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1.
Mycopathologia ; 189(4): 63, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38985209

ABSTRACT

The diagnosis of Talaromyces marneffei infection in HIV-negative patients remains challenging. There is an urgent need for rapid and convenient methods to diagnose this complicated disease. The aim of this study was to evaluate the diagnostic efficiency of metagenomic next-generation sequencing (mNGS) for talaromycosis in non-HIV-infected patients by comparing mNGS with traditional microbial culture. In total, 66 samples from 57 patients were analyzed via both mNGS and microbial culture. The ROC curve showed a sensitivity for mNGS of 97.22%, which was greater than that of microbial culture (61.11%). Samples from the respiratory tract, infectious skin lesions, and lymph nodes are recommended as routine samples for talaromycosis detection via mNGS. Furthermore, mNGS significantly reduced the diagnostic time compared to microbial culture. Overall, our study demonstrated that mNGS is a promising tool for rapid and accurate pathogenic detection in HIV-negative patients with talaromycosis.


Subject(s)
High-Throughput Nucleotide Sequencing , Metagenomics , Mycoses , Sensitivity and Specificity , Talaromyces , Humans , High-Throughput Nucleotide Sequencing/methods , Talaromyces/genetics , Talaromyces/isolation & purification , Male , Female , Metagenomics/methods , Adult , Mycoses/diagnosis , Mycoses/microbiology , Middle Aged , Aged , Young Adult , ROC Curve , Adolescent
2.
J Epidemiol Glob Health ; 14(1): 131-141, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38224387

ABSTRACT

BACKGROUNDS: Breast cancer screening plays an important role in the early detection, diagnosis and treatment of breast cancer. The aim of this study was to evaluate the screening results and explore the influencing factors of breast cancer detection rate in Guangdong. METHODS: This cross-sectional study was conducted among 2,024,960 women aged 35-64 in Guangdong Province during 2017-2021. The data about breast cancer screening information were collected from the Guangdong maternal and child health information system. Descriptive statistical analysis was used to explain demographic characteristics and results of breast cancer screening. The generalized linear regression model was applied to analyze the related influencing factors of breast cancer detection rate. RESULTS: The estimated detection rate of breast cancer in Guangdong Province is 70.32/105, with an early diagnosis rate of 82.06%. After adjusting covariates, those women with older age (45-55 [OR (95% CI) 2.174 (1.872, 2.526)], 55-65 [OR (95% CI) 2.162 (1.760, 2.657)]), education for high school ([OR (95% CI) 1.491 (1.254, 1.773)]) and older age at first birth ([OR (95% CI) 1.632 (1.445, 1.844)]) were more likely to have higher detection rate of breast cancer. No history of surgery or biopsy ([OR (95% CI) 0.527 (0.387, 0.718)]), no history of breast cancer check ([OR (95% CI) 0.873 (0.774, 0.985)]) and no family history of breast cancer ([OR (95% CI) 0.255 (0.151, 0.432)]) women were more likely to screen negative for breast cancer (P < 0.05). CONCLUSION: The detection rate of breast cancer in screening showed an increasing trend year by year in Guangdong Province. Older age, education for high school and older age at first birth were risk factors for breast cancer detection rate, while no surgery or biopsy history, no family history of breast cancer and no history of breast cancer check were protective factors.


Subject(s)
Breast Neoplasms , Early Detection of Cancer , Humans , Breast Neoplasms/diagnosis , Breast Neoplasms/epidemiology , Female , Early Detection of Cancer/statistics & numerical data , Early Detection of Cancer/methods , Middle Aged , Adult , China/epidemiology , Cross-Sectional Studies , Mammography/statistics & numerical data , Mass Screening/statistics & numerical data , Mass Screening/methods
3.
Int Microbiol ; 2023 Nov 06.
Article in English | MEDLINE | ID: mdl-37932582

ABSTRACT

To investigate the molecular characteristics and biofilm-forming ability of 116 Enterococcus faecium (Efm) and 72 Enterococcus faecalis (Efs) isolates obtained from patients with bloodstream infections (BSI) at a Chinese hospital between July 2011 and March 2018. The presence of glycopeptide resistance genes and five virulence genes (esp, gelE, asa1, hyl, and cylA) was screened using two multiplex PCR. MLST was used to assess the clonality. Crystal violet staining was used to detect biofilms. Vancomycin resistance was detected in 30.1% of Efm and 2.8% of Efs isolates, respectively. All VRE strains carried the vanA gene. The esp, gelE, asa1, and cylA genes in 72 Efs strains were detected at 62.5%, 84.7%, 84.7%, and 69.4%, respectively. Among the 116 Efm isolates, 74.1% and 25.8% carried esp and hyl, respectively. The esp gene was significantly associated with vancomycin-resistant Efm (VREfm) compared to vancomycin-susceptible Efm (VSEfm). In total, 91.7% of Efs and 20.0% of Efm produced biofilms. Twenty-six STs were identified among the 72 Efs isolates, with ST4 (29.2%) being the predominant. In total, 116 Efm strains were grouped into 26 STs, with ST78 (46.6%) being the predominant. Both VREfm (41.7%) and VSEfm (48.8%) were dominant in ST78. There is no clear evidence suggesting that some STs are associated with vancomycin resistance or biofilm formation. Both Efm and Efs BSI isolates showed a polyclonal pattern with a dominant clone and many unique types, implying the coexistence of clonal dissemination and an influx of new clones. The horizontal transmission of resistance genes may play a more important role in VREfm prevalence than clonal expansion.

4.
BMJ Open ; 13(9): e071461, 2023 09 11.
Article in English | MEDLINE | ID: mdl-37696638

ABSTRACT

OBJECTIVES: It is unclear whether remote interventions are effective in improving outcomes of informal caregivers of patients who had a stroke. We synthesised evidence for the impact of remote interventions on informal caregivers of patients who had a stroke. Moreover, we also analysed its potential effects on patients who had a stroke. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Excerpta Medica Database, Web of Science, the Cochrane Library, China National Knowledge Infrastructure, Wanfang Database and China Science and Technology Journal Database were searched from inception up to 1 February 2022. ELIGIBILITY CRITERIA: We included randomised controlled trials (RCTs) that assessed the effect of remote interventions on informal caregivers who provide unpaid care for patients who had a stroke living at home compared with traditional interventions, including with respect to caregivers' mood, care burden, life satisfaction and perceived competence. Moreover, we considered the potential impact of remote interventions on the depressive and anxiety symptoms, functional rehabilitation and re-admission of patients who had a stroke. Only studies published in Chinese or English were included. We excluded studies of interventions aimed at healthcare professionals or patients who had a stroke and those that could not provide complete data. DATA EXTRACTION AND SYNTHESIS: Data analyses were performed using RevMan V.5.3. The Cochrane Collaboration risk of bias tool for RCTs was used to evaluate the quality of the included studies, and the review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. For continuous outcomes, we calculated the mean difference or standardised mean difference (SMD) and 95% CIs. The Grading of Recommendations, Assessment, Development, and Evaluations method was used to assess the certainty of the evidence. RESULTS: Eight RCTs with a total of 733 participants were included. Compared with traditional interventions, for informal caregivers, we found that remote interventions did not produce significant effects on depressive symptoms (SMD -0.04, 95% CI -0.24 to 0.15), anxiety symptoms (SMD -0.26, 95% CI -0.94 to 0.43), care burden (SMD -0.06, 95% CI -0.56 to 0.45), life satisfaction (SMD -0.16, 95% CI -0.43 to 0.11), or perceived competence (SMD 0.37, 95% CI -0.23 to 0.96). Similarly, for patients who had a stroke, remote interventions had no significant effect on depression (SMD 0.16, 95% CI -0.61 to 0.93) or anxiety symptoms (SMD -0.34, 95% CI -0.72 to 0.04). The effects of remote interventions on functional rehabilitation and re-admission in patients who had a stroke were evaluated by three studies and two studies, respectively, but the studies were too varied to combine their data in meta-analysis. CONCLUSIONS: Current evidence suggests that remote interventions for informal caregivers of patients who had a stroke have no significant superiority over traditional interventions. However, the quality of the included studies was low and more high-quality evidence is required to determine the possible impacts of remote interventions. PROSPERO REGISTRATION NUMBER: CRD42022313544.


Subject(s)
Caregivers , Stroke , Humans , Caregiver Burden , Health Personnel , Patients
5.
iScience ; 26(10): 107809, 2023 Oct 20.
Article in English | MEDLINE | ID: mdl-37744031

ABSTRACT

Knowledge about the impact of different dissolved oxygen (DO) on the composition and function of gut bacteria of aquatic insects is largely unknown. Herein, we constructed freshwater environments with different DOs (hypoxia: 2.50 ± 0.50, normoxia: 7.00 ± 0.50, and hyperoxia: 13.00 ± 0.50 mg/L) where aquatic firefly Aquatica leii larvae lived for three months. Their gut flora was analyzed using the combination of 16S rRNA amplicon sequencing and metagenomics. The results showed no difference in alpha diversity of the gut flora between A. leii inhabiting various DOs. However, the relative abundance of several bacterial lineages presented significant changes, such as Pseudomonas. In addition, bacterial genes with an altered relative abundance in response to various DOs were primarily related to metabolism. The alteration of these functions correlated with the DO change. This is the first to uncover structure of gut flora under various DOs in aquatic insect larvae.

6.
Mycoses ; 66(9): 795-800, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37226871

ABSTRACT

BACKGROUND: Mucormycosis is a rare form of invasive, rapidly progressive and lethal opportunistic fungal infection caused by Mucorales. Although Rhizopus arrhizus (R. arrhizus) is the most commonly isolated Mucorales worldwide, infections caused by Apophysomyces variabilis (A. variabilis) are increasing. OBJECTIVES AND METHODS: We present a case of necrotizing fasciitis caused by A. variabilis in an immunocompetent woman. In order to further understand the characteristics of the strain isolated from the patient, we identified the strain through ITS sequencing, assessed the ability to tolerate salt concentrations and temperature conditions, in addition to performing in vitro drug susceptibility testing against common antifungal agents. RESULTS: The strain showed 98.76% identity with A. variabilis in the NCBI database, and it was found to tolerate higher temperatures and salt concentrations than previously reported strains. The strain was sensitive to amphotericin B and posaconazole, but not to voriconazole, itraconazole, 5-fluorocytosine and echinocandins. CONCLUSIONS: This case indicates that Mucorales caused by A. variabilis should be recognised as an emerging pathogen that can cause a high mortality rate in the absence of prompt diagnosis and proper treatment in China, aggressive surgical debridement combined with prompt and appropriate antifungal treatment may improve outcomes.


Subject(s)
Mucorales , Mucormycosis , Mycobacterium tuberculosis , Female , Humans , Microbial Sensitivity Tests , Antifungal Agents/therapeutic use , Mucormycosis/diagnosis , Mucormycosis/drug therapy , Mucormycosis/microbiology
8.
Front Microbiol ; 13: 1033211, 2022.
Article in English | MEDLINE | ID: mdl-36452929

ABSTRACT

Talaromyces (Penicillium) marneffei (T. marneffei) is a thermally dimorphic fungus that can cause opportunistic systemic mycoses. Our previous study demonstrated that concomitant use of berberine (BBR) and fluconazole (FLC) showed a synergistic action against FLC-resistant T. marneffei (B4) in vitro. In this paper, we tried to figure out the antifungal mechanisms of BBR and FLC in T. marneffei FLC-resistant. In the microdilution test, the minimum inhibitory concentration (MIC) of FLC was 256 µg/ml before FLC and BBR combination, and was 8 µg/ml after combination, the partial inhibitory concentration index (FICI) of B4 was 0.28. After the treatments of BBR and FLC, the studies revealed that (i) increase reactive oxygen species (ROS), (ii) reduce ergosterol content, (iii) destroy the integrity of cell wall and membrane, (iv) decrease the expression of genes AtrF, MDR1, PMFCZ, and Cyp51B however ABC1 and MFS change are not obvious. These results confirmed that BBR has antifungal effect on T. marneffei, and the combination with FLC can restore the susceptibility of FLC-resistant strains to FLC, and the reduction of ergosterol content and the down-regulation of gene expression of AtrF, Mdr1, PMFCZ, and Cyp51B are the mechanisms of the antifungal effect after the combination, which provides a theoretical basis for the application of BBR in the treatment of Talaromycosis and opens up new ideas for treatment of Talaromycosis.

9.
J Nurs Manag ; 30(8): 4024-4033, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36191302

ABSTRACT

AIM: This study aimed to investigate scheduling in COVID-19-designated hospitals, including working hours, rest days, adverse nursing outcomes and their relationship. BACKGROUND: Hospitals are at the forefront of COVID-19 prevention and control, and nurses are the main force on the frontline of the epidemic. Nursing shift is one of the most relevant and pressing issues for frontline nurses. However, there is a lack of national, large-sample surveys on scheduling and adverse nursing outcomes in COVID-19-designated hospitals. METHODS: Using a cross-sectional online survey, we used nurse-reported data to measure the characteristics of the work setting, samples and work schedule. A descriptive analysis was performed to assess the shift status and adverse outcomes of designated hospitals and frontline nurses. Logistic regression analysis was performed to determine the association between them. RESULTS: Basic data were collected from 217 departments of 69 COVID-19-designated hospitals in 31 provinces in China. Nurses in the severe isolation ward worked mainly for 4 h per shift, whereas those in the fever clinic and observation ward worked mainly for 6-8 h. Half of the nurses had only 1 day of rest per week. Long working hours, lack of adequate rest time and overtime can seriously affect the quality and safety of nurses' work, resulting in adverse outcomes. Frontline nurses hope that scheduling guarantees the time to rest while ensuring fairness. CONCLUSIONS: The current evidence showed that frontline nurses were faced with long working hours, insufficient rest and overtime, which has a negative impact on nurse satisfaction, physical and mental health and quality of care. The government, hospitals and administrators still face many problems to overcome in their nursing schedules. IMPLICATIONS FOR NURSING MANAGEMENT: Governments and hospitals should take these factors, such as the work setting characteristics and demographic features of the frontline nurses, into account when selecting nurses to fight COVID-19. Nurses have different working hours in different types of coronavirus unit; therefore, nursing managers should consider the working environment and nursing schedule needs, and in the future, we should pay attention to the fairness of nurses while ensuring their rest.


Subject(s)
COVID-19 , Nursing Staff, Hospital , Humans , COVID-19/epidemiology , Cross-Sectional Studies , Personnel Staffing and Scheduling , Hospitals , China/epidemiology , Surveys and Questionnaires , Nursing Staff, Hospital/psychology
10.
J Clin Med ; 11(18)2022 Sep 14.
Article in English | MEDLINE | ID: mdl-36143037

ABSTRACT

Originally considered to be a plant pathogen, reports of phaeohyphomycosis due to Curvularia lunata (C. lunata) in animals and humans are increasing. However, studies on the pathogenesis, virulence, and epidemiology of C. lunata have rarely been discussed. In the present study, BALB/c mice were experimentally inoculated with C. lunata suspension by different routes and the course of infection was evaluated. In addition, the in vitro antifungal susceptibility of C. lunata against six commonly used antifungals was evaluated using the microdilution method. Inoculation resulted in skin lesions in animals inoculated intraperitonially and subcutaneously. Infection was confirmed by both mycological and histopathologic examination. C. lunata spores and hyphae were detected in the histopathologic sections stained with hexamine silver staining. In addition, voriconazole (VRC) demonstrated greater activity against C. lunata when compared to the other antifungals, whereas fluconazole (FLC) was the least active antifungal with a minimum inhibitory concentration (MIC) range of 8-16 µg/mL. Further studies are necessary to understand the pathogenicity of C. lunata and uncover the mystery of this fungus.

11.
Microb Pathog ; 169: 105668, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35811021

ABSTRACT

Acinetobacter baumannii is a successful pathogen that can acquire various antibiotic resistance in a short time. However, little is known about how it can evolve from an antibiotic sensitive to a resistant phenotype. In this study, we investigated the roles of the type VI secretion system (T6SS) in the acquisition of antibiotic resistance of A. baumannii. T6SS gene cluster was found to be present in 51 of 77 A. baumannii clinical isolates, of which, it was found in 62% (8/13) of the multiple drug resistant (MDR) isolates, 90% (36/40) of the extensively drug-resistant (XDR) isolates and 26% (6/23) of the antibiotic sensitive isolates. There is a close relationship between the antimicrobial resistance and the presence of T6SS. Besides, T6SS + isolates showed lower biofilm formation activity and higher survival ability in the presence of normal human serum than T6SS- isolates. A. baumannii A152 with complete T6SS can outcompete E.coli effectively and can acquire the antibiotic resistance plasmids released by E.coli. In contrast, the T6SS core gene mutant A152Δhcp showed significantly decreased ability to acquire antimicrobial resistance plasmids from the prey bacteria. These results suggest that T6SS mediated bacterial competition plays important roles in the antimicrobial resistance of A. baumannii, which points out a new direction for us to study the antimicrobial resistance of A. baumannii.


Subject(s)
Acinetobacter baumannii , Type VI Secretion Systems , Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial/genetics , Drug Resistance, Multiple, Bacterial/genetics , Escherichia coli/genetics , Humans , Microbial Sensitivity Tests , Plasmids/genetics , Type VI Secretion Systems/genetics
12.
Dermatol Ther (Heidelb) ; 12(7): 1671-1683, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35754066

ABSTRACT

INTRODUCTION: Although pulsed dye laser (PDL) remains the gold standard for the treatment of port-wine stains (PWS), hematoporphyrin monomethyl ether photodynamic therapy (HMME-PDT) is another treatment modality that has been shown to be effective in the treatment of PWS. This study aimed to observe the clinical efficacy and therapeutic response of HMME-PDT in the treatment of pediatric Chinese patients with PWS and to analyze the association between the efficacy of therapy and the dermoscopic features of PWS. METHODS: Pediatric patients with PWS and negative HMME skin test were enrolled between December 2017 and May 2021. Patients received an intravenous injection of 5 mg/kg HMME, and lesions were irradiated with 532-nm LED green light with a power density of 70-80 mW/cm2 for 20-25 min. Digital photographs and dermoscopic images were taken before and after two treatment sessions, and the clinical response was observed. The relationship between the efficacy of HMME-PDT and the dermoscopic features of PWS was retrospectively analyzed. RESULTS: A total of 216 pediatric patients (1-14 years) were recruited. Sixty-six patients had the pink type, while 150 had the purple type. After two HMME-PDT sessions, 55 patients showed excellent efficacy (25.46%), 77 patients showed good efficacy (35.65%), 69 patients showed fair efficacy (31.94%), and 15 patients showed no improvement (6.95%). Dotted and globular vessels were highly associated with excellent efficacy (41.82%); linear vessels were mainly associated with good efficacy (54.55%); reticular vessels were mainly associated with fair (55.07%) and mixed vessels were mainly associated with no improvement (26.66%). CONCLUSION: HMME-PDT is an effective and safe treatment for pediatric patients with PWS. Dotted and globular vessels as well as linear vessels showed better efficacy compared to the other dermoscopic patterns in patients with PWS. Dermoscopy can provide useful clinical information about treatment outcomes.

13.
Mycopathologia ; 187(2-3): 291-298, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35244863

ABSTRACT

Tinea nigra is a superficial fungal infection usually caused by Hortaea werneckii (H. werneckii). We report a special case of tinea nigra in an immunocompetent child who developed a unilateral, rapidly growing pigmented lesion on her palm. Interestingly, Curvularia lunata (C. lunata) was isolated from the lesion scrapes and was identified by both morphological features and molecular biology methods. The lesion was completely cleared by topical naftifine hydrochloride and ketoconazole cream. We present-to the best of our knowledge-the first case of tinea nigra where the causative pathogen was identified as C. lunata. We therefore provide a brief literature review of previously reported cases of tinea nigra to broaden the knowledge of the potential causative pathogens. The etiology, demography, clinical features, diagnostic methods, and treatment of the reviewed cases are summarized and analyzed.


Subject(s)
Exophiala , Tinea , Child , Curvularia , Female , Humans , Tinea/diagnosis , Tinea/drug therapy , Tinea/microbiology
14.
Microb Pathog ; 160: 105199, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34560248

ABSTRACT

Neonatal bacterial meningitis is a life-threatening disease in newborns, and neonatal meningitis Escherichia coli (NMEC) is the second most frequent bacteria causing this disease worldwide. In order to further understand the characteristics of this pathogen, an E. coli isolate W224 N from newborns with meningitis was sequenced for detailed genetic characterization and the virulence was tested by a series of phenotypic experiments. W224 N has a circular chromosome and three plasmids. It belongs to ST95 and the serotype is O18:H7. Comparative genomic analysis showed that W224 N was closely related to E. coli neonatal meningitis isolates RS218 and NMEC O18. There are 11 genomic islands in W224 N and most of the GIs are specific to W224 N. W224 N has most of the virulence factors other neonatal meningitis isolates have. The virulence genes located both on the genome and plasmid. At the same time, we found a virulence factor cdiA only present in W224 N but absent in the other five genomes analyzed. In vitro experiment showed that W224 N has strong serum resistance ability, low biofilm formation ability and high flagellar motility. It also has a very strong toxicity to mice and amoeba. The whole genome as well as in vitro and in vivo experiments showed that W224 N is a high virulent strain. The results can help us better learn about the pathogenicity of neonatal meningitis E. coli.


Subject(s)
Escherichia coli Proteins , Escherichia coli/genetics , Genome, Bacterial , Meningitis, Escherichia coli , Animals , Escherichia coli/pathogenicity , Membrane Proteins , Meningitis, Escherichia coli/microbiology , Mice , Virulence , Virulence Factors/genetics
15.
Front Microbiol ; 12: 708280, 2021.
Article in English | MEDLINE | ID: mdl-34447360

ABSTRACT

This study analyzed the in vitro drug sensitivity of Cryptococcus spp. from Guangxi, Southern China. One hundred three strains of Cryptococcus were recovered from 86 patients; 14 were HIV positive and 72 were HIV negative. Ninety-two strains were identified as Cryptococcus neoformans var. grubii, while 11 strains were identified as Cryptococcus gattii (5 C. gattii sensu stricto and 6 Cryptococcus deuterogattii). The recovered strains were tested against commonly used antifungal drugs (fluconazole, amphotericin B, 5-fluorocytosine, itraconazole, and voriconazole) and to novel antifungal drugs (posaconazole and isavuconazole) using CLSI M27-A4 method. The results showed that all isolates were susceptible to most antifungal drugs, of which the minimum inhibitory concentration (MIC) ranges were as follows: 0.05-4 µg/ml for fluconazole, 0.25-1 µg/ml for amphotericin B; 0.0625-2 µg/ml for 5-fluorocytosine, 0.0625-0.25 µg/ml for itraconazole, 0.0078-0.25 µg/ml for voriconazole, 0.0313-0.5 µg/ml for posaconazole, 0.0020-0.125 µg/ml for isavuconazole for C. neoformans var. grubii isolates, and 1-16 µg/ml for fluconazole, 0.125-1 µg/ml for 5-fluorocytosine, 0.25-1 µg/ml for amphotericin B, 0.0625-0.25 µg/ml for itraconazole, 0.0156-0.125 µg/ml for voriconazole, 0.0156-0.25 µg/ml for posaconazole, and 0.0078-0.125 µg/ml for isavuconazole for C. gattii isolates. Furthermore, some C. neoformans var. grubii isolates were found to be susceptible-dose dependent to 5-fluorocytosine and itraconazole. In addition, a reduction in the potency of fluconazole against C. gattii is possible. We observed no statistical differences in susceptibility of C. neoformans var. grubii and C. gattii in the tested strains. Continuous observation of antifungal susceptibility of Cryptococcus isolates is recommended to monitor the emergence of resistant strains.

16.
J Immunol ; 206(11): 2527-2535, 2021 06 01.
Article in English | MEDLINE | ID: mdl-33980582

ABSTRACT

The T cell response is an important detection index in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine development. The present study was undertaken to determine the T cell epitopes in the spike (S) protein of SARS-CoV-2 that dominate the T cell responses in SARS-CoV-2-infected patients. PBMCs from rhesus macaques vaccinated with a DNA vaccine encoding the full-length S protein were isolated, and an ELISPOT assay was used to identify the recognized T cell epitopes among a total of 158 18-mer and 10-aa-overlapping peptides spanning the full-length S protein. Six multipeptide-based epitopes located in the S1 region, with four of the six located in the receptor-binding domain, were defined as the most frequently recognized epitopes in macaques. The conservation of the epitopes across species was also verified, and peptide mixtures for T cell response detection were established. Six newly defined T cell epitopes were found in the current study, which may provide a novel potential target for T cell response detection and the diagnosis and vaccine design of SARS-CoV-2 based on multipeptide subunit-based epitopes.


Subject(s)
Epitopes, T-Lymphocyte/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Macaca mulatta
17.
Emerg Microbes Infect ; 10(1): 342-355, 2021 Dec.
Article in English | MEDLINE | ID: mdl-33555988

ABSTRACT

The current study aims to develop a safe and highly immunogenic COVID-19 vaccine. The novel combination of a DNA vaccine encoding the full-length Spike (S) protein of SARS-CoV-2 and a recombinant S1 protein vaccine induced high level neutralizing antibody and T cell immune responses in both small and large animal models. More significantly, the co-delivery of DNA and protein components at the same time elicited full protection against intratracheal challenge of SARS-CoV-2 viruses in immunized rhesus macaques. As both DNA and protein vaccines have been proven safe in previous human studies, and DNA vaccines are capable of eliciting germinal center B cell development, which is critical for high-affinity memory B cell responses, the DNA and protein co-delivery vaccine approach has great potential to serve as a safe and effective approach to develop COVID-19 vaccines that provide long-term protection.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Spike Glycoprotein, Coronavirus/immunology , Vaccines, DNA/immunology , Vaccines, Subunit/immunology , Animals , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Cell Line , DNA/immunology , HEK293 Cells , Humans , Lymphocyte Count , Macaca mulatta , Mice , Mice, Inbred C57BL , Plasmids/genetics , Rabbits , Recombinant Proteins/immunology , SARS-CoV-2/genetics , SARS-CoV-2/immunology , T-Lymphocytes/immunology
18.
Ying Yong Sheng Tai Xue Bao ; 31(11): 3814-3822, 2020 Nov.
Article in Chinese | MEDLINE | ID: mdl-33300732

ABSTRACT

During atmospheric precipitation, the evaporation of raindrops falling from the bottom of cloud layer to the ground and passing through unsaturated air, a process was called sub-cloud secondary evaporation, which will change the isotopic composition of precipitation. Using the hydrogen and oxygen stable isotope method to understand the temporal and spatial variation of secondary evaporation effect under clouds and its causes is important to understand regional water cycle process. Based on hourly meteorological data of 187 meteorological stations in Shaanxi-Gansu-Ningxia region from March 2018 to February 2019, the spatial and temporal variations of evaporation surplus ratio (f) and precipitation excess deuterium variation (Δd) were analyzed using the improved Ste-wart model, and the relationships between f and meteorological elements and Δd were examined. The results showed that, at the hourly scale, the minimum values of f and Δd in all provinces of the region appeared in the daytime, and the maximum values appeared in the night, indicating that the secondary evaporation effect under the cloud was more obvious in the daytime. At the monthly scale, the monthly variation trend of f and Δd in each province was relatively consistent, with the minimum value appearing in the summer half year, and the maximum value appearing in the winter half year, indicating that the second evaporation effect under cloud was more significant in the summer half year. From the spatial perspective, the spatial variation of f and Δd values in the region was consistent with that at the seasonal scale. In spring, the eastern and western regions were larger while the central part was smaller. In summer, the northwest region was smaller, and other regions were larger. In autumn, it decreased from south to north. In winter, the central and southern regions were smaller, and the western and northeast regions were larger. The spatial differences of secondary evaporation effects under clouds in different seasons was significant. The slopes of the linear relationship between f and Δd in Shaanxi, Gansu and Ningxia provinces were all less than 1‰·%-1, which may be caused by the arid and semi-arid climate in this area. When air temperature was higher and the relative humidity, vapor pressure, precipitation and raindrop diameter were smaller, the value of Δd was smaller, and the secondary evaporation effect under the cloud was more obvious.


Subject(s)
Environmental Monitoring , Rain , China , Oxygen Isotopes/analysis , Seasons
19.
PLoS Pathog ; 16(11): e1008949, 2020 11.
Article in English | MEDLINE | ID: mdl-33180882

ABSTRACT

The COVID-19 has emerged as an epidemic, causing severe pneumonia with a high infection rate globally. To better understand the pathogenesis caused by SARS-CoV-2, we developed a rhesus macaque model to mimic natural infection via the nasal route, resulting in the SARS-CoV-2 virus shedding in the nose and stool up to 27 days. Importantly, we observed the pathological progression of marked interstitial pneumonia in the infected animals on 5-7 dpi, with virus dissemination widely occurring in the lower respiratory tract and lymph nodes, and viral RNA was consistently detected from 5 to 21 dpi. During the infection period, the kinetics response of T cells was revealed to contribute to COVID-19 progression. Our findings implied that the antiviral response of T cells was suppressed after 3 days post infection, which might be related to increases in the Treg cell population in PBMCs. Moreover, two waves of the enhanced production of cytokines (TGF-α, IL-4, IL-6, GM-CSF, IL-10, IL-15, IL-1ß), chemokines (MCP-1/CCL2, IL-8/CXCL8, and MIP-1ß/CCL4) were detected in lung tissue. Our data collected from this model suggested that T cell response and cytokine/chemokine changes in lung should be considered as evaluation parameters for COVID-19 treatment and vaccine development, besides of observation of virus shedding and pathological analysis.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/pathology , Pneumonia, Viral/pathology , Animals , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Cytokines/immunology , Disease Models, Animal , Lung/immunology , Lung/pathology , Macaca mulatta , Pandemics , Pneumonia, Viral/virology , SARS-CoV-2 , Viral Load/methods , Virulence , Virus Shedding , COVID-19 Drug Treatment
20.
Mycoses ; 63(11): 1235-1243, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33090565

ABSTRACT

BACKGROUND: In China, the prevalence of superficial fungal infections of the foot is high and recurrence is common. However, a prospective, large-scale and multicentre study on the aetiology of superficial fungal infections of the foot is still lacking. OBJECTIVES: To study the epidemiology of aetiological agents of superficial fungal infections of the foot in urban outpatients in mainland China, as well as to understand the aetiology features of the pathogenic agent. METHODS: The study was designed as a multicentre, prospective epidemiological survey. A total of 1704 subjects were enrolled from seven geographical areas in mainland China. For each subject, one mycological sample and one bacterial sample were collected. KOH wet mount examination and culture were performed at local laboratories. The bacterial results were only reported in those with positive mycology. Further morphological identification and, if necessary, molecular biological identification were conducted in a central laboratory. RESULTS: Of 1704 enrolled subjects, 1327 (77.9%) subjects had positive fungal culture results. The incidence of dermatophytes, yeasts and moulds was 90.1%, 8.1% and 1.1%, respectively. The most frequently isolated aetiological agent (fungus) was Trichophyton rubrum. Moccasin form was the most commonly reported clinical diagnosis of superficial fungal infections. The most frequently isolated bacterial genus in patients was Staphylococcus. CONCLUSION: This study prospectively investigated the clinical and mycological features of human dermatophytosis in mainland China. T rubrum was the most frequently isolated fungus, and moccasin form was the most commonly reported clinical diagnosis of superficial fungal infections.


Subject(s)
Dermatomycoses , Foot/microbiology , Adult , Arthrodermataceae/isolation & purification , Arthrodermataceae/pathogenicity , China/epidemiology , Dermatomycoses/epidemiology , Dermatomycoses/etiology , Dermatomycoses/pathology , Female , Foot/pathology , Fungi/isolation & purification , Fungi/pathogenicity , Humans , Incidence , Male , Mycoses/epidemiology , Mycoses/etiology , Mycoses/pathology , Outpatients , Prevalence , Prospective Studies , Yeasts/isolation & purification , Yeasts/pathogenicity
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