analyze the conditions of half lethal dose. Experiment 3:another thirty-two newborn piglets with an average body weight of about 1.5 kg were selected as experimental animals and randomly divided into 4 groups, with 8 piglets in each group. The groups were pPG-LFCA/LR-CO21 group, pPG/LR-CO21 group, control group and TGEV infect group. There were 8 replicates in each group and 1 piglet in each replicate. Each head of the experimental group was orally fed ppG-LFCA/LR-CO21, pPG/LR-CO21 and equal volume of PBS at a dose of 2..1010 CFU per day for 1 consecutive week. At 8 days of age, TGEV was infected by oral administration at half lethal dose, and samples were collected after 7 days of infection. The weight change and diarrhea of each group of piglets were recorded;hematoxylin-eosin staining was used to detect the length of intestinal villi and the depth of crypts;enzyme linked immunosorbent assay (ELISA) was used to determine total serum total immunoglobulin G (IgG) and total secretory immunoglobulin A (sIgA) antibody contents. RT-qPCR was used to detect the mRNA relative expression levels of Claudin-1, Occludin, tight junction protein-1 (ZO-1), inflammatory cytokines interleukin-6 (IL-6), interleukin-8 (IL-8), interferon-P (IFN-P), tumor necrosis factor-a (TNF-a) and Toll-like receptor 2 (TLR2). The flora structure of the contents of the piglet's cecum was analyzed. After oral recombinant porcine Lactobacillusreuteri, compared with the control group, the average daily gain of newborn piglets in the pPG-LFCA/LR-CO21 group was significantly increased (P < 0.01), while the diarrhea rate was significantly decreased (P < 0.01). Compared with TGEV infection group, the average daily gain of piglets in pPG-LFCA/LR-CO21 group was increased and diarrhea rate was decreased, and the differences were significant (P < 0.05). Villus height and the ratio of villus height to crypt depth in jejunum and ileum were significantly increased (P < 0.05). The contents of total IgG and intestinal mucosal total sIgA antibody in serum of piglets were significantly increased (P < 0.05);the mRNA relative expression levels of tight junction protein-related genes Claudin-1, Occludin and ZO-1 in intestinal mucosal tissue were extremely significantly increased (P < 0.01), and the serum TNF-a content was extremely significantly decreased (P < 0.01). Serum IFN-P, IL-6, IL-8 and TLR2 contents were significantly increased (P < 0.01), and the survival rate of piglets was improved. The analysis of the bacterial diversity in the contents of the piglets' cecum showed that the proportion of normal intestinal flora of piglets decreased after TGEV infection. Compared with the TGEV infect group, the proportion of pathogenic bacteria Bacteroides in piglet's intestinal flora decreased by o

10.
Biomed J ; 2022 Mar 31.
Article in English | MEDLINE | ID: covidwho-1767931

ABSTRACT

BACKGROUND: The impact of COVID-19 on public health has mandated an 'all hands on deck' scientific response. The current clinical study and basic research on COVID-19 are mainly based on existing publications or our knowledge of coronavirus. However, efficiently retrieval of accurate, relevant knowledge on COVID-19 can pose significant challenges for researchers. MATERIAL AND METHODS: To improve quality in accessing important literature findings, we developed a novel natural language processing (NLP) method to automatically recognize the associations among potential targeted host organ systems, associated clinical manifestations, and pathways. We further validated these associations through clinician experts' evaluations and prioritize candidate drug targets through bioinformatics network analysis. RESULTS: We found that the angiotensin-converting enzyme 2 (ACE2), a receptor that SARS-CoV-2 required for cell entry, is associated with cardiovascular and endocrine organ system and diseases. Furthermore, we found SARS-CoV-2 is associated with some important pathways such as IL-6, TNF-alpha, and IL-1 beta-induced dyslipidemia, which are related to inflammation, lipogenesis, and oxidative stress mechanisms, suggesting potential drug candidates. CONCLUSIONS: We prioritized the list of therapeutic targets involved in antiviral and immune modulating drugs for experimental validation, rendering it valuable during public health crises marked by stresses on clinical and research capacity. Our automatic intelligence pipeline also contributes to other novel and emerging disease management and treatments in the future.

11.
Hum Cell ; 2022 Mar 25.
Article in English | MEDLINE | ID: covidwho-1762779

ABSTRACT

Mechanical ventilation may cause ventilator-induced lung injury (VILI) in patients requiring ventilator support. Inhibition of autophagy is an important approach to ameliorate VILI as it always enhances lung injury after exposure to various stress agents. This study aimed to further reveal the potential mechanisms underlying the effects of geranylgeranyl diphosphate synthase large subunit 1 (GGPPS1) knockout and autophagy in VILI using C57BL/6 mice with lung-specific GGPPS1 knockout that were subjected to mechanical ventilation. The results demonstrate that GGPPS1 knockout mice exhibit significantly attenuated VILI based on the histologic score, the lung wet-to-dry ratio, total protein levels, neutrophils in bronchoalveolar lavage fluid, and reduced levels of inflammatory cytokines. Importantly, the expression levels of autophagy markers were obviously decreased in GGPPS1 knockout mice compared with wild-type mice. The inhibitory effects of GGPPS1 knockout on autophagy were further confirmed by measuring the ultrastructural change of lung tissues under transmission electron microscopy. In addition, knockdown of GGPPS1 in RAW264.7 cells reduced cyclic stretch-induced inflammation and autophagy. The benefits of GGPPS1 knockout for VILI can be partially eliminated through treatment with rapamycin. Further analysis revealed that Rab37 was significantly downregulated in GGPPS1 knockout mice after mechanical ventilation, while it was highly expressed in the control group. Simultaneously, Rab37 overexpression significantly enhances autophagy in cells that are treated with cyclin stretch, including GGPPS1 knockout cells. Collectively, our results indicate that GGPPS1 knockout results in reduced expression of Rab37 proteins, further restraining autophagy and VILI.

12.
Clin Infect Dis ; 2021 Nov 12.
Article in English | MEDLINE | ID: covidwho-1758700

ABSTRACT

BACKGROUND: To combat the COVID-19 pandemic, nonpharmaceutical interventions (NPI) were implemented worldwide, which impacted a broad spectrum of acute respiratory infections (ARI). METHODS: Etiologically diagnostic data from 142 559 cases with ARIs, who were tested for eight viral pathogens (influenza virus, IFV; respiratory syncytial virus, RSV; human parainfluenza virus, HPIV; human adenovirus; human metapneumovirus; human coronavirus, HCoV; human bocavirus, HBoV, and human rhinovirus, HRV) between 2012 and 2021, were analyzed to assess the changes of respiratory infections in China during the first COVID-19 pandemic year compared to pre-pandemic years. RESULTS: Test positive rates of all respiratory viruses decreased during 2020, compared to the average levels during 2012-2019, with changes ranging from -17·2% for RSV to -87·6% for IFV. Sharp decreases mostly occurred between February and August when massive NPIs remained active, although HRV rebounded to the historical level during the summer. While IFV and HMPV were consistently suppressed year round, RSV, HPIV, HCoV, HRV HBov resurged and went beyond historical levels during September, 2020-January, 2021, after NPIs were largely relaxed and schools reopened. Resurgence was more prominent among children younger than 18 years and in Northern China. These observations remain valid after accounting for seasonality and long-term trend of each virus. CONCLUSIONS: Activities of respiratory viral infections were reduced substantially in the early phases of the COVID-19 pandemic, and massive NPIs were likely the main driver. Lifting of NPIs can lead to resurgence of viral infections, particularly in children.

13.
Biosens Bioelectron ; 207: 114169, 2022 Mar 18.
Article in English | MEDLINE | ID: covidwho-1748198

ABSTRACT

Isothermal amplification methods are a promising trend in virus detection because of their superiority in rapidity and sensitivity. However, the generation of false positives and limited multiplexity are major bottlenecks that must be addressed. In this study, we developed a multiplex Argonaute (Ago)-based nucleic acid detection system (MULAN) that integrates rapid isothermal amplification with the multiplex inclusiveness of a single Ago for simultaneous detection of multiple targets such as SARS-CoV-2 and influenza viruses. Owing to its high specificity, MULAN can distinguish targets at a single-base resolution for mutant genotyping. Moreover, MULAN also supports portable and visible devices with a limit of detection of five copies per reaction. Validated by SARS-CoV-2 pseudoviruses and clinical samples of influenza viruses, MULAN showed 100% agreement with quantitative reverse-transcription PCR. These results demonstrated that MULAN has great potential to facilitate reliable, easy, and quick point-of-care diagnosis for promoting the control of infectious diseases.

14.
World wide web ; : 1-16, 2022.
Article in English | EuropePMC | ID: covidwho-1743840

ABSTRACT

Every epidemic affects the real lives of many people around the world and leads to terrible consequences. Recently, many tweets about the COVID-19 pandemic have been shared publicly on social media platforms. The analysis of these tweets is helpful for emergency response organizations to prioritize their tasks and make better decisions. However, most of these tweets are non-informative, which is a challenge for establishing an automated system to detect useful information in social media. Furthermore, existing methods ignore unlabeled data and topic background knowledge, which can provide additional semantic information. In this paper, we propose a novel Topic-Aware BERT (TABERT) model to solve the above challenges. TABERT first leverages a topic model to extract the latent topics of tweets. Secondly, a flexible framework is used to combine topic information with the output of BERT. Finally, we adopt adversarial training to achieve semi-supervised learning, and a large amount of unlabeled data can be used to improve inner representations of the model. Experimental results on the dataset of COVID-19 English tweets show that our model outperforms classic and state-of-the-art baselines.

15.
Water ; 14(5):720, 2022.
Article in English | ProQuest Central | ID: covidwho-1742773

ABSTRACT

At a low COD:TN ratio (≤5) in influent, maintaining a longer HRT (≥9 h) and longer SRT (≥30 d) are suggested to improve higher N removal efficiency in case of operation at low DO (Dissolved oxygen) level (0.9 ± 0.2 mg-O2/L). However, in case of operation at high DO level (4.0 ± 0.5 mg-O2/L), short HRT (1 h) and typical SRT (17 d) make it possible to achieve nitrogen removal. On the other hand, at a high COD:TN ratio (≥8.4), a typical HRT (9–15 h), SRT (12–19 d), and DO level (1.3–2.6 mg-O2/L) would be applied. Microbial distribution analysis showed an abundance of AOA (Ammonia-oxidizing archaea) under conditions of low DO (≤0.9 mg-O2/L). Nitrosomonas sp. are mostly found in the all investigated water resource recovery facilities (WRRFs). Nitrosospira sp. are only found under operating conditions of longer SRT for WRRFs with a low COD:TN ratio. In comparison between abundances of Nitrobacter sp. and Nitrospira sp., abundances of Nitrobacter sp. are proportional to low DO concentration rather than abundance of Nitrospira sp. A predominance of nosZ-type denitrifiers were found at low DO level. Abundance of denitrifiers by using nirS genes showed an over-abundance of denitrifiers by using nirK genes at low and high COD:TN ratios.

16.
PLoS One ; 17(3): e0264526, 2022.
Article in English | MEDLINE | ID: covidwho-1742006

ABSTRACT

With the advancements and developments in China's tourism industry, various autonomous forms of tourism have been gaining prominence. As such, to facilitate tourists and provide them with maximum experience while economizing on time and cost is essential. One approach toward achieving this is the optimization of tourism routes. However, so far the studies on this approach have focused primarily on inland tourist sites and have lacked a geographic perspective. Therefore, this study undertook the tourism resource data of Lushunkou District of 2020, used the ArcGIS accessibility evaluation model to analyze tourism resources, and finally used the Vehicle Routing Problem of network analysis technology to optimize the tourism route of Lushunkou District and obtain the general overall intellectual framework and technical methods for tourism route optimization. The results showed that the ArcGIS accessibility evaluation model could be used to integrate resources in the tourism area before using the Vehicle Routing Problem to optimize the analysis of tourism routes, thereby enabling the separation of different types of tourism. These divisions were based on the Vehicle Routing Problem to optimize routes for one-day and two-day tours. A new method and model for optimization for tourism routes was constructed to provide a basis and reference for the optimization of tourism routes in similar cities. The observations and results of the present study can facilitate the government in developing the tourism industry and maximizing the benefits obtained from them. Further, travel agencies and tourists will have the provision of designing optimum tourism routes.

17.
Biosaf Health ; 2022 Mar 11.
Article in English | MEDLINE | ID: covidwho-1734224

ABSTRACT

Due to the COVID-19 pandemic, the development of antiviral drugs has attracted increasing attention. Clinical antiviral drugs show weak solubility, low bioavailability, adverse side effects, or only limited targets. With the advancement of nanotechnology and material science, biosafety nanomaterials have been constructed for drug delivery systems of antiviral disease therapy, such as liposomes, polymers, gold nanoparticles, and graphene. These nanodrug systems can either deliver synthesized antiviral drugs siRNA/miRNA and small molecular compounds, deliver bioactive large molecular drug proteins and mRNA, or show antiviral activity by themselves. Nanodelivery systems could effectively enhance the efficiency of antiviral drugs by increasing drug loading and host cell uptake with a small size and high specific surface area. This review focused on the biosafety nanomaterials used for antiviral therapy and discussed the options for the design of antiviral drugs in the future.

18.
BMC Health Serv Res ; 22(1): 299, 2022 Mar 04.
Article in English | MEDLINE | ID: covidwho-1724483

ABSTRACT

BACKGROUND: The COVID-19 pandemic has exerted an unprecedented and universal impact on global health system, resulting in noticeable challenges in traditional chronic disease care, of which diabetes was reported to be most influenced by the reduction in healthcare resources in the pandemic. China has the world's largest diabetes population, and current diabetes management in China is unsatisfactory, particularly in rural areas. Studies in developed countries have demonstrated that physician-pharmacist collaborative clinics are efficient and cost-effective for diabetes management, but little is known if this mode could be adapted in primary hospitals in China. The aim of this proposed study is to develop and evaluate physician-pharmacist collaborative clinics to manage type 2 diabetes mellitus (T2DM) in primary hospitals in Hunan province. METHODS: A multi-site randomized controlled trial will be conducted to evaluate the effectiveness and cost-effectiveness of the physician-pharmacist collaborative clinics compared with usual care for Chinese patients with T2DM. Six primary hospitals will participate in the study, which will recruit 600 eligible patients. Patients in the intervention group will receive services from both physicians and pharmacists in the collaborative clinics, while the control group will receive usual care from physicians. Patients will be followed up at the 3rd, 6th, 9th and 12th month. Comparison between the two groups will be conducted by assessing the clinical parameters, process indicators and costs on diabetes. A satisfaction survey will also be carried out at the end of the study. DISCUSSION: If effective, the physician-pharmacist collaborative clinics can be adapted and used in primary hospitals of China to improve glycemic control, enhance medication adherence, decrease incidence of complications and reduce patients' dependence on physicians. Findings from the present study are meaningful for developing evidence-based diabetes care policy in rural China, especially in the COVID-19 pandemic era. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000031839 , Registered 12 April 2020.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Interprofessional Relations , Pharmacists , Physicians , COVID-19/epidemiology , China/epidemiology , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Hospitals , Humans , Multicenter Studies as Topic , Pandemics , Randomized Controlled Trials as Topic
19.
Chin Med J (Engl) ; 133(9): 1051-1056, 2020 May 05.
Article in English | MEDLINE | ID: covidwho-1722622

ABSTRACT

BACKGROUND: Medicines for the treatment of 2019-novel coronavirus (2019-nCoV) infections are urgently needed. However, drug screening using live 2019-nCoV requires high-level biosafety facilities, which imposes an obstacle for those institutions without such facilities or 2019-nCoV. This study aims to repurpose the clinically approved drugs for the treatment of coronavirus disease 2019 (COVID-19) in a 2019-nCoV-related coronavirus model. METHODS: A 2019-nCoV-related pangolin coronavirus GX_P2V/pangolin/2017/Guangxi was described. Whether GX_P2V uses angiotensin-converting enzyme 2 (ACE2) as the cell receptor was investigated by using small interfering RNA (siRNA)-mediated silencing of ACE2. The pangolin coronavirus model was used to identify drug candidates for treating 2019-nCoV infection. Two libraries of 2406 clinically approved drugs were screened for their ability to inhibit cytopathic effects on Vero E6 cells by GX_P2V infection. The anti-viral activities and anti-viral mechanisms of potential drugs were further investigated. Viral yields of RNAs and infectious particles were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and plaque assay, respectively. RESULTS: The spike protein of coronavirus GX_P2V shares 92.2% amino acid identity with that of 2019-nCoV isolate Wuhan-hu-1, and uses ACE2 as the receptor for infection just like 2019-nCoV. Three drugs, including cepharanthine (CEP), selamectin, and mefloquine hydrochloride, exhibited complete inhibition of cytopathic effects in cell culture at 10 µmol/L. CEP demonstrated the most potent inhibition of GX_P2V infection, with a concentration for 50% of maximal effect [EC50] of 0.98 µmol/L. The viral RNA yield in cells treated with 10 µmol/L CEP was 15,393-fold lower than in cells without CEP treatment ([6.48 ±â€Š0.02] × 10vs. 1.00 ±â€Š0.12, t = 150.38, P < 0.001) at 72 h post-infection (p.i.). Plaque assays found no production of live viruses in media containing 10 µmol/L CEP at 48 h p.i. Furthermore, we found CEP had potent anti-viral activities against both viral entry (0.46 ±â€Š0.12, vs.1.00 ±â€Š0.37, t = 2.42, P < 0.05) and viral replication ([6.18 ±â€Š0.95] × 10vs. 1.00 ±â€Š0.43, t = 3.98, P < 0.05). CONCLUSIONS: Our pangolin coronavirus GX_P2V is a workable model for 2019-nCoV research. CEP, selamectin, and mefloquine hydrochloride are potential drugs for treating 2019-nCoV infection. Our results strongly suggest that CEP is a wide-spectrum inhibitor of pan-betacoronavirus, and further study of CEP for treatment of 2019-nCoV infection is warranted.


Subject(s)
Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Betacoronavirus/genetics , COVID-19 , COVID-19 Testing , Cell Line , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Drug Approval , Humans , Pandemics , Pneumonia, Viral/diagnosis , RNA, Small Interfering/genetics , Real-Time Polymerase Chain Reaction , SARS-CoV-2 , Viral Load
20.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329417

ABSTRACT

SARS-CoV-2 has infected more than 400 million people around the globe and caused millions of deaths. Since its identification in November 2021, Omicron, a highly transmissible variant, has become the dominant variant in most countries. Omicron highly mutated spike protein, the main target of vaccine development, significantly compromises the immune protection from current vaccination. We develop an mRNA vaccine (SOmicron-6P) based on an Omicron-specific sequence. In mice, SOmicron-6P shows superior neutralizing antibodies inducing abilities to a clinically approved inactivated virus vaccine, a clinically approved protein subunit vaccine, and an mRNA vaccine (SWT-2P) with the same sequence of BNT162b2 RNA. Significantly, SOmicron-6P induces a 14.4~27.7-fold and a 28.3~50.3-fold increase of neutralizing activity against the pseudovirus of Omicron and authentic Omicron compared to SWT-2P, respectively. In addition, two doses SOmicron-6P significantly protects Syrian hamsters against challenge with SARS-CoV-2 Omicron variant and elicits high titers of nAbs in a dose-dependent manner in macaques. Our results suggest that SOmicron-6P offers advantages over current vaccines, and it will be helpful for those with weak immunity.

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