BACKGROUND:Numerous basic and clinical trials have confirmed that the low survival rate after bone marrow mesenchymal stem cell transplantation is a serious constraint on its long-term therapeutic effect.Previous studies have shown that apoptosis-related factors play an important role in the apoptosis of bone marrow mesenchymal stem cells,of which apoptosis-inducing factor may be a key factor. OBJECTIVE:Bone marrow mesenchymal stem cells,of which apoptosis-inducing factor was knocked down,were transplanted into infarcted myocardium of mice,aiming to certify the importance of apoptosis-inducing factor in the survival of bone marrow mesenchymal stem cells to further recover cardiac function after infarction. METHODS:Firstly,bone marrow mesenchymal stem cells were infected with LV-AIF-shRNA lentivirus to down-regulate the expression of apoptosis-inducing factor protein.Flow cytometry,western blot assay,and RT-qPCR were used to detect the infection efficiency of lentivirus.CCK-8 assay was used to detect the cell viability of bone marrow mesenchymal stem cells with apoptosis-inducing factor knockdown under hypoxic and ischemic conditions.Then,with the mouse model of acute myocardial infarction constructed,the normal bone marrow mesenchymal stem cells and bone marrow mesenchymal stem cells with apoptosis-inducing factor gene knockdown were transplanted into the model,respectively.The expression of apoptosis-inducing factor was examined by fluorescence immunoassay.Serum brain natriuretic peptide levels were detected by ELISA.Cardiac ultrasound was used to detect cardiac function.Myocardial fibrosis was observed by Masson staining.The expression of SRY gene was detected by RT-qPCR in apoptosis-inducing factor-knocked bone marrow mesenchymal stem cells after transplantation,reflecting cell survival. RESULTS AND CONCLUSION:(1)Bone marrow mesenchymal stem cells with apoptosis-inducing factor gene knockdown were successfully established by LV-AIF-shRNA lentivirus infection,following 97.7%of infection efficiency,and notably decline of the expression of apoptosis-inducing factor(P<0.001).(2)Under ischemia and hypoxia,the cell viability of apoptosis-inducing factor knockdown bone marrow mesenchymal stem cells was significantly increased compared with normal bone marrow mesenchymal stem cells.(3)Compared with normal bone marrow mesenchymal stem cells after transplantation,the survival number of bone marrow mesenchymal stem cells in the infarcted myocardium after apoptosis-inducing factor gene knockdown was significantly increased to 3.71 times(P<0.001),and the apoptosis-inducing factor protein expression and myocardial fibrosis degree in the infarcted area were significantly reduced.(4)Compared with normal bone marrow mesenchymal stem cells,the serum brain natriuretic peptide level of bone marrow stem cells with apoptosis-inducing factor gene knockdown after transplantation was significantly decreased(P<0.05),and left ventricular ejection fraction and left ventricular shortening fraction were significantly improved(P<0.05).(5)These findings confirm that apoptosis-inducing factor gene knockdown can reduce myocardial fibrosis and improve cardiac function after acute myocardial infarction via enhancing the bone marrow mesenchymal stem cell viability and increasing the bone marrow mesenchymal stem cell survival after transplantation in the donor.

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Objective: To explore the value of B-type natriuretic peptide (BNP) be used as a prognostic factor for community-acquired pneumonia. Methods: This was a multicenter, retrospective study. Data of patients hospitalized with community-acquired pneumonia during 2014/1/1 to 2015/12/31 from four tertiary hospitals were reviewed, including demographic and clinical features, and outcomes. Univariate analysis and logistic regression analysis were performed to determine risk factors for 30-day mortality. Receiver operating characteristic curves (ROCs) was performed to verify the accuracy of BNP>1 000 pg/ml, CURB-65 score and BNP>1 000 pg/ml+ CURB-65 score (B-CURB65) as 30-day mortality predictors in the study patients. Results: 1 786 patients hospitalized with community-acquired pneumonia (CAP) were entered into the final analysis. The 30-day mortality was 4.7%. Logistic regression analysis confirmed blood BNP>1 000 pg/ml was an independent risk factor associated with 30-day mortality of CAP patients. The area under the curve (AUC) of B-CURB65 was 0.774, which was higher than CURB-65 score (AUC=0.625, P=0.002). Conclusions Blood BNP is a valuable biomarker related to the 30-day mortality of CAP patients, which can increase the predicting accuracy of CURB-65 score.

Objective: To analyze the prognostic value of CD7 expression in newly diagnosed acute myeloid leukemia (AML) patients, and to further explore the correlation between CD7 expression and CEBPA mutation, and to clarify the prognostic value of CD7⁺ in AML patients with wild-type (WT) or mutant-type (MT) CEBPA. Methods: The clinical data of 298 newly diagnosed non-M₃ AML patients between January 2010 and December 2016 were analyzed retrospectively. The clinical characteristics and prognosis of CD7⁺ and CD7^- patients were respectively compared in all patients, and in patients with WT and MT CEBPA. The relationship between CD7 expression and CEBPA mutation was determined by chi-square, and the effects of CEBPA mutation on survival and prognosis in CD7⁺ group by Kaplan-Meier method. Results: In CD7⁺ group, the frequencies of CEBPA mutation were 10.1% (single site) and 33.9% (double site) , significantly higher than those of the CD7^- group (5.3% and 4.2%) (P=0.000) . Subgroup prognostic analysis showed a lower CR rate (P=0.001) and a higher RR (P=0.023) in CD7⁺ group comparing to those of CD7^- group in AML patients with wild type CEBPA. There were no statistical difference between CD7⁺ group and CD7^- group in overall survival (OS) and disease free survival (P>0.05) , while in the CEBPA mutant group the CD7⁺ group has higher OS (P=0.019) and DFS (P=0.010) . Based on the CD7 expression and CEBPA mutation, 298 cases were divided into 3 subgroups, named as CD7⁺-CEBPA MT group, CD7^- and CD7⁺-CEBPA WT group. The 3-year OS of the 3 groups were 80.2%, 48.0% and 30.6%, respectively (P<0.001) , and the 3-year DFS were 74.1%, 37.4% and 22.2%, respectively (P<0.001) . Conclusion The CEBPA mutation rate was higher in CD7⁺ AML patients then that of CD7^- patients. CD7 expression has opposite prognostic significance in AML patients carrying the wild-type or mutant-type CEBPA. Based on CD7 expression and CEBPA mutation, a new risk stratification model can be established, which is helpful to guide the clinical individualized treatment for AML patients.

Objective:To evaluate the impact of short-term low-medium dose of corticosteroids on the clinical outcomes of patients with community-acquired pneumonia due to influenza A (FluA-CAP).Methods:This was a multicenter, retrospective study, including 693 patients hospitalized with FluA-CAP from Beijing Jishuitan Hospital, Qingdao Municipal Hospital, Beijing Huimin Hospital, Beijing Chao-Yang Hospital and the 2nd People′s Hospital of Yunnan Province during January 1, 2013 to December 31, 2018. The clinical characteristics of patients with or without corticosteroids administration were compared. The first dose of corticosteroids was administrated within 72 hours after admission, with the average dose of methylprednisolone (0.6±0.3) mg/(kg·d) and duration of (4.0±1.2) days. An adjusted logistic regression model was performed to assess the impact of corticosteroids treatment on the clinical outcomes (noninvasive ventilation, invasive ventilation, vasopressor use, admittance to intensive care unit (ICU), 30-day mortality, hyperglycemia needing insulin treatment and gastrointestinal bleeding). Mann-Whitney test and χ2 test were used for the statistical analysis. Results:Among the 693 patients, 132 patients received corticosteroids. Logistic regression analysis revealed that asthma (odd ratios ( OR)=15.528, 95% confidence interval ( CI) 1.953-123.484, P=0.01), chronic obstructive pulmonary disease ( OR=21.904, 95% CI 4.548-105.504, P<0.01) and arterial partial pressure of oxygen (PaO 2)/fraction of inspired oxygen (FiO 2)<300 mmHg (1 mmHg=0.133 kPa, OR=2.701, 95% CI 1.513-4.822, P<0.01) were independent risk factors for corticosteroids use in the FluA-CAP patients. An adjusted logistic regression model showed that low-medium dose corticosteroids administration was associated with decreased risks for early (defined as zero to three days after the first dose of corticosteroids) noninvasive ventilation ( OR=0.342, 95% CI 0.156-0.750, P<0.01), and increased risk for late (defined as four to 14 days after the first dose of corticosteroids) vasopressor use ( OR=2.651, 95% CI 1.913-6.306, P<0.01), late hyperglycemia which needed insulin treatment ( OR=9.739, 95% CI 2.174-21.769, P=0.019), ICU admission ( OR=3.075, 95% CI 1.166-8.143, P<0.01) and the 30-day mortality ( OR=2.372, 95% CI 1.337-4.549, P<0.01). In patients with asthma or chronic obstructive pulmonary disease ( OR=2.343, 95% CI 1.145-4.073, P<0.01) and PaO 2/FiO 2<300 mmHg ( OR=1.961, 95% CI 1.029-4.212, P<0.01), corticosteroids administration increased the risk of 30-day mortality. Conclusion:Low-medium corticosteroids treatment is associated with poor outcomes of FluA-CAP patients, and is not recommended to be used routinely.

Objective To assess the impact of short-term, low-dose systemic glucorticosteroids treatment on the clinical outcomes in patients with severe community-acquired pneumonia (SCAP). Methods A multi-center retrospective study was conducted. Data of patients hospitalized with SCAP in five teaching hospitals from Beijing, Shandong and Yunnan Provinces from January 1st, 2013 to December 31st, 2015 were reviewed. Patients were divided into steroids group and non-steroids group according to whether treated with glucorticosteroids during the disease course or not. Data of patients were reviewed, including gender, age, underlying disease, blood routine, biochemical examination and radiology findings (the worst value was recorded if there were more than one value), supportive treatment, complications (hyperglycemia needing insulin treatment and gastrointestinal bleeding) and clinical outcomes [early (0-3 days) treatment failure, late (4-14 days) treatment failure and 30-day mortality, treatment failure was defined as one of the followings: needing noninvasive or invasive ventilation, needing vasopressor use or death]. Univariate and multivariate Logistic regression was performed to evaluate the impact of short-term, low-dose systemic glucorticosteroids on the clinical outcomes in SCAP patients. Results Overall, 3 561 immunocompetent adult and adolescent patients with community-acquired pneumonia (CAP) were screened, 132 SCAP patients were entered into final analysis, including 24 patients in steroids group and 108 patients in non-steroids group. The patients in steroids group were prescribed with methylprednisolone (0.6±0.1) mg·kg-1·d-1 for (4.0±1.7) days. Compared with patients in non-steroids group, patients in steroids group showed younger age [years old: 70.5 (59.0, 75.0) vs. 80.0 (76.0, 85.0)], less frequency of male [41.7% (10/24) vs. 72.2% (78/108)], less comorbidities with cardiovascular [16.7% (4/24) vs. 42.6% (46/108)] and cerebrovascular disease [0% (0/24) vs. 40.7% (44/108)], less confusion [16.7% (4/24) vs. 40.7% (44/108)]; more frequency of chronic obstructive pulmonary disease [COPD, 41.7% (10/24) vs. 13.0% (14/108)], asthma [25.0% (6/24) vs. 1.9% (2/108)], chronic hepatic disease [8.3% (2/24) vs. 0% (0/108)] and respiratory rate≥30 times/min [33.3% (8/24) vs. 9.3% (10/108)] with significant differences (all P < 0.05), the proportion of guideline-based empirical antimicrobial therapy, early needing noninvasive ventilation, late gastrointestinal bleeding, early and late hyperglycemia needing insulin treatment were higher in steroids group than non-steroids group [50.0% (12/24) vs. 21.3% (23/108), 33.3% (8/24) vs. 7.4% (8/108), 20.8% (5/24) vs. 4.6% (5/108), 20.8% (5/24) vs. 1.9% (2/108), 37.5% (9/24) vs. 2.8% (3/108), all P < 0.05]. Adjusted by gender, age, comorbidities and empirical antimicrobial therapy, Logistic regression confirmed short-term, low-dose systemic glucorticosteroids was associated with higher risk for vasopressor usage [odds ratio (OR) = 3.369, 95% confidence interval (95%CI) = 1.369-6.133, P = 0.035], hyperglycaemia needing insulin treatment (OR = 4.738, 95%CI = 1.890-8.652, P = 0.017) in late stage and 30-day mortality (OR = 2.187, 95%CI = 1.265-4.743, P = 0.002). Conclusion Adjunctive treatment with short-term, low-dose systemic glucorticosteroids worsen the clinical outcomes and should not be used to SCAP patients routinely.

Objective:To develop an HPLC wavelength switching method for the determination of seven components in Shenrong Guben tablets simultaneously.Methods:A Waters Sunfire C18column (250 mm ×4.6 mm,5 μm) was adopted. The column temperature was set at 30 ℃. The mobile phase was acetonitrile-0.1% phosphate solution with gradient elution. The flow rate was 0.9 ml·min-1. The detection wavelength were set at 330 nm for verbascoside and martinoside,230 nm for albiflorin and paeoniflorin,and 203 nm for ginsenoside Rg1, ginsenoside Re and ginsenoside Rb1. Results:The linear range of verbascoside, martinoside,albiflorin, paeoniflorin, ginsenoside Rg1, ginsenoside Re and ginsenoside Rb1was 6.38-159.50 μg·ml-1(r =0.999 3),3.19-79.75 μg·ml-1(r =0.999 9),4.37-109.25 μg·ml-1(r =0.999 5),14.26-356.50 μg·ml-1(r =0.999 4), 1.95-48.75 μg·ml-1(r = 0.999 8), 2.21- 55.25 μg·ml-1(r = 0.999 7) and 2.09- 52.25 μg·ml-1(r = 0.999 1), respectively. The average recovery and the corresponding RSD was 98.24% (1.11%),97.64% (1.43%),99.23% (0.80%), 100.13% (0.65%),96.99% (1.56%),98.10% (1.24%) and 97.75%(1.37%),respectively. Conclusion:The developed method can determine the contents of verbascoside, martinoside, albiflorin, paeoniflorin, ginsenoside Rg1, ginsenoside Re and ginsenoside Rb1in Shenrong Guben tablets simultaneously,which can be applied in the quality control of Shenrong Guben tablets.

Objective To identify primary gout biomarkers. Methods Isobaric tags for relative and absolute quantitation (iTRAQ) technique combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to screen differentially expressed proteins, and to identify potential biomarkers by analysis of the biological process, cellular components, molecular functions, KEGG pathways and protein-protein interactions. Difference between two groups were measured byt test. Results We identified 95 differentially expressed proteins (50 up-regulated proteins and 45 down-regulated proteins, respectively), and 20 significant KEGG pathways. Among them, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), α-enolase (ENOA), phosphoglycerate kinase (PGK1), glucose-6-phosphate isomerase (G6PI) and moesin might play a role in the pathogenesis of primary gout. Conclusion iTRAQ technology can detect differentially expressed proteins from proteome, provides a strong theoretical basis for the study of biomarkers and evidence for the mechanisms in primary gout. However, further studies are needed.

Objective:To investigate the prognostic significance of high sensitivity-C reactive protein (Hs-CRP) in patients with peripher-al T-cell lymphoma (PTCL). Methods:A total of 234 newly diagnosed PTCL patients with a median age of 48 years were analyzed retro-spectively. Serum Hs-CRP levels and other factors, including tumor stage and international prognostic index (IPI), were determined. Af-ter a median follow-up of 23 months, the relationship between Hs-CRP and overall survival (OS) was observed. Results:Serum Hs-CRP level positively correlated with IPI score (r=0.132, P<0.001), tumor stage (r=0.183, P=0.005), B symptoms (r=0.225, P=0.001), and lactic dehydrogenase (r=0.169, P=0.009), but negatively correlated with plasma albumin levels (r=?0.343, P<0.001), hemoglobin concentra-tion (r=?0.239, P<0.001), and platelet count (r=0.131, P=0.045), and is uncorrelated with age (P>0.05), gender (P>0.05), fitness score (P>0.05), and leukocyte count (P>0.05). Patients with serum Hs-CRP levels≤10 mg/L had better OS than patients with serum Hs-CRP levels>10 mg/L. Univariate and multivariate Cox regression models showed that platelet count, Hs-CRP, albumin levels, and IPI score were independent adverse prognostic factors. Conclusion:The baseline Hs-CRP level can serve as a major indicator of prognosis in PT-CL patients.

Objective:To conduct clinical psychological intervention for the perioperative patients through solu-tion focused approach, excavate potential and improve the adaptation ability. Methods: On the basis of establis-hing a good nurse-patient relationship, the application of the solution focused approach was conducted in the peri-operative patients ( description of the problem, the construction of specific aims, and discussion on the exception, giving feedback, and evaluation of progress) . Results:After the intervention of solution focused approach, the pa-tients′negative emotion such as nervousness, anxiety, fear and depression decreased significantly (P <0. 05). Conclusion:Psychological intervention could effectively eliminate the negative mood of patients, improve the doc-tor-patient relationship, dissolve the contradiction between doctors and patients, reduce the incidence of medical disputes, and thereby enhance mutual understanding, trust and respect between doctors and patients, which makes the doctor-patient relationship more harmonious.