Phase II study of novel orally PI3Kα/δ inhibitor TQ-B3525 in relapsed and/or refractory follicular lymphoma.

This registration study assessed clinical outcomes of TQ-B3525, the dual phosphatidylinositol-3-kinase (PI3K) α/δ inhibitor, in relapsed and/or refractory follicular lymphoma (R/R FL). This phase II study (ClinicalTrials.gov NCT04324879. Registered March 27, 2020) comprised run-in stage and stage 2. R/R FL patients after ≥2 lines therapies received oral 20 mg TQ-B3525 once daily in a 28-day cycle until intolerable toxicity or disease progression. Primary endpoint was independent review committee (IRC)-assessed objective response rate (ORR). Based on results (ORR, 88.0%; duration of response [DOR], 11.8 months; progression-free survival [PFS], 12.0 months) in 25 patients at run-in stage, second stage study was initiated and included 82 patients for efficacy/safety analysis. Patients received prior-line (median, 3) therapies, with 56.1% refractory to previous last therapies; 73.2% experienced POD24 at baseline. At stage 2, ORR was 86.6% (71/82; 95% CI, 77.3-93.1%), with 28 (34.2%) complete responses. Disease control rate was 95.1% due to 7 (8.5%) stable diseases. Median time to response was 1.8 months. Among 71 responders, median DOR was not reached; 18-month DOR rate was 51.6%. with median follow-up of 13.3 months, median PFS was 18.5 (95% CI, 10.2-not estimable) months. Median overall survival (OS) was not reached by cutoff date; 24-month OS rate was estimated as 86.1%. Response rates and survival data were consistent across all subgroups. Grade 3 or higher treatment-related adverse events were observed in 63 (76.8%) cases, with neutropenia (22.0%), hyperglycemia (19.5%), and diarrhea (13.4%) being common. TQ-B3525 showed favorable efficacy and safety for R/R FL patients after ≥2 lines prior therapies.

Ixazomib-based frontline therapy followed by ixazomib maintenance in frail elderly newly diagnosed with multiple myeloma: a prospective multicenter study.

Background: Frail elderly patients with newly diagnosed multiple myeloma (NDMM) have inferior survival and less benefit from high-dose therapies. This prospective study aimed to investigate the efficacy, safety, and quality of life (QoL) of induction treatment of ixazomib/lenalidomide/dexamethasone (IRd) and ixazomib/pegylated liposomal doxorubicin/dexamethasone (IDd) followed by ixazomib/dexamethasone (Id) maintenance therapy in frail, elderly patients with NDMM. Methods: From July 2019 to December 2021, this non-randomized concurrent controlled clinical study enrolled 120 NDMM patients aged ≥65 years with frailty defined by the International Myeloma Working Group (IMWG) frailty score or Mayo geriatric scoring system. The enrolled patients received 6-8 cycles of IRd or IDd followed by Id maintenance therapy for a minimum of 2 years at the discretion of physicians based on patient's clinical characteristics (chiCTR1900024917). Findings: The median age was 71 years and 55% of the patients were males. The overall response rate (ORR) was 82% and 77%, complete response (CR) rate was 25% and 12% for IRd and IDd groups, respectively. The difference in ORR of the Idd group minus the IRd group was -5.36% (95% CI: -18.9% to 8.19%), indicating that the ORR of the IDd group was neither inferior nor non-inferior to the IRd group. After a median follow-up of 34.3 months, the median progression-free survival (PFS) was 21.6 and 13.9 months, OS was not reached and 29.2 months in IRd and IDd groups, respectively. 28 and 33 patients discontinued induction therapy, 20 and 19 discontinued maintenance therapy in IRd and IDd groups, respectively. Cumulative Grade 3 or higher hematological adverse events (AEs) occurred in 10 of the 60 patients (17%) and non-hematological AEs occurred in 15 of the 60 patients (25%) in the IRd group, while 13 of the 60 patients (22%) and 21 of the 60 patients (35%) in the IDd group. Patients were observed with clinically significant improvement in QoL when compared with that at baseline in both IRd and IDd groups by evaluation per cycle (P < 0.0001). Interpretation: The results demonstrated that compared with IRd regimen, IDd regimen showed no significant advantage, but the survival of the IDd group was shorter than that of the IRd group, indicating an all-oral outpatient triplet regimen with IRd, which has low toxicity and has improved QoL, could be the viable first-line treatment option for frail NDMM patients. Funding: The Young Elite Scientist sponsorship program by bast of Beijing Association for Science and Technology (No. BYESS2023116) and Beijing Medical Award Foundation (No. YXJL-2018-0539-0073).

Aponermin or placebo in combination with thalidomide and dexamethasone in the treatment of relapsed or refractory multiple myeloma (CPT-MM301): a randomised, double-blinded, placebo-controlled, phase 3 trial.

BACKGROUND: Aponermin, a circularly permuted tumor necrosis factor-related apoptosis-inducing ligand, is a potential death receptor 4/5-targeted antitumour candidate. Previous phase 1/2 studies have demonstrated the efficacy of aponermin in patients with relapsed or refractory multiple myeloma (RRMM). To confirm the superiority of aponermin plus thalidomide and dexamethasone (aponermin group) over placebo plus thalidomide and dexamethasone (placebo group) in RRMM, a randomized, double-blinded, placebo controlled phase 3 trial was performed. METHODS: Four hundred seventeen patients with RRMM who had previously received at least two regimens were randomly assigned (2:1) to receive aponermin, thalidomide, and dexamethasone or placebo, thalidomide, and dexamethasone. The primary endpoint was progression-free survival (PFS). Key secondary endpoints included overall survival (OS) and overall response rate (ORR). RESULTS: A total of 415 patients received at least one dose of trial treatment (276 vs. 139). The median PFS was 5.5 months in the aponermin group and 3.1 months in the placebo group (hazard ratio, 0.62; 95% confidence interval [CI], 0.49-0.78; P < 0.001). The median OS was 22.4 months for the aponermin group and 16.4 months for the placebo group (hazard ratio, 0.70; 95% CI, 0.55-0.89; P = 0.003). Significantly higher rates of ORR (30.4% vs. 13.7%, P < 0.001) and very good partial response or better (14.1% vs. 2.2%, P < 0.0001) were achieved in the aponermin group than in the placebo group. Treatment with aponermin caused hepatotoxicity in some patients, as indicated by the elevated alanine transaminase, aspartate transaminase, or lactate dehydrogenase levels (52.2% vs. 24.5%, 51.1% vs. 19.4% and 44.9% vs. 21.6%, respectively), mostly grade 1/2, transient and reversible. The main grade 3/4 adverse events included neutropenia, pneumonia and hyperglycemia. The incidence of serious adverse events was similar between the two groups (40.6% vs. 37.4%). There was no evidence that aponermin leads to hematological toxicity, nephrotoxicity, cardiotoxicity, or secondary tumors. CONCLUSIONS: Aponermin plus thalidomide and dexamethasone significantly improved PFS, OS and ORR with manageable side effects in RRMM patients who had received at least two prior therapies. These results support the use of aponermin, thalidomide, and dexamethasone as a treatment option for RRMM patients. TRIAL REGISTRATION: The trial was registered at http://www.chictr.org.cn as ChiCTR-IPR-15006024, 17/11/2014.

Radiotherapy in Philadelphia chromosome­positive acute lymphoblastic leukemia with pericardial invasion after transplantation: A case report.

The present report describes a case of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) with pericardial invasion following bone marrow transplantation. The patient exhibited recurrent pericardial effusion accompanied by wheezing symptoms. Despite undergoing multiple pericardial punctures and drainage procedures, pericardial injections, and systemic treatment, the patient continued to experience recurrent pericardial effusion. Ultimately, the patient underwent whole-heart radiotherapy, resulting in complete resolution of the pericardial effusion. After a follow-up period of 10 months, the pericardial effusion remained well-controlled, and there were no significant impairments in cardiac function. In conclusion, radiotherapy may be considered as a viable treatment option for refractory leukemia cases presenting with pericardial effusion.

[MiR-203a-5p Inhibits Multiple Myeloma Cell Proliferation and Cell Cycle Progression via Targeting JAG1].

OBJECTIVE: To investigate the biological function of miR-203a-5p and the underlying mechanism in multiple myeloma (MM). METHODS: Three miRNA expression profiles (GSE16558, GSE24371 and GSE17498) were downloaded from the GEO database. The three miRNA expression profiles contained 131 MM samples and 17 normal plasmacyte samples. The robust rank aggregation (RRA) method was used to identify the differentially expressed miRNAs between MM and normal plasmacytes. In order to carry out cytological experiments, MM cell line with stable over-expression of miR-203a-5p was constructed with lentivirus. Expression levels of miR-203a-5p in MM cells were quantified by qRT-PCR. The effects of miR-203a-5p on MM cells were investigated using assays of cell viability and cell cycle. Cell proliferation was measured using the Cell Counting kit (CCK)8 assay. The percentage of cells in each cell cycle was measured with a FACSCalibur system. Xenograft tumor models were established to evaluate the role of miR-203a-5p in tumorigenesis in vivo . To elucidate the underlying molecular mechanisms of miR-203a-5p in mediating cell proliferation inhibition and cell cycle arrest in MM, we used TargetScan and miRanda to predict the candidate targets of miR-203a-5p. The potential target of miR-203a-5p in MM cells was explored using the luciferase reporter assay, qRT-PCR, and Western blot. RESULTS: An integrated analysis of three MM miRNA expression datasets showed that the levels of miR-203a-5p in MM were notably downregulated compared with those in normal plasmacytes. Accordingly, the relative expression levels of miR-203a-5p were decreased in MM cell lines. In addition, overexpression of miR-203a-5p inhibited the proliferation and cell cycle progression of RPMI8226 and U266 cells. In vivo experiments demonstrated that upregulation of miR-203a-5p expression could significantly inhibit the tumorigenesis of subcutaneous myeloma xenografts in nude mice. Mechanistic investigation led to the identification of Jagged 1 (JAG1) as a novel and direct downstream target of miR-203a-5p. Interestingly, the reintroduction of JAG1 abrogated miR-203a-5p-induced MM cell growth inhibition and cell cycle arrest. CONCLUSION: Our data demonstrate that miR-203a-5p inhibits cell proliferation and cell cycle progression in MM cells by targeting JAG1, supporting the utility of miR-203a-5p as a novel and potential therapeutic agent for miRNA-based MM therapy.

Identification of Survival-Related Genes in Acute Myeloid Leukemia (AML) Based on Cytogenetically Normal AML Samples Using Weighted Gene Coexpression Network Analysis.

The prognosis of acute myeloid leukemia (AML) remains a challenge. In this study, we applied the weighted gene coexpression network analysis (WGCNA) to find survival-specific genes in AML based on 42 adult CN-AML samples from The Cancer Genome Atlas (TCGA) database. Eighteen hub genes (ABCA13, ANXA3, ARG1, BTNL8, C11orf42, CEACAM1, CEACAM3, CHI3L1, CRISP2, CYP4F3, GPR84, HP, LTF, MMP8, OLR1, PADI2, RGL4, and RILPL1) were found to be related to AML patient survival time. We then compared the hub gene expression levels between AML peripheral blood (PB) samples (n = 162) and control healthy whole blood samples (n = 337). Seventeen of the hub genes showed lower expression levels in AML PB samples. The gene expression analysis was also done among AML BM (bone marrow) samples of different stages: diagnosis (n = 142), posttreatment (n = 42), and recurrent (n = 12) stages. The results showed a significant increase of ANXA3, CEACM1, RGL4, RILPL1, and HP in posttreatment samples compared to diagnosis and/or recurrent samples. Transcription factor (TF) prediction of the hub genes suggested LTF as the top hit, overlapping 10 hub genes, while LTF itself is just one of the hub genes. Also, 3671 correlation links were shown between 128 mRNAs and 209 lncRNAs found in survival time-related modules. Generally, we identified candidate mRNA biomarkers based on CN-AML data which can be extensively used in AML prognosis. In addition, we mapped their potential regulatory mechanisms with correlated lncRNAs, providing new insights into potential targets for therapies in AML.

Developing and validating a mortality prediction model for ICH in ITP: a nationwide representative multicenter study.

Intracranial hemorrhage (ICH) is a rare and life-threatening hemorrhagic event in patients with immune thrombocytopenia (ITP). However, its mortality and related risk factors remain unclear. Herein, we conducted a nationwide multicenter real-world study of ICH in adult ITP patients. According to data from 27 centers in China from 2005 to 2020, the mortality rate from ICH was 33.80% (48/142) in ITP adults. We identified risk factors by logistic univariate and multivariate logistic regression for 30-day mortality in a training cohort of 107 patients as follows: intraparenchymal hemorrhage (IPH), platelet count ≤10 × 109/L at ICH, a combination of serious infections, grade of preceding bleeding events, and Glasgow coma scale (GCS) level on admission. Accordingly, a prognostic model of 30-day mortality was developed based on the regression equation. Then, we evaluated the performance of the prognostic model through a bootstrap procedure for internal validation. Furthermore, an external validation with data from a test cohort with 35 patients from 11 other centers was conducted. The areas under the receiver operating characteristic (ROC) curves for the internal and external validation were 0.954 (95% confidence interval [CI], 0.910-0.998) and 0.942 (95% CI, 0.871-1.014), respectively. Both calibration plots illustrated a high degree of consistency in the estimated and observed risk. In addition, the decision curve analysis showed a considerable net benefit for patients. Thus, an application (47.94.162.105:8080/ich/) was established for users to predict 30-day mortality when ICH occurred in adult patients with ITP.

All-trans retinoic acid plus low-dose rituximab vs low-dose rituximab in corticosteroid-resistant or relapsed ITP.

The study aimed to compare the efficacy and safety of all-trans retinoic acid (ATRA) plus low-dose rituximab (LD-RTX) with LD-RTX monotherapy in corticosteroid-resistant or relapsed immune thrombocytopenia (ITP) patients. Recruited patients were randomized at a ratio of 2:1 into 2 groups: 112 patients received LD-RTX plus ATRA, and 56 patients received LD-RTX monotherapy. Overall response (OR), defined as achieving a platelet count of ≥30 × 109/L confirmed on ≥2 separate occasions (≥7 days apart), at least a doubling of the baseline platelet count without any other ITP-specific treatment, and the absence of bleeding within 1 year after enrollment, was observed in more patients in the LD-RTX plus ATRA group (80%) than in the LD-RTX monotherapy group (59%) (between-group difference, 0.22; 95% CI, 0.07-0.36). Sustained response (SR), defined as maintenance of a platelet count >30 × 109/L, an absence of bleeding, and no requirement for any other ITP-specific treatment for 6 consecutive months after achievement of OR during 1 year following enrollment, was achieved by 68 (61%) patients in the combination group and 23 (41%) patients in the monotherapy group (between-group difference, 0.20; 95% CI, 0.04-0.35). The 2 most common adverse events (AEs) for the combination group were dry skin and headache or dizziness. Our findings demonstrated that ATRA plus LD-RTX significantly increased the overall and sustained response, indicating a promising treatment option for corticosteroid-resistant or relapsed adult ITP. This study is registered at www.clinicaltrials.gov as #NCT03304288.

Cost-Efficient Film-Forming Additive for High-Voltage Lithium-Nickel-Manganese Oxide Cathodes.

The operating voltage of lithium-nickel-manganese oxide (LiNi0.5Mn1.5O4, LNMO) cathodes far exceeds the oxidation stability of the commercial electrolytes. The electrolytes undergo oxidation and decomposition during the charge/discharge process, resulting in the capacity fading of a high-voltage LNMO. Therefore, enhancing the interphasial stability of the high-voltage LNMO cathode is critical to promoting its commercial application. Applying a film-forming additive is one of the valid methods to solve the interphasial instability. However, most of the proposed additives are expensive, which increases the cost of the battery. In this work, a new cost-efficient film-forming electrolyte additive, 4-trifluoromethylphenylboronic acid (4TP), is adopted to enhance the long-term cycle stability of LNMO/Li cell at 4.9 V. With only 2 wt % 4TP, the capacity retention of LNMO/Li cell reaches up to 89% from 26% after 480 cycles. Moreover, 4TP is effective in increasing the rate performance of graphite anode. These results show that the 4TP additive can be applied in high-voltage LIBs, which significantly increases the manufacturing cost while improving the battery performance.

Treatment patterns and a prognostic scoring system for elderly acute myeloid leukemia patients: a retrospective multicenter cohort study in China.

OBJECTIVE: Acute myeloid leukemia (AML) is primarily a malignant disorder affecting the elderly. We aimed to compare the outcomes of different treatment patterns in elderly AML patients and to propose a prognostic scoring system that could predict survival and aid therapeutic decisions. METHODS: Patients aged ≥ 60 years who had been diagnosed with AML at 7 hospitals in China were enrolled (n = 228). Treatment patterns included standard chemotherapy, low intensity therapy, and best supportive care (BSC). RESULTS: The early mortality rates were 31%, 6.8%, and 6.3% for the BSC, low intensity therapy, and standard chemotherapy groups, respectively. The complete remission rate of the standard chemotherapy group was higher than that of the low intensity therapy group. The median overall survival (OS) was 561 days and 222 days for the standard chemotherapy and low intensity therapy groups, respectively, and were both longer than that of the BSC group (86 days). Based on multivariate analyses, we defined a prognostic scoring system that enabled classification of patients into 3 risk groups, in an attempt to predict the OS of patients receiving chemotherapies and low intensity therapies. Low and intermediate risk patients benefited more from standard chemotherapies than from low intensity therapies. However, the median OS was comparable between standard chemotherapies and low intensity therapies in high risk patients. CONCLUSIONS: Our prognostic scoring system could predict survival and help select appropriate therapies for elderly AML patients. Standard chemotherapy is important for elderly AML patients, particularly for those categorized into low and intermediate risk groups.

Risk stratification and outcomes of intracranial hemorrhage in patients with immune thrombocytopenia under 60 years of age.

Intracranial hemorrhage (ICH) is a devastating complication of immune thrombocytopenia (ITP). However, information on ICH in ITP patients under the age of 60 years is limited, and no predictive tools are available in clinical practice. A total of 93 adult patients with ITP who developed ICH before 60 years of age were retrospectively identified from 2005 to 2019 by 27 centers in China. For each case, 2 controls matched by the time of ITP diagnosis and the duration of ITP were provided by the same center. Multivariate analysis identified head trauma (OR = 3.216, 95%CI 1.296-7.979, P =.012), a platelet count ≤ 15,000/µL at the time of ITP diagnosis (OR = 1.679, 95%CI 1.044-2.698, P =.032) and severe/life-threatening bleeding (severe bleeding vs. mild bleeding, OR = 1.910, 95%CI 1.088-3.353, P =.024; life-threatening bleeding vs. mild bleeding, OR = 2.620, 95%CI 1.360-5.051, P =.004) as independent risk factors for ICH. Intraparenchymal hemorrhage (OR = 5.191, 95%CI 1.717-15.692, P =.004) and a history of severe bleeding (OR = 4.322, 95%CI 1.532-12.198, P =.006) were associated with the 30-day outcome of ICH. These findings may facilitate ICH risk stratification and outcome prediction in patients with ITP.

Immune prognostic risk score model in acute myeloid leukemia with normal karyotype.

Acute myeloid leukemia with normal karyotype (NK-AML) is a group of diseases with high heterogeneity and immunological processes are significantly associated with its initiation and development. The implication of the immunogenomic landscape in the prognosis of patients with NK-AML has remained largely elusive. In the present study, the expression profiles of immune-related genes (IRGs) were examined and their association with overall survival (OS) was determined in 60 patients with NK-AML from The Cancer Genome Atlas dataset and 104 patients from the Gene Expression Omnibus (GEO) dataset no. GSE71014. Univariate Cox regression analysis was used to identify 42 and 203 IRGs in the two respective cohorts, which were significantly associated with OS in NK-AML. A risk model was constructed based on the regression coefficient and expression values of nine survival-associated IRGs shared between the two datasets [zinc finger CCCH-type containing, antiviral 1 like; transferrin receptor; suppressor of cytokine signaling 1; ELAV like RNA binding protein 1; roundabout guidance receptor 3; unc-93 homolog B1, Toll-like receptor signaling regulator; protein tyrosine phosphatase non-receptor type 6; interleukin 2 receptor subunit alpha (IL2RA) and IL3RA]. Using this risk model, patients with NK-AML may be divided into high- and low-risk groups in prognostic predictions. The area under the receiver operating characteristic curve for predicting OS was 0.793. The prognostic role of this risk model was successfully verified in another independent cohort (GEO dataset no. GSE71014). The prognostic risk score was positively associated with age and fms related receptor tyrosine kinase 3 mutation and correlated with infiltration by T regulatory cells. In conclusion, the results of the present study provided an IRG score model for prognostic stratification of adult patients with NK-AML, as well as further insight into the implication of IRGs in NK-AML that may lead to the development of novel immunotherapy approaches for this disease.

Antiproliferative effects of L-asparaginase in acute myeloid leukemia.

The antitumor enzyme L-asparaginase (L-Asp) has commonly been used for the treatment of acute lymphoblastic leukemia. However, the effects of L-Asp on acute myeloid leukemia (AML) and their underlying mechanisms have not been fully elucidated. In the present study, the effects of L-Asp on cell proliferation and apoptosis were investigated using the AML cell lines U937, HL-60 and KG-1a. The effects of combining L-Asp with mitoxantrone (MIT) and cytarabine (Ara-c) were also analyzed. The combination of MIT and Ara-C is known as MA therapy, and is a widely used therapeutic regimen for the treatment of elderly patients with refractory AML. When applied alone, L-Asp inhibited cell proliferation and induced apoptosis in each of the cell lines tested. Furthermore, the combined use of L-Asp with MA therapy further potentiated the inhibition of cell proliferation while increasing the induction of apoptosis. These findings provide evidence for the potential antitumor effect of L-Asp in AML, and indicate that improved efficacy maybe achieved by combining L-Asp with MIT and Ara-c. This combination may provide a promising new therapeutic strategy for the treatment of AML.

Development and validation of a prediction model (AHC) for early identification of refractory thrombotic thrombocytopenic purpura using nationally representative data.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare and life-threatening haematological emergency. Although therapeutic plasma exchange together with corticosteroids achieve successful outcomes, a considerable number of patients remain refractory to this treatment and require early initiation of intensive therapy. However, a method for the early identification of refractory iTTP is not available. To develop and validate a model for predicting the probability of refractory iTTP, a cohort of 265 consecutive iTTP patients from 17 large medical centres was retrospectively identified. The derivation cohort included 94 patients from 11 medical centres. For the validation cohort, we included 40 patients from the other six medical centres using geographical validation. An easy-to-use risk score system was generated, and its performance was assessed using internal and external validation cohorts. In the multivariable logistic analysis of the derivation cohort, three candidate predictors were entered into the final prediction model: age, haemoglobin and creatinine. The prediction model had an area under the curve of 0.886 (95% CI: 0.679-0.974) in the internal validation cohort and 0.862 (95% CI: 0.625-0.999) in the external validation cohort. The calibration plots showed a high agreement between the predicted and observed outcomes. In conclusion, we developed and validated a highly accurate prediction model for the early identification of refractory iTTP. It has the potential to guide tailored therapy and is a step towards more personalized medicine.

Understanding and Suppressing the Destructive Cobalt(II) Species in Graphite Interphase.

Co2+ species dissolved from LiCoO2 in lithium-ion batteries have been well-established to be responsible for the cell performance fading, especially when the cells are charged to high voltage or at elevated temperatures. The accepted underlying mechanism is the deposition of Co2+ on the graphite anode that destroys the interphase. In this work, we report that the dissolved Co2+ exists in the form of both Co0 and Co2+ on the graphite anode surface, while Co0 formed at lithium insertion potential can be reoxidized to Co2+ during charging. Moreover, Co0 shows a higher catalytic activity than Co2+ toward the reductive decomposition of carbonate electrolyte. An interphase of ∼4 nm was thus engineered from a film-forming additive 3-sulflone, which completely eliminates the destructive effect of the deposited Co species. The understanding of the destructive role of the dissolved Co2+ on the interphasial stability of the graphite electrode and an effective strategy to suppress such a failure mechanism provides fresh insight into the failure mechanism of manganese-based cathode chemistries, which serves as a better guideline for electrolyte design for future batteries.

Stabilizing a High-Voltage Lithium-Rich Layered Oxide Cathode with a Novel Electrolyte Additive.

We report a novel electrolyte additive, bis(trimethylsilyl)carbodiimide, that effectively stabilizes high-voltage lithium-rich oxide cathode. Charge/discharge tests demonstrate that even trace amounts of bis(trimethylsilyl)carbodiimide in a baseline electrolyte improve the cycling stability of this cathode significantly, either in Li-based half cells or graphite-based full cells, where the capacity retention after 200 cycles between 2 and 4.8 V at 0.5C is enhanced from 40 to 72% and 49 to 77%, respectively. Analyses using physical characterization and theoretical calculations reveal that this additive not only builds a protective film on the cathode but also eliminates detrimental hydrogen fluoride via its strong coordination with hydrogen fluoride or protons.

Prognostic Nomogram for the Overall Survival of Patients with Newly Diagnosed Multiple Myeloma.

To establish a nomogram for predicting the overall survival (OS) of patients with newly diagnosed multiple myeloma (MM), 304 patients with newly diagnosed MM were recruited between June 1, 2010, and June 30, 2015, from the Beijing Chaoyang Hospital, Capital Medical University, and randomly divided into training (n=214) and validation (n=90) cohorts. The Kaplan-Meier method and the Cox proportional hazards regression model were used to evaluate the prognostic effects of multiple clinical and laboratory parameters on survival. Significant prognostic factors were combined to build a nomogram. The discriminative ability and predictive accuracy of the nomogram were evaluated using the index of concordance (C-index) and calibration curves and compared with the five staging systems currently used for MM. Multivariate analysis of the training cohort revealed that the age at diagnosis, clonal bone marrow plasma cells, serum lactate dehydrogenase, serum ß2-microglobulin, and del (17p) were independent risk factors for OS and were used to establish the nomogram. The C-index value of the nomogram for predicting OS was 0.749, which was significantly higher than the C-indices of the five most common staging systems currently used for MM. In the validation cohort, the C-index for nomogram-based predictions was 0.711 for OS, and the nomogram discrimination was better than the above mentioned five staging systems (P<0.001). All calibration curves revealed good consistency between predicted and actual survivals. The proposed nomogram is more accurate in predicting the prognoses of patients with newly diagnosed MM.

Stabilizing LiCoO2/Graphite at High Voltages with an Electrolyte Additive.

The energy density of commercial Li-ion batteries (LIBs) using LiCoO2 is adversely affected by the limited access to the Li stored in the CoO2 lattice, which is imposed partially by the instability of carbonate-based electrolytes at potentials higher than 4.5 V. In this work, we report a novel approach to fully utilize these extra Li via simultaneously stabilizing anode and cathode interfaces with a designed additive, 4-propyl-[1,3,2]dioxathiolane-2,2-dioxide (PDTD), which strongly coordinates with Co ions dissolved in electrolytes while decomposing to form protective interphases on both cathode and anode surfaces. The Co ions present in the electrolyte deposit on the anode in the form of a coordination complex with PDTD, avoiding the formation of Co metal that will catalyze the reduction decomposition of the additive-free electrolyte. The presence of PDTD in the electrolyte enables a higher charging potential of 4.45 V for LiCoO2/graphite cells, which significantly improves the energy density and cycling stability of this cathode chemistry that has already been used extensively in commercial LIBs.

The impact of inflammation and cytokine expression of PM2.5 in AML.

Environmental and health issues have become a major focus of research worldwide in recent years. Particulate matter with diameter ≤2.5 µm (PM2.5) is a common air pollutant that has been demonstrated to be associated with various diseases, including acute myeloid leukemia (AML). In the present study, the effects of PM2.5 on the proliferation and inflammation were assessed using three human acute myeloid cell lines (U937, HL-60 and KG-1a) in vitro. Additionally, the levels of several cytokines [interleukin (IL)-2, IL-10, IL-17A and tumor necrosis factor (TNF)α] in AML cells and Sprague Dawley rats were evaluated to investigate the effects of PM2.5 on cytokine expression in AML. The results revealed that PM2.5 was capable of enhancing inflammatory responses in AML cells, and increasing IL-2, IL-10, IL-17A and TNFα mRNA expression in AML cells to different degrees. Furthermore, PM2.5 increased IL-2 and IL-10 contents in rats following 12 weeks of exposure. These results suggested that PM2.5 may serve a role in promoting the occurrence and progression of leukemia by affecting cytokine expression, and that there may be various mechanisms active in different AML subtypes.