Publications by authors named "Jianyong Li"

342 Publications

Co-occurrence of and mutations defines an adverse prognostic core-binding factor acute myeloid leukemia.

Leuk Lymphoma 2021 May 24:1-10. Epub 2021 May 24.

Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.

Molecular abnormalities are frequent in core-binding factor (CBF) AMLs, but their prognostic relevance is controversial. Sixty-two patients were retrospectively analyzed and 47 harbored at least one gene mutation with a next-generation-sequencing assay. The most common molecular mutation was mutation (30.6%), followed by (24.2%) and (14.5%) mutations, which was associated with a higher number of bone marrow blasts ( = .049) and older age ( = .027). The survival analysis showed mutation adversely affected the overall survival (OS) ( = .046). mutation was associated with inferior OS ( = .016) and RFS ( = .039). Eight patients carried co-mutations of and and had worse OS ( = .012) and RFS ( = .034). The multivariate analysis showed age ≥60 years and additional chromosomal abnormalities were significant adverse factors for OS. Thus, co-mutations of and were significantly associated with a poor prognosis and should be taken into account when assessing for prognostic stratification in patients with CBF-AML.
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http://dx.doi.org/10.1080/10428194.2021.1919660DOI Listing
May 2021

A nano-integrated microfluidic biochip for enzyme-based point-of-care detection of creatinine.

Chem Commun (Camb) 2021 May;57(38):4726-4729

Division of Physical Biology, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, P. R. China. and University of Chinese Academy of Sciences, Beijing 100049, P. R. China and Institute of Molecular Medicine, Renji Hospital, School of Medicine and School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Jiao Tong University, Shanghai 200127, P. R. China.

A nano-integrated portable enzymatic microfluidic electrochemical biochip was developed for single-step point-of-care testing of creatinine. The biochip could automatically eliminate a lot of interferences from practical biological samples and enzymatic intermediate products. Gold nanostructure- and carbon nanotube-based screen-printed carbon electrodes were integrated into microfluidic structures to improve the detection performance for creatinine. The microfluidic electrochemical biochip holds promise to become a practical device for medical diagnosis, especially POCT.
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http://dx.doi.org/10.1039/d1cc00825kDOI Listing
May 2021

Multichannel Immunosensor Platform for the Rapid Detection of SARS-CoV-2 and Influenza A(H1N1) Virus.

ACS Appl Mater Interfaces 2021 May 9;13(19):22262-22270. Epub 2021 May 9.

Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, P. R. China.

The coronavirus disease 2019 (COVID-19) can present a similar syndrome to an influenza infection, which may complicate diagnosis and clinical management of these two important respiratory infectious diseases, especially during the peak season of influenza. A rapid and convenient point-of-care test (POCT) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus is of great importance for prompt and efficient control of these respiratory epidemics. Herein, a multichannel electrochemical immunoassay (MEIA) platform was developed based on a disposable screen-printed carbon electrode (SPCE) array for the on-site detection of SARS-CoV-2 and A(H1N1). The developed MEIA was constructed with eight channels and allowed rapid detection on a single array. On the SPCE surface, monoclonal antibodies against influenza A(H1N1) hemagglutinin (HA) protein or SARS-CoV-2 spike protein were coated to capture the target antigens, which then interacted with a horseradish peroxidase (HRP)-labeled detection antibody to form an immuno-sandwich complex. The results showed that the MEIA exhibited a broader linear range than ELISA and comparable sensitivity for A(H1N1) HA and SARS-CoV-2 spike protein. The detection results on 79 clinical samples for A(H1N1) suggested that the proposed MEIA platform showed comparable results with ELISA in sensitivity (with a positive rate of 100% for positive samples) but higher specificity, with a false-positive rate of 5.4% for negative samples versus that of 40.5% with ELISA. Thus, it offers great potential for the on-the-spot differential diagnosis of infected patients, which would significantly benefit the efficient control and prevent the spread of these infectious diseases in communities or resource-limited regions in the future.
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http://dx.doi.org/10.1021/acsami.1c05770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130191PMC
May 2021

Establishment of a Novel Temozolomide Resistant Subline of Glioblastoma Multiforme Cells and Comparative Transcriptome Analysis With Parental Cells.

Anticancer Res 2021 May;41(5):2333-2347

Division of Plastic and Reconstructive Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.;

Background/aim: Glioblastoma multiforme (GBM) is a lethal disease with a high rate of chemoresistance to temozolomide (TMZ). The aim of the study was to establish a TMZ-resistant subline from the GBM-8401 cell line to determine the mechanisms of resistance and identify novel effective therapeutics for TMZ-resistant GBM.

Materials And Methods: Comparative transcriptome analysis of GBM-8401/TMZR cells and the parental line was performed using Ion Torrent sequencing. Differentially expressed genes (DEGs) between the GBM-8401/TMZR and GBM-8401 cell lines were analyzed.

Results: Transcriptomic profiling of GBM-8401/TMZR cells revealed DEGs involved in the retinoblastoma (RB) signaling, DNA damage response (DDR) pathway, and DNA repair mechanisms.

Conclusion: In vitro and in vivo cell-based GBM models should be used in further biomedical studies to investigate the underlying mechanisms of TMZ-resistant GBM.
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http://dx.doi.org/10.21873/anticanres.15008DOI Listing
May 2021

Anti-tumor activity of a novel proteasome inhibitor D395 against multiple myeloma and its lower cardiotoxicity compared with carfilzomib.

Cell Death Dis 2021 Apr 30;12(5):429. Epub 2021 Apr 30.

Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, 210029, China.

Carfilzomib, a second-generation proteasome inhibitor, has significantly improved the survival rate of multiple myeloma (MM) patients, but its clinical application is still restricted by drug resistance and cardiotoxicity. Here, we identified a novel proteasome inhibitor, D395, and assessed its efficacy in treating MM as well as its cardiotoxicity at the preclinical level. The activities of purified and intracellular proteasomes were measured to determine the effect of D395 on the proteasome. CCK-8 and flow cytometry experiments were designed to evaluate the effects of D395 on cell growth and apoptosis. The effects of D395 and carfilzomib on serum enzyme activity, echocardiography features, cardiomyocyte morphology, and hERG channels were also compared. In our study, D395 was highly cytotoxic to MM cell lines and primary MM cells but not normal cells, and it was well tolerated in vivo. Similar to carfilzomib, D395 inhibited osteoclast differentiation in a dose-dependent manner. In particular, D395 exhibited lower cardiotoxicity than carfilzomib in all experiments. In conclusion, D395 is a novel irreversible proteasome inhibitor that has remarkable anti-MM activity and mild cardiotoxicity in vitro and in vivo.
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http://dx.doi.org/10.1038/s41419-021-03701-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087809PMC
April 2021

Conventional Treatments Cannot Improve Outcomes of Early-Stage Primary Breast Marginal Zone Lymphoma.

Front Oncol 2020 13;10:609512. Epub 2021 Apr 13.

Department of Hematology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, China.

Introduction: Primary breast marginal zone lymphoma (PBMZL) is a rare occurrence and less is known about its characteristics, treatments, and outcomes.

Methods: We retrospectively reviewed 370 cases of early-stage PBMZL from the Surveillance, Epidemiology, and End Results database. Statistical analyses were performed to describe clinical features, determine prognostic factors, and compare different therapeutic strategies.

Results: At a median follow-up of 68.5 months, the 5-year overall survival (OS) and disease-specific survival (DSS) rate were 81.2 and 95.4%, respectively. We divided the cohort into four treatment groups and compared their characteristics and survival: radiotherapy (RT) ± surgery (Sx) (n = 142, 38.4%), Sx alone (n = 71, 19.2%), any chemotherapy (CT) (n = 63, 17.0%), and none of the above (n = 94, 25.4%). Age of onset and laterality of lesions tended to relate to the choice of different treatments. Multivariate Cox analysis showed that advanced age (>60 years), concomitant tumor, and any CT ( RT ± Sx) predicted poorer OS, while for DSS, there was no meaningful indicator (P > 0.05). Patients aged >60 years or treated with any CT seemed to have shorter DSS, but the difference only approached statistical significance. Then we applied a propensity score-matched analysis to demonstrate that neither RT- nor Sx-containing therapy could bring a better OS or DSS. The competing risk model suggested that CT was the only contributor to higher PBMZL-specific mortality.

Conclusion: Our results show an indolent behavior of early-stage PBMZL with long-term survival. Conventional oncological treatments fail to bring survival benefits; especially CT is detrimental to survival, suggesting that observation may be advisable in the management of early-stage PBMZL, and further research on novel targeted agents is warranted for patients in need.
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http://dx.doi.org/10.3389/fonc.2020.609512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076799PMC
April 2021

A Carbon-Based Antifouling Nano-Biosensing Interface for Label-Free POCT of HbA1c.

Biosensors (Basel) 2021 Apr 12;11(4). Epub 2021 Apr 12.

Division of Physical Biology, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China.

Electrochemical biosensing relies on electron transport on electrode surfaces. However, electrode inactivation and biofouling caused by a complex biological sample severely decrease the efficiency of electron transfer and the specificity of biosensing. Here, we designed a three-dimensional antifouling nano-biosensing interface to improve the efficiency of electron transfer by a layer of bovine serum albumin (BSA) and multi-walled carbon nanotubes (MWCNTs) cross-linked with glutaraldehyde (GA). The electrochemical properties of the BSA/MWCNTs/GA layer were investigated using both cyclic voltammetry and electrochemical impedance to demonstrate its high-efficiency antifouling nano-biosensing interface. The BSA/MWCNTs/GA layer kept 92% of the original signal in 1% BSA and 88% of that in unprocessed human serum after a 1-month exposure, respectively. Importantly, we functionalized the BSA/MWCNTs/GA layer with HbA1c antibody (anti-HbA1c) and 3-aminophenylboronic acid (APBA) for sensitive detection of glycated hemoglobin A (HbA1c). The label-free direct electrocatalytic oxidation of HbA1c was investigated by cyclic voltammetry (CV). The linear dynamic range of 2 to 15% of blood glycated hemoglobin A (HbA1c) in non-glycated hemoglobin (HbAo) was determined. The detection limit was 0.4%. This high degree of differentiation would facilitate a label-free POCT detection of HbA1c.
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http://dx.doi.org/10.3390/bios11040118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069255PMC
April 2021

Optimal Bounded Ellipsoid Identification With Deterministic and Bounded Learning Gains: Design and Application to Euler-Lagrange Systems.

IEEE Trans Cybern 2021 Apr 19;PP. Epub 2021 Apr 19.

This article proposes an effective optimal bounded ellipsoid (OBE) identification algorithm for neural networks to reconstruct the dynamics of the uncertain Euler-Lagrange systems. To address the problem of unbounded growth or vanishing of the learning gain matrix in classical OBE algorithms, we propose a modified OBE algorithm to ensure that the learning gain matrix has deterministic upper and lower bounds (i.e., the bounds are independent of the unpredictable excitation levels in different regressor channels and, therefore, are capable of being predetermined a priori). Such properties are generally unavailable in the existing OBE algorithms. The upper bound prevents blow-up in cases of insufficient excitations, and the lower bound ensures good identification performance for time-varying parameters. Based on the proposed OBE identification algorithm, we developed a closed-loop controller for the Euler-Lagrange system and proved the practical asymptotic stability of the closed-loop system via the Lyapunov stability theory. Furthermore, we showed that inertial matrix inversion and noisy acceleration signals are not required in the controller. Comparative studies confirmed the validity of the proposed approach.
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http://dx.doi.org/10.1109/TCYB.2021.3066639DOI Listing
April 2021

Clinical characteristics and outcomes in HIV-associated diffuse large B-cell lymphoma in China: A retrospective single-center study.

J Cancer 2021 15;12(10):2903-2911. Epub 2021 Mar 15.

Department of Infectious Diseases, Yunnan Provincial Infectious Diseases Hospital/Yunnan AIDS Care Center, Kunming, 650000, China.

Human immunodeficiency virus (HIV) infection is associated with an increased risk of aggressive lymphoma, especially diffuse large B cell lymphoma (DLBCL). There are few data regarding HIV-associated DLBCL in China. Therefore, we analyzed the characteristics and outcomes of patients with HIV-associated DLBCL from our center. We retrospectively studied HIV-infected patients with DLBCL from 2011 to 2019. Data on HIV infection and lymphoma characteristics, treatments and outcomes were retrieved and analyzed. In 78 patients with HIV-associated DLBCL, most had poor performance status (PS) (74%), elevated lactate dehydrogenase (LDH) levels (95%), B symptoms (74%), advanced Ann Arbor stages (81%), bulky diseases (64%) and extranodal involvement (70%) at diagnosis. The median CD4 T cell count was 162/µl, and 26 patients were already on combination antiretroviral therapy (cART) treatment at diagnosis of DLBCL. Elevated whole blood EBV DNA copy number was detected in 38 patients (66%, 38/58). Of the 45 patients evaluated at the end of treatment, 26 (58%) achieved CR, 6 (13%) achieved PR and 6 (13%) experienced progressive disease. The 2-year progression-free survival (PFS) and overall survival (OS) rates were 56.4% and 62.7%, respectively. Factors associated with decreased PFS and OS in univariate analysis were unfavorable PS and high international prognostic index. Elevated EBV DNA copy number was inclined to be associated with worse outcome. We did not observe a significant difference in survival between R-EPOCH and R-CHOP regimens. In our population, patients with HIV-associated DLBCL presented with aggressive characteristics and exhibited poor survival outcomes, even in the modern cART era.
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http://dx.doi.org/10.7150/jca.51027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040883PMC
March 2021

Clinical risk score for predicting invasive fungal disease after allogeneic hematopoietic stem cell transplantation: Analysis of the China Assessment of Antifungal Therapy in Hematological Diseases (CAESAR) study.

Transpl Infect Dis 2021 Apr 7:e13611. Epub 2021 Apr 7.

Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University Institute of Hematology, Peking University, People's Hospital, Beijing, People's Republic of China.

Background And Objective: Invasive fungal disease (IFD) is associated with a high mortality for patients with hematological malignancies undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study aimed not only to develop a proven/probable IFD risk-scoring model but to identify high-risk populations that would benefit from anti-fungal prophylaxis.

Methods: Data from the China Assessment of Antifungal Therapy in Hematological Diseases (CAESAR) study were retrieved, and all patients (n = 1053) undergoing allo-HSCT were randomly divided into the training set (n = 685) for model development and the validation set (n = 368) for model verification. A weighted risk score for proven or probable IFD was established through multivariate logistic regression analysis.

Results: The study population had a mean age of 28.95 years and the majority underwent myeloablative transplantation in complete remission 1 (53.4%). Five risk factors of IFD were identified, namely neutropenia lasting longer than 14 days, corticosteroid use, diabetes, haploidentical donor, and unrelated donor. Based on the risk score for IFD, the patients were categorized into three groups: low risk (score 0-4, 1.5%-4.0%), intermediate risk (score 5-8, 9.8%), and high risk (score>8, 24.7%-14.0%). Anti-fungal prophylaxis may provide benefits for patients with intermediate (8.5% vs. 18.5%, P = .0085) or high risk (19.4% vs. 30.8%, P = .4651) but not low risk (2.1% vs. 3.8%, P = .6136) of IFD.

Conclusion: A practical weighted risk score for IFD in patients receiving allo-HSCT was established, which can aid decision-making regarding the administration of anti-fungal prophylaxis.
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http://dx.doi.org/10.1111/tid.13611DOI Listing
April 2021

CircRNA May Not Be "Circular".

Front Genet 2021 19;12:633750. Epub 2021 Feb 19.

Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.

Circular RNA (circRNA) is a novel regulatory non-coding RNA and participates in diverse physiological and pathological processes. However, the structures and molecular mechanisms of circRNAs remain unclear. In this study, taking advantage of openly databases and bioinformatics analysis, we observed lots of internal complementary base-pairing sequences (ICBPS) existed in plenty of circRNAs, especially in extremely long circRNAs (el-circRNAs, > 5,000 nt). The result indicated that circRNA may not be a simple circular structure. In addition, we put forward the hypothesis of "open-close effect" in the transition for specific circRNA from normal state to morbid state. Taken together, our results not only expand the knowledge of circRNAs, but also highlight the potential molecular mechanism of circRNAs.
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http://dx.doi.org/10.3389/fgene.2021.633750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934283PMC
February 2021

Targeting Bruton tyrosine kinase using non-covalent inhibitors in B cell malignancies.

J Hematol Oncol 2021 Mar 6;14(1):40. Epub 2021 Mar 6.

Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029, China.

B cell receptor (BCR) signaling is involved in the pathogenesis of B cell malignancies. Activation of BCR signaling promotes the survival and proliferation of malignant B cells. Bruton tyrosine kinase (BTK) is a key component of BCR signaling, establishing BTK as an important therapeutic target. Several covalent BTK inhibitors have shown remarkable efficacy in the treatment of B cell malignancies, especially chronic lymphocytic leukemia. However, acquired resistance to covalent BTK inhibitors is not rare in B cell malignancies. A major mechanism for the acquired resistance is the emergence of BTK cysteine 481 (C481)  mutations, which disrupt the binding of covalent BTK inhibitors. Additionally, adverse events due to the off-target inhibition of kinases other than BTK by covalent inhibitors are common. Alternative therapeutic options are needed if acquired resistance or intolerable adverse events occur. Non-covalent BTK inhibitors do not bind to C481, therefore providing a potentially effective option to patients with B cell malignancies, including those who have developed resistance to covalent BTK inhibitors. Preliminary clinical studies have suggested that non-covalent BTK inhibitors are effective and well-tolerated. In this review, we discussed the rationale for the use of non-covalent BTK inhibitors and the preclinical and clinical studies of non-covalent BTK inhibitors in B cell malignancies.
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http://dx.doi.org/10.1186/s13045-021-01049-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937220PMC
March 2021

Impact of pre-transplantation minimal residual disease (MRD) on the outcome of Allogeneic hematopoietic stem cell transplantation for acute leukemia.

Hematology 2021 Dec;26(1):295-300

Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, People's Republic of China.

Objective: To investigate the impact of minimal residual disease (MRD) before allogeneic hematopoietic stem cell transplantation (allo-HSCT) on the outcome of acute leukemia.

Methods: Data from 114 patients who were diagnosed with acute leukemia (AL) and underwent allo-HSCT between Jan 2013 and Dec 2019 were collected and analyzed. The patients were attributed into MRD positive (MRD+) group and MRD negative (MRD-) group.

Results: Among the 114 acute leukemia patients, there were 32 MRD+ patients before transplantation, and 82 MRD- patients. No significant difference was found between the MRD+ group and the MRD- group in the incidence of acute graft-versus-host disease (aGvHD)  = 0.09). Compared with the MRD+ group, the MRD- group had a higher incidence of chronic graft-versus-host disease (cGvHD) ( = 0.008). There is no significance in relapse between the two groups ( = 0.084), while the incidence of relapse was seemingly higher in the MRD+ group: 36.9% Vs 19.7% . We attributed to the lack of sample size and NRM in MRD+ group was remarkably higher. The MRD+ group had significantly worse one-year overall survival (OS) ( ,  = 0.003) and one-year progression-free survival (PFS) (,  = 0.009). In the multivariate analysis, MRD+ was an independent prognostic factor for OS (HR = 1.898; 95%CI 1.042-3.457;  = 0.036).

Conclusion: Pre-transplantation MRD positive status is a risk factor for survival and prognosis after HSCT. Upon this, emphasis should be put on (1) screening more efficient chemo regimen with targeted agents, to help patients reach and keep MRD- status before transplantation; (2) designing better management with different GvHD prophylaxis treatment, timely disease monitoring and preemptive intervention on relapse.
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http://dx.doi.org/10.1080/16078454.2021.1889162DOI Listing
December 2021

Eltrombopag restores erythropoiesis in refractory adult acquired pure red cell aplasia.

Int J Hematol 2021 Jul 21;114(1):124-128. Epub 2021 Feb 21.

Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029, China.

Acquired pure red cell aplasia is a rare condition characterized by normocytic normochromic anemia with severe reticulocytopenia. In refractory acquired pure red cell aplasia, the low response rate of immunosuppressive therapy also constitutes a challenge. We herein report the case of a 58-year-old male with refractory acquired pure red cell aplasia that was successfully treated by eltrombopag at a dose of 75 mg/day. After application of eltrombopag, the patient achieved complete remission and tolerated the treatment very well, with only mild bilirubin elevation. These preliminary findings showed that eltrombopag may be effective and well tolerated in adult patients with refractory acquired pure red cell aplasia.
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http://dx.doi.org/10.1007/s12185-021-03100-2DOI Listing
July 2021

Etanercept as a new therapeutic option for cytokine release syndrome following chimeric antigen receptor T cell therapy.

Exp Hematol Oncol 2021 Feb 19;10(1):16. Epub 2021 Feb 19.

Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, 210029, China.

Cytokine release syndrome (CRS) is the most common toxicity induced by chimeric antigen receptor (CAR) T cell therapy. At present, anti-IL-6 agents including tocilizumab and siltuximab have been applied in the treatment of CRS. However, tocilizumab and siltuximab are expensive and some patients fail to respond to anti-IL-6 therapy, which urges the need for new drugs. In clinical practice, we found some patients with multiple myeloma developed markedly increased levels of tumor necrosis factor (TNF)- α during the CRS period after anti-BCMA CAR T cell infusion. Here we present the successful use of TNF-α inhibitor (etanercept) to cure CRS in three patients. The introduction of etanercept did not alter patients' response to CAR T cell therapy and no adverse event was observed directly related to the administration of etanercept. Furthermore, in vitro experiments confirmed that etanercept did not affect the proliferation and effector function of CAR T cells. Our results indicate that etanercept could be considered as a treatment option for CRS in patients with significantly elevated TNF-α levels.
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http://dx.doi.org/10.1186/s40164-021-00209-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893957PMC
February 2021

Development of a factorial water policy simulation approach from production and consumption perspectives.

Water Res 2021 Apr 2;193:116892. Epub 2021 Feb 2.

Institute of Hydroecology, MWR & CAS, Wuhan 430079, China.

Industrial water-management policies are prevalent around the world to alleviate global water scarcity. It is indispensable to simulate the effects of different water-management policies on various industries in the socioeconomic system to explore the most effective water consumption reduction pathways. In this study, a factorial water policy simulation model is developed to investigate the composite effects of multidimensional interactive water-management policies from both production and consumption perspectives. Structural path analysis and factorial analysis are introduced simultaneously to help support policy formulation according to local reality and further examine the impacts of the main factors and their interactions respectively. The developed model has been applied to the Municipality of Chongqing, China to demonstrate the applicability and superiority of the factorial water policy simulation model. It was found that the impacts of industrial technology upgrade policies on different industries vary significantly. The consumption-orientation policies have a similar performance on direct water consumption reductions. In the Municipality of Chongqing, industrial technology upgrade policies applied to the primary industry will generate larger reductions of water consumption (i.e., 10.1 units reduction of total water consumption) in the system since the primary industry can influence other industries through intermediate utilization. The contribution of interactions for the reductions of direct water consumption was 10.38%, where policies implemented on the primary industry and construction industry have the most significant interaction. In addition, the industry of production and supply of water is closely related to most of the industries since its technical improved can reduce the indirect water consumption of the majority of industries. The results provide bases for supporting the Municipality's efforts in formulating desired water-management policies.
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http://dx.doi.org/10.1016/j.watres.2021.116892DOI Listing
April 2021

[Improved Research of Adjustable External Fixation Device for Lower Limbs Based on Semiconductor Refrigeration Sheet].

Zhongguo Yi Liao Qi Xie Za Zhi 2020 Dec;44(6):499-502

Jilin Central Hospital, Jilin, 132011.

A kind of adjustable external fixation device for lower extremity is designed. The circuit is mainly composed of TEC1-00703 semiconductor refrigeration chip, HZC-30A pressure sensor, STC89C52RC single chip microcomputer and other electrical components. It can realize the timing intelligent temperature control and meet the local fixed-point refrigeration. The design of adjustable structure and the application of intelligent air cushion can satisfy the full fixation of lower limbs of different individuals. Its operation does not need much medical knowledge. It can solve the problem of emergency transportation and follow-up treatment of lower limb injury in ice and snow sports. It has a good application prospect and universality.
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http://dx.doi.org/10.3969/j.issn.1671-7104.2020.06.007DOI Listing
December 2020

A Carbon-Based DNA Framework Nano-Bio Interface for Biosensing with High Sensitivity and a High Signal-to-Noise Ratio.

ACS Sens 2020 12 23;5(12):3979-3987. Epub 2020 Nov 23.

Shanghai Synchrotron Radiation Facility, Zhangjiang Lab, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210, China.

Biosensing interface based on screen-printed carbon electrodes (SPCE) has been widely used for electrochemical biosensors in the field of medical diagnostics, food safety, and environmental monitoring. Nevertheless, SPCE always has a rough surface, which is easy to result in the disorder of nucleic acid capture probes, the nonspecific adsorption of signaling probes, the steric hindrance of target binding, and decrease in the signal-to-noise ratio and sensitivity of biosensors. So far, it still remains extremely challenging to develop high-efficiency carbon-based biosensing interfaces, especially for DNA probe-based assembly and functionalization. In this paper, we first used a specific DNA framework, DNA tetrahedron to solve the defects of the carbon interface, improving the biosensing ability of SPCE. With covalent coupling, the DNA tetrahedron could be immobilized on the carbon surface. Biosensing probe sequences extending from the DNA tetrahedron can be changed for different target molecules. We demonstrated that the improved SPCE could be applied for the detection of a variety of bioactive molecules. Typically, we designed gap hybridization, aptamer "sandwich" and aptamer competition reduction strategy for the detection of miRNA-141, thrombin, and ATP, respectively. High signal-to-noise ratio, sensitivity, and specificity were obtained for all of these kinds. Especially, the DNA tetrahedron-modified SPCE can work well with serum samples. The carbon-based DNA framework nano-bio interface would expand the use of SPCE and make electrochemical biosensors more available and valuable in clinical diagnosis.
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http://dx.doi.org/10.1021/acssensors.0c01745DOI Listing
December 2020

Survival trends and prognostic factors in patients with solitary plasmacytoma of bone: A population-based study.

Cancer Med 2021 01 3;10(2):462-470. Epub 2020 Nov 3.

Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.

Solitary plasmacytoma of bone (SPB) is a single, isolated plasmacytoma originated from the bone. The survival trends of patients with SPB in recent years remain unknown. And the prognostic system of SPB may also need to be refined. The 18 Surveillance, Epidemiology, and End Results (SEER) databases of the National Cancer Institute in the United States were used to extract data for this study. The third edition of the International Classification of Disease for Oncology (ICD-O-3) code 9731 was used to identify cases of SPB. For each case, factors including age at the time of diagnosis, sex, race, marital status, insurance status, primary sites of tumors, and the use of surgery were collected. The outcomes of patients with SPB were compared between two groups. And the prognostic impacts of baseline characteristics and use of surgery was studied. A total of 4103 (from 1976 to 2016) cases of SPB were identified. The median age was 65 years old. Patients in time period-2 (2008-2016) show better survival as compared to those in time period-1(1976-2007) (median overall survival: 88 months vs. 73 months, p = 0.0332). Age ≤ 65 years and being male were associated with better outcomes. The widowed individuals had significantly inferior survival and myeloma-specific survival than the single, married, or divorced individuals (p values all <0.0001). Patients with lesions in bones of skull and face and associated joints had longer survival as compared with those with bone lesions in other sites (median overall survival: 107 months vs. 79 months, p = 0.0694). The use of surgery was significantly associated with improved survival (median survival: surgery performed 98 months vs. not performed 73 months, hazards ratio [HR]: 0.7623, 95% CI: 0.7009-0.8472; p < 0.0001) and myeloma-specific survival (median myeloma-specific survival: surgery 160.0 months vs. no surgery 143.0 months, HR: 0.8469, 95% CI: 0.7493-0.9572; p = 0.0078). Multivariable analysis revealed that surgery, marital status, and age were independent prognostic factors for overall survival in patients with SPB. The improvement in the survival of patients with SPB has been observed in recent years. And several potential prognostic factors were identified. Future prospective studies are warranted to explore the roles of novel agents, surgery, and systemic chemotherapy in the treatment of SPB.
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http://dx.doi.org/10.1002/cam4.3533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877371PMC
January 2021

SHC014748M, a novel selective inhi-bitor of PI3Kδ, demonstrates promising preclinical antitumor activity in B cell lymphomas and chronic lymphocytic leukemia.

Neoplasia 2020 12 23;22(12):714-724. Epub 2020 Oct 23.

Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, China. Electronic address:

PI3Kδ (phosphatidylinositol 3-kinase-δ), one of the class I PI3Ks, is found expressed primarily in leukocytes and plays an essential role in B-cell development and function. This provides a rationale for the development of small molecule inhibitors that selectively target p110δ for patients with indolent non-Hodgkin lymphomas. Here in this paper, we comprehensively evaluated the in vitro and in vivo antitumor activity of SHC014748M, an oral selective inhibitor of PI3Kδ under Phase I clinical evaluation. Biochemical and cell-based assays were used to measure compound potency and selectivity in lymphoma cell lines as well as primary chronic lymphocytic leukemia (CLL) cells. Scid mice were subcutaneously inoculated with the SU-DHL-6 cell line. SHC014748M was more selective for PI3Kδ inhibition relative to other class I PI3K enzymes and showed in vitro activity in most of 23 B lymphoma cell lines and primary CLL cells. SHC014748M also inhibited phosphorylation of AKT, targets downstream of PI3Kδ, in both lymphoma cells and primary CLL cells. In vivo study revealed that SHC014748M significantly reduced lymphoma cell growth in the treatment group compared with control mice. CCL4, CCL17, CCL22 and CXCL13 in patient serum decreased sharply after SHC014748M treatment. According to the results, SHC014748M appeared to be a novel promising compound in the treatment of B cell lymphomas and CLL.
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http://dx.doi.org/10.1016/j.neo.2020.10.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586065PMC
December 2020

[Research progress of lymphoma associated hemophagocytic syndrome].

Zhonghua Xue Ye Xue Za Zhi 2020 09;41(9):788-792

Department of Hematology, Key Laboratory of Hematology of Nanjing Medical University, Jiangsu Province Hospital/The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China; Pukou CLL Center, Pukou Division of Jiangsu Province Hospital, Nanjing 211800, China.

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http://dx.doi.org/10.3760/cma.j.issn.0253-2727.2020.09.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595859PMC
September 2020

Clinical significance of CD200 expression in newly diagnosed multiple myeloma patients and dynamic changing during treatment.

Leuk Lymphoma 2021 03 27;62(3):709-715. Epub 2020 Oct 27.

Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.

The aim of our study was to determine the impact of CD200 expression in newly diagnosed myltiple myeloma (MM) patients. CD200 patients had significantly shorter median overall survival time (OS) than CD200 patients (41.0 months not reached,  = .009). The ratio of CD4 to CD8 T cells was lower in CD200 patients and this reduction was significantly related to the increase of CD8 T cells ( = .021). Moreover, we analyzed dynamic changes of CD200 expression in 47 CD200 patients during treatment. Thirty-eight (80.9%) patients switched to CD200 during treatment. Those patients had a favorable survival compared with the others (median OS, 65.0 32.0 months,  < .001; median PFS, 29.0 11.5 months,  = .027). We concluded that CD200 expression is an independent marker for MM prognostic estimation during treatment.
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http://dx.doi.org/10.1080/10428194.2020.1839653DOI Listing
March 2021

Flumatinib versus Imatinib for Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia: A Phase III, Randomized, Open-label, Multi-center FESTnd Study.

Clin Cancer Res 2021 Jan 14;27(1):70-77. Epub 2020 Sep 14.

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology, Chinese Academy of Medical Sciences, Tianjin, P.R. China.

Purpose: Flumatinib has been shown to be a more potent inhibitor of BCR-ABL1 tyrosine kinase than imatinib. We evaluated the efficacy and safety of flumatinib versus imatinib, for first-line treatment of chronic phase Philadelphia chromosome-positive chronic myeloid leukemia (CML-CP).

Patients And Methods: In this study, 394 patients were randomized 1:1 to flumatinib 600 mg once daily ( = 196) or imatinib 400 mg once daily ( = 198) groups.

Results: The rate of major molecular response (MMR) at 6 months (primary endpoint) was significantly higher with flumatinib than with imatinib (33.7% vs. 18.3%; = 0.0006), as was the rate of MMR at 12 months (52.6% vs. 39.6%; = 0.0102). At 3 months, the rate of early molecular response (EMR) was significantly higher in patients receiving flumatinib than in those receiving imatinib (82.1% vs. 53.3%; < 0.0001). Compared with patients receiving imatinib, more patients receiving flumatinib achieved molecular remission 4 (MR4) at 6, 9, and 12 months (8.7% vs. 3.6%, = 0.0358; 16.8% vs. 5.1%, = 0.0002; and 23.0% vs. 11.7%, = 0.0034, respectively). No patients had progression to accelerated phase or blast crisis in the flumatinib arm versus 4 patients in the imatinib arm by 12 months. Adverse events of edema, pain in extremities, rash, neutropenia, anemia, and hypophosphatemia were more frequent in imatinib arm, whereas diarrhea and alanine transaminase elevation were more frequent in flumatinib arm.

Conclusions: Patients receiving flumatinib achieved significantly higher rates of responses, and faster and deeper responses compared with those receiving imatinib, indicating that flumatinib can be an effective first-line treatment for CML-CP. This trial was registered at www.clinicaltrials.gov as NCT02204644..
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http://dx.doi.org/10.1158/1078-0432.CCR-20-1600DOI Listing
January 2021

[Detection of del(17p13) among newly diagnosed multiple myeloma cases using cytoplasmic light chain immunofluorescence combined with FISH and its clinical significance].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2020 Oct;37(10):1087-1091

Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, Jiangsu 210029, China.

Objective: To detect chromosomal aberrations by using cytoplasmic light chain immunofluorescence with fluorescence in situ hybridization (cIg-FISH), and to explore the correlation of del(17p13) with clinical characteristics, drug response and prognosis among patients with newly diagnosed multiple myeloma (NDMM).

Methods: Clinical data of 198 cases of NDMM was collected. cIg-FISH and a specific probe (TP53) were used to detect karyotypic abnormalities in bone marrow samples derived from the patients. Correlation between karyotypic abnormalities and clinical data was analyzed.

Results: Nineteen of the 198 patients (9.6%) were found to have a karyotype involving del(17p13). The overall survival (OS) and progression-free survival (PFS) for patients with or without del(17p13) was significantly different (P<0.01). No significant difference was found in OS and PFS between patients carrying a del(17p13) on bortezomib and non-bortezomib regimen (OS: P = 0.873; PFS: P = 0.610).

Conclusion: cIg-FISH is a simple and convenient method for the detection of karyotypic anomalies in multiple myeloma. Del(17p13) is an indicator for poor prognosis for multiple myeloma patients. Bortezomib cannot improve the survival disadvantage of del(17p13).
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http://dx.doi.org/10.3760/cma.j.cn511374-20190604-00279DOI Listing
October 2020

A Novel Predictive Model for Idiopathic Multicentric Castleman Disease: The International Castleman Disease Consortium Study.

Oncologist 2020 11 18;25(11):963-973. Epub 2020 Sep 18.

Division of Hematopathology and Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA.

Background: Patients with multicentric Castleman disease (MCD) who are negative for human immunodeficiency virus and human herpesvirus 8 are considered to have idiopathic MCD (iMCD). The clinical presentation of iMCD varies from mild constitutional symptoms to life-threatening symptoms or death. The treatment strategy varies from "watchful waiting" to high-dose chemotherapy. This diverse clinical presentation calls for a classification stratification system that takes into account the severity of the disease.

Subjects, Materials, And Methods: We analyzed the clinical, laboratory, and pathologic abnormalities and treatment outcomes of 176 patients with iMCD (median follow-up duration 12 years) from the U.S. and China to better understand the characteristics and prognostic factors of this disease. This discovery set of iMCD results was confirmed from the validation set composed of additional 197 patients with iMCD organized from The International Castleman Disease Consortium.

Results: Using these data, we proposed and validated the iMCD international prognostic index (iMCD-IPI), which includes parameters related to patient characteristics (age > 40 years), histopathologic features (plasma cell variant), and inflammatory consequences of iMCD (hepatomegaly and/or splenomegaly, hemoglobin <80 g/L, and pleural effusion). These five factors stratified patients according to their performance status and extent of organ dysfunction into three broad categories: low risk, intermediate risk, and high risk. The iMCD-IPI score accurately predicted outcomes in the discovery study cohort, and the results were confirmed on the validation study cohort.

Conclusion: This study represents the largest series of studies on patients with iMCD in the field and proposed a novel risk-stratification model for iMCD-IPI that could be used to guide risk-stratified treatment strategies in patients with iMCD.

Implications For Practice: Patients with idiopathic multicentric Castleman disease (iMCD) can benefit from care based on clinical symptoms and disease severity. This study in 176 patients with iMCD constructed an iMCD-IPI score based on five clinical factors, including age >40 years, plasmacytic variant subtype, hepatomegaly and/or splenomegaly, hemoglobin <80 g/L, and pleural effusion, and stratified patients into three risk categories: low risk, intermediate risk, and high risk. The predictive value was validated in an independent set of 197 patients with iMCD from The International Castleman Disease Consortium. The proposed novel model is valuable for predicting clinical outcome and selecting optimal therapies using clinical parameters.
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http://dx.doi.org/10.1634/theoncologist.2019-0986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648372PMC
November 2020

IL-21 Stimulates the expression and activation of cell cycle regulators and promotes cell proliferation in EBV-positive diffuse large B cell lymphoma.

Sci Rep 2020 07 23;10(1):12326. Epub 2020 Jul 23.

Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, 210009, China.

The clinical features of EBV-positive diffuse large B cell lymphoma (DLBCL) indicate a poorer prognosis than EBV-negative DLBCL. Currently, there is no efficacious drug for EBV-positive DLBCL. The cytokine interleukin-21 (IL-21) has been reported to be pro-apoptotic in DLBCL cell lines and is being explored as a new therapeutic strategy for this type of lymphomas. However, our previous studies showed that IL-21 stimulation of EBV-positive DLBCL cell lines leads to increased proliferation. Here, analysis of a rare clinical sample of EBV-positive DLBCL, in combination with a NOD/SCID mouse xenograft model, confirmed the effect of IL-21 on the proliferation of EBV-positive DLBCL cells. Using RNA-sequencing, we identified the pattern of differentially-expressed genes following IL-21 treatment and verified the expression of key genes at the protein level using western blotting. We found that IL-21 upregulates expression of the host MYC and AP-1 (composed of related Jun and Fos family proteins) and STAT3 phosphorylation, as well as expression of the viral LMP-1 protein. These proteins are known to promote the G1/S phase transition to accelerate cell cycle progression. Furthermore, in NOD/SCID mouse xenograft model experiments, we found that IL-21 treatment increases glucose uptake and angiogenesis in EBV-positive DLBCL tumours. Although more samples are needed to validate these observations, our study reconfirms the adverse effects of IL-21 on EBV-positive DLBCL, which has implications for the drug development of DLBCL.
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http://dx.doi.org/10.1038/s41598-020-69227-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378064PMC
July 2020

Fabrication of Microspheres from High-Viscosity Bioink Using a Novel Microfluidic-Based 3D Bioprinting Nozzle.

Micromachines (Basel) 2020 Jul 14;11(7). Epub 2020 Jul 14.

Advanced Medical Research Institute, Shandong University, Jinan 250012, China.

Three-dimensional (3D) bioprinting is a novel technology utilizing biocompatible materials, cells, drugs, etc. as basic microcomponents to form 3D artificial structures and is believed as a promising method for regenerative medicine. Droplet-based bioprinting can precisely generate microspheres and manipulate them into organized structures with high fidelity. Biocompatible hydrogels are usually used as bioinks in 3D bioprinting, however, the viscosity of the bioink could be increased due to the additives such as cells, drugs, nutrient factors and other functional polymers in some particular applications, making it difficult to form monodispersed microspheres from high-viscosity bioink at the orifice of the nozzle. In this work, we reported a novel microfluidic-based printing nozzle to prepare monodispersed microspheres from high-viscosity bioink using the phase-inversion method. Different flowing conditions can be achieved by changing the flow rates of the fluids to form monodispersed solid and hollow microspheres using the same nozzle. The diameter of the microspheres can be tuned by changing the flow rate ratio and the size distribution of the microspheres is narrow. The prepared calcium alginate microspheres could also act as micro-carriers in drug delivery.
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http://dx.doi.org/10.3390/mi11070681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408603PMC
July 2020