Retrospective Study of Three Cases of Congenital Leukemia with Clinical Presentations and Particular Cytogenetic Abnormality.

BACKGROUND: The goal is to assess the prognosis of cytogenetic abnormality, because cytogenetic abnormality is rarely encountered in clinical practice. METHODS: We retrospectively report three cytogenetic abnormality cases with clinical, cytogenetic, and genetic characteristic. RESULTS: All cases occurred within one month of birth and had prominent hepatosplenomegaly, including acute myeloid leukemia (case 1, case 2) and acute leukemia (case 3). Moreover, case 1 appeared as leukemia cutis at birth, case 2 was born with respiratory distress, and both showed hyperleukocytosis. The R-banded karyotype detected cytogenetic abnormality in three cases, case 1 with 46,XY,t(8;12)(q21;p13), case 2 with 47,XX,+21 and case 3 with 46,XY,t(6;X)(q22:p12), respectively. Especially in case 1, reverse transcription-polymerase chain reaction analysis showed MLL-AF10 rearranged. CONCLUSIONS: In our studies, all cases had not received chemotherapy and survived about 1 - 2 months. It suggests that cytogenetic disorders are closely related to disease development and likely result in fatal outcome if untreated. Thus, we proposed that a proper treatment decision is urgently needed in congenital leukemia.

Psychometric Properties of the Chinese Warwick-Edinburgh Mental Well-being Scale in Medical Staff: Cross-sectional Study.

BACKGROUND: Worldwide, mental well-being is a critical issue for public health, especially among medical staff; it affects professionalism, efficiency, quality of care delivery, and overall quality of life. Nevertheless, assessing mental well-being is a complex problem. OBJECTIVE: This study aimed to evaluate the psychometric properties of the Chinese-language version of the 14-item Warwick-Edinburgh Mental Well-being Scale (WEMWBS) in medical staff recruited mainly from 6 hospitals in China and provide a reliable measurement of positive mental well-being. METHODS: A cross-sectional online survey was conducted of medical staff from 15 provinces in China from May 15 to July 15, 2020. Confirmatory factor analysis (CFA) was conducted to test the structure of the Chinese WEMWBS. The Spearman correlations of the Chinese WEMWBS with the 5-item World Health Organization Well-Being Index (WHO-5) were used to evaluate convergent validity. The Cronbach α and split-half reliability (λ) represented internal consistency. A graded response model was adopted for an item response theory (IRT) analysis. We report discrimination, difficulty, item characteristic curves (ICCs), and item information curves (IICs). ICCs and IICs were used to estimate reliability and validity based on the IRT analysis. RESULTS: A total of 572 participants from 15 provinces in China finished the Chinese WEMWBS. The CFA showed that the 1D model was satisfactory and internal consistency reliability was excellent, with α=.965 and λ=0.947, while the item-scale correlation coefficients ranged from r=0.727 to r=0.900. The correlation coefficient between the Chinese WEMWBS and the WHO-5 was significant, at r=0.746. The average variance extraction value was 0.656, and the composite reliability value was 0.964, with good aggregation validity. The discrimination of the Chinese WEMWBS items ranged from 2.026 to 5.098. The ICCs illustrated that the orders of the category thresholds for the 14 items were satisfactory. CONCLUSIONS: The Chinese WEMWBS showed good psychometric properties and can measure well-being in medical staff.

Isochromosome 11q is Associated with Unique Characteristics and Poor Prognosis in Patients with Acute Myeloid Leukemia.

BACKGROUND: Isochromosome 11q in patients with acute myeloid leukemia is rarely reported, and little is known about its main features. METHODS: The presence of isochromosome 11q was identified in four patients (three adults and one child) from screening 441 patients with an acute myeloid leukemia diagnosis between 2009 and 2018 by using R-banding and fluorescence in situ hybridization. RESULTS: The child, patient 1 with unreported isochromosome (partial 11q isochromosome), accompanied with t(1;11) translocation, initially achieved remission after receiving chemotherapy. However, 4 months later this patient experienced a relapse. While multiple treatments were tried, it had no effect and the patient survived for 16 months. The remaining patients with isochromosome 11q exhibited numerical/structural chromosomal abnormal-ities involving myelodysplastic syndrome-related chromosomes 5, 7, 8, and 20. In patients 2 and 3, we found a derivative chromosome 21. Patient 3 was newly diagnosed with acute myeloid leukemia and was treated with many chemotherapy protocols, unfortunately with no effect. The patient then received traditional Chinese medicine and survived for 10 months, although she still has not achieved complete remission. Patients 2 and 4 received chemotherapy but experienced rapid disease progression and died within 2 months. CONCLUSIONS: In summary, patients with isochromosome 11q/partial 11q isochromosome have a poorer prognosis, especially for isochromosome 11q. Furthermore, these chromosome aberrations may be risk factors for the presence of isochromosome 11q or myelodysplastic syndrome-related genes, both of them may be associated with a failure to respond to treatment and poor outcomes. Hence, these discoveries may lay a foundation to study mechanisms and explore treatments.

Applicability and cross-cultural validation of the Chinese version of the Warwick-Edinburgh mental well-being scale in patients with chronic heart failure.

BACKGROUND: The mental well-being of patients with chronic heart failure is likely to influence their health-related quality of life and decrease the utilization of public health resources. This study assessed the mental well-being of patients with chronic heart failure and evaluated the reliability and validity of the Warwick-Edinburgh Mental Well-Being Scale. METHODS: We conducted a cross-sectional survey from July 2016 to July 2017 among 191 patients with chronic heart failure, and examined psychometric properties of the Warwick-Edinburgh Mental Well-Being Scale, such as internal consistency, reliability, test-retest reliability, and factorial validity of the Chinese version of the Warwick-Edinburgh Mental Well-Being Scale. RESULTS: One-dimensional construct validity was demonstrated by confirmatory factor analysis. The psychometric properties of the Chinese version of the Warwick-Edinburgh Mental Well-Being Scale were satisfactory in our sample of patients with chronic heart failure. The internal consistency reliability was .948 and the test-retest reliability .925. The item-total correlations ranged from .405 to .872. There was a strong correlation (r = .79) between the Chinese version of the Warwick-Edinburgh Mental Well-Being Scale and the five-item World Health Organization Well-Being Index. The Chinese version of the Warwick-Edinburgh Mental Well-Being Scale appears acceptable for use in patients with chronic heart failure, and we were able to verify its reliability and validity with our sample. CONCLUSIONS: The Chinese version of the Warwick-Edinburgh Mental Well-Being Scale is a reliable quantitative tool for evaluating mental well-being in patients with chronic heart failure in clinical settings, and this has important implications for overall assessments of mental well-being in patients with chronic heart failure.

The change of nuclear LC3 distribution in acute myeloid leukemia cells.

Making sure the change of nuclear LC3 distribution in the autophagy of acute myeloid leukemia (AML) cell and finding out the regulation mechanism may lead to a breakthrough for killing AML cells. Western blots were performed to assess the expression of autophagy proteins. Changes in the LC3 distribution were monitored by immunofluorescence assays together with western blots, and the expression levels of Sirt1, DOR, Beclin1, HMGB1, and AMPK mRNA were detected via fluorescent quantitative PCR. The effects of Sirt1 and DOR on cell proliferation and survival were analyzed by MTT, flow cytometry, and western blotting assays. We found that treating AML cells with Ara-c or Sorafenib resulted in autophagy enhancement, and when autophagy was enhanced, nuclear LC3 moved into the cytoplasm. Notably, when autophagy was inhibited by blocking the nuclear LC3 shift, the cytotoxicity of drugs was enhanced. Our results also identified Sirt1 and DOR as regulatory molecules for the observed nuclear LC3 shift, and these molecules further affected the expression of Beclin1, HMGB1, and AMPK. Our results suggest the distribution of nuclear LC3 can be a novel way for further studying death of AML cells,and the regulatory molecules may be new targets for treating AML.

LncRNA PDIA3P interacts with c-Myc to regulate cell proliferation via induction of pentose phosphate pathway in multiple myeloma.

Multiple myeloma (MM), the second most common hematologic malignancy, is an incurable disease characterized by the accumulation of malignant plasma cells within the bone marrow. Though great progresses have been made in understanding the mechanisms of MM, metabolic plasticity and drug resistance remain largely unknown. In this study, we found lncRNA Protein disulfide isomerase family A member 3 pseudogene 1 (PDIA3P) is highly expressed in MM and is associated with the survival rate of MM patients. PDIA3P regulates MM growth and drug resistance through Glucose 6-phosphate dehydrogenase (G6PD) and the pentose phosphate pathway (PPP). Mechanistically, we revealed that PDIA3P interacts with c-Myc to enhance its transactivation activity and binding to G6PD promoter, stimulating G6PD expression and PPP flux. Our study identified PDIA3P as a novel c-Myc interacting lncRNA and elucidated crucial roles for PDIA3P in metabolic regulation of MM, providing a potential therapeutic target for MM patients.

The reliability and validity of Chinese version of SF36 v2 in aging patients with chronic heart failure.

BACKGROUND: Chronic heart failure (CHF), a major public health problem worldwide, seriously limits health-related quality of life (HRQOL). How to evaluate HRQOL in older patients with CHF remains a problem. AIM: To evaluate the reliability and validity of the Chinese version of the Medical Outcomes Study Short Form version 2 (SF-36v2) in CHF patients. METHODS: From September 2012 to June 2014, we assessed QOL using the SF-36v2 in 171 aging participants with CHF in four cardiology departments. Convergent and discriminant validity, factorial validity, sensitivity among different NYHA classes and between different age groups, and reliability were determined using standard measurement methods. RESULTS: A total of 150 participants completed a structured questionnaire including general information and the Chinese SF-36v2; 132 questionnaires were considered valid, while 21 patients refused to take part. 25 of the 50 participants invited to complete the 2-week test-retest questionnaires returned completed questionnaires. The internal consistency reliability (Cronbach's α) of the total SF-36v2 was 0.92 (range 0.74-0.93). All hypothesized item-subscale correlations showed satisfactory convergent and discriminant validity. Sensitivity was measured in different NYHA classes and age groups. Comparison of different NYHA classes showed statistical significance, but there was no significant difference between age groups. DISCUSSION: We confirmed the SF-36v2 as a valid instrument for evaluating HRQOL Chinese CHF patients. Both reliability and validity were strongly satisfactory, but there was divergence in understanding subscales such as "social functioning" because of differing cultural background. CONCLUSIONS: The reliability, validity, and sensitivity of SF-36v2 in aging patients with CHF were acceptable.

A Meta-Analysis for Effects of Elevated Pre-Transplantation Serum Ferritin on the Outcomes in Patients Undergoing Hematopoietic Stem Cell Transplantation.

The level of pre-transplantation serum ferritin (SF) is one of the factors related to outcome for patients undergoing allogeneic hematopoietic stem cell transplantation. We searched PubMed and Cochrane Library databases from 2000 to 2014. The primary efficacy outcome was overall survival rate and non-relapse mortality. Twenty clinical trials were selected from 189 studies identified. The combined hazard ratio indicated a significantly lower overall survival rate and a higher non-relapse mortality rate in patients with elevated SF before transplantation. This indicates that elevated pre-transplantation SF affects outcome in patients undergoing allogeneic hematopoietic stem cell transplantation.

Expression of AQP1 Was Associated with Apoptosis and Survival of Patients in Gastric Adenocarcinoma.

RATIONALE AND OBJECTIVE: Recently, interest in the role of aquaporin 1 (AQP1) in human gastrointestinal carcinogenesis has developed. However, to date no studies have examined relationships between AQP1 expression and specific characteristics of gastric adenocarcinoma. METHODS: We investigated 109 specimens of primary gastric adenocarcinoma and their corresponding normal gastric mucosa using immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) to determine AQP1 expression. We then evaluated disease free survival (DFS) and overall survival (OS) in these patients in association with AQP1 expression. RESULTS: Both immunohistochemical and RT-PCR analyses identified increased AQP1 expression in tumors from patients with gastric adenocarcinoma (p < 0.001). The 3-year DFS and OS rates were higher in the AQP1-negative group than in the positive group (DFS: 77.2 vs. 52.8%, p < 0.001; OS: 85.1 vs. 70.7%, p < 0.001). The 5-year DFS and OS rates exhibited a similar trend (p < 0.001). Subgroup analysis of patients with early gastric adenocarcinoma (stages I and II) revealed a total 5-year OS of 90.0%, with 5-year OS being higher in the AQP1-negative group than in the positive group (95.2 vs. 84.2%). Furthermore, incidence of tumor recurrence following surgical treatment was significantly higher in the AQP1-positive group (4/19, 21.1%) compared with the negative group (0/21, 0%). CONCLUSIONS: Our study demonstrates that AQP1 plays an important role in gastric adenocarcinoma and may therefore represent a novel therapeutic target and prognostic marker in this disease.

Downregulation of T-bet/GATA-3 ratio induced by IL-11 treatment is responsible for Th1/Th2 balance restoration in human immune thrombocytopenic purpura (ITP).

Abnormal cellular immunity induced by deranged Th1/Th2 profile has been revealed to play a critical role in the pathogenesis of immune thrombocytopenic purpura (ITP). Correction of the shifted Th1/Th2 balance represents a potential therapeutic approach to treat ITP. Here, we investigated the effects of IL-11 on the restoration of Th1/Th2 balance in the peripheral blood mononuclear cells (PBMCs) isolated from adult ITP patients. As shown here, we observed a higher ratio of T-bet/GATA-3 gene expression by quantitative real-time PCR in the PBMCs from ITP patients, consistent with the presence of an abnormally high Th1/Th2 ratio. Remarkably, upon IL-11 treatment, a reversal of T-bet/GATA-3 ratio in ITP was achieved and was shown to be responsible for the restoration of Th1/Th2 balance, with IL-11 at 100 ng/ml demonstrating the highest efficiency. T-bet and GATA-3 are the two transcriptional factors that have been indicated to be the master regulators for Th1 and Th2 lineage commitment, respectively. In the presence of 100 ng/ml IL-11, GATA-3 transcript abundance rose up to ~85-fold of that measured in untreated cells, whereas T-bet transcripts were lowered merely to ~41%, suggesting that GATA-3 was the major contributor for the reversal of T-bet/GATA-3 ratio. Thus, our findings may very well encourage the development of novel medicines that specifically target and correct the T-bet/GATA-3 imbalance identified in ITP.

Synthesis and in vitro biological evaluation of hybrids from tetrahydro-ß-carboline and hydroxylcinnamic acid as antitumor carcinoma agents.

Novel hybrids 8a-j and 9a-j were designed and synthesized by coupling the carboxyl group of hydroxylcinnamic acids with tetrahydro-ß-carboline alkaloids which were linked with different substituted nitrogen-containing heterocycles at the positions-N9, and their in vitro biological activities were evaluated. It was found that most hybrids showed good to moderate anti-tumor activities. Especially, compound 9j had a great potency superior to 5-fluorouracil (5-FU) and comparable to adriamycin in human cancer cells, and could selectively inhibit tumor cells, but not inhibit non-tumor cell proliferation in vitro. More importantly, apoptosis assay indicated that 9j could significantly induce tumor cell apoptosis in a dose-dependent manner. Therefore, our novel findings may provide a new framework for the design of new hybrids for the intervention of human cancers.

Investigating the levels, spatial distribution, and trophic transfer patterns of short-chain chlorinated paraffins in the Southern Bohai Sea, China.

The marine environment of the southern Bohai Sea is severely polluted by short-chain chlorinated paraffins (SCCPs). To improve understanding of how SCCPs occur and of how they migrate, are transformed, and transferred in this area, we collected seawater, sediment, and organism samples, and determined the SCCP contents using a new approach based on high-resolution mass spectrometry. The ΣSCCP concentrations in the seawater, sediment, and organism samples ranged from 57.5 to 1150.4 ng/L, 167.7-1105.9 ng/g (dry weight), and 11.4-583.0 ng/g (wet weight), respectively. Simulation of the spatial distribution of SCCPs using Kriging interpolation showed that SCCPs were markedly influenced by land-based pollution. Substantial quantities of SCCPs were transported to the marine environment via surface runoff from rivers that passed through areas of major SCCP production. Once discharged from such rivers into the Bohai Sea, these SCCPs were further dispersed under the influence of ocean currents. Furthermore, the logarithmic bioaccumulation factor that varied from 2.12 to 3.20 and the trophic magnification factor that reached 5.60 (r2 = 0.750, p < 0.01) suggest that organisms have the ability to accumulate and biomagnify SCCPs through the food chain, which could potentially present risks to both marine ecosystems and human health.

A novel necroptosis-related gene signature in acute myeloid leukemia.

OBJECTIVE: Necroptosis has been reported to play an important role in different cancers, including leukemia. However, biomarkers of necroptosis-related genes (NRGs) that help predict the prognosis of AML are still lacking. Our research aims to build a novel signature of NRGs that could enhance our understanding of the molecular heterogeneity in leukemia. METHOD: Gene expression profiles as well as clinical features were downloaded from TCGA and GEO databases. Data analysis were executed using R software version 4.2.1 and GraphPad Prism version 9.0.0. RESULT: Univariate cox regression and lasso regression were applied to identify survival-specific genes. Four genes including FADD, PLA2G4A, PYCARD and ZBP1 were considered as independent risk factors that affect the prognosis of patients. Risk scores were calculated according to the coefficient of four genes. Then clinical characteristics and risk scores were enrolled to construct a nomogram. CellMiner was also used to screen potential drugs and analyze the correlations between genes and drug sensitivity. CONCLUSION: In general, we established a signature of four genes related to necroptosis that could be helpful for future risk stratification in patients with AML.

Health-related quality of life in Chinese medical staff: a latent profile analysis.

Objective: To investigate subgroups of health-related quality of life (HRQoL) in the Chinese medical staff and identify the demographic factors associated with these profiles. Methods: 574 Chinese medical staff were surveyed online. HRQoL was measured by using the 36-Item Short Form Health Survey, Version 2. Latent profile analysis (LPA) was used to identify the profiles of HRQoL. The associations between HRQoL profiles and covariates were assessed using multinomial logistic regression. Results: Three HRQoL profiles were developed: low HRQoL at 15.6%, moderate HRQoL at 46.9%, and high HRQoL at 37.6%. Multinomial logistic regression showed night shift times, aerobic exercise conditioning, and personality type significantly predicted the profile membership. Conclusion: Our findings develop earlier approaches that only used total scores to evaluate this group's HRQoL and help them with tailored interventions to promote better HRQoL.

Evidence for ABL Amplification in Multiple Myeloma and Therapeutic Implications.

Background: Cytogenetic abnormalities are considered initiating events in the pathogenesis of multiple myeloma (MM) and are assumed to be of clinical significance. Methods: Fluorescence in situ hybridization (FISH) was used to analyze chromosomal architecture in 101 patients with MM. We evaluated overall patient survival and assessed the cytotoxicity of imatinib against MM cells using a CCK8 assay. Results: ABL gene amplification was detected in 67 patients (66.3%). However, ABL gene amplification was not associated with clinical features, cytogenetic abnormalities (c-Myc amplification, IGH rearrangement, RB1 deletion, p53 deletion, or 1q21 amplification), or overall survival. ABL amplification in MM cell lines (LP-1 and U266) was revealed by FISH. Furthermore, the ABL protein was easily detectable in MM cell lines and some tumor cells by western blotting. A CCK8 assay indicated limited cytotoxicity of imatinib against MM cells. Conclusions: Our study firstly discussed ABL gene amplification was prevalent in MM cells, and we believe that the ABL gene would potentially be a useful target in the treatment of combination strategy for MM with ABL amplification in the future.

Bioinformatics analysis of the network of histone H3 lysine 9 trimethylation in acute myeloid leukaemia.

Changes in histone H3 lysine 9 trimethylation (H3K9me3) may be related to the development of drug­resistant acute myeloid leukaemia (AML); insights into the network of H3K9me3 may improve patient prognosis. Patient data were derived from the Gene Expression Omnibus (GEO) database and data from AML cells treated with chidamide, a novel benzamide chemical class of histone deacetylase inhibitor (HDACi), in vitro were derived from ChIP­seq. Patients and AML cell data were analysed using GEO2R, GOseq, KOBAS, the STRING database and Cytoscape 3.5.1. We identified several genes related to the upregulation or downregulation of H3K9me3 in AML patients; some of these genes were related to apoptosis, autophagy, and the pathway of cell longevity. AML cells treated with chidamide in vitro showed the same gene changes. The protein interactions in the network did not have significantly more interactions than expected, suggesting the need for more research to identify these interactions. One compelling result from the protein interaction study was that sirtuin 1 (SIRT1) may have an indirect interaction with lysine­specific demethylase 4A (KDM4A). These results help explain alterations of H3K9me3 in AML that may direct further studies aimed at improving patient prognosis. These results may also provide a basis for chidamide as a treatment strategy for AML patients in the future.

Novel SAHA­bendamustine hybrid NL­101 in combination with daunorubicin synergistically suppresses acute myeloid leukemia.

Acute myeloid leukemia (AML) is a highly aggressive disease with high mortality and recurrence rates, for which novel therapeutic approaches are required. Hybrid anticancer agents with dual effects have been reported to possess therapeutic potential to treat AML. However, the efficacy and underlying toxicity of these hybrids in combination with other agents remain unclear. NL­101 is a novel hybrid formed by fusing the DNA damage­inducing agent bendamustine with the histone deacetylase inhibitor vorinostat. In the present study, NL­101 treatment was combined with the conventional chemotherapeutic drug daunorubicin (DNR) in AML cells, and it was revealed that these two compounds exerted synergistic anti­AML effects. In addition, NL­101 enhanced DNR­induced cell apoptosis, as assessed by flow cytometry and as indicated by the upregulation of cleaved­poly (ADP­ribose) polymerase, cleaved­caspase­3, cleaved­caspase­7, BAD and BIM. Mechanistically, the DNA double­strand breaks marker γ­H2AX, and other proteins associated with DNA damage, were investigated, and it was demonstrated that NL­101 in combination with DNR synergistically promoted the DNA damage response. In vivo, this combination significantly delayed the progression of AML and prolonged the survival time in mice. Collectively, the present results suggested that NL­101 in combination with daunorubicin could be an alternative novel therapeutic strategy for treating leukemia.

Chidamide Enhances the Cytotoxicity of Cytarabine and Sorafenib in Acute Myeloid Leukemia Cells by Modulating H3K9me3 and Autophagy Levels.

Previous studies showed that chidamide enhances the cytotoxicity of drugs in acute myeloid leukemia (AML) cells. Therefore, we examined whether chidamide enhanced the cytotoxicity of drugs in AML cells by affecting H3K9me3 and autophagy levels. AML cells (THP-1 and MV4-11 cells) were treated with chidamide, cytarabine (Ara-c), or sorafenib alone or in combination. Cell proliferation and survival rates were analyzed by MTT, flow cytometry, and Western blotting assays. The results showed that a low dose of chidamide enhanced the cytotoxicity of Ara-c or sorafenib in AML cells, decreasing proliferation and increasing apoptosis. H3K9me3 levels as assessed by Western blotting were upregulated by chidamide treatment. Chromatin immunoprecipitation sequencing, which was used to investigate potential signaling pathways, indicated that the autophagy pathway might play a role in the effects of chidamide. The level of autophagy induced in AML cells upon treatment with Ara-c or sorafenib was inhibited by chidamide, and autophagy markers (LC3, P62) were tested by Western blotting. SIRT1 messenger RNA (mRNA) and protein levels were lower in AML cells treated with Ara-c or sorafenib in combination with chidamide than those in cells treated with these drugs alone. Additionally, the Integrative Genomics Viewer results indicate that the H3K9me3 changes were related to SIRT1-binding sites. Together, these results show that chidamide enhances the cytotoxicity of two chemotherapy drugs in AML cells by increasing the H3K9me3 level and inhibiting autophagy via decreasing the expression of SIRT1. Chidamide may be a potential treatment strategy for AML in the future, especially for refractory AML patients.

A novel alkylating deacetylase inhibitor molecule EDO-S101 in combination with cytarabine synergistically enhances apoptosis of acute myeloid leukemia cells.

Acute myeloid leukemia (AML) is a devastating disease. Hybrid agents with dual activity, which have been shown to possess anti-cancer effect, are expected to potentially improve the prognosis of AML patients. EDO-S101 is a novel alkylating deacetylase inhibitor molecule synthesized by the addition of the hydroxamic acid of histone deacetylases inhibitor vorinostat into bendamustine, a DNA-damaging agent. However, the effect of EDO-S101 in combination with traditional chemotherapy drugs has not been studied in AML. In this study, we investigated the effect of EDO-S101 in combination with cytarabine in treating AML cells. The synergic activity against AML was identified by remarkable reduction of cell viability, significant apoptosis enhancement and the upregulation of the cleaved PARP, Casepase-3 and -7 proteins compared with monotherapy. To explain the drivers, we detected the DNA damage pathway including DNA double-strand breaks marker γ-H2AX and DNA damage checkpoint proteins, which was supposed to be responsible for the enhanced apoptosis activity. In summary, our data demonstrated that EDO-S101 in combination with cytarabine could synergistically induce the apoptosis of AML cells and it might be a potential regimen for treating leukemia.

Once-weekly bortezomib had similar effectiveness and lower thrombocytopenia occurrence compared with twice-weekly bortezomib regimen in treating patients with newly diagnosed multiple myeloma in China.

The study aims to examine the treatment effect and adverse reactions of patients with newly diagnosed MM receiving different bortezomib-based regimens.This was a retrospective study of patients with newly diagnosed MM and who were treated with bortezomib-based combined chemotherapy at the Department of Hematology of the 2 affiliated hospitals of Wenzhou Medical University between July 2009 and May 2016. Cox proportion hazard multivariate analyses were carried out to assess the differences in treatment effect and adverse events between standard (1.3 mg/m on days 1, 4, 8, 11) and weekly (1.6 mg/m on days 1, 8, 15) cohorts, as well as the differences between intravenous injection and subcutaneous injection therapy. Progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier method and the log-rank test.Among the 117 patients, 78 patients were treated with bortezomib standard therapy and 39 patients were treated with bortezomib weekly therapy (all with intravenous injection). In all patients, the treatment strategy was not independently associated with PFS or OS. The patients in the weekly therapy group had less thrombocytopenia events than those in the standard therapy group. The subcutaneous route had similar treatment effect as the intravenous route, but the incidence of peripheral neuropathy was lower.The once-weekly bortezomib regimen was similar in effectiveness to standard therapy in treating patients with newly diagnosed MM, but the incidence of thrombocytopenia was lower with the weekly regimen compared with the standard regimen.