Preliminary immunological evaluation of Mycobacterium tuberculosis multicomponent protein vaccine candidates EPDPA015f and EPDPA015m / 中华微生物学和免疫学杂志

Objective:To preliminarily evaluate the immunogenicity and efficacy of two novel tuberculosis vaccine candidates (a fusion multicomponent protein EPDPA015f and a mixed multicomponent protein EPDPA015m) and to provide a new antigen combination for the development of tuberculosis vaccines.Methods:Recombinant plasmids for the expression of EPDPA015f and EPDPA015m proteins were constructed. Six-week-old BALB/c mice were immunized with EPDPA015f or EPDPA015m in combination with aluminium adjuvant (50 μg/mouse) for three times with an interval of 10 d. The mice were sacrificed 10 d after the last immunization to collect blood and spleen samples. Serum antibody titers and cytokine levels were measured by ELISA, Luminex technique and enzyme-linked immunospot assay (ELISPOT). Mycobacterial growth inhibition assay (MGIA) was used to detect the ability of mouse splenocytes to inhibit the growth of Mtb in vitro. One-way analysis of variance and t-test were used for statistical analysis. Results:Both EPDPA015f and EPDPA015m could induce the production of various cytokines and IgG antibodies at a high level. The levels of cytokines related to Th1 (IL-2, TNF-α, IFN-γ), Th2 (IL-4, IL-6, IL-10) and Th17 (IL-17) as well as other proinflammatory cytokines (GM-CSF, IL-12) were higher in the EPDPA015f group than in the adjuvant group ( P<0.05). The titer of IgG antibody induced by EPDPA015f was as high as 1∶4×10 6. The results of MGIA showed that the numbers of Mtb (lgCFU) in the PBS, adjuvant, EPDPA015f and EPDPA015m groups were 3.46±0.11, 3.51±0.06, 2.98±0.09 and 3.19±0.08, respectively. The number of colonies in the EPDPA015f group was the least as compared with that in the other three groups ( P<0.001, P<0.001, P<0.01). Conclusions:The vaccine candidate EPDPA015f could elicit more comprehensive and high-level cellular and humoral immune responses, and exhibited superior in vitro inhibitory activity against the growth of Mtb. EPDPA015f had the potential to be used as a preventive vaccine or a booster vaccine

Establishment and effect of extended nursing service model for outpatient intravenous treatment / 中华临床营养杂志

Objective To establish an extended nursing service model for intravenous treatment in outpatient,so that patients with venous catheters nearby can receive catheter maintenance,which can reduce the medical cost and the incidence of complications during the maintenance of the catheters.Methods A three-level network of catheter maintenance was established in the area to evaluate the rate of return maintenance and the incidence of complications [catheter-related infection,medical adhesive-related skin injuries (MARSI) and catheter blockage] during catheterization.Results The rate of patient return maintenance as statistically signif-icant between the first half of 2015 and the second half of 2016 (60.0％ vs.29.7％,P=0.000).Compared with the first half of 2015,the incidence of catheter-related infections decreased in the second half of 2016 from 8.6％ to 3.3％,the incidence of MARSI decreased from 29.7％ to 10.1％,and the incidence of catheter blockage decreased from 8.5％ to 0.6％.(All P =0.000).Conclusion The comprehensive extended service mode for outpatient with venous catheters can reduce the incidence of complications during catheter maintenance,which can reduce the workload of outpatient intravenous treatment and also provide patients the convenience of catheter maintenance,and is worthy of clinical promotion.

Drug sensitivity of thirty-four reference slowly growing mycobacteria to first and second line antituberculous agents / 中国人兽共患病学报

Slowly growing mycobacteria (SGM ) are distributed in the environment ,for example in soil and dirty water . SGM can cause human infections ,especially lung diseases .In this article ,first and second line antituberculous agents were ex‐amined in order to identify the optimum drugs for the treatment of SGM disorders .The fewest SGM in our study (4/34) were susceptible to isoniazid .Rifampicin (13/34) and ethambutol (14/34) were effective against similar numbers of strains .Ofloxa‐cin (23/34) ,kanamycin (26/34 ) , tobramycin (26/34 ) and streptomycin (27/34 ) were active against most of the tested strains .Ciprofloxacin (31/34) ,levofloxacin (31/34) ,amikacin (33/34) and capreomycin (33/34) showed an excellent range of activity .Moxifloxacin (34/34) showed the widest range of activity against the SGM species .Among the tested SGM spe‐cies ,M .simiae and M .af ricanum were resistant to the highest number of drugs .M .szulgai and M .duvalii were susceptible to all the first and second line antituberculous agents tested .Overall ,the second‐line antituberculous agents were good candi‐dates for the treatment of infection by SGM species and can be widely used in the therapy of SGM diseases .

Association of drug efflux pump gene expression with Mycobacterium tuberculosis drug resistance / 中华检验医学杂志

Objectives To explore the associations between drug efflux pump gene expression and phenotypic drug resistance as well as gene mutation patterns related to drug resistance of Mycobacterium tuberculosis.Methods Forty-five Mycobacterium tuberculosis isolates resistant to one or more of drugs including isoniazid, rifampicin, streptomycin and ethambutol, and 26 isolates all sensitive to the above four drugs from Tianjin Tuberculosis Control Institute in 2007 were involved in this study. Direct sequencing was applied to detect the mutations in the corresponding resistance genes(isoniazid:katG, inhA, oxyR-ahpC, ndh, rifampicin:rpoB, streptomycin:rpsL, rrs, and ethambutol:embB, embC and embA). After RNA extration and reverse transcription, real-time PCR was conducted to assess the expressions of putative drug efflux pump genes Rv1410c, Rv2136c, Rv0783c and Rv2136c, and Students' t test and ANOVA analysis were used to analyze the expression differences in Mycobacterium tuberculosis with different phenotypic drug resistance and drug resistance related gene mutation patterns.Results Compared to pan-sensitive isolates[(5.67±3.29)×10-5], Rv1410c showed higher expression in streptomycin[(8.48±6.33)×10-5, t'=2.18, P<0.05], isoniazid[(8.43±6.38)×10-5, t'=2.20, P<0.05], rifampicin[(9.59±7.27)×10-5, t'=2.29, P<0.05], multi-drug[(10.37±7.86)×10-5, t'=2.34, P<0.05] resistant isolates, and in isoniazid + streptomycin resistant isolates[(9.39±6.81)×10-5, t'=2.43, P<0.05];Rv2136c showed higher expression in isoniazid resistant[(3.51±2.43)×10-5, t'=2.03, P<0.05], multidrug-resistant isolates[(4.21±2.94)×10-5, t'=2.22, P<0.05] and resistant to isoniazid+streptomycin[(3.81±2.46)×10-5, t'=2.28, P<0.05] isolates . The expression of Rv0783c in rifampicin resistant isolates with rpoB 531 mutations [(5.41±3.03)×10-6] was higher than those with wild type of rpoB 531[(2.29±1.62)×10-6, t=2.81, P<0.05].Conclusions The expression of Rv1410c and Rv2136c are associated with mutiple-drug resistance of Mycobacterium tuberculosis.The expression of Rv0783c in rifampicin resistant isolates is associated with mutation in rpoB 531.

Pulmonary Cryptococcosis and Its Clinical Feature Analysis / 中华医院感染学杂志

OBJECTIVE To explore the clinical features for pulmonary cryptococcosis due to Cryptococcus neoformans,and to improve diagnosis and treatment of the disease.METHODS The clinical features of inpatients with pulmonary cryptococcosis were studied retrospectively.RESULTS There were nine cases of pulmonary cryptococcosis from 1999 to 2006 of all inpatients in our hospital.Mals 5(56%),females 4(44%),and 3 cases(33%) were more than 60 years old.Three cases(33%) were immunocompromised hosts,6 cases(67%) had clinical symptoms.Chest X-ray and computed tomography were various included single or poly patching or nodule shadows,some had cavity(33%) and some had pleural effusions(22%).Six cases had positive results with serum cryptococcal antigen test.All nine patients were treated with fluconazole and improved or cured.CONCLUSIONS Pulmonary cryptococcosis is seldom seen in clinic,it can be observed in humans with normal immune responses or immunocompromised hosts and has no significant clinic manifestations,serum cryptococcal antigen test is helpful,definitive diagnosis needs early lung biopsy.The therapeutic effect is well.

A case report of lymphomatoid granulomatosis and review of the literature / 北京大学学报(医学版)

To explore the clinical manifestation of lymphomatoid granulomatosis (LG) and the early diagnosis. Retrospective analyses of the clinical features of LG and pathology features by open lung bio-psies were conducted. The patient was a 42-year-old female with irregular fever,and her chest X-ray and computed tomography showed nodules with cavity and pleural effusion. Open lung biopsy proved LG. LG is seldom seen in clinic. Open lung biopsy is very important for pathology diagnosis. Early diagnosis and treatment are the key to improving survival in these patients. The therapeutic effect is good.

H_3N_2 subtype of human influenza pneumonia with staphylococcal sepsis and staphylococcal pneumonia:Report of one case / 北京大学学报(医学版)

To investigate the clinical characteristics, diagnosis and therapy of influenza pneumonia with staphylococcal infection. One patient in our hospital was diagnosed and the literatures on the subject were reviewed. The patient presented with high fever and dyspnea. Arterial gas analysis indicated type 1 respiratory failure. Chest X ray photographs showed bilateral infiltrations and bilatera encapsulated pleural effusions. Viral separation and culture of pharyngeal swab indicated H3N2 subtype of human influenza virus. Blood, sputum and bronchoalveolar lavage fluid (BALF) cultures showed Staphylococcus aureus. Pleural effusion was complex parapneumonic pleural effusion. After the administration of anti-virus, anti-staphylococcal antibiotics and pleural cavity drainage, the patient was cured. The infection of staphylococcus aureus is a typical characteristic of influenza pneumonia, and anti-staphylococcal antibiotic therapy (with MRSA activity in MRSA endemic regions) should be initiated in hospitalized cases of influenza pneumonia. If complex parapneumonic pleural effusion or empyema complicated, we should perform pleural cavity drainage in time. The oral neuraminidase inhibitor (oseltamivir) could significantly improve prognosis.