[The Value of CD44+ Mononuclear Cells and Spleen Stiffness Measurement in Minimal Residual Disease in Acute Myeloid Leukemia and Its Prognosis].

OBJECTIVE: To investigate the value of CD44+ mononuclear cells (MNC) and spleen stiffness measurement (SSM) in minimal residual disease (MRD) in acute myeloid leukemia (AML) and its prognosis. METHODS: Flow cytometry was used to detected the proportion of CD44+ and CD24+ MNC in 44 AML patients after induction chemotherapy. The SSM was tested by FS. The value of MNC and SSM in MRD and its prognosis was explored. RESULTS: The percentage of CD44+ MNC and SSM in MRD positive group were significantly higher than those in MRD negative group (P<0.05). In MRD positive group, there were positive correlation between CD44+ MNC, SSM and MRD level (r=0.998, r=0.939, P<0.05). The median EFS and OS in HCD44+ MNC and HSSM groups were significantly shorter than those in LCD44+ MNC and LSSM (P<0.05). CD24+ MNC showed no association with MRD and its prognosis. CONCLUSION: HCD44+ MNC and HSSM may be used to predict high level MRD and poor prognosis.

[Relationship between Leukocytes Derived Microparticles and Minimal Residual Disease and Prognosis of Acute Myeloid Leukemia].

OBJECTIVE: To detect the relationship between leukocytes derived microparticle (CD45+ MP) and minimal residual disease (MRD) and prognosis of acute myeloid leukemia (AML). METHODS: The expression of CD45+ MP, CD44+ MP and CD24+ MP in peripheral blood of 47 AML patients at the time after induction chemotherapy were detected by using flow cytometry, and the relationship between MP, MRD and prognosis were analyzed. RESULTS: The percentages of CD45+ MP, CD44+ MP and CD24+ MP in MRD positive group were significantly higher than those in MRD negative group. In MRD positive group, there were positive correlation between CD45+ MP, CD44+ MP, CD24+ MP and MRD level. The AUC of CD45+ MP, CD44+ MP, CD24+ MP in predicting positive MRD was 0.949, 0.782, and 0.817, respectively. The EFS and OS in HCD45+ MP, HCD44+ MP and HCD24+ MP groups were significantly shorter than low level group. CONCLUSION: High level of CD45+ MP, CD44+ MP, CD24+ MP can be used to predict high level MRD and poor prognosis.

Bone marrow-derived mesenchymal stem cells modulate autophagy in RAW264.7 macrophages via the phosphoinositide 3-kinase/protein kinase B/heme oxygenase-1 signaling pathway under oxygen-glucose deprivation/restoration conditions.

BACKGROUND: Autophagy of alveolar macrophages is a crucial process in ischemia/reperfusion injury-induced acute lung injury (ALI). Bone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent cells with the potential for repairing injured sites and regulating autophagy. This study was to investigate the influence of BM-MSCs on autophagy of macrophages in the oxygen-glucose deprivation/restoration (OGD/R) microenvironment and to explore the potential mechanism. METHODS: We established a co-culture system of macrophages (RAW264.7) with BM-MSCs under OGD/R conditions in vitro. RAW264.7 cells were transfected with recombinant adenovirus (Ad-mCherry-GFP-LC3B) and autophagic status of RAW264.7 cells was observed under a fluorescence microscope. Autophagy-related proteins light chain 3 (LC3)-I, LC3-II, and p62 in RAW264.7 cells were detected by Western blotting. We used microarray expression analysis to identify the differently expressed genes between OGD/R treated macrophages and macrophages co-culture with BM-MSCs. We investigated the gene heme oxygenase-1 (HO-1), which is downstream of the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. RESULTS: The ratio of LC3-II/LC3-I of OGD/R treated RAW264.7 cells was increased (1.27 ±â€Š0.20 vs. 0.44 ±â€Š0.08, t = 6.67, P  < 0.05), while the expression of p62 was decreased (0.77 ±â€Š0.04 vs. 0.95 ±â€Š0.10, t = 2.90, P  < 0.05), and PI3K (0.40 ±â€Š0.06 vs. 0.63 ±â€Š0.10, t = 3.42, P  < 0.05) and p-Akt/Akt ratio was also decreased (0.39 ±â€Š0.02 vs. 0.58 ±â€Š0.03, t = 9.13, P  < 0.05). BM-MSCs reduced the LC3-II/LC3-I ratio of OGD/R treated RAW264.7 cells (0.68 ±â€Š0.14 vs. 1.27 ±â€Š0.20, t = 4.12, P  < 0.05), up-regulated p62 expression (1.10 ±â€Š0.20 vs. 0.77 ±â€Š0.04, t = 2.80, P  < 0.05), and up-regulated PI3K (0.54 ±â€Š0.05 vs. 0.40 ±â€Š0.06, t = 3.11, P  < 0.05) and p-Akt/Akt ratios (0.52 ±â€Š0.05 vs. 0.39 ±â€Š0.02, t = 9.13, P  < 0.05). A whole-genome microarray assay screened the differentially expressed gene HO-1, which is downstream of the PI3K/Akt signaling pathway, and the alteration of HO-1 mRNA and protein expression was consistent with the data on PI3K/Akt pathway. CONCLUSIONS: Our results suggest the existence of the PI3K/Akt/HO-1 signaling pathway in RAW264.7 cells under OGD/R circumstances in vitro, revealing the mechanism underlying BM-MSC-mediated regulation of autophagy and enriching the understanding of potential therapeutic targets for the treatment of ALI.

Prolonged progression-free survival and overall survival are associated with diabetes mellitus but inversely associated with levels of blood glucose in patients with lung cancer.

BACKGROUND: Previous studies have provided conflicting evidence about the increased overall survival (OS) in lung cancer patients with diabetes mellitus (DM) compared with those without DM. This study assessed progression-free survival (PFS)/OS in lung cancer patients with or without DM and tentatively analyzed the impact of blood glucose levels on PFS/OS in lung cancer patients. METHODS: Data were collected from lung cancer patients based upon admission records from January 2010 to January 2012 and follow-up records from January 2010 to January 2015 in the Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai. The data included patient sex, age, body mass index (BMI), smoking status, history of DM, level of blood glucose, pathological type, clinical stage of cancer, chemotherapy regimen, and history of anti-DM drugs. The Cox regression model and Kaplan-Meier method were used for the analysis of hazard factors and PFS/OS. For comparison of PFS/OS in lung cancer with or without DM, patients were divided into three groups: lung cancer with DM, lung cancer without DM but with elevated level of blood glucose, lung cancer without DM or elevated level of blood glucose. RESULTS: In total, the data from 200 lung cancer patients (138 males/62 females, aged 29.0 to 78.0 years, mean 60.0 ±â€Š8.6 years) were collected. For the comparison of PFS/OS in lung cancer patients with or without DM, patients were divided into three groups: lung cancer with DM (n = 31); lung cancer without DM but with elevated levels of blood glucose (n = 40); and lung cancer without both DM and elevated levels of blood glucose (n = 128), whereas 1 patient dropped out of the study. All the patients underwent complete chemotherapy and were followed up for 36.0 to 60.0 months. Kaplan-Meier survival analysis showed that lung cancer patients with DM had increased PFS and OS compared with those without DM (log-rank, P < 0.05, P < 0.01); the median PFS in lung cancer with DM was 12.0 months (95% confidence interval [CI], 4.0-16.0) vs. 6.0 months in those without DM (95% CI, 5.8-6.3); and the median OS in lung cancer patients with DM was 37.0 months (95% CI, 29.0-46.6) vs. 12.0 months in those without DM (95% CI, 10.9-13.1). For the other two groups of patients without DM, there was a trend toward a shorter PFS and OS in patients with elevated blood glucose compared with those without elevated blood glucose. Cox regression showed that PFS in lung cancer patients was favorably associated with the usage of anti-DM drugs, BMI, clinical stage of cancer, and chemotherapy regimen (all P < 0.05) but was inversely associated with the level of blood glucose (P < 0.05). CONCLUSIONS: Lung cancer patients with DM have prolonged PFS and OS compared with those without DM, and the level of blood glucose was inversely associated with PFS. The current results indicate that PFS may be a meaningful intermediate endpoint for OS and that the levels of blood glucose hopefully represent a prognostic factor in lung cancer patients.

Decompression of acute left-sided malignant colorectal obstruction: comparing transanal drainage tube with metallic stent.

BACKGROUND AND AIM: Acute left-sided colorectal malignant obstruction is a life-threatening condition and need emergent treatment. Many nonsurgical treatments to palliate obstruction have been developed in clinics. The aim of this study was to evaluate the clinical effects of transanal drainage tube (TDT) and metallic stent for the decompression of acute left-sided malignant colorectal obstruction. MATERIALS AND METHODS: Twenty-nine patients with acute left-sided malignant colorectal obstruction were enrolled in this study from January 2005 to December 2010, they were randomly divided into TDT group (13 patients) and metallic stent group (16 patients). RESULTS: There were 13 cases in TDT group (male:female=8:5, age from 65 to 80 y, mean age was 72.6±4.7 y). The sites of lesions were located in the rectum of 3 patients, sigmoid colon of 7 patients, and descending colon of 3 patients. TDT was successfully inserted in 11 cases (84.6%). Among the 11 patients, 1-stage operation with sufficient lymph node dissection was performed in 8 cases after adequate lavage without complications. One case underwent emergent Hartmann operation because of colonic tumor perforation 3 days after ileus tube decompression. Two cases were discharged without surgery after relief of symptom. There were 16 cases in the metallic stent group (male:female=10:6 age from 48 to 86 y, mean age was 73.3±8.5 y). The sites of the lesions were located in the rectum of 4 patients, sigmoid colon of 6 patients, and descending colon of 6 patients. Successful stent placement was achieved in 13 cases (81.3%) with no severe complications. Among the 13 patients, 1-stage operation with sufficient lymph node dissection was performed in 7 cases and 6 cases refused to underwent surgery with stent as the definitive palliative treatment. The price of a TDT is only one third of an expandable metallic stent. CONCLUSIONS: Both TDT and metallic stent can achieve preoperative colonic lavage for 1-stage operation for patients with acute left-sided malignant colorectal obstruction with no increase in complications.

[Significance of urinary nucleosides in diagnosis of gastric carcinoma].

BACKGROUND & OBJECTIVE: It was reported that urinary modified nucleosides with abnormally high amounts were found in many cancer patients. This study was designed to investigate the usefulness of urinary nucleosides in the diagnosis of gastric carcinoma. METHODS: The concentrations of 15 kinds of urinary nucleosides from 50 healthy persons and 48 patients with gastric carcinoma were determined by high-performance liquid chromatography (HPLC). Of 48 patients with gastric carcinoma, 25 underwent serum CEA examination. RESULTS: The average levels of 14 kinds of urinary nucleosides, m5U excepted, from patients with gastric carcinoma were higher than those from health persons (P< 0.05). Pseu 22.91+/-4.90, 34.87+/-21.41; U 0.34+/-0.32, 0.62+/-0.82; A 0.58+/-0.16, 0.96+/-0.75; C 0.17+/-0.15,0.24+/-0.19; m5U 0.03+/-0.07,0.07+/-0.06; I 0.26+/-0.10, 0.43+/-0.36; m1I 1.34+/-0.34, 2.44+/-1.39; ac4C 0.75+/-0.24, 1.08+/-0.72; G 0.09+/-0.04, 0.14+/-0.10; X 1.20+/-0.42, 1.90+/-1.09; m2G 0.61+/-0.16, 1.00+/-0.69; m6A 0.04+/-1.13, 0.07+/-0.08; m1A 2.26+/-0.56, 3.71+/-2.21; m22G 1.34+/-0.27, 2.25+/-1.39; m1G 0.80+/-0.25, 1.41+/-0.86. The level of nucleoside I was positively correlated with the tumor size (P< 0.05). The level of nucleoside X was positively correlated with lymph node metastasis (P< 0.05). Using the concentrations of 15 nucleosides as the data vectors, principal component analysis was applied to classify gastric cancer patients and normal adults, 63%(30/48) of cancer patients were correctly classified, in which the identification rate was higher than that of CEA method (12%). CONCLUSION: Urinary modified nucleoside increased in the patients with gastric carcinoma, and it may be helpful in the diagnosis of gastric carcinoma.