Publications by authors named "Wenjun Wu"

218 Publications

Dynamic Evolution and Spatial Convergence of the Virtual Cultivated Land Flow Intensity in China.

Int J Environ Res Public Health 2021 Jul 4;18(13). Epub 2021 Jul 4.

College of Land Management, Nanjing Agricultural University, Nanjing 210095, China.

Exploring the flow intensity of virtual cultivated land is the key to improving the ecological compensation and food security policy. This study aimed to analyze the dynamic evolution, spatial convergence, and its affecting factors of the virtual cultivated land flow intensity. The spatial convergence model was used in this study. The results showed that, during 2000-2018, the growth rate of the surplus state of virtual cultivated land at the national level is less than that of the deficit state of virtual cultivated land in China. Moreover, the number of deficit provinces of virtual cultivated land flow intensity is increasing. The absolute β-convergence characteristics of the virtual cultivated land flow intensity are significant at the national, northeast, central, and western regions. Additionally, the conditional β-convergence exists at the national and four regional levels. Meanwhile, cultivated land resource endowment, population scale, regional economic development level, and agricultural mechanization level play an important role in the convergence process of inter-regional virtual cultivated land flow intensity. However, the influence degree of different control variables on different regional virtual cultivated land flow intensity is not consistent. Therefore, policymakers should pay attention to cultivated land resources' spatial transfer mechanism when making regional cultivated land ecological compensation policies to coordinate the interesting relationship between the deficit area and surplus area of virtual cultivated land. Therefore, it is necessary to take the virtual cultivated land flow intensity as the reference index and use the combination of market guidance and government control to stimulus the stakeholders to protect cultivated land by taking different measures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijerph18137164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297327PMC
July 2021

New-Onset Severe Cytopenia After CAR-T Cell Therapy: Analysis of 76 Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia.

Front Oncol 2021 30;11:702644. Epub 2021 Jun 30.

Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Although chimeric antigen receptor T (CAR-T) cell therapy has proven to be effective in treating relapsed or refractory B-cell hematological malignancies, severe hematological toxicities remain an intractable issue. This retrospective study assessed the characteristics and risk factors of new-onset severe cytopenia following CAR-T cell infusion in 76 patients with r/r acute lymphoblastic leukemia. The rates of new-onset severe cytopenia were high, including severe neutropenia (SN) (39/56, 70%), severe anemia (SA) (35/66, 53%), and severe thrombocytopenia (ST) (31/64, 48%). Comparatively, cohorts with higher cytokine release syndrome (CRS) grades had higher incidence of severe cytopenia with prolonged duration. Multivariable analyses showed that elevated maximum (max) lg D-dimer and delayed peak time of CRS are independent risk factors for SN recovery; increased max lg IL-10 and delayed CRS recovery are risk factors for SA; high max lg ferritin is a risk factor for ST; and longer period to CRS onset or CRS recovery and higher grade of CRS are risk factors for prolonged hematological toxicities. These observations led to the conclusion that profiles of CRS, including its duration, severity and serum markers are correlated to the incidence and recovery of new-onset severe cytopenia, prompting clinical intervention for post-CAR-T severe cytopenia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.702644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278328PMC
June 2021

Different Patient Subgroup Different Maintenance, Proteasome Inhibitors or Immunomodulators Maintenance for Newly Diagnosed Multiple Myeloma: A 7-Year Single-Center Date in China.

Front Oncol 2021 14;11:665217. Epub 2021 Jun 14.

Bone Marrow Transplantation Center, Department of Hematology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Introduction: We analyzed different patient subgroups to determine optimal maintenance therapy in newly diagnosed multiple myeloma (NDMM) patients.

Methods: A total of 226 NDMM patients in our center were included in the study. The characteristics, survival, and adverse reactions were compared among patients who received maintenance therapy or not, and patients who received proteasome inhibitors (PIs) or immunomodulators (IMiDs) maintenance. The survival of different maintenance durations of bortezomib-based regimens was also analyzed.

Results: The maintenance therapy not only upgraded more patient responses (34.3 13.3%, = 0.006), but also significantly prolonged their progression-free survival (PFS) (median PFS: 41.1 10.5 months, < 0.001) and overall survival (OS) (median OS: not reached 38.6 months, < 0.001). Compared with IMiDs, the PFS (median PFS: 43.7 38.5 months, = 0.034) and OS (median OS: not reached 78.5 months, = 0.041) were both enhanced by PIs maintenance. Patients younger than 65 years who received PIs had a significantly prolonged OS ( = 0.032). Patients achieving only a partial response (PR) after induction and consolidation therapy had significantly longer PFS and OS after PIs maintenance compared to IMiDs ( = 0.007, 0.002). High-risk patients (ISS 2-3, DS 2-3, and RISS 2-3) given PIs maintenance benefit from a prolonged PFS ( = 0.002, 0.02, 0.06) and OS ( = 0.059, 0.047, 0.044, respectively) compared with IMiDs therapy. OS was significantly prolonged in patients who received ≥ 12 months of bortezomib-based maintenance therapy compared to those who were treated for < 12 months ( < 0.001), but no difference was observed in OS between patients who received 12 to 24 or ≥ 24 months of bortezomib-based maintenance therapy ( = 0.292).

Conclusion: PIs maintenance was superior to IMiDs in overall PFS and OS. The beneficial effect was most evident in patients achieving PR after induction and consolidation therapy, and in high-risk patients. Moreover, younger patients also benefited from PIs maintenance with an increased OS. A bortezomib-based maintenance therapy duration of 12 to 24 months after induction and consolidation therapy produced satisfactory OS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.665217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236810PMC
June 2021

Incidence and Risk Factors Associated with Infection after Chimeric Antigen Receptor T Cell Therapy for Relapsed/Refractory B-cell Malignancies.

Cell Transplant 2021 Jan-Dec;30:9636897211025503

Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Chimeric antigen receptor T cells (CAR-Ts) constitute a novel therapeutic strategy for relapsed/refractory B-cell malignancies. With the extensive application of CAR-T therapy in clinical settings, CAR-T-associated toxicities have become increasingly apparent. However, information regarding the associated infections is limited. We aimed to evaluate the incidence of infection during CAR-T therapy and identify the potential risk factors. Especially, we evaluated infections and the associated risk factors in 92 patients. The cohort included patients with acute lymphoblastic leukemia ( = 58) and non-Hodgkin lymphoma ( = 34). Fifteen cases of infection (predominantly bacterial) were observed within 28 days of CAR-T therapy, with an infection density of 0.5 infections for every 100 days-at-risk. Neutropenia before CAR-T therapy ( = .005) and prior infection ( = .046) were independent risk factors associated with infection within 28 days after CAR-T therapy; corticosteroid treatment during cytokine release syndrome ( = .013) was an independent risk factor during days 29-180 after CAR-T infusions. Moreover, the 2-year survival duration was significantly shorter in patients with infections than in those without (126 vs 409 days; = .006). Our results suggested that effective anti-infection therapies may improve prognosis of patients who have a high infection risk. The risk of bacterial infections during the early stages of CAR-T therapy and the subsequent risk of viral infections thereafter should be considered to provide the appropriate treatment and improve patient prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/09636897211025503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216343PMC
June 2021

Pure organic quinacridone dyes as dual sensitizers in tandem photoelectrochemical cells for unassisted total water splitting.

Chem Commun (Camb) 2021 Jun;57(46):5634-5637

Key Laboratory for Advanced Materials, Institute of Fine Chemicals, School of Chemistry and Molecular Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, P. R. China.

Pure organic dye QAP-C8 based on quinacridone (QA) with octyl side chains as the donor and pyridine dicarboxylic acid (PDA) as the acceptor was first used in both the photoanode and the photocathode of photoelectrochemical cells. A tandem device with QAP-C8 as the photosensitizer realized overall water splitting and showed a STH of 0.11% under neutral pH conditions without an external bias.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1cc01570bDOI Listing
June 2021

Potential Synergy Mechanism of Processing Methods for the Basic Remedies of Qixue Shuangbu Prescription Based on Integrated Metabolomics Strategy and Network Pharmacology Study.

J Chromatogr Sci 2021 May 10. Epub 2021 May 10.

Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225001, PR China.

Qixue Shuangbu Prescription (QSP) is a famous traditional Chinese medicine (TCM) formula widely used for the treatment of chronic heart failure (CHF). Previous clinical studies have found that the efficacy of processed QSP has been significantly enhanced in the treatment of CHF. However, the synergistic mechanisms of processed QSP to enhance the treatment of CHF are still unclear. Generally, the changes in clinical effects mainly result from the variations of inside chemical basis caused by the TCM processing procedure. In this study, we developed a network pharmacology-integrated metabolomics strategy to clarify the difference of the effective compounds between crude and processed QSP, and further explain the mechanism of processed QSP to produce a synergistic effects. As a result, 69 different compounds were successfully screened, identified, quantified and verified as the most potential marker compounds. These different chemical components may play an anti-CHF and enhance the therapeutic effect through 52 action pathways such as estrogen signaling pathway, ubiquitin mediated proteolysis, protein processing in endoplasmic reticulum, etc. This study revealed that the proposed network pharmacology-integrated metabolomics strategy was a powerful tool for explaining the mechanism of synergistic action in the processing of QSP, further controlling the quality and understanding the processing mechanism of TCM formulae.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/chromsci/bmab053DOI Listing
May 2021

Discovery and validation of PZP as a novel serum biomarker for screening lung adenocarcinoma in type 2 diabetes mellitus patients.

Cancer Cell Int 2021 Mar 10;21(1):162. Epub 2021 Mar 10.

Department of Oncology, Wuxi People's Hospital Affiliated to Nanjing Medical University, No. 299 Qingyang Road, Wuxi, 214023, China.

Background: Patients with type 2 diabetes mellitus (T2DM) have an increased risk of suffering from various malignancies. This study aimed to identify specific biomarkers that can detect lung adenocarcinoma (LAC) in T2DM patients for the early diagnosis of LAC.

Methods: The clinical information of hospitalized T2DM patients diagnosed with various cancers was collected by reviewing medical records in Wuxi People's Hospital Affiliated to Nanjing Medical University from January 1, 2015, to June 30, 2020. To discover diagnostic biomarkers for early-stage LAC in the T2DM population, 20 samples obtained from 5 healthy controls, 5 T2DM patients, 5 LAC patients and 5 T2DM patients with LAC (T2DM + LAC) were subjected to sequential windowed acquisition of all theoretical fragment ion mass spectrum (SWATH-MS) analysis to identify specific differentially-expressed proteins (DEPs) for LAC in patients with T2DM. Then, these results were validated by parallel reaction monitoring MS (PRM-MS) and ELISA analyses.

Results: Lung cancer was the most common malignant tumor in patients with T2DM, and LAC accounted for the majority of cases. Using SWATH-MS analysis, we found 13 proteins to be unique in T2DM patients with early LAC. Two serum proteins were further validated by PRM-MS analysis, namely, pregnancy-zone protein (PZP) and insulin-like growth factor binding protein 3 (IGFBP3). Furthermore, the diagnostic values of these proteins were validated by ELISA, and PZP was validated as a novel serum biomarker for screening LAC in T2DM patients.

Conclusions: Our findings indicated that PZP could be used as a novel serum biomarker for the identification of LAC in T2DM patients, which will enhance auxiliary diagnosis and assist in the selection of surgical treatment at an early stage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12935-021-01861-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7945354PMC
March 2021

Radiotherapy and immunotherapy converge on elimination of tumor-promoting erythroid progenitor cells through adaptive immunity.

Sci Transl Med 2021 02;13(582)

Ludwig Center for Metastasis Research, Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL 60637 USA.

Tumor-induced CD45Ter119CD71 erythroid progenitor cells, termed "Ter cells," promote tumor progression by secreting artemin (ARTN), a neurotrophic peptide that activates REarranged during Transfection (RET) signaling. We demonstrate that both local tumor ionizing radiation (IR) and anti-programmed death ligand 1 (PD-L1) treatment decreased tumor-induced Ter cell abundance in the mouse spleen and ARTN secretion outside the irradiation field in an interferon- and CD8 T cell-dependent manner. Recombinant erythropoietin promoted resistance to radiotherapy or anti-PD-L1 therapies by restoring Ter cell numbers and serum ARTN concentration. Blockade of ARTN or potential ARTN signaling partners, or depletion of Ter cells augmented the antitumor effects of both IR and anti-PD-L1 therapies in mice. Analysis of samples from patients who received radioimmunotherapy demonstrated that IR-mediated reduction of Ter cells, ARTN, and GFRα3, an ARTN signaling partner, were each associated with tumor regression. Patients with melanoma who received immunotherapy exhibited favorable outcomes associated with decreased expression of GFRα3. These findings demonstrate an out-of-field, or "abscopal," effect mediated by adaptive immunity, which is induced during local tumor irradiation. This effect, in turn, governs the therapeutic effects of radiation and immunotherapy. Therefore, our results identify multiple targets to potentially improve outcomes after radiotherapy and immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/scitranslmed.abb0130DOI Listing
February 2021

Ibrutinib and venetoclax target distinct subpopulations of CLL cells: implication for residual disease eradication.

Blood Cancer J 2021 02 18;11(2):39. Epub 2021 Feb 18.

Fox Chase Cancer Center, Philadelphia, PA, USA.

Ibrutinib inhibits Bruton tyrosine kinase while venetoclax is a specific inhibitor of the anti-apoptotic protein BCL2. Both drugs are highly effective as monotherapy against chronic lymphocytic leukemia (CLL), and clinical trials using the combination therapy have produced remarkable results in terms of rate of complete remission and frequency of undetectable minimal residual disease. However, the laboratory rationale behind the success of the drug combination is still lacking. A better understanding of how these two drugs synergize would eventually help develop other rational combination strategies. Using an ex vivo model that promotes CLL proliferation, we show that modeled ibrutinib proliferative responses, but not viability responses, correlate well with patients' actual clinical responses. Importantly, we demonstrate for the first time that ibrutinib and venetoclax act on distinct CLL subpopulations that have different proliferative capacities. While the dividing subpopulation of CLL responds to ibrutinib, the resting subpopulation preferentially responds to venetoclax. The combination of these targeted therapies effectively reduced both the resting and dividing subpopulations in most cases. Our laboratory findings help explain several clinical observations and contribute to the understanding of tumor dynamics. Additionally, our proliferation model may be used to identify novel drug combinations with the potential of eradicating residual disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41408-021-00429-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893066PMC
February 2021

Inhibition of B-cell receptor signaling disrupts cell adhesion in mantle cell lymphoma via RAC2.

Blood Adv 2021 01;5(1):185-197

Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA.

Inhibition of the B-cell receptor (BCR) signaling pathway is highly effective in B-cell neoplasia through Bruton tyrosine kinase inhibition by ibrutinib. Ibrutinib also disrupts cell adhesion between a tumor and its microenvironment. However, it is largely unknown how BCR signaling is linked to cell adhesion. We observed that intrinsic sensitivities of mantle cell lymphoma (MCL) cell lines to ibrutinib correlated well with their cell adhesion phenotype. RNA-sequencing revealed that BCR and cell adhesion signatures were simultaneously downregulated by ibrutinib in the ibrutinib-sensitive, but not ibrutinib-resistant, cells. Among the differentially expressed genes, RAC2, part of the BCR signature and a known regulator of cell adhesion, was downregulated at both the RNA and protein levels by ibrutinib only in sensitive cells. RAC2 physically associated with B-cell linker protein (BLNK), a BCR adaptor molecule, uniquely in sensitive cells. RAC2 reduction using RNA interference and CRISPR impaired cell adhesion, whereas RAC2 overexpression reversed ibrutinib-induced cell adhesion impairment. In a xenograft mouse model, mice treated with ibrutinib exhibited slower tumor growth, with reduced RAC2 expression in tissue. Finally, RAC2 was expressed in ∼65% of human primary MCL tumors, and RAC2 suppression by ibrutinib resulted in cell adhesion impairment. These findings, made with cell lines, a xenograft model, and human primary lymphoma tumors, uncover a novel link between BCR signaling and cell adhesion. This study highlights the importance of RAC2 and cell adhesion in MCL pathogenesis and drug development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/bloodadvances.2020001665DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805322PMC
January 2021

Two-Dimensional IV-V Monolayers with Highly Anisotropic Carrier Mobility and Electric Transport Properties.

J Phys Chem Lett 2021 Jan 20;12(3):1058-1065. Epub 2021 Jan 20.

Department of Chemistry, University of Nebraska-Lincoln, Lincoln, Nebraska 68588, United States.

Two-dimensional (2D) semiconductors with anisotropic properties (e.g., mechanical, optical, and electric transport anisotropy) have long been sought in materials research, especially 2D semiconducting sheets with strong anisotropy in carrier mobility, e.g., -type in one direction and -type in another direction. Here, we report a comprehensive study of the carrier mobility and electric transport anisotropy of a class of 2D IV-V monolayers, XAs (X = Si or Ge), by using density functional theory methods coupled with deformation potential theory and non-equilibrium Green's function method. We find that the polarity of room-temperature carrier mobility μ of the 2D XAs monolayer is highly dependent on the lattice direction. In particular, for the SiAs monolayer, the μ values of the electron (e) and hole (h) are 1.25 × 10 and 0.39 × 10 cm V s, respectively, in the direction and 0.31 × 10 and 1.12 × 10 cm V s, respectively, for the direction. The computed electric transport properties also show that the SiAs monolayer exhibits strong anisotropy in the biased voltage in the range of -1 to 1 V. In particular, the current reflects the ON state in the direction but the OFF state in the direction. In addition, we find that the uniaxial strain can significantly improve the electric transport performance and even lead to the negative differential conductance at 10% strain. The unique transport properties of the 2D XAs monolayers can be exploited for potential applications in nanoelectronics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jpclett.0c03656DOI Listing
January 2021

Bortezomib-Based Regimens for Newly Diagnosed Multiple Myeloma in China: A Report of 12-Year Real-World Data.

Front Pharmacol 2020 11;11:561601. Epub 2020 Dec 11.

Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Improve the treatment quality might affect patients' efficacy and survival. Five hundred thirty multiple myeloma patients treated in four hematological centers in China from February 2006 to August 2018 were enrolled. General characteristics, treatment regimens and cycles, efficacy, survival and adverse events of the patients treated before and after August 2013 (later refer to as the before-2013 and after-2013 group) were analyzed and compared. The results suggested that patients who received optimized treatment regimen and route of administration completed more cycles of treatment in the after-2013 group. Although the overall response rate was similar between the two groups (88.6 vs. 90.5%), patients in the after-2013 group had higher complete remission rate (39.1 vs. 28.6%) and better progression-free survival. Subgroup analysis suggested that patients aged 65 years and older, with non-high-risk D-S, ISS, and R-ISS stages, had a significant benefit in progression-free survival. Therefore, in clinical practice in China, by reducing the economic burden brought by the treatment on patients and optimizing the treatment regimen, more patients can be treated with better regimens in a prolonged duration to achieve better efficacy and survival, especially in elderly and non-high-risk patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2020.561601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759685PMC
December 2020

Identification of miR-4793-3p as a potential biomarker for bacterial infection in patients with hepatitis B virus-related liver cirrhosis: A pilot study.

Exp Ther Med 2021 Feb 3;21(2):120. Epub 2020 Dec 3.

Department of Severe Hepatopathy, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian 350002, P.R. China.

Hepatitis B virus-related liver cirrhosis (HBV-LC) is susceptible to bacterial infections, which could lead to adverse prognosis in patients. MicroRNAs (miRs/miRNAs) are easily detected in peripheral blood and are involved in multiple liver diseases. The present pilot study aimed to investigate differentially expressed (DE) miRNAs in the serum of patients with HBV-LC and bacterial infection, and to identify potential biomarkers. The first batch of clinical samples was collected, including four patients with HBV-LC and infection, four patients with HBV-LC without infection, four patients with chronic hepatitis B (CHB) and four healthy controls. miRNA expression was analyzed by Affymetrix GeneChip miRNA 4.0 Array. A total of 385 DE miRNAs (upregulated, 160; downregulated, 225) were detected in patients with HBV-LC and infection compared with patients with HBV-LC without infection. miR-4793-3p was significantly upregulated in patients with HBV-LC and infection compared with its levels in the other three groups: HBV-LC without infection [log-transformed fold change (logFC)=7.96; P=0.0458), CHB (logFC=34.53; P=0.0003) and healthy controls (logFC=3.34; P=0.0219)]. Reverse transcription-quantitative PCR (RT-qPCR) was performed to validate miR-4793-3p expression in another batch of clinical samples. RT-qPCR showed that miR-4793-3p was highly expressed in patients with HBV-LC and infection compared with its levels in patients with HBV-LC without infection (P<0.05). The non-parametric random forest regression model was built to access the diagnostic value of miR-4793-3p, and the receiver operating characteristic curve demonstrated that the area under the curve was 92.2%. Target gene analysis with bioinformatics tools and Gene Expression Omnibus data (GSE46955) showed that miR-4793-3p could participate in the TGF-β signaling pathway. Functional experiments revealed that overexpressed miR-4793-3p could impair TGF-β function by downregulating Gremlin-1. The present pilot study suggests that miR-4793-3p could be a feasible indicator for bacterial infection in patients with HBV-LC, and it would be valuable for further research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/etm.2020.9552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739867PMC
February 2021

Identification and mechanism of insecticidal periplocosides from the root bark of Periploca sepium Bunge.

Pest Manag Sci 2021 Apr 26;77(4):1925-1935. Epub 2020 Dec 26.

College of Plant Protection, Northwest A&F University, Yangling, China.

Background: The Periploca sepium bark root (PSBR) has been regarded as a potential botanical insecticide because of its significant insecticidal activity of secondary metabolites. Several periplocosides were isolated from it as promising pesticides to control crop pests in agriculture.

Results: In our research, two new periplocosides, along with four known periplocosides were isolated from PSBR. The names of new periplocosides were periplocoside T (PST) and periplocoside U (PSU) while another four periplocosides were known as follows: periplocoside A (PSA), periplocoside F (PSF), periplocoside E (PSE) and periplocoside D (PSD). All periplocosides were evalulated for insecticidal activity against 3rd Mythimna separata (Walker) and Plutella xylostella. The biometric data showed that periplocoside T, PSD and PSF had remarkable insecticidal activity against tested insects. Its values of LD were 1.31, 3.94 and 3.42 μg·lavare against 3rd M. separata respectively, while the activity of those compounds against 3rd P. xylostella were 5.45, 12.17 and 13.95 μg·lavare , respectively. It was apparent after further study of the mechanism of action against M. separata was conducted that PST possessed the most significant insecticidal activity. The results of enzymatic activity displayed that powerful activation of tryptase, especially weak alkaline tryptase might be a dominant factor causing death of M. separata in vivo.

Conclusion: We herein report isolation and the mechanisms of action of insecticidal periplocosides, which established the fundamental development of natural agents to prevent pest damage to crops. © 2020 Society of Chemical Industry.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ps.6220DOI Listing
April 2021

Single-Cell Transcriptomic Analysis Reveals BCMA CAR-T Cell Dynamics in a Patient with Refractory Primary Plasma Cell Leukemia.

Mol Ther 2021 02 3;29(2):645-657. Epub 2020 Dec 3.

Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, China; Institute of Hematology, Zhejiang University, Hangzhou 310058, China; Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou 310058, China; Zhejiang Laboratory for Systems & Precision Medicine, Zhejiang University Medical Center, Hangzhou 310058, China. Electronic address:

Chimeric antigen receptor T cell (CAR-T) therapy has revolutionized the clinical treatment of hematological malignancies due to the prominent anti-tumor effects. B cell maturation antigen (BCMA) CAR-T cells have demonstrated promising effects in patients with relapsed/refractory multiple myeloma. However, the dynamics of CAR-T cell proliferation and cytotoxicity in clinical patients remains unexplored. Here, we longitudinally profiled the transcriptomes of 55,488 T cells including CAR-T products, CAR-T cells, and endogenous T cells at the peak and remission phases in a plasma cell leukemia (PCL) patient treated with BCMA CAR-T cells by single-cell transcriptomic analysis. Our results showed distinct CAR-T and endogenous T cell subsets indicating stage-specific expression in proliferation, cytotoxicity, and intercellular signaling pathways. Furthermore, we found that CAR-T cells at peak phase gradually convert to a highly cytotoxic state from a highly proliferative state along a development trajectory. Moreover, re-analysis of a single cell study from CD8 CD19 CAR-T confirmed our findings. These commonalities suggest conserved mechanisms for CAR-T treatment across hematological malignancies. Taken together, our current study provides insight into CAR-T cell dynamics during CAR-T therapy and proves that both BCMA CAR-T and CD19 CAR-T have similar transcriptional characteristics, especially at the CAR-T peak phase.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ymthe.2020.11.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854300PMC
February 2021

Two-year changes of biochemical profiles and bone mineral density after percutaneous ultrasound-guided microwave ablation for primary hyperparathyroidism.

Endocrine 2021 02 6;71(2):476-483. Epub 2020 Oct 6.

Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Ouhai District, Wenzhou, Zhejiang, China.

Purpose: To investigate the changes of the serum parathyroid hormone (PTH) and calcium level, as well as bone mineral density (BMD), after percutaneous ultrasound-guided microwave ablation (MWA) for primary hyperparathyroidism (pHPT) caused by single hyperfunctional nodule.

Methods: The study enrolled 20 patients with a total of 20 nodules of MWA treatment to pHPT in one session. The normalization rate of the serum PTH and calcium was evaluated at every 6 months during 2-year follow-up after MWA. The bone mineral density (BMD) at lumbar spine and femoral neck were also compared before and after the procedure.

Results: The normalization rate of both PTH and serum calcium at 6-, 12-, 24-month follow-up was 66.6%, 80.0%, and 62.5%, respectively. Though the normalization rate of serum calcium level at 6-, 12-, and 24-month visit after MWA was 100%. The BMD increased 12, 24 months after MWA at lumbar spine (1.022 ± 0.155, 1.057 ± 0.151 vs 0.965 ± 0.145 g/cm, p < 0.01) and femoral neck at 2-year assessment (0.819 ± 0.094 vs 0.771 ± 0.102 g/cm, p = 0.015). Seven nodules disappeared in 20 nodules (35.0%), average ablation time was 122.29 ± 107.54 s (34-460 s). Six patients encountered voice change during the procedure, one participant was confirmed recurrent laryngeal injuries but recovered within 2 months.

Conclusions: Percutaneous ultrasound-guided microwave ablation results in improvement of biochemical profiles and bone mineral density in subjects with single hyperfunctional parathyroid nodule. However, the long-term efficacy of the MWA remains to be verified.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12020-020-02511-1DOI Listing
February 2021

Visualization of the morphology and pathology of the peripheral branches of the cranial nerves using three-dimensional high-resolution high-contrast magnetic resonance neurography.

Eur J Radiol 2020 Nov 20;132:109137. Epub 2020 Jun 20.

Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China. Electronic address:

Purpose: To assess the feasibility and advantages of high-resolution high-contrast magnetic resonance neurography (HRHC-MRN) for visualizing the morphology and pathology of the peripheral branches of cranial nerves.

Materials: cMRN (3D SPACE STIR sequence) and HRHC-MRN (contrast enhanced 3D SPACE STIR sequence) were performed at 3 T MR unit on 16 volunteers and 12 patients with head and neck tumors. Quantitative measurements such as SNR, CNR and CR were calculated. Three readers evaluated the continuity of the 10 major peripheral branches of cranial nerves using a 5-score scale (scores 0-4). Interobserver variability was tested. Quantitative measurements and scores were compared between cMRN and HRHC-MRN. The imaging features of the nerve pathology were analyzed.

Results: The CRs of nerve to bone marrow, nerve to muscle, and nerve to gland were significantly higher with HRHC-MRN than with cMRN (P = 0.014, P = 0.02, P <0.001, respectively). The scores of all nerve trunks were significantly higher with HRHC-MRN than with cMRN (all, P < 0.001). For all nerves on HRHC-MRN, the interobserver consistency was excellent across the three readers (all κ > 0.8). The scores of the inferior alveolar nerve, hypoglossal nerve, lingual nerve, facial nerve, infraorbital nerve, masseteric nerve, glossopharyngeal/vagus nerve, supraorbital nerve, auriculotemporal nerve and buccal nerve were 3.95, 3.77, 3.63, 3.25, 3.15, 3.04, 3.04, 2.87, 2.79, 1.88, respectively.

Conclusion: HRHC-MRN provides improved visualization of the peripheral branches of cranial nerves and is a promising nerve-selective imaging method for evaluating cranial nerve morphology and pathology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejrad.2020.109137DOI Listing
November 2020

Corrigendum: Altered Gray Matter Volume in Patients With Type 1 Diabetes Mellitus.

Front Endocrinol (Lausanne) 2020 28;11:604. Epub 2020 Aug 28.

Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

[This corrects the article DOI: 10.3389/fendo.2020.00045.].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2020.00604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484998PMC
August 2020

Synthesis and Insecticidal Activity Evaluation of Virtually Screened Phenylsulfonamides.

J Agric Food Chem 2020 Oct 7;68(42):11665-11671. Epub 2020 Oct 7.

College of Chemistry & Pharmacy, Shaanxi Key Laboratory of Natural Products & Chemical Biology, Northwest A&F University, Yangling, Shaanxi 712100, P. R. China.

The fastest and most effective way to control pests is to use pesticides. However, with the accumulation of pesticide resistance and the difficulties of rapidly producing new pesticides, it is of great significance to create new pesticides through new synthetic methods. In this study, we report a computer-aided drug design (CADD)-assisted method to obtain two lead sulfonamides by homology modeling and virtual screening. On this basis, the lead compounds were synthesized from -chlorocresol by four steps of esterification, sulfonation, sulfonamidation, and amidation. Further, 71 derivatives were synthesized by optimizing the lead compounds, and their insecticidal activities against were evaluated by the leaf-dipping method. Notably, seven sulfonamides (, , , , , , and ) with excellent insecticidal activity were obtained, and the possible binding modes between receptors and active groups in sulfonamides were verified by structure-activity relationship and docking simulation, which provided theoretical support for the subsequent development of these novel candidate insecticides.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jafc.0c02153DOI Listing
October 2020

Transcriptome analysis of Plantago major as a phytoremediator to identify some genes related to cypermethrin detoxification.

Environ Sci Pollut Res Int 2021 Feb 21;28(5):5101-5115. Epub 2020 Sep 21.

Institute of Pesticide Science, College of Plant Protection, Northwest A&F University, Yangling, 712100, Shaanxi, China.

Cypermethrin (CYP) is a toxic manmade chemical compound belonging to pyrethroid insecticides contaminating the environment. Plantago major (PM) has numerous excellent advantages like high biomass yield and great stress tolerance, which make it able to increase the efficacy of phytoremediation. So far, no study has directly or indirectly made a transcriptome analysis (RNA-seq) of PM under CYP stress. The aim of this study is to identify the genes in PM related to CYP detoxification (10 μg mL) and compared with control. In this study, BGISEQ-500 high-throughput sequencing technology independently developed by BGI was used to sequence the transcriptome of P. major. Six libraries were constructed including (CK_1, CK_2, and CK_3) and (CYP_1, CYP_2, and CYP_3) were sequenced for transcripts involved in CYP detoxification. Our data showed that de novo assembly generated 138,806 unigenes with an average length of 1129 bp. Analyzing the annotation results of the KEGG database between the samples revealed 37,177 differentially expressed genes (DEGs), 18,062 down- and 19,115 upregulated under CYP treatment compared with control. A set of 107 genes of cytochrome P450 (Cyt P450), 43 genes of glutathione S-transferases (GST), 25 genes of glycosyltransferases (GTs), 113 genes from ABC transporters, 21 genes from multidrug and toxin efflux (MATE), 11 genes from oligopeptide transporter (OPT), and 3 genes of metallothioneins (MT) were upregulated notably. By using quantitative real-time PCR (qRT-PCR), the results of gene expression for 12 randomly selected DEGs were confirmed, showing the different patterns of response to CYP in PM tissues. Furthermore, the enzyme activity of Cyt P450 and GST in PM under CYP stress was significantly increased in roots and leaves than in control. This study introduces a clue to understand the metabolic pathways of plants used in phytoremediation by identifying the highly expressed genes related to phytoremediation which would be utilized to enhance pesticide detoxification and reduce pollution problem.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11356-020-10774-4DOI Listing
February 2021

Isoliquiritigenin attenuates diabetic cardiomyopathy via inhibition of hyperglycemia-induced inflammatory response and oxidative stress.

Phytomedicine 2020 Nov 1;78:153319. Epub 2020 Sep 1.

Department of Endocrinology, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China. Electronic address:

Background: Inflammation and oxidative stress play essential roles in the occurrence and progression of diabetic cardiomyopathy (DCM). Isoliquiritigenin (ISL), a natural chalcone, exhibits strong anti-inflammatory and antioxidant activities.

Hypothesis/purpose: In this study, we aimed to investigate the protective effects of ISL on DCM using high glucose (HG)-challenged cultured cardiomyocytes and streptozotocin (STZ)-induced diabetic mice.

Study Design And Methods: Embryonic rat heart-derived H9c2 cells challenged with a high concentration of glucose were used to evaluate the anti-inflammatory and antioxidant effects of ISL. STZ-induced diabetic mice were used to study the effects of ISL in DCM in vivo. Furthermore, cardiac fibrosis, hypertrophy, and apoptosis were explored both in vitro and in vivo.

Results: ISL effectively inhibited HG-induced hypertrophy, fibrosis, and apoptosis probably by alleviating the inflammatory response and oxidative stress in H9c2 cells. Results from in vivo experiments showed that ISL exhibited anti-inflammatory and antioxidant stress activities that were characterized by the attenuation of cardiac hypertrophy, fibrosis, and apoptosis, which resulted in the maintenance of cardiac function. The protective effects of ISL against inflammation and oxidative stress were mediated by the inhibition of mitogen-activated protein kinases (MAPKs) and induction of nuclear factor-erythroid 2 related factor 2 (Nrf2) signaling pathway, respectively.

Conclusion: Our results provided compelling evidence that ISL, by virtue of neutralizing excessive inflammatory response and oxidative stress, could be a promising agent in the treatment of DCM. Targeting the MAPKs and Nrf2 signaling pathway might be an effective therapeutic strategy for the prevention and treatment of DCM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phymed.2020.153319DOI Listing
November 2020

Impact of Glycosylated Hemoglobin on the Prognosis of Patients with Acute Ischemic Stroke Treated with Arterial Thrombolysis.

Heart Surg Forum 2020 Jul 2;23(4):E447-E451. Epub 2020 Jul 2.

Department of Neurology, Zhongshan City People's Hospital, Zhongshan, China.

Background: To investigate the impact of glycosylated hemoglobin (HbA1c) on the prognosis of patients with acute ischemic stroke (AIS) treated with intra-arterial thrombolysis (IAT).

Methods: The clinical data of 136 patients with AIS treated with IAT at the Zhongshan City People's Hospital were retrospectively analyzed. The patients were divided into a high HbA1c group (HHbA1c) (≥6.5%) and a normal HbA1c group (NHbA1c) (<6.5%). According to National Institutes of Health Stroke Scale (NIHSS) score after thrombolysis, patients were divided into a good prognosis group (GP) (≥4 or <4 points reduction) and a poor prognosis group (PP) (≤4 or >4 points reduction).

Results: There were significant differences in the HbA1c and glucose levels, NIHSS scores at admission and at discharge, complication rates, and mortality rates between groups HHbA1c and NHbA1c (P < .05) and between groups GP and PP (P < .05). The multivariate logistic regression analysis showed that HbA1c level (odds ratio [OR] 0.717; 95% confidence interval [CI] 0.545 to 0.889) and NIHSS score at admission (OR 0.894; 95% CI 0.814 to 0.982) were risk factors for neurological improvement in IAT-treated patients with AIS.

Conclusions: HbA1c level is associated with neurological function improvement in IAT-treated patients with AIS and can be used as a serological indicator of poor prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1532/hsf.2929DOI Listing
July 2020

The inverse association between parity and bone health is independent of lifestyle in postmenopausal Chinese women.

Endocr J 2020 Oct 12;67(10):1039-1045. Epub 2020 Jun 12.

Department of Endocrine and Metabolic Diseases, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.

This study aimed to investigate the association between parity and bone mineral density in postmenopausal Chinese women, as well as the interference of physical activity and sedentary time on this association. A total of 1,712 participants were enrolled in this study. Participants were separated into three groups according to the number of parities: group 1, 1-2; group 2, 3-4; group 3, ≥5. Physical activity level was assessed according to the International Physical Activity Questionnaire. Calcaneus bone mineral density (BMD) and bone quality were assessed by qualitative ultrasound. As a result, logistic regression showed that compared to that in group 1, the risk of fracture in group 3 was increased significantly (p < 0.001). A greater number of parities was associated with a lower BMD, broadband ultrasonic attenuation (BUA), quantitative ultrasound index (QUI), speed of sound (SOS), and T-score among the three groups after adjustment for age (All p for trend < 0.05). The number of parities was an independent factor negatively correlated with BMD, BUA, QUI, SOS and T-score (All p < 0.05). BMD, BUA, QUI, SOS, and T-score were significantly increased in the physically a participants independent of parity (all p < 0.05), and decreased in the sedentary participants independent of parity (p < 0.05, except BUA). A great number of parities was negatively associated with bone health. Physical activity was positively correlated and sedentary time was negatively correlated with bone health independent of parity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1507/endocrj.EJ20-0132DOI Listing
October 2020

Idiopathic thrombocytopenic purpura treatment in a relapsed/refractory multiple myeloma patient after chimeric antigen receptor T cell therapy.

Regen Ther 2020 Jun 15;14:271-274. Epub 2020 May 15.

Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310000, China.

The adoptive transfer of CAR-T cells, which are modified T cells expressing chimeric antigen receptors (CARs), to target B cell maturation antigen (BCMA) has demonstrated impressive results in treating relapsed/refractory multiple myeloma. Although BCMA CAR-T therapy induces certain complications in some patients, idiopathic thrombocytopenic purpura (ITP) has not been reported as one of them. To the best of our knowledge, this is the first report of the successful treatment of ITP that arose in a relapsed/refractory multiple myeloma patient following anti-BCMA CAR-T cell infusion. Herein, we describe this relatively uncommon complication and provide guidance on its treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.reth.2020.03.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232090PMC
June 2020

Construction of 5G all-wireless network and information system for cabin hospitals.

J Am Med Inform Assoc 2020 06;27(6):934-938

Department of Computer Management, Wuhan Asia General Hospital, Wuhan, China.

The epidemic of coronavirus disease 2019 (COVID-19) broke out in Wuhan, China, in early 2020. In an effort to curb the spread of the epidemic, the government has requisitioned a variety of venues and plant buildings and built more than 20 cabin hospitals to receive patients with mild symptoms within 48 hours. Under this circumstance, we worked out a 5G all-wireless solution to divide the overall network system of the cabin hospital into multiple network units by function. While ensuring good signal coverage of the local unit, each network unit was independently connected to the host hospital's data center over a virtual private network (VPN) tunnel built on the 5G wireless network. Our successful experience with the application of this 5G + VPN all-wireless network system well points to the bright prospect of 5G wireless network. In addition, the 5G + VPN solution can also be used for multihospital network interconnection and rapid network recovery during the failure of wired network.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jamia/ocaa045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454648PMC
June 2020

Detection of Microsatellite Instability from Circulating Tumor DNA by Targeted Deep Sequencing.

J Mol Diagn 2020 07 16;22(7):860-870. Epub 2020 May 16.

Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China; Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China. Electronic address:

Currently, microsatellite instability (MSI) detection is limited to tissue samples with sufficient tumor content. Detection of MSI from blood has been explored but confounded by low sensitivity due to limited circulating tumor DNA (ctDNA). We developed a next-generation sequencing-based algorithm, blood MSI signature enrichment analysis, to detect MSI from blood. Blood MSI signature enrichment analysis development involved three major steps. First, marker sites that can effectively distinguish high MSI (MSI-H) from microsatellite stable tumors were extracted. Second, MSI signature enrichment analysis was performed based on hypergeometric probability, under the null hypothesis that plasma samples have similar MSI-H and microsatellite stable read coverage patterns for particular marker sites as the white blood cells from the training data set. Finally, enrichment scores of marker sites were normalized, and all markers were collectively considered to determine the MSI status of a plasma sample. In vitro dilution experiments with cell lines and in silico simulation experiments based on mixtures of MSI-H plasma and paired white blood cell DNA demonstrated 98% sensitivity and 100% specificity at a minimum of 1% ctDNA and 91.8% sensitivity and 100% specificity with 0.4% ctDNA. An independent validation cohort of 87 colorectal cancer patients with orthogonal confirmation of MSI status of tissues confirmed performance, achieving 94.1% sensitivity (16/17) and 100% specificity (27/27) for samples with ctDNA >0.4%.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jmoldx.2020.04.210DOI Listing
July 2020

Comparison of Fontan Surgical Options for Patients with Apicocaval Juxtaposition.

Pediatr Cardiol 2020 Jun 6;41(5):1021-1030. Epub 2020 May 6.

Amrita Institute of Medical Sciences and Research Centre, Kochi, India.

Apicocaval juxtaposition (ACJ) is a rare form of viscerocardiac malpositions in association with single-ventricle congenital heart defects. The Fontan surgery is the common palliation, and possible surgical options include ipsilateral, contralateral, and intra-atrial conduits. Concerns include lower hemodynamic performances or risks of conduit compression by the cardiac mass. This study investigates the hemodynamics and clinical outcomes of ACJ patients and potential surgical improvements. Ten consecutive ACJ patients were included, along with a reference cohort of ten non-ACJ patients. Magnetic resonance images were acquired at 6 ± 0.6 year follow-up for anatomical analysis and hemodynamic assessments using computational fluid dynamics. Metrics of interest are deformation index (DI), indexed power loss (iPL), and hepatic flow distribution (HFD). A "virtual" surgery was performed to explore potential hemodynamic improvements using a straightened conduit. DI for ACJ patients fell within the DI range of non-ACJ patients. Contralateral conduits had insignificantly higher iPL (0.070 [0.032,0.137]) than ipsilateral conduits (0.041 [0.013,0.095]) and non-ACJ conduits (0.034 [0.011,0.061]). HFD was similar for the ipsilateral (21 [12,35]), contralateral (26 [7,41]), and non-ACJ Fontan conduits (17 [0,48]). Virtual surgery demonstrated that a straightened conduit reduced HFD and iPL for the contralateral and ipsilateral conduits, potentially leading to improved clinical outcomes. In this limited sample, the hemodynamic performance of ACJ patients was not significantly different from their non-ACJ counterparts. The use of a straightened conduit option could potentially improve patient outcomes. Additionally, the fear of significant compression of conduits for ACJ patients was unsupported.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00246-020-02353-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325867PMC
June 2020

Pre-transplant MRD negativity predicts favorable outcomes of CAR-T therapy followed by haploidentical HSCT for relapsed/refractory acute lymphoblastic leukemia: a multi-center retrospective study.

J Hematol Oncol 2020 05 4;13(1):42. Epub 2020 May 4.

Hematology and Bone Marrow Transplantation Division, Chaim Sheba Medical Center, Tel-Hashomer, Israel.

Background: Consolidative allogeneic hematopoietic stem cell transplantation is a controversial option for patients with relapsed/refractory acute lymphoblastic leukemia after chimeric antigen receptor T cell (CAR-T) therapy. We performed a multicenter retrospective study to assess whether patients can benefit from haploidentical hematopoietic stem cell transplantation after CAR-T therapy.

Methods: A total of 122 patients after CAR-T therapy were enrolled, including 67 patients without subsequent transplantation (non-transplant group) and 55 patients with subsequent haploidentical hematopoietic stem cell transplantation (transplant group). Long-term outcome was assessed, as was its association with baseline patient characteristics.

Results: Compared with the non-transplant group, transplantation recipients had a higher 2-year overall survival (OS; 77.0% versus 36.4%; P < 0.001) and leukemia-free survival (LFS; 65.6% versus 32.8%; P < 0.001). Multivariate analysis showed that minimal residual disease (MRD) positivity at transplantation is an independent factor associated with poor LFS (P = 0.005), OS (P = 0.035), and high cumulative incidence rate of relapse (P = 0.045). Pre-transplant MRD-negative recipients (MRD- group) had a lower cumulative incidence of relapse (17.3%) than those in the non-transplant group (67.2%; P < 0.001) and pre-transplant MRD-positive recipients (MRD+ group) (65.8%; P = 0.006). The cumulative incidence of relapse in MRD+ and non-transplant groups did not differ significantly (P = 0.139). The 2-year LFS in the non-transplant, MRD+, and MRD- groups was 32.8%, 27.6%, and 76.1%, respectively. The MRD- group had a higher LFS than the non-transplantation group (P < 0.001) and MRD+ group (P = 0.007), whereas the LFS in the MRD+ and non-transplant groups did not differ significantly (P = 0.305). The 2-year OS of the MRD- group was higher than that of the non-transplant group (83.3% versus 36.4%; P < 0.001) but did not differ from that of the MRD+ group (83.3% versus 62.7%; P = 0.069). The OS in the non-transplant and MRD+ groups did not differ significantly (P = 0.231).

Conclusion: Haploidentical hematopoietic stem cell transplantation with pre-transplant MRD negativity after CAR-T therapy could greatly improve LFS and OS in patients with relapsed/refractory acute lymphoblastic leukemia.

Trial Registration: The study was registered in the Chinese clinical trial registry (ChiCTR1900023957).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13045-020-00873-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7199358PMC
May 2020

Factors Associated with Costs in Chimeric Antigen Receptor T-Cell Therapy for Patients with Relapsed/Refractory B-Cell Malignancies.

Cell Transplant 2020 Jan-Dec;29:963689720919434

Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Background: Chimeric antigen receptor T cells (CAR-Ts) constitute a novel therapeutic strategy for relapsed/refractory B-cell malignancies. CAR-T therapy has been extensively applied in the clinical setting; however, few systematic studies have evaluated the cost of CAR-T treatment. This study was conducted to evaluate the total cost and cost structure of CAR-T therapy and identify potential risk factors leading to increased costs.

Methods: We identified the associated risk factors in 89 patients in a phase 1/2 study. The cohort included patients with acute lymphoblastic leukemia (ALL, = 55) and non-Hodgkin's lymphoma (NHL, = 34).

Results: Overall, the treatment of the ALL cohort was costlier than that of the NHL cohort ( < 0.001). Furthermore, in the ALL cohort, it was costlier to treat patients with a high tumor burden ( < 0.001), high cytokine release syndrome (CRS) grade ( < 0.001), and complications of infection after CAR-T cell infusion (CTI) in the whole cohort ( = 0.013) than patients with a low tumor burden, with low CRS grade, and without infection, respectively. CRS grade and length of stay ( ≤ 0.005) were independent risk factors associated with the total cost in both the ALL and NHL cohorts during CAR-T therapy. A high tumor burden, duration of fever, and treatment with tocilizumab were independent risk factors associated with the total cost in the ALL cohort ( < 0.05).

Conclusions: CAR-T treatment should be extended to patients with a low tumor burden or patients in a state of complete remission, and a corticosteroid approach, as opposed to tocilizumab, may reduce costs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0963689720919434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444226PMC
June 2021