共查询到20条相似文献，搜索用时 31 毫秒
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Amani M. Ali Samah Selim Maggie M. Abbassi Nirmeen A. Sabry 《Annals of allergy, asthma & immunology》2017,118(5):557-563
Background
Despite the use of alfacalcidol in the management of corticosteroid-induced osteoporosis, it has never been considered an adjunct treatment for asthma management. It can target vitamin D deficiency, a possible risk factor for asthma, and, hence, improve pulmonary function of patients with asthma.Objective
To explore the effect of alfacalcidol administration on pulmonary function and study the pattern of vitamin D deficiency in adults with asthma in Egypt.Methods
Serum 25-hydroxyvitamin D was measured in 115 adults: 33 healthy subjects and 82 patients with asthma. Then, patients with asthma were randomized to receive standard asthma treatment only (n = 39) or receive it in addition to 1 μg of alfacalcidol daily for 4 months (n = 43). Randomization was stratified by the stage of asthma severity. Spirometry and measurement of 25-hydroxyvitamin were performed at baseline and end of follow-up.Results
Vitamin D deficiency was more common in patients with asthma (57.3%) than in healthy subjects (21.2%; P < .001). In patients with asthma, alfacalcidol significantly improved forced expiratory volume in the first second and forced vital capacity (P < .001 for the 2 tests). Moreover, more patients in the intervention arm showed improvement in asthma severity stage (P = .04). A nonsignificant difference was observed in improvement of forced expiratory volume in the first second between patients with vitamin D deficiency and those without deficiency in the intervention group (P > .05).Conclusion
Alfacalcidol supplementation improved the pulmonary function and severity stage of adult patients with asthma regardless of deficiency.3.
Melishia Bansa Darryl Brown Daniela DeFrino Nicholas Mahoney Alexandria Saulsberry Monika Marko-Holguin Joshua Fogel Tracy R.G. Gladstone Benjamin W. Van Voorhees 《Journal of the National Medical Association》2018,110(2):130-142
Background
This study explored the implementation of Chicago Urban Resiliency Building (CURB), a randomized clinical trial designed as an Internet-based primary care depression prevention intervention for urban African American and Latino adolescents.Methods
We utilized a mixed methods analysis to explore four aims. First, we estimated the percent of at-risk adolescents that were successfully screened. Second, we examined clinic site factors and performance. Third, primary care providers (n = 10) and clinic staff (n = 18) were surveyed to assess their knowledge and attitudes about the intervention. Fourth, clinic staff (nursing and medical assistant) interviews were analyzed using thematic analysis to gather perspectives of the implementation process.Results
We found that the estimated percent of at-risk adolescents who were successfully screened in each clinic varied widely between clinics with a mean of 14.48%. Daily clinic communication was suggestive of greater successful screening. Feasibility of screening was high for both primary care providers and clinic staff. Clinic staff exit interviews indicated the presence of community barriers that inhibited successful implementation of the intervention.Conclusion
This study shares the challenges and successes for depression screening and implementing Internet-based mental health interventions for urban racial/ethnic minority adolescents in primary care settings. 相似文献4.
Peter C. Boettger Charles L. Knupp Darla K. Liles Kaitlyn Walker 《Journal of the National Medical Association》2017,109(1):36-43
Introduction
Vitamin D levels in adult black Americans with sickle cell disease (SCD) are comparatively lower than those found in the general population of black Americans. The objectives of this study were to examine the prevalence of Vitamin D deficiency (VDD) in adults with various subtypes of sickle cell disease and identify risk factors for vitamin D deficiency.Methods
In a retrospective study serum Vitamin D25(OH)D and/or VitaminD1,25(OH)2D levels were obtained in 120 subjects with sickle cell disease. Baseline studies also included LFTs, total protein, albumin, total bilirubin, and creatinine levels. In a portion of subjects that were treated with oral ergocalciferol vitamin D levels and chemistries were obtained within 6 months of treatment. Data was statistically analyzed with Welch two sample t-tests and individual simple linear regressions (including logarithmic values) for each variable.Results
Vitamin D25(OH)D levels were found to be significantly lower in a group of subjects with Hgb SS disease, than in a group with other subtypes of sickle cell disease. In both groups combined, significant (p = 0.05) and clinically suggestive negative correlations with Vitamin D25(OH)D were seen for total bilirubin and total protein, respectively. When total bilirubin and total protein levels were compared between the Hgb SS and HgbS/other groups, t-test revealed these levels were significantly higher in the Hgb SS group levels at p < 0.001 and p = 0.005, respectively.Implications
Low total Vitamin D25(OH)D levels in adults with sickle cell disease may be a reflection of chronic inflammation and overall disease severity. 相似文献5.
Ting-Chun Lin Jhong-Yong Wu Ming-Ling Kuo Liang-Shiou Ou Kuo-Wei Yeh Jing-Long Huang 《Journal of microbiology, immunology, and infection》2018,51(1):110-114
Background
Vitamin D deficiency has been associated with systemic lupus erythematosus (SLE), but there is no consensus on the role of serum vitamin D in evaluating or predicting disease activity. This study aimed to demonstrate the direct correlation between vitamin D level and pediatric-onset SLE disease activity by a retrospective cohort study design.Patients and methods
Thirty-five patients with pediatric-onset SLE and paired sera at the active and inactive disease states were enrolled. Disease activity was defined by Systemic Lupus Erythematosus Disease Activity Index 2000, and active lupus nephritis (LN) was defined as active urine sediment, and proteinuria >2+ on stick or >500 mg/day. All data were reviewed and calculated from previous medical records. The levels of both vitamin D2 and vitamin D3 were checked by electrochemiluminescence immunoassay.Results
Serum 25-hydroxyvitamin D (25-OH D) levels in the active status were significantly lower compared to that in inactive disease status (12.0 ± 7.2 ng/mL vs. 15.4 ± 7.4 ng/mL, p = 0.005). A subgroup analysis revealed that at active disease status, patients with LN had lower 25-OH D levels than patients without LN (16.3 ± 8.2 ng/mL vs. 9.8 ± 5.6 ng/mL, p = 0.023). Moreover, there is a significant inverse correlation between serum 25-OH D levels and Systemic Lupus Erythematosus Disease Activity Index 2000 at both inactive (r = ?0.335, p = 0.003) and active (r = ?0.373, p = 0.016) disease status.Conclusion
Serum vitamin D levels are inversely correlated with SLE disease activity at both active and inactive disease status, and also with the presence of LN at active disease stage. 相似文献6.
Kimberly S. Johnson Kevin L. Thomas Sandro O. Pinheiro Laura P. Svetkey 《Journal of the National Medical Association》2018,110(4):305-313
Background
Disparities in health and healthcare are widely documented for underrepresented racial and ethnic populations across a spectrum of diseases and care settings. An evidence base for addressing racial and ethnic disparities in health and healthcare requires investigators trained to conduct health disparities research.Objective
To increase knowledge, stimulate interest, teach skills to evaluate and conduct, and foster collaborations in health disparities research.Design
We designed, implemented and evaluated a Health Disparities Research Curriculum (HDRC).Participants were early-stage investigators.Intervention
HDRC included twelve monthly sessions during 2015–2016. Instructors were mostly HDR investigators. Sessions combined didactic presentations, discussions, small group activities, and participant presentations.Measures
Pre- and post-surveys to assess participants' perceptions of knowledge and skills.Results
Of 21 enrollees, 13 were from under-represented groups and 14 were women. Four reported some prior training in HDR, and 12 reported currently conducting HDR.Among the 12 participants who completed both the pre and post HDRC survey, initially the most commonly cited barriers to pursuing HDR were lack of knowledge (N = 6) and funding (N = 7). In the post-survey, the number citing lack of knowledge decreased (N = 2) and the number listing lack of funding increased (N = 9). There were increases in the number of participants reporting increased knowledge of HDR methods (pre-post: 4 vs. 8) and competence to design (3 vs. 7) and implement (2 vs. 9) HDR research.Conclusions
The Duke HDRC augments efforts to reduce health disparities by providing training in HDR for young investigators. Our data indicate that the course was feasible, well-received, and increased perceived knowledge and competence. HDRC and similar courses may increase the quantity, quality and scope of HDR and thus move us closer to health equity. 相似文献7.
Linda Jones Herbert Priya Mehta Hemant Sharma 《Annals of allergy, asthma & immunology》2017,118(3):345-350
Background
Food allergies are increasingly prevalent in the pediatric population. Balancing allergen avoidance with the promotion of healthy eating behaviors can be challenging for families.Objective
To characterize mealtime behaviors among parents of young children with food allergy.Methods
Seventy-four parents of young children with food allergies (≤7 years of age) completed measures of mealtime behavior, perceptions of food allergy risk and severity, pediatric parenting stress, and food allergy–related quality of life. Mealtime behavior reports were compared with published data regarding typically developing children, young children with type 1 diabetes, and children with diagnosed feeding disorders (with or without related medical factors).Results
Parents of young children with food allergies reported frequent mealtime concerns. Specifically, they reported significantly more mealtime behavioral concerns than typically developing peers, comparable mealtime behavioral concerns to young children with type 1 diabetes, and significantly fewer mealtime behavioral concerns than children with diagnosed feeding disorders. Parental mealtime concerns were positively correlated with other parent perceptions of food allergy, such as risk of allergen exposure, illness-related parenting stress, and food allergy–related quality of life.Conclusion
Young children with food allergy and their parents are more likely to exhibit mealtime behavioral concerns than typically developing peers and their parents. Future research should investigate the effect of food allergies and maladaptive mealtime behaviors on children's nutrition to provide clinical guidelines for parents who may benefit from psychosocial and/or nutritional support. 相似文献8.
Charlotte Baker Jill Powell Dominic Le Melissa S. Creary Lori-Ann Daley Mary Anne McDonald Charmaine DM. Royal 《Journal of the National Medical Association》2018,110(6):564-573
Objective
To describe the perspectives and experiences of athletic trainers, coaches, and student-athletes approximately three years post-implementation of the NCAA sickle cell trait (SCT) screening policy.Participants
Two-hundred and eight student-athletes, 32 athletic trainers, and 43 coaches from 10 NCAA Division I (DI) institutions in North Carolina from January to June 2014.Methods
Two online surveys were used to assess knowledge, perspectives, and experiences.Results
Athletic staff were more supportive than student-athletes of the need for the policy. Noted challenges included variation in implementation and follow-up for SCT-positive athletes, financial costs to institutions and athletes, and timing of the screening.Conclusions
More education about SCT is needed for student-athletes and athletic staff in order to help make the implementation more successful. All parties need to be in agreement regarding the importance of knowing which student-athletes have SCT and how that information will be utilized. 相似文献9.
Background
The reported associations of blood lipid profiles with asthma are ambiguous.Objective
To explore the association between asthma and the serum levels of high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C).Methods
A systematic search was performed in the PubMed, MEDLINE, Cochrane Library, and Chinese Biomedical Literature databases. Ten studies were identified. We divided these studies into 2 subgroups according to age: children (<18 years old) and adults (≥18 years old).Results
In children, the asthma group had lower HDL-C levels (weighted mean difference, ?3.44; 95% confidence interval [CI], ?5.83 to ?1.04; P = .005) compared with the nonasthma group, whereas the serum levels of LDL-C in these 2 groups were not statistically different. In contrary, in adults, the asthma group had higher LDL-C levels (weighted mean difference, 8.95; 95% confidence interval, 3.55–14.35; P = .001) compared with the nonasthma group, whereas the HDL-C levels were not statistically different.Conclusion
There is a significant association between asthma and the serum levels of HDL-C and LDL-C. Moreover, this association differs in children and adults. 相似文献10.
Eun Lee Si Hyeon Lee Young-Ho Kim Hyun-Ju Cho Jisun Yoon Song-I. Yang Young-Ho Jung Hyung Young Kim Ju-Hee Seo Ji-Won Kwon Hyo-Bin Kim So Yeon Lee Ho-Jang Kwon Soo-Jong Hong 《Annals of allergy, asthma & immunology》2017,118(5):542-550.e1
Background
Although previous studies have investigated the association between atopy phenotypes and allergic diseases, atopy characterizations in association with the development of allergic diseases remain poorly understood.Objective
To identify atopy phenotypes in school-age children and to evaluate the association between atopy phenotypes and allergic diseases.Methods
We enrolled 616 children with atopy defined as 1 or more positive allergen responses on skin prick tests and 665 children without atopy from the Children's Health and Environmental Research (CHEER) study. All children were followed up for 4 years at 2-year intervals. Atopy phenotypes were classified using latent class analysis.Results
Four atopy phenotypes were characterized: later sensitization to indoor allergens (cluster 1); multiple early sensitization (cluster 2); early sensitization to outdoor allergens, especially Alternaria, and later sensitization to indoor allergens, including Aspergillus (cluster 3); and early sensitization to indoor allergens and later sensitization to outdoor allergens (cluster 4). New cases of asthma during follow-up were increased in clusters 2 and 3 (adjusted odds ratio [aOR], 2.76 and 4.25, respectively). The risk of new-onset bronchial hyperresponsiveness was highest in cluster 3 (aOR, 5.03). Clusters 2 and 4 had an increased risk of allergic rhinitis (aOR, 7.21 and 2.37, respectively).Conclusion
Identification of atopy phenotypes facilitates prediction of the development of asthma and bronchial hyperresponsiveness in school-age children. Our study suggests prevention of additional sensitization is required to modify the progression of allergic diseases. 相似文献11.
Patrick M. Brunner Donald Y.M. Leung Emma Guttman-Yassky 《Annals of allergy, asthma & immunology》2018,120(1):34-41
Objective
To provide an overview of studies contributing to the understanding of immunologic, microbial, and epithelial interactions in atopic dermatitis.Data Sources
PubMed literature review (2000–2017) and meeting abstracts from recent international dermatology conferences.Study Selections
Articles discussing primarily human disease.Results
Clinical studies showed that atopic dermatitis is a type 2 immune-centered disease with a systemic inflammatory component but with heterogeneous treatment responses. This suggests that other factors are likely involved in shaping the skin disease phenotype, including microbial dysbiosis and epidermal barrier dysfunction.Conclusion
Recent clinical investigation has significantly expanded our knowledge on disease pathogenesis in atopic dermatitis, and current and future clinical trials will most likely further help to elucidate this complex, heterogeneous skin disease. 相似文献12.
Hong-Yi Lee Yu-Chia Hsieh Ching-Chuan Liu Yi-Chuan Huang Kuang-Yi Chang Hsin Chi Luan-Yin Chang Yhu-Chering Huang Li-Min Huang 《Journal of microbiology, immunology, and infection》2018,51(2):199-206
Background
In Taiwan, the age group with the greatest incidence of invasive pneumococcal disease is 2–5 years of age, which is different from other countries. This study was conducted to identify risk factors and different 13-valent pneumococcal conjugate vaccine (PCV13) schedules associated with vaccine-type invasive pneumococcal pneumonia (IPP) despite prior vaccination.Methods
A case–control study was conducted prospectively between August 2012 and December 2015 at five participating medical centers. The study enrolled children <15 years of age who were admitted to one of the five medical centers for CAP. Blood samples and acute-phase serum specimens were collected and Streptococcus pneumoniae was identified by using a real-time polymerase-chain-reaction (RT-PCR) assay targeting the lytA gene.Results
A total of 25 children diagnosed with vaccine-type IPP and 124 controls were enrolled. Vaccine-type IPP occurred in 6 (28.6%), 14 (24.1%), and 5 (7.1%) children receiving vaccines on a not-age-appropriate schedule (n = 21), primary infant schedule (n = 58), and toddler catch-up schedule (n = 70) (P = 0.008), respectively. Of 25 children, the mean age at disease onset was 36 ± 11 months; serotype 19A was responsible for 84% (21/25).Conclusion
After adjustment for confounding factors, the risk of vaccine-type IPP was significantly higher among children receiving vaccines on a not-age-appropriate schedule, or on a primary infant schedule, compared with children receiving vaccines on a toddler catch-up schedule. Duration of vaccine immunity should be investigated to direct strategies for maintaining individual and population immunity against pneumococcal disease. 相似文献13.
Tohru Daikoku Mineyuki Mizuguchi Takayuki Obita Takeshi Yokoyama Yoshihiro Yoshida Masaya Takemoto Kimiyasu Shiraki 《Journal of microbiology, immunology, and infection》2018,51(5):581-586
Background
T-705 (favipiravir) is a potent inhibitor of RNA-dependent RNA polymerases of influenza viruses and no favipiravir-resistant virus has been isolated. Poliovirus RNA polymerase has been well characterized and isolation of resistant virus was examined in poliovirus.Methods
Susceptibility variants of poliovirus I (Sabin strain) were isolated during passages in the presence of favipiravir and characterized for their susceptibility and the sequence of RNA polymerase.Results
Five variants with 0.47–1.88 times the 50% inhibitory concentration for plaque formation of the parent poliovirus had amino acid variations in the 3D gene of the RNA polymerase. The distribution of amino acid variations was not related to ribavirin resistance, and two amino acid variation sites were found near the finger domain.Conclusion
Favipiravir as a chain terminator would not be incorporated and replicate to cause lethal mutagenesis as a mutagen like ribavirin, and resistant mutants were not isolated. A high replication level would generate mutations leading to favipiravir resistance as ribavirin resistance was generated, but generated mutations would be lethal to the RNA polymerase function. 相似文献14.
Johanna P.M. van der Valk Irene Berends Roy Gerth van Wijk Nicolette. J.T. Arends Maurits S. van Maaren Hans de Groot Harry J. Wichers Joyce A.M. Emons Anthony E.J. Dubois Nicolette W. de Jong 《Annals of allergy, asthma & immunology》2018,120(3):300-303
Background
Severe allergic reactions, including anaphylaxis, occur during oral food challenges (OFCs) and the first-line treatment of anaphylaxis is epinephrine.Objective
To evaluate the percentage of anaphylactic reactions treated with epinephrine during OFCs and to identify associated factors for the administration of epinephrine.Methods
Children who underwent an OFC with peanut, hazelnut, cow's milk, hen's egg, or cashew nut from 2005 through 2015 in the Netherlands were evaluated. Children with reactions meeting the criteria for anaphylaxis according to the European Academy of Allergy and Clinical Immunology guidelines for food allergy and anaphylaxis were included. Children with an anaphylactic reaction treated with vs without epinephrine were compared. Possible factors associated with the administration of epinephrine, such as age, sex, symptoms consistent with asthma, history of an allergic reaction to the tested allergen, and symptom types during the anaphylactic reaction, were evaluated using logistic regression analysis.Results
Eighty-three children in clinical and research settings (43% boys; median age, 7 years; range, 1–17) who met the criteria for anaphylaxis were included in this study. Thirty-two of 83 children (39%) with anaphylaxis were treated with epinephrine. Respiratory symptoms during the OFC were treated significantly more often with epinephrine than gastrointestinal symptoms (P = .01).Conclusion
Only 39% of children with anaphylaxis, according to the guideline criteria, were treated with epinephrine during the OFC and most of these children had respiratory symptoms. There is need for an easy-to-use international guideline for the treatment of allergic symptoms during OFCs. 相似文献15.
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Peng Li Miao Ge Congxia Wang Jinwei He Shaofang Yang Jing Jing Dezhi Wei 《Journal of the National Medical Association》2018,110(4):334-342
Objectives
This study aims to explore the spatial characteristics of the alpha-fetoprotein (AFP) reference value in healthy Chinese adults, and its relationship to geographical location.Methods
A total of 9396 AFP reference values were collected from patients in 96 administrative units. A correlation analysis and support vector machine (SVM) were employed to extract dependent geographical factors and predict the reference values in the entire country, respectively. A geostatistics analysis was developed to reveal the spatial characteristics of the value.Results
Under the long-term influence of geographical environment, AFP reference values show spatial autocorrelation and regional variation. The values are higher in western and northern areas than in eastern and southern areas of China.Conclusions
The AFP reference values show regional differences, and this difference should be considered in clinical practice. 相似文献17.
Kai-Wen Wu Shih-Min Wang Ching-Fen Shen Tzong-Shiann Ho Jen-Ren Wang Ching-Chuan Liu 《Journal of microbiology, immunology, and infection》2018,51(6):749-755
Background
Human parainfluenza viruses (HPIV) 1–4 had been analyzed as being one of the most frequent causes of hospitalizations for young children with respiratory tract illnesses.Methods
This retrospective study was performed from children virologically confirmed as HPIV infection through throat swab or nasopharyngeal aspirates at a tertiary care university hospital, between January 2012 and December 2014. HPIV4 was not checked and analyzed, due to not include in the commercial kit. The demographic, epidemiological, clinical presentations, diagnosis, treatment, outcomes, and laboratory data were analyzed.Results
Totally 398 cases were enrolled, including 39 (9.8%) of HPIV1, 67 (16.8%) of HPIV2, and 292 (73.4%) of HPIV3. The mean age of HPIV-infected children was 2.9 year-old, and 50.5% were among one to three year-old. A total of 56.8% HPIV3-infected children were among one to three years old, however, no HPIV2-infected children was younger than one year-old. The HPIV1-infected patients were more common to develop wheezing and diagnose as acute bronchiolitis. HPIV2-infected children were more likely to have hoarseness (23.9%), and were associated with croup (25.4%). HPIV3 was isolated from two fatal cases, with neurological underlying diseases.Conclusion
The impact caused by HPIVs infections is significant in hospitalized children. In the current study, our results contribute to the epidemiologic, clinical and laboratory information of HPIV infection in children in the important areas of respiratory tract infection that could support the development of optimization management. 相似文献18.
Nel Dąbrowska-Leonik Ewa Bernatowska Małgorzata Pac Wiktor Filipiuk Jan Mulawka Barbara Pietrucha Edyta Heropolitańska-Pliszka Katarzyna Bernat-Sitarz Beata Wolska-Kuśnierz Bożena Mikołuć 《Advances in medical sciences》2018,63(1):173-178
Purpose
The objective of this study was to evaluate thevitamin D concentration in patients with recurrent respiratory infections with or without immunoglobulin G, A or M (IgG, IgA, IgM) deficiency, and to find a correlation between the vitamin D concentration and the response to hepatitis B vaccination.Materials and method
The study involved 730 patients with recurrent respiratory infections. The concentration of 25-hydroxyvitamin D (25(OH)D), immunoglobulins G, A and M, anti-HBs was determined.Results
The tests showed that 11% of patients presented IgG levels below the age related reference values. Children with reduced IgG concentration were also found to have significantly lower vitamin D concentrations in comparison to children with normal IgG. Vitamin D deficiency was observed in schoolchildren between 7 and 18 years of age. No correlation was found between 25(OH)D concentration and Hbs antibody levels.Conclusions
An investigation of a large group of patients who have recurrent infection found patients with IgG deficiency to whom special proceeding have to be performed: 1. Significantly lower vitamin D concentration observed in the group of children with IgG deficiency implicated in long-lasting monitoring of vitamin D level require adding to the practice guidelines for Central Europe 2013. 2. Intervention treatment with suitable doses of vitamin D to clarified metabolism of vitamin D has to be plan for children with IgG deficiency and significant lower vitamin D concentration. 相似文献19.
Robert L. Jacobs Daniel A. Ramirez Cynthia G. Rather Charles P. Andrews Daniel C. Jupiter Fernando Trujillo David G. Shulman 《Annals of allergy, asthma & immunology》2017,118(1):86-93.e2
Background
There are few direct data concerning symptom dynamics of allergic conjunctivitis (AC) in an allergen challenge chamber (ACC).Objective
To determine the AC dynamics on subsequent exposures to ragweed pollen (RW) in individuals with allergic rhinitis in an ACC. To determine whether consecutive exposures in an ACC have any persistent detrimental ocular physical effects.Methods
Participants underwent 3 exposures to RW in an ACC. Ocular symptoms of itching and tearing were self-assessed. Ocular redness and lid swelling were assessed by trained ophthalmic technicians. Complete ophthalmic examinations (COEs) were performed by an ophthalmologist.Results
A total of 188 of 201 participants (93%) developed an ocular redness score of 2 or more in each eye in ACC exposure 1. Reproducibility of redness occurred in approximately 70% of individuals completing ACC exposures 1 through 3. There were no significant changes between baseline COE and end of study COE. Phenotypes were identified by redness responses during and after exposure. Baseline total ocular symptom scores, at 24 hours after a priming exposure, were identified as late-phase reactions rather than enhanced sensitivity.Conclusion
When assessed by trained professionals, AC was present with a very high frequency in selected individuals allergic to RW monitored in an ACC. Intrasubject reproducibility of redness was consistent across 3 ACC allergen exposures. Phenotypes were identified as early-phase responses, protracted early-phase responses, dual responses, and late-phase responses.20.
Kuang-Yao Chen Chuan-Min Yen Kao-Pin Hwang Lian-Chen Wang 《Journal of microbiology, immunology, and infection》2018,51(4):559-564