Effects of Lifestyle Interventions on Health and Life Quality of Colorectal Cancer Survivors: A Systematic Review and Meta-analysis.

BACKGROUND: The results of previous studies on the effects of lifestyle interventions on the quality of life (QoL) in colorectal cancer (CRC) survivors remain controversial, and there have been several new publications in this area in recent years. OBJECTIVES: To assess whether lifestyle interventions can lead to favorable health outcomes and improved QoL in CRC survivors, we performed a meta-analysis. METHODS: PubMed, EMBASE, Web of Science, and Cochrane Library were systematically searched to obtain relevant literature published from January 1, 1990, to November 1, 2021. The required data were extracted and summarized to compare the physical activity levels, QoL, mental health assessment, and anthropometric data between lifestyle interventions and routine nursing. RESULTS: Twelve studies were included. Compared with the control group, lifestyle interventions could significantly increase the physical activity time (weighted mean difference [WMD], 9.84; 95% confidence interval [CI], 1.20-18.48; P = .026), metabolic equivalent task levels (WMD, 10.40; 95% CI, 5.30-15.49; P < .001), and Functional Assessment of Cancer Therapy Scale-Colorectal scores (WMD, 3.12; 95% CI, 0.24-5.99; P = .034). However, lifestyle interventions were not noticeably able to improve the fatigue, depression levels, anxiety levels, waist circumference, or body mass index in CRC survivors. CONCLUSION: Lifestyle interventions could generate an increase in physical activity time, metabolic equivalent task levels, and QoL in CRC survivors. IMPLICATIONS FOR PRACTICE: Lifestyle interventions in the future that include physical activity, diet, or comprehensive programs are needed to increase physical activity levels and improve QoL in CRC survivors.

CCL17 acts as an antitumor chemokine in micromilieu-driven immune skewing.

BACKGROUND: Chemokines are critical players in the local immune responses to tumors. CCL17 (thymus and activation-regulated chemokine, TARC) and CCL22 (macrophage-derived chemokine, MDC) can attract CCR4-bearing cells involving the immune landscape of cancer. However, their direct roles and functional states in tumors remain largely unclear. METHODS: We analyzed the lymphoma-related scRNA-seq and bulk RNA-seq datasets and identified the CCL17/CCL22-CCR4 axis as the unique participant of the tumor microenvironment. Then we edited the A20 lymphoma cell line to express CCL17 and CCL22 and assessed their function using three mouse models (Balb/C mouse, Nude mouse, and NSG mouse). In addition, we retrospectively checked the relationship between the CCL17/CCL22-CCR4 axis and the survival rates of cancer patients. RESULTS: The active CCL17/CCL22-CCR4 axis is a distinctive feature of the Hodgkin lymphoma microenvironment. CCR4 is widely expressed in immune cells but highly exists on the surface of NK, NKT, and Treg cells. The tumor model of Balb/C mice showed that CCL17 acts as an anti-tumor chemokine mediated by activated T cell response. In addition, the tumor model of Nude mice showed that CCL17 recruits NK cells for inhibiting lymphoma growth and enhances the NK-cDC1 interaction for resisting IL4i1-mediated immunosuppression. Interestingly, CCL17-mediated antitumor immune responses depend on lymphoid lineages but not mainly myeloid ones. Furthermore, we found CCL17/CCL22-CCR4 axis cannot be regarded as biomarkers of poor prognosis in most cancer types from the TCGA database. CONCLUSION: We provided direct evidence of antitumor functions of CCL17 mediated by the recruitment of conventional T cells, NKT cells, and NK cells. Clinical survival outcomes of target gene (CCL17, CCL22, and CCR4) expression also identified that CCL17/CCL22-CCR4 axis is not a marker of poor prognosis.

FTO promotes Bortezomib resistance via m6A-dependent destabilization of SOD2 expression in multiple myeloma.

Drug resistance is the main reason for the failure of Bortezomib (Bort) in the treatment of multiple myeloma (MM), which seriously affects the efficacy of Bort. Therefore, the exploration of Bort resistance to treat MM will be very beneficial. Thus, this study aims to study the function and mechanism of Fat mass and obesity associated (FTO) on the Bort resistance of MM. In the present study, we demonstrated that FTO promotes Bort resistance via m6A-dependent destabilization of SOD2 expression in MM. These findings may provide a substantial evidence for the Bort resistance in MM.

Effect of exercise interventions for sleep quality in patients with chronic kidney disease: a systematic review and meta-analysis.

INTRODUCTION: Sleep disorder is a common and unpleasant symptom in patients with chronic kidney disease (CKD), bringing a heavy burden on the patients and families. As a non-pharmacological therapy, exercise interventions are widely recommended for CKD patients. However, whether exercise can improve overall sleep quality in such a population remains ambiguous. The systematic review and meta-analysis aimed to evaluate the effect of exercise interventions on sleep quality in CKD patients. METHODS: PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from inception to April 22, 2022. A randomized controlled trial (RCT) added an exercise intervention to conventional treatment/usual care to assess the effect on sleep quality in CKD patients. Two authors independently selected literature, extracted data, assessed the risk of bias using the Cochrane risk of bias tool 2, and assessed the certainty of the evidence using the Grading of Recommendations, Assessment, Development, and Evaluation. The outcome was analyzed using a random-effect model using the Hartung-Knapp-Sidik-Jonkman method as a standardized mean difference (SMD). Additional statistical analysis includes the Egger regression test, subgroup analysis, sensitivity analysis, and meta-regression. RESULTS: Nineteen articles (20 RCTs) enrolling 989 patients with CKD were included. The pooled SMD suggested favorably associated exercise interventions (SMD - 0.16; 95% CI - 0.62 to 0.31; very low evidence) with substantial heterogeneity (I2 = 87%). Subgroup analyses demonstrated that SMD for sleep quality favored moderate intensity and aerobic exercise, no matter the time, but not statistically significant. Meta-regression showed that the effect size of exercise interventions on sleep quality was not associated with the total sample size, the proportion of males, duration of intervention, mean age, and exercise volume but was associated with baseline sleep scores. In addition, there may be an exercise threshold for the effect of exercise on sleep in CKD patients (i.e., 80 min/week). CONCLUSION: This systematic review and meta-analysis suggest that exercise interventions may be associated with improved sleep quality in patients with CKD. However, high heterogeneity and a small effect size limit this result. More studies and standardized reporting of exercise intervention characteristics should be conducted in the future to strengthen the most convincing evidence in this field.

Therapeutic effects of exercise interventions for patients with chronic kidney disease: an umbrella review of systematic reviews and meta-analyses.

OBJECTIVE: To conduct an overview of meta-analyses evaluating the impact of exercise interventions on improving health outcomes in patients with chronic kidney disease (CKD). DESIGN: An umbrella review of systematic review and meta-analyses of intervention trials was performed. DATA SOURCES: PubMed, Web of Science, Embase and the Cochrane Database of Systematic Reviews were searched from inception to 9 March 2021 for relevant articles. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Eligible meta-analyses compared the effects of usual care with and without exercise in patients with CKD. Health outcomes included those related to cardiovascular risk factors, physical fitness, dialysis-related symptoms, dialysis adequacy and health-related quality of life. Systematic reviews and meta-analyses that included fewer than 3 RCTs or fewer than 100 participants were excluded from the analysis. RESULTS: A total of 31 eligible systematic reviews and meta-analyses were included that assessed 120 outcomes. For physical fitness, there was a moderate effect size for cardiorespiratory fitness, muscle strength and body composition and small effect size for muscle endurance. The effect sizes for cardiovascular risk factors, dialysis-related symptoms and health-related quality of life outcomes were small. According to the Grading of Recommendations Assessment, Development and Evaluation framework, most outcomes were low or very low quality. CONCLUSION: Exercise appears to be a safe way to affect concomitant cardiovascular risk factors, such as blood pressure, improve physical fitness and health-related quality of life and reduce dialysis-related symptoms in patients with CKD. PROSPERO REGISTRATION NUMBER: CRD42020223591.

Systematic review and meta-analysis of the risk factors of surgical site infection in patients with colorectal cancer.

Background: Surgical site infection (SSI) influenced the result of surgical treatment, which was known as the second most prevalent hospital-based infection. But, the factors of SSI are not uniform. The purpose of this study was to identify the risk factors of SSI in patients with colorectal cancer. We conducted a meta-analysis of epidemiological research to provide a scientific basis for the prevention of SSI. Methods: The PubMed, Medline, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang databases were independently searched by 2 researchers to identify all relevant studies. Studies were selected if they met the selection criteria, which was defined according to the PICOS principles. The quality of the evidence was assessed using Egger's P value, study heterogeneity, and sample size. Studies were categorized into 3 groups as follows: low quality (Class 4), moderate quality (Class 2/3), and high quality (Class 1). The meta-analysis was performed using RevMan 5.3 software. Results: A total of 17 studies involving 61,611 patients were included in the meta-analysis. The results identified 7 patient-related risk factors of SSI, including male gender, obesity, diabetes mellitus, American Society of Anesthesiologists (ASA) score, cigarette smoking, tumor location, and serum albumin level, and 5 treatment-related risk factors, including laparoscopic surgery, operation time, blood loss, blood transfusion, and abdominal surgical history. Age was not directly related to SSI in colorectal cancer. Conclusions: It is possible that patients can be treated effectively by identifying these factors of SSI.

Exercise-Based Renal Rehabilitation: A Bibliometric Analysis From 1969 to 2021.

Chronic kidney disease (CKD) is a growing global health challenge with an increasing incidence rate. Exercise-based renal rehabilitation is an evidence-based, multidisciplinary, and comprehensive intervention designed to improve the physical and psychological condition of patients with CKD. The knowledge structure, research hotspots, and development trends in exercise-based renal rehabilitation have not been systematically described. The aim of this study was to provide a bibliometric perspective of the progress in this field. Publications about exercise-based renal rehabilitation were retrieved from the Web of Science Core Collection, using the terms "exercise," "physical activity," and "chronic kidney disease." Annual publications, subject categories, countries, authors, references, and keywords in this field were visually analyzed using the Citespace, VOSview, and Excel software. A total of 4,610 publications were analyzed, with a steady increase in publications in the field. Overall, the United States is the major contributor to the study of exercise-based renal rehabilitation. Johansen KL and Painter P are the key researchers in this field. Keyword analysis shows that research hotspots in this field include exercise/physical activity for different stages of CKD, exercise-based renal rehabilitation for frailty, and physical activity management for CKD. These findings will make understanding exercise-based renal rehabilitation research better and inform about future research ideas.

The Role of Physical Activity and Mortality in Hemodialysis Patients: A Review.

Available data indicated that physical activity was related to improved outcomes in hemodialysis patients. Multiple observational studies involving different cohorts have reported that increased physical activity level was associated with decreased mortality among hemodialysis patients. Therefore, promoting physical activity has become an increasingly critical and promising approach to improving cardiovascular health and clinical outcomes in hemodialysis patients. This review summarizes the published articles regarding physical activity and hemodialysis patients, focusing on mortality and strategy to promote physical activity.

[Gene Mutation and Overexpression of Newly Diagnosed Multiple Myeloma Patients].

OBJECTIVE: To analyze the characteristics of gene mutation and overexpression in newly diagnosed multiple myeloma (NDMM) patients. METHODS: Bone marrow cells from 208 NDMM patients were collected and analyzed. The gene mutation of 28 genes and overexpression of 6 genes was detected by DNA sequencing. Chromosome structure abnormalities were detected by fluorescence in situ hybridization (FISH). RESULTS: Gene mutations were detected in 61 (29.33%) NDMM patients. Some mutations occurred in 5 or more cases, such as NRAS, PRDM1, FAM46C, MYC, CCND1, LTB, DIS3, KRAS, and CRBN. Overexpression of six genes (CCND1, CCND3, BCL-2, CCND2, FGFR3, and MYC) were detected in 83 (39.9%) patients, and cell cycle regulation gene was the most common. Single nucleotide polymorphisms (SNP) changes were detected in 169 (81.25%) patients, the TP53 P72R gene SNP (70.17%) was the most common. Abnormality in chromosome structure was correlated to gene overexpression. Compared to the patients with normal chromosome structure, patients with 14q32 deletion showed higher proportion of CCND1 overexpression. Similarly, patients with 13q14 deletion showed higher proportion of FGFR3 overexpression, whereas patients with 1q21 amplification showed higher proportion of CCND2, BCL-2 and FGFR3 overexpression. CONCLUSION: There are multiple gene mutations and overexpression in NDMM. However, there is no dominated single mutation or overexpression of genes. The most common gene mutations are those in the RAS/MAPK pathway and the genes of cyclin family CCND are overexpression.

Downregulation of GNA15 Inhibits Cell Proliferation via P38 MAPK Pathway and Correlates with Prognosis of Adult Acute Myeloid Leukemia With Normal Karyotype.

BACKGROUND: The prognosis of acute myeloid leukemia (AML) with a normal karyotype is highly heterogonous, and the current risk stratification is still insufficient to differentiate patients from high-risk to standard-risk. Changes in some genetic profiles may contribute to the poor prognosis of AML. Although the prognostic value of G protein subunit alpha 15 (GNA15) in AML has been reported based on the GEO (Gene Expression Omnibus) database, the prognostic significance of GNA15 has not been verified in clinical samples. The biological functions of GNA15 in AML development remain open to investigation. This study explored the clinical significance, biological effects and molecular mechanism of GNA15 in AML. METHODS: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the mRNA expression level of GNA15 in blasts of bone marrow specimens from 154 newly diagnosed adult AML patients and 26 healthy volunteers. AML cell lines, Kasumi-1 and SKNO-1, were used for lentiviral transfection. Cell Counting Kit-8 (CCK8) and colony formation assays were used to determine cell proliferation. Cell cycle and apoptosis were analyzed by flow cytometry. The relevant signaling pathways were evaluated by Western blot. The Log-Rank test and Kaplan-Meier were used to evaluate survival rate, and the Cox regression model was used to analyze multivariate analysis. Xenograft tumor mouse model was used for in vivo experiments. RESULTS: The expression of GNA15 in adult AML was significantly higher than that in healthy individuals. Subjects with high GNA15 expression showed lower overall survival and relapse-free survival in adult AML with normal karyotype. High GNA15 expression was independently correlated with a worse prognosis in multivariate analysis. Knockdown of GNA15 inhibited cell proliferation and cell cycle progression, and induced cell apoptosis in AML cells. GNA15-knockdown induced down-regulation of p-P38 MAPK and its downstream p-MAPKAPK2 and p-CREB. Rescue assays confirmed that P38 MAPK signaling pathway was involved in the inhibition of proliferation mediated by GNA15 knockdown. CONCLUSIONS: In summary, GNA15 was highly expressed in adult AML, and high GNA15 expression was independently correlated with a worse prognosis in adult AML with normal karyotype. Knockdown of GNA15 inhibited the proliferation of AML regulated by the P38 MAPK signaling pathway. Therefore, GNA15 may serve as a potential prognostic marker and a therapeutic target for AML in the future.

[Effect of CDK1 Interferes with the Regulation of PLK1, Aurora B and TRF1 on the Proliferation of Leukemia Cells].

OBJECTIVE: To investigate the effect of CDK1 interference regulation of PLK1, Aurora B and TRF1 on the proliferation of leukemia cells. METHODS: The human myelogenous leukemia cell line HL-60 was selected as the research object, and the effect of TRF1 expression and its changes on cell proliferation and cycle was investigated by regulating intracellular CDK1 expression. The objects were divided into 5 groups, including control group, shRNA-NC group, CDK1-shRNA group, pcDNA group and pcDNA-CDK1 group. RT-PCR was used to detect the CDK1 expression of cells in each group; colony formation was used to detect the proliferation of the cells. Western blot was used to detect the expression of CDK1, PLK1, Aurora B, TRF1, and cyclin p53, p27, cyclinA. RESULTS: The phosphorylation level of PLK1, Aurora B and the expression of TRF1 in the CDK1-shRNA group were significantly down-regulated as compared with those in the control group (P<0.05). Compared with the control group, the cells in CDK1-shRNA group showed lower clone formation rate, the increasing of cycle-associated proteins p53 and p27 and the decreasing of cyclinA expression (P<0.05). It was shown that interfered CDK1 expression could inhibit the proliferation of HL-60 cells and prolong the time that they enter mitosis, thereby extending the cell cycle. Compared with the control group, the overexpressed CDK1 in the pcDNA-CDK1 group made the phosphorylation level of PLK1, Aurora B, and TRF1 expression increase significantly (P<0.05), also the colony formation rate (P<0.05). The cycle-related proteins p53 and p27 was down-regulated, while cyclinA expression was up-regulate significantly (P<0.05). The results indicted that overexpressed CDK1 could stimulate adverse reactions, thereby promoting the proliferation of HL-60 cells and shortening the cell cycle. CONCLUSION: Knocking out CDK1 can inhibit the phosphorylation of PLK1 and Aurora B and negatively regulate TRF1, thereby inhibiting the proliferation of leukemia cells.

[Gene Mutation in Acute Lymphoblastic Leukemia by DNA Sequencing].

OBJECTIVE: To analyze the characteristics of gene mutation in adult ALL and its clinical significance. METHODS: Clinical data of 134 primary adult ALL patients and DNA sequencing results of 16 kinds of gene mutation were collected. The characteristic of gene mutation and clinical significances were statistically analyzed. RESULTS: In 31 cases of 134 ALL cases (23.13%) the gene mutations were detected as follows: 19 cases of 114 B-ALL cases (16.67%), 11 cases of 19 T-ALL cases (57.89%) and 1 case of T/B-ALL. The incidence of T-ALL gene mutation was significantly higher than that of B-ALL (χ2=13.574, P<0.01). Twelve gene mutations were found, and the mutation rates was IL7R, NOTCH1, FLT3, TP53, FBXW7, PAX5, IKZF1, CREBBP, JAK3, JAK1, PHF6 and PTEN from high to low. Among 108 non-transplantable follow-up patients there was no significant difference in 1-year overall survival rate (49.7% vs 67.4%) and median non-recurrence survival time (214 days vs 260 days) between the gene mutation group (23 cases, 21.30%) and the non-mutation group(85 cases, 78.70%). There was a significant difference in 1-year survival rate between NOTCH1 mutation group (4 cases, 3.77%) and non-mutation group (102 cases, 96.23%) (50.0% vs 65.8%,χ2=9.840, P<0.01). CONCLUSION: There may be multiple gene mutations in adult ALL patients. IL7R and NOTCH1 are the most common gene mutations and NOTCH1 mutation may indicate poor prognosis. Detection of gene mutations is helpful to understand the pathogenesis of ALL and evaluate the prognosis of adult ALL patients.

Walnut protein hydrolysates, rich with peptide fragments of WSREEQEREE and ADIYTEEAGR ameliorate UV-induced photoaging through inhibition of the NF-κB/MMP-1 signaling pathway in female rats.

Skin photoaging is a complicated pathological process, and the imbalance of inflammatory regulation is associated highly with photoaging progression. Previously, prepared walnut protein hydrolysates (WPH), rich with peptide fragments of WSREEQEREE and ADIYTEEAGR demonstrated desirable photoprotection. However, it remains unclear if the photoprotection is mediated by the targeted inhibition of the NF-κB signaling pathway. Herein, we examined the regulation of WPH on inflammatory cytokine expression, and elucidated the modulation of the NF-κB/MMP-1 signaling pathway by WPH in a photoaging SD rat model. WPH significantly reduced the expression level of inflammatory cytokines IL-1ß and IL-6, but significantly increased the level of IL-2 (all P < 0.05). Furthermore, WPH dramatically inhibited the activation of the NF-κB signaling pathway by mitigating the phosphorylation of IκB and p-65 proteins in a dose-dependent manner. The histopathological results indicated that WPH predominately attenuated epidermal hyperplasia, reduced the inflammatory filtration, and promoted collagen deposition in the photoaging skin tissue. Furthermore, WPH significantly stimulated the expression of TGF-ß and procollagen type I, and inhibited the MMP-1 activities (all P < 0.05). Overall, the underlying mechanism of WPH ameliorating skin photoaging may be attributed to the synergistic modulation via reversing the inflammatory imbalance, suppressing the activation of the NF-κB signal pathway, stimulating procollagen type I synthesis, and inhibiting MMP-1 activities. According to these results, it can be concluded that WPH has the potential as an anti-photoaging agent in functional foods.

Silencing long non-coding RNA XIST suppresses drug resistance in acute myeloid leukemia through down-regulation of MYC by elevating microRNA-29a expression.

BACKGROUND: Long non-coding RNAs (lncRNAs) are biomarkers participating in multiple disease development including acute myeloid leukemia (AML). Here, we investigated molecular mechanism of X Inactive-Specific Transcript (XIST) in regulating cellular viability, apoptosis and drug resistance in AML. METHODS: XIST, miR-29a and myelocytomatosis oncogene (MYC) expression in AML bone marrow cells collected from 62 patients was evaluated by RT-qPCR and Western blot analysis. Besides, the relationship among XIST, miR-29a and MYC was analyzed by dual luciferase reporter assay, RIP, and RNA pull down assays. AML KG-1 cells were treated with anti-tumor drug Adriamycin. The role of XIST/miR-29a/MYC in cellular viability, apoptosis and drug resistance in AML was accessed via gain- and loss-of-function approaches. At last, we evaluated role of XIST/miR-29a/MYC on tumorigenesis in vivo. RESULTS: XIST and MYC were up-regulated, and miR-29a was down-regulated in AML bone marrow cells. Silencing XIST inhibited cellular activity and drug resistance but promoted cellular apoptosis of KG-1 cells by down-regulating MYC. XIST inhibited miR-29a expression to up-regulate MYC. Moreover, silencing XIST inhibited tumorigenesis of AML cells in vivo. CONCLUSIONS: Overall, down-regulation of XIST decreased MYC expression through releasing the inhibition on miR-29a, thereby reducing drug resistance, inhibiting viability and promoting apoptosis of AML cells.

Effect of intradialytic progressive resistance exercise on physical fitness and quality of life in maintenance haemodialysis patients.

Purpose: To investigate the impact of intradialytic progressive resistance exercise (IPRE) on physical fitness and quality of life in maintenance haemodialysis (MHD) patients. Methods: Subjects were allocated randomly to the exercise group received IPRE and the control group underwent a haemodialysis session alone. Outcomes measured were including physical fitness ascertained by 6-min walk test, sit-to-stand 10 test and handgrip strength. Kidney Disease Quality of Life Instrument was used to assess the quality of life, and also recorded the adverse event at each exercise session. Results: A total of 87 patients were analysed: 43 in the exercise group and 44 in the control group. After 12 weeks, there were significant improvements in physical fitness and past of the dimension of the scale in the exercise group. Conclusions: IPRE can improve the physical fitness and quality of life in patients underwent MHD with no serious adverse events or safety issues.

Mutational spectrum and prognosis in NRAS-mutated acute myeloid leukemia.

The mutational spectrum and prognostic factors of NRAS-mutated (NRASmut) acute myeloid leukemia (AML) are largely unknown. We performed next-generation sequencing (NGS) in 1,149 cases of de novo AML and discovered 152 NRASmut AML (13%). Of the 152 NRASmut AML, 89% had at least one companion mutated gene. DNA methylation-related genes confer up to 62% incidence. TET2 had the highest mutation frequency (51%), followed by ASXL1 (17%), NPM1 (14%), CEBPA (13%), DNMT3A (13%), FLT3-ITD (11%), KIT (11%), IDH2 (9%), RUNX1 (8%), U2AF1 (7%) and SF3B1(5%). Multivariate analysis suggested that age ≥ 60 years and mutations in U2AF1 were independent factors related to failure to achieve complete remission after induction therapy. Age ≥ 60 years, non-M3 types and U2AF1 mutations were independent prognostic factors for poor overall survival. Age ≥ 60 years, non-M3 types and higher risk group were independent prognostic factors for poor event-free survival (EFS) while allogenic hematopoietic stem cell transplantation was an independent prognostic factor for good EFS. Our study provided new insights into the mutational spectrum and prognostic factors of NRASmut AML.

WT1 overexpression predicted good outcomes in adult B-cell acute lymphoblastic leukemia patients receiving chemotherapy.

Objectives: The prognostic role of WT1 in acute lymphoblastic leukemia (ALL) is still controversial. No study has focused on the prognostic role of WT1 expression in adult B-ALL patients receiving chemotherapy only.Methods: Using TaqMan-based real time quantitative PCR (RQ-PCR), we detected the WT1 transcript levels of 162 de-novo adult B-ALL patients at the time of diagnosis and analysed their clinical features.Results: WT1 overexpression was defined as a transcript level higher than 0.50%, which is the upper limit in normal bone marrow. WT1 overexpression was identified in 66.0% of the patients and was an independent positive prognostic factor for CIR, RFS and OS in patients who received chemotherapy only (CIR: HR = 0.236 [95% confidence interval 0.094-0.592]; P = 0.002; RFS: HR = 0.223 [0.092-0.543]; P = 0.001; OS: HR = 0.409 [0.214-0.783]; P = 0.007) and in patients who did not have BCR-ABL fusion or KMT2A rearrangements (CIR: HR = 0.431 [0.201-0.921]; P = 0.030; RFS: HR = 0.449 [0.224-0.899]; P = 0.024; OS: HR = 0.521 [0.278-0.977]; P = 0.042). However, WT1 overexpression had no prognostic value in patients who received allogenic hematopoietic stem cell transplantation (allo-HSCT). Furthermore, allo-HSCT could improve the prognosis of patients with low WT1 expression.Conclusion: Therefore, testing for WT1 expression at the time of diagnosis may predict outcomes in adult B-ALL patients who receive only chemotherapy and who do not have the BCR-ABL fusion gene or KMT2A rearrangements. Allo-HSCT may improve the prognosis of patients with low WT1 transcript levels.

[Adiponectin Receptor Agonist AdipoRon Inhibits the Proliferation of Myeloma Cells via the AMPK/Autophagy Pathway].

OBJECTIVE: To investigate the inhibitory effect of adiponectin receptor agonist AdipoRon on proliferation of myeloma cell lines and its possible mechanism. METHODS: The myeloma cell lines Sp2/0-Ag14 and MPC-11 were treated with different concentration of AdipoRon. The cell proliferation was detected by CCK-8. Western blot was used to determine the protein level of the signaling pathway. RT-PCR was used to quantify the mRNA copy number of adiponectin receptor AdipoR1 and AdipoR2 in the bone marrow cells from 21 patients with multiple myeloma (MM). Twenty-three normal bone marrow samples were served as control. RESULTS: AdipoRon significantly inhibited the proliferation of MM cell lines Sp2/0-Ag14 and MPC-11 in a concentration-dependent and time-dependent manner. Western blot showed that AdipoRon induced an increase of the expression levels of apoptosis-related proteins cleaved caspase-3 and cleaved PARP. AdipoRon upregulated p-AMPK and its downstream p-ACC in MPC-11. In addition, AdipoRon upregulated LC3-II/LC3-I level and down-regulated the protein level of p62. The expression level of AdipoR1 in MM cells was significantly higher than that in normal controls, and the expression level of AdipoR2 in MM cells was significantly lower than that in normal controls. CONCLUSION: Adiponectin receptors are expressed differentially between MM patients and normal subjects. AdipoRon, an adiponectin receptor agonist, can inhibit myeloma cell proliferation and induce apoptosis, and AMPK/autophagy pathway may be one of its mechanisms.

High RASD1 transcript levels at diagnosis predicted poor survival in adult B-cell acute lymphoblastic leukemia patients.

B-cell acute lymphoblastic leukemia (B-ALL) in adults remains a highly challenging disease. Identifying new prognostic biomarkers is necessary to help select the best therapeutic schedules and to improve prognosis. We performed bioinformatics analyses of transcriptomic data to identify aberrantly-expressed mRNA transcripts in B-ALL and focused on RASD1 (Ras-related dexamethasone-induced 1). To date, no information is available on the prognostic value of RASD1 in B-ALL. Fifty-three consecutive adults with de novo B-ALL were enrolled in this study. Our data suggested that RASD1 was abnormally overexpressed in B-ALL. High RASD1 transcript levels at diagnosis were associated with lower survival probabilities (44% [20%-61%] vs. 79% [60%-97%]; P = 0.037) and were also an independent prognostic factor in adult B-ALL (HR = 4.9 [1.5-15.9]; P = 0.008). Functional in vitro analyses and bioinformatic analyses indicated that RASD1 promoted cell proliferation, cell cycle progression and chemotherapy resistance and inhibited cell apoptosis. These data demonstrated that RASD1 might serve as a novel prognostic biomarker for adult B-ALL and as a potential therapeutic target in adult B-ALL patients.

[Metformin Induces Apoptosis of Human Multiple Myeloma Cell U266 through the Mitochondrial Apoptotic Pathway].

OBJECTIVE: Metformin (Met) can inhibit the proliferation of tumor cells in vitro, its effects on multiple myeloma and action mechanisms have been not yet understood. The purpose of this study was to investigate the effect and molecular mechanism of metformin on human myeloma cells U266. METHODS: U266 cells were treated with different concentration of Met, the MTT was used to detect cell proliferation, the PI staining was used to detect the cell cycle, and the protein expression of BCL-2 family and the release of cytochrome C were assessed by Western blot. RESULTS: Metformin could inhibit the proliferation of U266 cell in a time- and concentration- dependent manner. The U266 cells were arrested in G1/G0 phase after metformin treatment for 48 h, as compared with non-treated U266 cells. The proteins expression of BCL-2 and BCL-XL was down-regulated and the protein expression of BAX was up-regulated. The released of cytochrome C from mitochondria to cytoplasm was increased, and protein splicing of PARP was also enhanced. CONCLUSION: Metformin can inhibit the cell proliferation and induce U266 cell apoptosis through the mitochondrial apoptotic pathway.