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BACKGROUND@#Previous research demonstrated that a homozygous mutation of g.136372044G>A (S12N) in caspase recruitment domain family member 9 ( CARD9 ) is critical for producing Aspergillus fumigatus -induced ( Af -induced) T helper 2 (T H 2)-mediated responses in allergic bronchopulmonary aspergillosis (ABPA). However, it remains unclear whether the CARD9S12N mutation, especially the heterozygous occurrence, predisposes the host to ABPA.@*METHODS@#A total of 61 ABPA patients and 264 controls (including 156 healthy controls and 108 asthma patients) were recruited for sequencing the CARD9 locus to clarify whether patients with this heterozygous single-nucleotide polymorphisms are predisposed to the development of ABPA. A series of in vivo and in vitro experiments, such as quantitative real-time polymerase chain reaction, flow cytometry, and RNA isolation and quantification, were used to illuminate the involved mechanism of the disease.@*RESULTS@#The presence of the p.S12N mutation was associated with a significant risk of ABPA in ABPA patients when compared with healthy controls and asthma patients, regardless of Aspergillus sensitivity. Relative to healthy controls without relevant allergies, the mutation of p.S12N was associated with a significant risk of ABPA (OR: 2.69 and 4.17 for GA and AA genotypes, P = 0.003 and 0.029, respectively). Compared with patients with asthma, ABPA patients had a significantly higher heterozygous mutation (GA genotype), indicating that p.S12N might be a significant ABPA-susceptibility locus ( aspergillus sensitized asthma: OR: 3.02, P = 0.009; aspergillus unsensitized asthma: OR: 2.94, P = 0.005). The mutant allele was preferentially expressed in ABPA patients with heterozygous CARD9S12N , which contributes to its functional alterations to facilitate Af -induced T H 2-mediated ABPA development. In terms of mechanism, Card9 wild-type ( Card9WT ) expression levels decreased significantly due to Af -induced decay of its messenger RNA compared to the heterozygous Card9S12N . In addition, ABPA patients with heterozygous CARD9S12N had increased Af -induced interleukin-5 production.@*CONCLUSION@#Our study provides the genetic evidence showing that the heterozygous mutation of CARD9S12N , followed by allele expression imbalance of CARD9S12N , facilitates the development of ABPA.
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Humans , Aspergillosis, Allergic Bronchopulmonary/complications , Aspergillus fumigatus/genetics , Asthma/genetics , Aspergillus , Mutation/genetics , CARD Signaling Adaptor Proteins/geneticsABSTRACT
Objective:To investigate the awareness and knowledge of influenza and vaccine among primary care providers in Shanghai.Methods:An online questionnaires survey was conducted by Shanghai Alliance for Respiratory Diseases in Primary Care from December 2017 to August 2018, healthcare providers in district central hospitals and community health care centers of Shanghai were invited to participate in the survey. The questionnaire contained the following items: the basic information of respondents; knowledge of influenza and its vaccine; current status of influenza vaccination; factors affecting promoting vaccination; the intention, attitude, perception of promoting vaccination and the influencing factors, and suggestions on promoting influenza vaccination.Results:A total of 1 542 valid questionnaires were collected, 88.3% (1 361/1 542) responders correctly recognized main symptoms of influenza; 58.2% (898/1 542) ignored the contact transmission of influenza; 41.6% (641/1 542) didn′t know the frequency of influenza vaccination; 82.7% (1 276/1 542) failed to recognize that pregnant women should also receive influenza vaccination. The survey showed that 31.2% (481/1 542) of responders had been vaccinated against influenza. The vaccination rate in community health care institutions was significantly higher than that in district central hospitals [39.1% (304/778) vs. 23.2% (177/764), χ 2=45.44, P<0.05]. Factors affecting vaccination for healthcare providers were: influenza antigen was variable, and vaccination had no effects [49.5% (404/816)]; the efficacy of the flu vaccine was doubt [48.8% (634/1 298)]; the vaccine wasn′t free [46.5%(604/1 298)]. The respondents believed that the main ways to improve the influenza vaccination were to formulate relevant national vaccination policies [79.7%(1 229/1 542)], to regularly publicize knowledge of influenza and influenza vaccine to residents through communities [65.8% (1 015/1 542)], and to recommend the patients by primary care medical staff [64.4% (993/1 542)]. Conclusion:Many healthcare providers have insufficient knowledge about influenza and vaccine. The vaccination rate of community health institutions is higher than that in district central hospitals in Shanghai. The willingness to promote influenza vaccination can be influenced by some factors. Increasing the willingness of healthcare providers might be helpful to improve the vaccination coverage among residents in the community.
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Based on the current status of allocation, demands and utilization of medical care resources and the needs for future development in Shanghai, the overall objectives, principles, key plans of allocation of medical care resources in the 12th Five-years Plan in Shanghai and the leading role of health bureaus at all levels were discussed.
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The article summarized relevant theories and successful practical experience about medical resource integration, analyzed the background of regional medical-trust in Shanghai, and discussed three different model of regional medical-trust building, and their own advantages and disadvantages. Furthermore it discussed the main framework of regional medical-trust pilot reform,including administrative and operational model, insurance-payment model and visiting-doctor model. Then, it introduced the reform strategies of regional medical-trust pilot and present progress.
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According to the basic principle, this paper reviews and summarizes the separated management of income and expenses in CHCs(community health centers)in Shanghai. Through summarizing the practice and experience, analyzes the effect, and extracts the necessity, core, key points and difficulties, which can be used in the CHCs in other areas.
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The relevant policies of national essential medicine system were reviewed, major concerns and actions in the implementation of essential medicine system in Shanghai were introduced, and the suggestions to improve the implementation of essential medicine system of Shanghai were made. These provided the information for policy making and provided a useful experience for facilitating the establishment of essential medicine system and the improvement of its implementation in Shanghai as well as China.
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Objective To establish the model of invasive pulmonary aspergillosis (IPA) and assay the influence on the host defense against Aspergillus infection when immunity was suppressed in mice.Methods Immunocompromised mice were made by treatment with cyclophosphamide administered intraperitoneally (i.p.).Suspension of conidia was applied to the nostrils of mice to make the model of IPA.Lungs were harvested and homogenized.Portions of homogenates were cultured to determine the number of CFU.IFN-? in bronchoalveolar lavage fluid was determined by a cytokine-specific ELISA kit.Reverse transcription PCR (RT-PCR) analysis was done to determine the mRNA of IFN-? in lung cells.Mortality of different rice was calculated.Results Compared with immunocompetent mice,the immunocompromised mice demonstrated a high mortality and had significantly higher concentration of infectious Aspergillus organisms in their lung tissues.In accordance with the increase of Aspergillus organisms,the levels of IFN-? in lung tissues got higher.Lung sections from immunocompromised mice revealed patterns of lesions characterized by signs of bronchial wall damage,peribronchial necrosis,and the presence of numerous infiltrating inflammatory cells.Conidia and hyphae were seen in these mice.In contrast,these features were not observed in immunocompetent mice whose lungs were characterized by few inflammatory cells infiltration,and few fungal growth after inoculation.Conclusion The levels of IFN-? in lung tissues are related to the infectious Aspergillus organisms.The immunity and T cells play a major role in host defense against Aspergillus infection.
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<p><b>OBJECTIVE</b>To characterize the differences between clinical manifestations in immunocompromised patients (ICPs) and non-immunocompromised patients (non-ICPs) with tuberculosis.</p><p><b>METHODS</b>Underlying diseases, clinical presentations, misdiagnosis, treatment and prognosis, etc, were analyzed retrospectively in 115 tuberculosis patients, including 39 ICPs and 76 non-ICPs.</p><p><b>RESULTS</b>Compared with non-ICPs, the individuals who were ICP had more expectoration (64.1% vs 35.5%), pulmonary moist rale (41.0% vs 9.2%), miliary pulmonary tuberculosis (30.8% vs 2.6%), pleural effusion (48.7% vs 25.0%) and lymphadenopathy (18.0% vs 4.0%). ICPs had less lung cavity (15.4% vs 22.4%) and pleural thickening (15.4% vs 23.7%) compared to non-ICPs. Pulmonary tuberculosis in ICPs was prone to be misdiagnosed as pneumonia (23.1% vs 6.6%). Pulmonary tuberculosis was found in the apicoposterior segment (SI + SII) in more cases in non-ICPs (21.7%, 10/46) than ICPs (10.3%, 3/29). The diagnostic value of tuberculin skin test and adenosine deaminase in pleural effusions was limited in ICPs. ICPs had significantly poorer prognoses than non-ICPs.</p><p><b>CONCLUSION</b>The clinical manifestations of ICPs with tuberculosis are atypical, misdiagnosis often occurs, resulting in a worse prognosis.</p>
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Adult , Aged , Female , Humans , Male , Middle Aged , Immunocompromised Host , Physiology , Tuberculosis, Lymph Node , Diagnosis , Tuberculosis, Miliary , Diagnosis , Tuberculosis, Pulmonary , DiagnosisABSTRACT
ObjectiveTo predict the opportunity of infection and evaluate the severity of illness and prognosis for patients with lower resp iratory tract infections in intensive care unit (ICU) using the acute physiology and chronic health evaluation Ⅲ (APACHEⅢ) MethodsThe clini cal data of 115 cases with infections of pseudomonas aeruginosa (PA) in lowe r respiratory tract and 116 cases without PA infections were analyzed and evalua ted with APACHEⅢ score system ResultsAPACHEⅢ scores of non -survivors were significantly higher than those of survivors [(55 29?15 83) vs (25 97?14 39),P
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Objective To investigate the endotoxemia initiated systemic and pulmonary inflammation and acute lung injury in endotoxin tolerant rats MethodsEndotoxi n tolerance (ET) models of SD rats were induced by four daily intraperitoneal in jections of 0 6 mg?kg -1 ?d -1 Escherichia coli LPS (serotype 055:B5).Normal control (NC) rats received intraperitoneal injections of the sa me volume saline On the fifth day,rats were injected with high dose of LPS (6 mg/kg) to induce endotoxemia and lung inflammation Blood,left bronchoalveolar lavage fluid (BALF) and right lung tissue were collected before and 2,6,24,48 ,72 hours after the high dose injection of LPS (six rats for each time point) Cytological examination of blood and BALF and histopathological examination wer e performed Bromine methylphenol green was adopted for measurement of serum alb umin BALF albumin was measured by en z yme-linked immunosorbent assay (ELISA) and adjusted by the ratio to serum album in to evaluate the permeability of pulmonary microvascular Results The symptomes such as less activity,accelerated respiratory rate and weight loss in NC rats was not found in ET rats after the high dose injectio n of LPS BALF albumin as well as the ratio of BALF albumin to serum albumin in c reasedt 2 hours after injection of 6 mg/kg LPS and reached their zenith at 6 hou rs in NC rats,while no increase in ET rats In NC rats the blood white cell dif f erentiating shifted from lymphocyte to PMN,and PMN percentage of BALF also incr eased from (0 443?0 345)% to (8 000?2 896)% with its peak at 24 hours a fter the injection (P
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There are several bewilderments in diagnosis and management of pulmonary infection in immunocompromised patients,including broadly combinational empirical antimicrobial therapy which joined three enven four or five antimicrobial agents;taking antibiotic therapy protocol change as major issues and ignoring detection of pathogen when fever and lung infilitration was occurred;neglecting the differentiation of non-infectious causes in lung infilitrations of immunocompromised patinets;modulating or halt of corticosteroid for immunocompromised patients with fever and lung infilitration.key words immunocompromised patients pulmonary infections diagnosis and management bewilderment remark
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Pulmonary surfactant ( PS ) compromises lipids and surfactant proteins (SP) and lines on the alveolar air-liquid interface. It can reduce surface tension, prevent alveoli from collapse and reduce alveoli edema by disaturated dipalmitoylphosphatidylcholine. It also modulates the pulmonary immunology by SP-A and SP-D. In this study,we established a rat model of immunocompromised host (ICH) with pulmonary infection of Pseudomonas aeruginosa (P. aeruginosa), then studied its pulmonary inflammatory reaction and analyzed the concentration of lipids and SP-A in bronchoalveolar lavage fluid (BALF) during infection.
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Animals , Male , Rats , Bronchoalveolar Lavage Fluid , Chemistry , Microbiology , Lipids , Lung , Microbiology , Neutrophils , Physiology , Pneumonia, Bacterial , Allergy and Immunology , Metabolism , Proteolipids , Pseudomonas Infections , Allergy and Immunology , Metabolism , Pulmonary Surfactant-Associated Protein A , Pulmonary Surfactant-Associated Proteins , Pulmonary Surfactants , Rats, Sprague-DawleyABSTRACT
In March,2009,novel influenza pandemic A(H1N1)virus emerged in Mexico and rapidly disseminated worldwide.Secondary pulmonary infection is a predominant contributor to the death of novel influenza A(H1N1),The most common causative pathogens of secondary pulmonary infection in novel influenza A(H1N1)include Streptococcus pneumoniae,Haemophilus influenzae and Staphylococcus aureus.The recognization of the pathogenesis of secondary pulmonary infection in novel influenza A(H1N1)is critically significant to the strategy in diagnosis and treatment of novel influenza A(H1N1).Therefore,we elaborate the current situation of secondary pulmonary infection in novel influenza A(H1N1)and provide insight into the clinical diagnosis and treatment of novel influenza A(H1N1).
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Virus infection is a cause of respiratory tract infections and predisposes the patients to secondary bacterial infections. With the graying” of the population and the increase of organ transplantation, immunocompromised hosts (ICH) and the rate of human immunodeficiency virus (HIV) infection as well as the emergence of such new pathogens as Hantavirus and Ebola virus in recent years, the morbidity of respiratory tract infections is growing high. There come the new challenges in the management of the respiratory tract infections. This paper is to introduce the application of antiviral drugs in the treatment of respiratory tract infections and discuss about the methodology of the administration of these drugs.
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@#Objective To study the alteration of surfactant protein A and D(sp-A,SP-D)result-ing from pneumcystis carinil pneumonia(PCP)and investigate its implication in the pathogenesis of PCP.Methods SD rat models of PCP were induced by subcutaneous injection of 25 mg cortisone acetate,normal control and negative control as well as bacterial pneumonia group were set up for comparison.During 8～12weeks.broncboalveolar lavage fluid (BALF) of rats was collected.Total nucleate cells of BALF were counted and differentiated as well as the concentrations of surfactant protein A(SP-A)and surfactant pro-tein D(SP-D)were measured by immunoblotting assay.Results The rats were divided into three im-munosuppressive groups,plus a norrflal control group. Group A: normal control(n=6)consisted of healthy SD rats;group B:negative control(n=6)employed rats with cortisone acetate injection over 8weekz without tung infection;group C:bacterial pneumonia(n=11),rats were injected with cortisone ac-etate over 8 weeks and resulted in bacterial pneumonia without other pathogens isolated;group D(n=14):rats were injected with cortisone acetate during 8～12 weeks and resulted in PCP without other pathogens isolated.During PCP infection,the total cell counts and the percentage of polymorphonuclears (PMNs)in BALF were significantly increased(P<0.01),but were lower than those in the bacterial pneumonia group.The concentration of SP-A of BALF in PCP(45.1 μg/ml 4±22.1 μg/m1)was signifi-cantly increased in comparison with that in negative control group(16.2 μg/ml±9.9 gg/ml,P<0.05)and that in bacterial pneumonia group(6.2 μg/ml±5.6 μg/ml,P<0.001).We also found that the rela-tive content of SP-D was significantly higher in PCP(24 249±4 780 grey values)than that in both nega-tive control(13 384±2 887 grey values,P<0.001)and bacterial pneumonia group(11 989±2 750 grey values,P<0.001).SP-A and SP-D were also higher in moderate to severe group of PCP than those seen in mild group(P<0.01,P<0.001).Conclusion There was obvious increase of SP-A and SP-D in PCP rats,and particularly,the change of which was greater than that in bacterial pneumonia.Therefore,the alteration of SP-A and SP-D may be of implication in the prevention and management of PCP.
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OBJECTIVE To observe a time course of keratinocyte growth factor(KGF) and surfactant protein A(SPA) changes in rats with Pseudomonas aeruginosa pneumonia and to find out the significances of them.METHODS Specific pathogen-free male Sprague-Dawley rats were used to study.Standard P.aeruginosa strain ATCC 27853 was instilled into airway by the tracheal route to induce model of pneumonia.Samples of lung tissue and BALF were harvested before infection,and 6 h,9 h and 72 h after infection.Six rats per each point were sacrificed for harvesting samples.Expression of KGF protein in lungs was detected by Western blotting.Western-dot-blot was used to detect SPA expressions in BALF.RESULTS After infected with P.aeruginosa,KGF protein in lungs was markedly increased,reached the peak at 72 h postinfection.KGF protein level at 72 h postinfection was markedly higher than that of before infection(P