This study aimed to investigate the immune adjuvant effect and mechanism induced by chitosan nanoparticles carrying pJME/GM-CSF. In this study, plasmid DNA (pJME/GM-CSF) was encapsulated in chitosan to prepare chitosan-pJME/GM-CSF nanoparticles using a complex coacervation process. Immunohistochemistry was used to detect the type of infiltrating cells at the site of intramuscular injection. The phenotype and functional changes of splenic DCs were measured by flow cytometry after different immunogens were injected intramuscularly. The killing activity of CTLs was assessed using the lactate dehydrogenase (LDH) release assay. The preparation of chitosan-pJME/GM-CSF nanoparticles matched the expected theoretical results. Our results also found that, after pJME/GM-CSF injection, the incoming cells were a mixture of macrophages, neutrophils, and immature DCs. Meanwhile, pJME/GM-CSF increased the expression of MHC class II molecules on splenic DCs, and enhanced their Ag capture and presentation functions. Cell-mediated immunity was induced by the vaccine. Furthermore, chitosan-pJME/GM-CSF nanoparticles outperformed the administration of standard pJME/GM-CSF in terms of DC recruitment, antigen processing and presentation, and vaccine enhancement. These findings reveal that chitosan could be used as delivery vector for DNA vaccine intramuscular immunizations, and enhance pJME/GM-CSF-induced cellular immune responses.
Adjuvants, Immunologic ; administration & dosage ; Animals ; Chitosan ; administration & dosage ; immunology ; Dendritic Cells ; immunology ; virology ; Encephalitis Virus, Japanese ; genetics ; immunology ; Encephalitis, Japanese ; immunology ; prevention & control ; virology ; Female ; Granulocyte-Macrophage Colony-Stimulating Factor ; administration & dosage ; genetics ; immunology ; Humans ; Immunity, Cellular ; Japanese Encephalitis Vaccines ; administration & dosage ; genetics ; immunology ; Mice ; Mice, Inbred BALB C ; Nanoparticles ; administration & dosage ; Spleen ; immunology ; T-Lymphocytes, Cytotoxic ; immunology ; virology ; Vaccines, DNA ; administration & dosage ; genetics ; immunology

China ; epidemiology ; Humans ; Venous Thromboembolism ; diagnosis ; drug therapy ; epidemiology

Heat sensitive protein medicines are increasingly exhibiting their critical importance on treatment of various diseases at present. But their popularization and application meet a great challenge because of their heat instability. In the present study, insulin was taken as a heat sensitive protein medicine and amino acid as bio-protective agent in order to investigate if these amino acids can protect the insulin from losing its bioactivity due to desiccation. The experiment was performed by using replica exchange molecular simulation (REMD) method and Gromacs software with Gromos96 (53a6) force field. The REMD results indicated that these amino acids could protect the bioactive structure of insulin during desiccation. The configurations of the protected insulin were preserved very well. Those results proved that amino acid is a kind of good bioactive protective agent for the heat sensitive protein medicines.
Amino Acids ; chemistry ; Desiccation ; Drug Stability ; Insulin ; chemistry ; Molecular Dynamics Simulation ; Software

Since 1973 the World Symposia on Pulmonary Hypertension(WSPH)proceedings have summarised the scientific advances and future needs in this field through the efforts of multiple task forces, each focusing on a different aspect of pulmonary hypertension(PH). The task forces presented their consensus opinion after the 6 th WSPH held in Nice in 2018.This is an interpretation for the overview of the 6 th WSPH,which includes the following four aspects, translational medicine and precision medicine of PH, clinical research on PH, relevant research on several common types of PH, patient management and patient association.Among them, the most significant change is the new definition of hemodynamic standard of PH, but the implementation and use of the new standard, as well as the diagnosis and treatment of patients between the two standards still need further research and exploration. In addition, the importance of patient participation and management in the diagnosis and treatment and effective care of PH was clearly proposed for the first time.

Objective Acute pulmonary thromboembolism(PTE)patients with right ventricular dysfunction(RVD)may benefit from thrombolytic therapy but may end up with worse prognosis.RVD was assessed in prognosis to which a model on it was constructed to decide the indexes correlated to the best prognosis.Methods This prospective study included 520 consecutive acute PTE patients from 41 hospitals in China between June 2002 and February 2005.All the patients were evaluated by transthoracic echocardiography(TTE),CT pulmonary angiography(CTPA),laboratory tests,and blood gas analysis.Physicians were asked to record all the clinical manifestations.Data from Univariate analysis demonstrated the parameters correlated with an 14-day clinically adverse outcomes.Multiple logistic regression analysis was used to decide the independent predictors and to construct a prognostic model.Results Mcan age of the patients was 57.4±14.1 years and 323 of them(62.1%)were male.The 14-day mortality in normotensive patients with RVD was higher(2.0%vs0.4%,P＜0.01)than those without.ROC curve showed the best cut.ofr values of RVED/LVED and SPAP for 14-day prognosis were 0.67 and 60 mm Hg,respectively.SPAP independently predicted 3-month clinicaI outcomes(P＜0.01).Results from Univariate analysis demonstrated tllat 24 parameters were correlated with an adverse 14-day clinical outcomes.which include palpation,syncope,panic,cyanosis,respiratory rate≥30/min,pulse≥110/min,jugular vein,accentuation of P2,murmurs in tricuspid area,time interval from onset,creatine phosphokinase(CPK),lactate dehydrogenase (LDH).alveolar-arterial PO2 difierence(PA-aO2),white blood cell(WBC)＜4.0×109/L or＞10.0×109/L,platelet.thrombus on TTE,RV/LV＞1.1,TRPG＞30 mm Hg,IVCmin＜8 mm,RVD,RVED/LVED＞0.6,SPAP＞60 mm Hg.RVWM.PTE range larger than two lobes or seven segments on CTPA.Furthermore,a multiple logistic regression model implied 8 predictors including RVD,RVED/LVED＞0.6,SPAP＞60 mm Hg,pulse≥110/min,accentuation of P2,Syncope,CPK,WBC＜4.0×109/L or＞10.0×109/L be independent predictors of an 14-day clinically adverse outcome(P＜0.01).This model seemed to fit well (P＜0.001).Wle chose a cut-off value as P≥0.2 and compared the model to the original derivation samples.Data showed that the sensitivity(true positive rate)was 81.82%,specificity was 92.11%.false positive rate was 18.18%.coincidence was 91.14%.and the concordarlCe rate was 80.96%.Conclusion RVD seemed a nice discriminator for poor prognosis in norrnotensive patients.Early detection of RVD(especially RVED/LVED＞0.67 and/or SPAP＞60 mm Hg)was beneficial for identifying patients at high-risk and the multiple logistic regression model(P＜0.001)could be well fitted.

OBJECTIVETo identify the risk factors of deep venous thrombosis(DVT) in patients with acute pulmonary thromboembolism (PTE).

METHODSPost hoc analysis on data from a prospective multicenter through a randomized control trial on thrombolysis and anticoagulant among 454 patients with acute symptomatic PTE from June 2002 to December 2004. All patients were confirmed PTE by CT pulmonary angiography (CTPA) and/or ventilation perfusion scan or by magnetic resonance pulmonary angiography. Data of PTE patients with DVT was compared with those without DVT to identify the DVT risk factors. The effect of other variable on DVT was assessed by logistic regression analysis.

RESULTSWhen comparing the age, sex body weight index and underlying diseases including hypertension, coronary heart disease, chronic obstructive pulmonary disease, cerebral accident and malignant tumor between groups of DVT and no DVT,data showed that there was no statistically significant difference except for diabetes (chi2 = 4.481, P = 0.034) among them.However,results from multi-analysis showed that edema of lower-limb [odd ratio (OR), 2.255; 95% CI, 1.493 to 3.408], phlebitis (OR, 2.380; 95% CI, 1.426 to 3.973) and the entire swollen (calf swelling > or =1 cm) larger than asymptomatic side (OR, 3.834; 95% CI, 2.561 to 5.738) were independent risk factors for DVT.

CONCLUSIONEdema of lower-limb, phlebitis and calf swelling > or =1 cm seemed to be risk factors for DVT.

Adolescent ; Adult ; Aged ; Edema ; Female ; Humans ; Logistic Models ; Lower Extremity ; pathology ; Male ; Middle Aged ; Phlebitis ; Pulmonary Embolism ; complications ; Randomized Controlled Trials as Topic ; Retrospective Studies ; Risk Factors ; Venous Thrombosis ; etiology ; Young Adult

BACKGROUNDPulmonary endarterectomy is safe and effective surgical treatment for chronic thromboembolic pulmonary hypertension. This study aimed to evaluate the efficacy of pulmonary endarterectomy in treatment of thromboembolic pulmonary hypertension.

METHODSA retrospective study of 15 patients who underwent pulmonary endarterectomy in Beijing Chaoyang Hospital was performed. Obvious pulmonary hypertension and hypoxemia were observed in all patients. Bilateral pulmonary endarterectomy was performed under cardiopulmonary bypass with profound hypothermic circulatory arrest.

RESULTSTwo patients (2/15) died of residual postoperative pulmonary hypertension and bleeding complication. The other 13 cases had significant decrease in systolic pulmonary artery pressure ((92.8 +/- 27.4) mmHg vs. (49.3 +/- 18.6) mmHg) and pulmonary vascular resistance ((938.7 +/- 464.1) dynesxsxcm(-5) vs. (316.8 +/- 153.3) dynesxsxcm(-5)), great improvement in cardiac index ((2.31 +/- 0.69) Lxmin(-1)xm(-2) vs. (3.85 +/- 1.21) Lxmin(-1)xm(-2)), arterial oxygen saturation (0.67 +/- 0.11 vs. 0.96 +/- 0.22) and mixed venous O(2) saturation (0.52 +/- 0.12 vs. 0.74 +/- 0.16) postoperatively compared to preoperative data. Mid-term follow-up showed that the cardiac function of all cases returned to NYHA class I or II, with great improvement in 6-minute walking distance ((138 +/- 36) m) and quality of life.

CONCLUSIONSBilateral pulmonary endarterectomy using cardiopulmonary bypass with the aid of deep hypothermia and circulatory arrest can effectively reduce pulmonary hypertension and provide good mid-term hemodynamic and symptomatic results with low surgical mortality rate and few complications.

Adolescent ; Adult ; Echocardiography ; Endarterectomy ; adverse effects ; methods ; Female ; Hemodynamics ; Humans ; Hypertension, Pulmonary ; surgery ; Male ; Middle Aged ; Retrospective Studies ; Thromboembolism ; surgery ; Young Adult

BACKGROUNDAcute pulmonary thromboembolism (APE) causes right ventricular dysfunction (RVD) and cardiac troponin I (cTnI) elevation. Patients with RVD and cTnI elevation have a worse prognosis. Thus, early detection of RVD and cTnI elevation is beneficial for risk stratification. In this study, we assessed 14-day adverse clinical events and combined RVD on transthoracic echocardiography (TTE) with cTnI in risk stratification among a broad spectrum of APE patients.

METHODSThe prospective multi-centre trial included 90 patients with confirmed APE from 12 collaborating hospitals. Acute RVD on TTE was diagnosed in the presence of at least 2 of the following: right ventricular dilatation (without hypertrophy), loss of inspiratory collapse of inferior vena cava (IVC), right ventricular (RV) hypokinesis, tricuspid regurgitant jet velocity > 2.8 m/s. The study patients were divided into two groups according to clinical and echocardiographic findings at presentation: Group I: 50 patients with RVD; Group II: 40 patients without RVD.

RESULTSMore than half of the patients (50/90, 55.6%) had RVD. Nearly one third (26/90, 28.9%) of patients had elevated cTnI at presentation and only 4.2% on the fourth day after initial therapy. A multiple Logistic regression model implied RVD, right and left ventricular end-diastolic diameter ratio (RVED/LVED), and cTnI independently predict an adverse 14-day clinical outcome (P < 0.01). Receiver operating characteristics (ROC) curves revealed that the cut-off values of RVED/LVED and cTnI yielding the highest discriminating power were 0.65 and 0.11 ng/ml, respectively. Furthermore, the incidence of an adverse 14-day clinical event in patients with RVD and elevated cTnI was greater (40.7%) than in patients with elevated cTnI or positive RVD alone (0% and 8.3%, respectively) (P < 0.001).

CONCLUSIONSRVD, RVED/LVED, and cTnI are independent predictors of 14-day clinical outcomes. The patients with RVED/LVED greater than 0.65 and cTnI higher than 0.11 ng/ml at presentation possibly have adverse 14-day events. RVD combined with cTnI can identify a subgroup of APE patients with a much more guarded prognosis.

Acute Disease ; Adult ; Aged ; Echocardiography ; Female ; Humans ; Male ; Middle Aged ; Prognosis ; Pulmonary Embolism ; blood ; complications ; diagnostic imaging ; Troponin I ; blood ; Ventricular Dysfunction, Right ; diagnosis

Animals ; China ; epidemiology ; Disease Models, Animal ; Humans ; Polymorphism, Genetic ; Venous Thromboembolism ; diagnosis ; epidemiology ; genetics

OBJECTIVETo pool the data of studies about anticoagulation in non-massive pulmonary thromboembolism (PTE) and evaluate the efficacy and safety of low molecular weight heparin (LMWH) and unfractionated heparin (UFH) as the initial treatment.

METHODSMEDLINE CD-ROM from January 1966 to August 2003 and CBM CD-ROM from January 1978 to August 2003 were chosen for searching the randomized clinical trials (RCTs) that compared the efficacy or safety of LMWH and UFH in non-massive PTE. A meta-analysis was employed to evaluate the results of these two therapies.

RESULTSFive RCTs including 999 cases were analyzed. Compared with UFH, the combined odds ratio (OR) of LMWH in treating PTE was as follows: (1) The total OR of mortality of PTE patients treated with LMWH was 0.81 (95%CI 0.36-1.81, P > 0.05); (2) The total OR of recurrence of venous thromboembolism (VTE) in PTE patients treated with LMWH was 0.37 (95%CI 0.14-1.00, P=0.05); (3) The total OR of bleeding in LMWH was 0.47 (95%CI 0.16-1.39, P > 0.05);(4) The total OR of heparin-induced thrombocytopenia (HIT) in LMWH was 0.66 (95%CI 0.06-6.92, P > 0.05).

CONCLUSIONSLMWH and UFH can reduce the mortality and recurrence of VTE in patients with PTE in the same degree. The risk of major bleeding was similar in the two treatment groups. Initial subcutaneous therapy with the LMWH appeared to be as effective and safe as intravenous UFH in the initial treatment of PTE.

Adult ; Anticoagulants ; therapeutic use ; Female ; Heparin ; therapeutic use ; Heparin, Low-Molecular-Weight ; therapeutic use ; Humans ; Male ; Odds Ratio ; Pulmonary Embolism ; drug therapy ; mortality ; Randomized Controlled Trials as Topic ; Recurrence ; Thrombolytic Therapy ; Treatment Outcome