Clinical and genetic characteristics of patients with newly diagnosed acute promyelocytic leukemia: a single-center retrospective of 790 cases / 中华血液学杂志

Objective: To retrospectively analyze the data of Chinese patients with newly diagnosed acute promyelocytic leukemia (APL) to preliminarily discuss the clinical and cytogenetic characteristics. Methods: From February 2004 to June 2020, patients with newly diagnosed APL aged ≥ 15 years who were admitted to the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College were chosen. Clinical and laboratory features were retrospectively analyzed. Results: A total of 790 cases were included, with a male to female ratio of 1.22. The median age of the patients was 41 (15-76) years. Patients aged between 20 and 59 predominated, with 632 patients (80%) of 790 patients classified as low and intermediate risk and 158 patients (20%) of 790 patients classified as high risk. The white blood cell, platelet, and hemoglobin levels at diagnosis were 2.3 (0.1-176.1) ×10(9)/L, 29.5 (2.0-1220.8) ×10(9)/L, and 89 (15-169) g/L, respectively, and 4.8% of patients were complicated with psoriasis. The long-form type of PML-RARα was most commonly seen in APL, accounting for 58%. Both APTT extension (10.3%) and creatinine>14 mg/L (1%) are rarely seen in patients at diagnosis. Cytogenetics was performed in 715 patients with newly diagnosed APL. t (15;17) with additional chromosomal abnormalities were found in 155 patients, accounting for 21.7%; among which, +8 was most frequently seen. A complex karyotype was found in 64 (9.0%) patients. Next-generation sequencing was performed in 178 patients, and 113 mutated genes were discovered; 75 genes had an incidence rate>1%. FLT3 was the most frequently seen, which accounted for 44.9%, and 20.8% of the 178 patients present with FLT3-ITD. Conclusions: Patients aged 20-59 years are the most common group with newly diagnosed APL. No obvious difference was found in the ratio of males to females. In terms of risk stratification, patients divided into low and intermediate risk predominate. t (15;17) with additional chromosomal abnormalities accounted for 21% of 715 patients, in which +8 was most commonly seen. The long-form subtype was most frequently seen in PML-RARα-positive patients, and FLT3 was most commonly seen in the mutation spectrum of APL.

Over-expression of BMSC FoxM1 Attenuates LPS-induced Apoptosis of Alveolar Epithelial cells / 中山大学学报(医学科学版)

@#【Objective】To investigate whether bone marrow mesenchymal stem cells（BMSC）over-expressing FoxM1genecanattenuatelipopolysaccharide（LPS）-inducedapoptosisofalveolarepithelialcells，andexploreitspossi⁃ blemechanism.【Methods】SDratBMSCwereisolatedandculturedbywholebonemarrowadherencemethod.FoxM1 genewasoverexpressedinBMSCbylentiviraltransfection.TheexpressionofthetargetgeneFoxM1wasverifiedbyWestern blot.ApoptosisofA549cellswasmeasuredbyTUNELandflowcytometry.Andthemulti-factorlevelofsupernatantin BMSC-A549co-culturesystemwasdetectedbyMilliplexmethod.【Results】TUNELandflowcytometryconfirmedthat theapoptosisrateofA549inducedbyLPSdecreasedafterco-culturewithBMSCoverexpressingFoxM1，andthediffer⁃ encewasstatisticallysignificant（P <0.05）.MilliplexassayshowedthatthelevelsofIL-13，IL-21，IL-23，MIP-1a， MIP-1bandinBMSCoverexpressing FoxM1 geneandA549co-culturesystemweresignificantlyincreased，whilethe MIP-3alevelissignificantlyreduced.【Conclusion】BMSCoverexpressingFoxM1genecanattenuateLPS-inducedapop⁃ tosisofalveolarepithelialcells.BMSCmayplayananti-apoptoticrolebychangingthelevelsofinflammation-related cytokinesreleasedbyA549cells.

Effects of Ghrelin on Inflammatory Signaling Akt,NF-κB and iNOS in Alveolar Macrophages from Septic Rats / 中山大学学报(医学科学版)

[Objective]To investigate the effects of ghrelin on inflammatory signaling protein kinase B(Akt),nuclear factor-κB(NF-κB)and inducible nitric oxide synthase(iNOS)in alveolar macrophage(AM).[Methods]24 Male SD rats were randomly divided into Sham,CLP,CLP+ghrelin,and Sham+ghrelin groups. Cecal ligation and puncture(CLP)was used to induce sepsis. Ghrelin(20 nmol/kg)was administered by intraperitoneal injection at 3 h and 15 h post-operation. Histopathological changes of lungs were observed and scored.AM were extracted from bronchoalveolar lavage fluid(BALF). Interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in BALF were detected by ELISA. IL-1β,TNF-α,and IL-6 mRNA in AM were detected by qPCR.NF-κB p65,IκBα,p-IκBα,Akt,p-Akt and iNOS in AM were detected by immunofluorescence(IF)and Western blotting.[Results]The histologic score(6.7±0.8),BALF IL-1β[(146±12)pg/mL]and IL-6[(182±10)pg/mL]from CLP+ghrelin group were respectively 35.4%,44.5% and 46.42% lower than those from CLP group[(10.3±0.7),(263±17)pg/mL,and(273±5)pg/mL],P<0.05.No significant difference was found in BALF TNF-α between CLP group and CLP+ghrelin group.The IL-1β,TNF-α and IL-6 mRNA in AM from CLP+ghrelin group were respectively 54.38%,53.6% and 46.42% lower than those from CLP group,P<0.05. The nuclear NF-κB p65 and cytoplasmic p-IκBα,p-Akt and iNOS from CLP+ghrelin group were respectively 32.58%,45.42%,27.6% and 48.33% lower than those from CLP group,P<0.05. There was no significant difference in all data between Sham group and Sham+ghrelin group.[Conclusion]Ghrelin can decrease the activity of inflammatory signaling proteins Akt,NF-κB and iNOS in AM,therefore restricts AM expressing pro-inflammatory cytokines IL-1β,TNF-α,and IL-6,thus alleviates sep-sis-induced acute lung injury(ALI).

Isolation and culture of mouse bone marrow mesenchymal stem cells and induced differentiation into alveolar epithelial cells / 医学研究生学报

Objective It has traditionally been difficult to isolate and culture mouse bone marrow mesenchymal stem cells (BMSC),which has low success rate.And thus restricts the development of related research to some extent.We aimed to optimize the whole bone marrow adherent method for isolation and culture of mouse bone marrow mesenchymal stem cells and search for an effective method of inducing BMSCs to differentiate into alveolar epithelial cells.Methods Bone marrow contents harvested from the tibia and femur of C57BL/6 mice were cultured based on the whole bone marrow adherent method.The timing and split ratios of passage were determined according to the size and number of cell colonies.After 6 passages,cells were counted to detect cell proliferation ability,surface markers were examined by flow cytometry and Small Airway Epithelial Cell Medium (SAEpiCM) was used to induce the differentiation of BMSCs.Results With the increase of passages and the purity of BMSCs,the proliferation of cells at passages 6 tended to be stable.Flow cytometry showed that they were strongly positive for bone marrow mesenchymal stem cell surface markers CD29 and Sca-1 (99.1％,88.5％),but almost negative for the surface marker of hematopoietic stem cells CD117 (0.008 2％).BMSCs cultured in SA-EpiCM showed an epithelium-like morphological change and expressed surfactant associated protein C,a specific marker of alveolar epithelial cells.Conclusion It is effective to isolate and culture mouse bone marrow mesenchymal stem cells by adjusting the timing and split ratios of passage according to the size and number of the clonal cell colonies,which possessed the potential to differentiate into alveolar epithelial cells.

Effects of Ghrelin on human alveolar epithelial cell apoptosis in response to lipopolysaccharide through AKT/ERK signaling pathway / 中国免疫学杂志

Objective:To investigate the protective effects of Ghrelin on LPS-induced apoptosis of human alveolar epithelial A549 cells,along with the possible molecular mechanisms.Methods: CCK-8 assay was used to examine the cell viability of A549 treated by LPS.Apoptosis of A549 cells was measured by TUNEL.NO(Nitric oxide)production was detected by NO-specific fluorescent probe 3-Amino,4-aminomethyl-2′,7′-difluoresceindiacetate(DAF-FM DA).Western blot was also performed to examine the expressions of iNOS(inducible nitric oxide synthase),AKT,ERK,p-AKT,p-ERK and apoptotic proteins,such as Bcl-2,Bax,and cleaved caspase-3.Results: LPS exposure impaired cell viability and increased apoptosis of A549 cells significantly in concentration-and time-dependent manners accompanied with increased Bax and cleaved caspase-3 production,coupled with decreased Bcl-2 levels.Meanwhile,LPS promoted iNOS expression and the production of NO.Ghrelin pretreatment ameliorated LPS-caused alterations in the ratio of Bax/Bcl-2 and cleaved caspase-3 expression.TUNEL analysis showed that Ghrelin could decrease the apoptosis induced by LPS in A549(P<0.05).Simultaneously,LPS remarkably decreased the expression of p-AKT and p-ERK in A549 cells,which was abrogated by Ghrelin pretreatment.However,Ghrelin had no significant effect on NO production induced by LPS.Conclusion: Ghrelin reduces LPS-induced apoptosis of human alveolar epithelial cells partly through activating the AKT and ERK pathway,but the level of iNOS derived NO could not be reduced.

The value of soluble urokinase plasminogen activator receptor in diagnosis and severity assessment of sepsis / 中华急诊医学杂志

Objective To determine the diagnostic and assessment value of soluble urokinase plasminogen activator receptor (suPAR) level in septic patients.Methods Totally 82 septic patients in the Department of Intensive Care Unit of The First Affiliated Hospital,Sun Yat-Sen University were prospectively analyzed from June 2013 to March 2014.Another 29 patients with systemic inflammatory response syndrome (SIRS) and 15 healthy subjects served as controls.Septic patients were divided into sepsis group (n =27),severe sepsis group (n =27) and septic shock group (n =28) according to the severity,and there was no significant difference in age and sex among these groups.Measurement of plasma suPAR,serum procalcitonin (PCT) and C-reactive protein (CRP) levels,and calculation of acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and sequential organ failure assessment (SOFA) score were performed.Comparison of group differences for continuous variables was done by oneway ANOVA or nonparametric Kruskal-Wallis test.Spearman rank correlation analysis was applied to establish the relation between variables.Receiver operating characteristics (ROC) curve was created and area under curve (AUC) was calculated to determine the diagnostic value of these variables in sepsis.Results The levels of plasma suPAR in SIRS group,sepsis group,severe sepsis group,septic shock group,and healthy control group were (8.22±0.61),(11.45±1.12),(12.99±1.28),(15.75± 1.23) and (4.65 ±0.30) ng/mL,respectively.Plasma suPAR levels in SIRS group and sepsis group were higher than that in healthy control group (P ＜ 0.01),and elevated plasma suPAR was accompanied by increased severity of sepsis (P ＜ 0.05).PCT levels of sepsis group (17.66 ± 8.42) ng/mL,severe sepsis group (9.67 ±3.56) ng/mL and septic shock group (29.19 ± 10.78) ng/mL were greater than that in SIRS group (1.10 ± 0.78) ng/mL,P ＜ 0.01.CRP levels elevated in all groups,but there were no significant differences among them.When suPAR and CRP were applied to distinguishing sepsis from SIRS,the AUC values from suPAR and combination of suPAR and PCT were 0.817 (P ＜ 0.01,95 ％ CI:0.714-0.921) and 0.927 (P＜0.01,95％ CI:0.870-0.985),respectively.Using9.52 ng/mL suPAR as the best cut-off to distinguish sepsis from SIRS,there were 71.93％ sensitivity and 95.46％ specificity.The levels of plasma suPAR positively correlated with PCT levels (r =0.326),APACHE Ⅱ score (r =0.492) and SOFA score (r =0.386),P ＜ 0.01.Conclusions Plasma suPAR levels significantly elevated in septic patients and correlated with the severity of sepsis.Sepsis and SIRS may be discerned by plasma suPAR levels.Joint use of suPAR and PCT could greatly increase the specificity of diagnosis of sepsis.

Comparison of the effects of dexmedetomidine with midazolam on the respiration and circulation of mechanically ventilated patients / 中华急诊医学杂志

Objective To compare the effects of dexmedetomidine on the respiration and circulation with midazolam in mechanically ventilated patients.Methods A total of 62 patients supported with mechanical ventilation in medical intensive care unit were randomly (random number) divided into two groups:midazolam group ( group A,n =38 ) and dexmedetomidine group ( B group,n =24).The patients in group A were intravenously administered with midazolam in bolus dose of 0.05 mg/kg given over 30 - 60 s,and then maintained with 0.05 -0.15 mg/(kg ·h) by venous pump.The patients in group B were intravenously administered dexmedetomidine in bolus dose of 1.0 μg/kg given in more than 10 min,and then maintained with 0.2 - 0.7 μg/( kg · h) by venous pump.When the patients' sedation degree were required to reach Ⅲ - Ⅳ Ramsay Grade,the heart rate,mean arterial pressure,respiratory rate and SpO2 before sedation were compared with those 10 min,30 min and 2 hours after sedation between two groups.Results Respiratory rate or heart rate after sedation significantly decreased compared with those of presedation ( P ＜ 0.05 ).Blood pressure after sedation did not decrease significantly compared with that of presedation in Dexmedetomidine group.In midazolam group,blood pressure was (83.11 ± 12.95 ) mm Hg before sedation,and there was a significant decrease to (74.13 + 12.50) mm Hg in 10 min after sedation (P ＜ 0.05 ),while there were no significant difference between ( 80.53 + 12.93 ) mm Hg 30 min after sedaton and (82.47 ± 12. 15 ) mm Hg 2 hours after sedation.Conclusions There is no difference in effects on respiration of mechanically ventilated patients between dexmedetomidine and midazolam,and the effect of dexmedetomidine on circulation was less than that of midazolam.

Combined APACH II score and arterial blood lactate clearance rate to predict the prognosis of ARDS patients

OBJECTIVE@#To explore the easily applicable indicators of practical value to evaluate the prognosis of acute respiratory distress syndrome (ARDS).@*METHODS@#Blood and biochemical tests and blood-gas analyses were performed upon entry into the ICUs, 12 h, 24 h, 48 h and 72 h after that in 72 ARDS patients (who were admitted to the ICUs of our hospital from January 2000 to December 2009). Then APACHE II scores were achieved by combining relevant physiological parameters and laboratory results.@*RESULTS@#There was a statistical difference between the death group and survival group at different time points upon entering the ICUs in terms of APACHE II score, alveolar-arterial oxygen difference and arterial blood lactate clearance rate. PaO(2)/FiO(2) values were recorded to be statistically different between the death group and survival group 24 h, 48 h and 72 h, respectively after entry into the ICUs. In addition, registered linear regression existed between APACHE II score, alveolar-arterial oxygen difference or PaO(2)/FiO(2) value and time. APACHE II score 24 h and 72 h after entering ICUs predicted mortality with an area under the ROC curve (AUC) standing respectively at 0.919 and 0.955. Arterial blood lactate clearance rate 12 h, 24 h, 48 h and 72 h after entering ICUs predicted mortality with an area under the ROC curve (AUC) at 0.918, 0.918, 0.909 and 0.991, respectively.@*CONCLUSIONS@#APACHE II score applied in combination with arterial blood lactate clearance rate is of clinical significance in assessing the prognosis of ARDS patients.

Effects of cyclic and continuous nutrition infusion on serum nutritional indicators in patients with mechanical ventilated respiratory failure / 中华全科医师杂志

Objective To observe different effects of cyclic and continuous nutrition infusion on serum nutritional indicators, peripheral white blood cell counts (WBC), arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2) and acute physiology and chronic health evaluation Ⅲ (APACHE Ⅲ ) score in patients with mechanical ventilated respiratory failure (MVRF).Methods A cross-over and self-controlled trial was conducted in 48 patients with MVRF treated in a medical intensive care unit during December 2006 to June 2009, and continuous nutrition (group A) and cyclic nutrition (group B) were infused respectively for patients of the two groups.Serum levels of albumin (ALB), pre-albumin (PA), transferrin (TR), PaO2, PaCO2, WBC and APACHE Ⅲ score were measured for the patients with 24-hour continuous nutrition (group A) and 16-hour cyclic nutrition (group B)infusion.Effects of the two nutritional therapies were compared.Results After nutrition infusion, serum levels of ALB, PA and TR were (34±3)g/L, (196±28)mg/L and (2.1±0.3 ) g/L in group A, and (35 ±4) g/L, (198 ±25) mg/L and (2.0 ±0.4) g/L in group B, respectively; and PaO2 and PaCO2levels were (92 ± 12) mm Hg ( 1 mm Hg =0.133 kPa) and (42 ± 10) mm Hg in group A, and (91 ±9)mm Hg and (42 ± 10) mm Hg in group B, respectively.WBC and APACHE Ⅲ score were ( 11.8 ± 1.7) ×109/L and 38 ±7 in group A, and ( 12.6 ± 1.2) × 109/L and 40 ±6 in group B, respectively.Significant difference in serum levels of PA and TR was found between the two groups (PPA =0.019 and PTR =0.013),while there was no significant difference in other indictors between the two groups.Conclusions 24-hour continuous nutrition infusion for patients with MVRF can obviously improve their serum levels of PA and TR,but has no effect on serum level of ALB, PaO2, WBC and APACHE Ⅲ score in critical ill patients, as compared to those with 16-hour cyclic nutrition infusion.

Analysis of the risk factors of pulmonary fungal infections related to mechanical ventilation and prognosis of the patients / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the risk factors of pulmonary fungal infections related to mechanical ventilation and the prognosis of patients.</p><p><b>METHODS</b>A retrospective case-controlled study was conducted to analyze the culture results of the pulmonary secretions in patients with pulmonary fungal and nonfungal infections in association with mechanical ventilations. The risk factors of pulmonary fungal infections related to mechanical ventilation were identified and their impact on the clinical outcome of the patients was evaluated.</p><p><b>RESULTS</b>Of the 127 patients included in this study, 81 (63.78%) were positive and 46 (36.22%) negative for pulmonary fungal infections according to the diagnostic criteria of ventilator-associated pneumonia (VAP). The mortality of the patients with fungal infection was 82.7%, significantly higher than that of patients with non-fungal infection (67.39%, chi2=3.910, P<0.05). Univariate analysis and multivariate logistic regression showed that such factors as old age, duration of mechanical ventilation, tracheal intubation or incision for over 7 days, diabetes, blood glucose over 6.1 mmol/L, multi-organ dysfunction, combined use of antibiotics, at least 3-time changes antibiotics, administration of glucocorticosteroid for over 7 days, and immunodepressant use were all the independence risk factors of pulmonary fungal infection related to mechanical ventilation. Old age, multi-organ dysfunction, blood glucose over 6.1 mmol/L, glucocorticosteroid use for over 7 days, anesthetic use for over 3 days and high APACHE III scores were the risk factors for mortality in patients with the infections.</p><p><b>CONCLUSIONS</b>Pulmonary fungal infection associated to mechanical ventilation is often the results of presence of multiple risk factors, and early identification of these factors for timely antifungal treatment may improve the prognostics of the patients and help reduce the mortality rate.</p>

Oxidative stress status in patients with chronic obstructive pulmonary disease and its relation to glucocorticoid receptor levels / 南方医科大学学报

<p><b>OBJECTIVE</b>To study changes in the levels of systematic and airway local oxidative stress in patients in different stages of chronic obstructive pulmonary diseases (COPD), and explore the association between oxidative stress and glucocorticoid receptor (GR) level in the peripheral blood leukocytes.</p><p><b>METHODS</b>The levels of malonaldehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) in induced sputum and plasma, as well as GR levels in peripheral blood leukocytes and plasma levels of cortisol and adrenocorticotrophic hormone (ACTH), were examined in 33 patients with acute exacerbations of COPD (AECOPD, group A), 27 with stable COPD (group B), and 28 healthy volunteers (including 15 smokers as group C, and 15 nonsmokers as group D).</p><p><b>RESULTS</b>MDA level in induced sputum and plasma decreased, whereas the levels of GSH, SOD and GSH-PX increased significantly in the order of groups A, B, C, and D (P<0.05). The activity of SOD in induced sputum and plasma were significantly lower in group C than in group D. No significant difference was noted in the other oxidative stress indices between groups C and D (P>0.05). The plasma levels of cortisol and ACTH showed no significant difference between the 4 groups, while the GR level in peripheral blood leukocytes increased significantly in the order of groups A, B, C and D (1565-/+719, 2069-/+488, 2739-/+926, and 4793 -/+1415 U, respectively, P<0.05). After controlling for the factor of smoking status, the plasma and sputum SOD activity were both positively correlated to GR, with the partial correlation coefficient of 0.512 and 0.564, respectively (P<0.001).</p><p><b>CONCLUSION</b>Patients in different stages of COPD, especially those with AECOPD, may sustain systematic and local oxidation and anti-oxidation imbalance. Decreased SOD activity may contribute to GR level decrement in peripheral blood leukocytes in these patients.</p>

A case control study on the impact of CYP450 MSPI and GST-M1 polymorphisms on the risk of lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the correlation of polymorphisms of CYP1A1 MSPI and glutathiones S-transferase (GST-M1) independently and in combination with the risk of lung cancer.</p><p><b>METHODS</b>A case control study which included 91 cases of lung cancer and 138 controls collected from the First Affiliated Hospital of Sun Yat-sen University of Medical Sciences, Guangzhou Tumor Hospital and The Red Cross Hospital of Guangzhou or conmunity area. All subjects were investigated with a uniform questionnaire. Blood samples were collected from all cases and controls for detecting CYP1A1 MSPI and GST-M1 polymorphisms which were analyzed by PCR and RFLP.</p><p><b>RESULTS</b>It showed that there was no significant difference in frequencies of this genotypes of CYP1A1 MSPI between the two groups. The frequency of GST-M1 null (0/0) genotype was higher in the case group than in the control group, with an OR of 1.38 (95% CI 0.81 - 2.38), but there was no statistical significance. However, combination of several genotypes was strongly associated with lung cancer. There was a synergistic interaction between the m2m2 genotype of CYP1A1 MSPI and GST-M1 (0/0) genotype, with an OR of 2.47 (95% CI 1.03 - 5.90).</p><p><b>CONCLUSION</b>The combination of two genetic polymorphisms significantly increases the risk of lung cancer.</p>