Fen Zhou

Huazhong University of Science and Technology

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Runming Jin

Northwest A&F University

Aimee Landar

University of Louisville

Jiaoyang Cai

Shanghai Hospital Development Center

Frances E. Lund

University of Alabama at Birmingham

R. Glenn King

University of Alabama at Birmingham

Yongjun Fang

Second Affiliated Hospital of Nanjing Medical University

Troy D. Randall

Center for Rheumatology

Ching‐Hon Pui

St. Jude Children's Research Hospital

Dale A. Parks

University of Alabama at Birmingham

Heng Mei

Second Affiliated Hospital of Nanjing Medical University

Cooperative Institutions

Huazhong University of Science and Technology

University of Alabama at Birmingham

Union Hospital

Shanghai Jiao Tong University

Chinese Academy of Sciences

Union Hospital

Chinese Academy of Medical Sciences & Peking Union Medical College

Wuhan Union Hospital

Sun Yat-sen University

Soochow University

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Delineation of features, responses, outcomes, and prognostic factors in pediatric PDGFRB‐positive acute lymphoblastic leukemia patients: A retrospective multicenter study

Cancer (2024)

Xiaoyan Zhang Yaqin Wang Xin Tian Lirong Sun Hua Jiang

PDGFRB fusions in acute lymphoblastic leukemia (ALL) is rare. The authors identified 28 pediatric PDGFRB-positive ALL. They analyzed the features, outcomes, and prognostic factors of this disease.

PDGFRB

Cumulative incidence

Univariate analysis

10.1002/cncr.35481

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Citations (0)

The influence of MTHFR genetic polymorphisms on methotrexate therapy in pediatric acute lymphoblastic leukemia

Open Life Sciences (2021)

Yaqing Shen Zhu‐Jun Wang Fen Zhou Runming Jin

MTHFR is a crucial enzyme in folate metabolism. This study aimed to determine the relationship between MTHFR genetic polymorphism and elimination and toxicities of methotrexate (MTX). To do that, the study enrolled 145 patients diagnosed with acute lymphoblastic leukemia, who received chemotherapy following the Chinese Children's Cancer Group Acute Lymphoblastic Leukemia (CCCG-ALL)-2015 protocol (clinical trial number: ChiCTR-IPR-14005706). We analyzed the effects of MTHFR C677T and A1298C polymorphisms on MTX elimination and toxicities. Patients with the MTHFR C677T TT genotype could tolerate a significantly higher MTX dose than those with the CC/CT genotype. However, patients with C677T TT genotypes had an increased risk of hypokalemia (1.369 to CC and 1.409 to CT types). The MTX infusion rate in patients with the MTHFR A1298C AC genotype was slightly lower than that in those with CC or AA genotypes. Patients with the A1298C AA genotype had a 1.405-fold higher risk of hepatotoxicity than those with the AC genotype (P > 0.05). There was no significant difference between the prevalence of other toxicities among MTHFR C677T or A1298C genotypes (P > 0.05). Neither MTHFR C677T nor A1298C polymorphisms were significantly associated with delayed MTX clearance. To conclude, MTHFR polymorphisms were not good predictors of MTX-related toxicities.

10.1515/biol-2021-0121

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Citations (9)

A single intranasal administration of AdCOVID protects against SARS-CoV-2 infection in the upper and lower respiratory tracts

Human Vaccines & Immunotherapeutics (2022)

Michael D. Schultz John J. Suschak Davide Botta Aarón Silva-Sánchez R. Glenn King

The coronavirus disease 2019 (COVID-19) pandemic has illustrated the critical need for effective prophylactic vaccination to prevent the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Intranasal vaccination is an attractive approach for preventing COVID-19 as the nasal mucosa is the site of initial SARS-CoV-2 entry and viral replication prior to aspiration into the lungs. We previously demonstrated that a single intranasal administration of a candidate adenovirus type 5-vectored vaccine encoding the receptor-binding domain of the SARS-CoV-2 spike protein (AdCOVID) induced robust immunity in both the airway mucosa and periphery, and completely protected K18-hACE2 mice from lethal SARS-CoV-2 challenge. Here we show that a single intranasal administration of AdCOVID limits viral replication in the nasal cavity of K18-hACE2 mice. AdCOVID also induces sterilizing immunity in the lungs of mice as reflected by the absence of infectious virus. Finally, AdCOVID prevents SARS-CoV-2 induced pathological damage in the lungs of mice. These data show that AdCOVID not only limits viral replication in the respiratory tract, but it also prevents virus-induced inflammation and immunopathology following SARS-CoV-2 infection.

Respiratory tract

Coronavirus

Viral Shedding

10.1080/21645515.2022.2127292

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Research on the Difference of Effects of Heterogeneous Environmental Regulations on Green Transformation of Manufacturing Enterprises in China Under the Target of "Double Carbon"—Mediating Effect Analysis Based on Managers' Green Cognition

Yongjun Tang Yuqiu Qi Fen Zhou Lei Hua

This study investigates if there are variations in the effects of diverse environmental rules on the high-quality development and transformation of China's manufacturing industry against the backdrop of broadly advocating the objective of "peak carbon dioxide emissions and carbon neutrality". This paper thoroughly examines the mechanism and impact effect differences of diverse environmental regulations on the green transformation of manufacturing enterprises under the target of "double carbon", and reveals the mechanism of corporate managers' cognition of green transformation in this process of a sample of manufacturing listed companies in Shanghai and Shenzhen A-shares in China from 2015 to 2021. According to the study, three environmental regulation tools—environmental administrative supervision, environmental economic regulation, and environmental soft constraint—can greatly support the transformation of manufacturing organizations into green businesses. Following environmental soft constraint and environmental administrative supervision, environmental economic regulation has the greatest impact on the green transformation of manufacturing enterprises. Mechanism analysis shows that managers' green cognition plays a part of mediating effect between environmental administrative supervision, environmental economic regulation and environmental soft constraint and the green transformation of manufacturing enterprises. Among them, environmental administrative supervision can improve managers' green cognition most, followed by environmental economic regulation and finally by environmental soft constraint. According to further analysis, when the policy of the region where the enterprise is located is uncertain or located in the eastern region and the enterprise is a state-owned enterprise. The study presented in this paper gives theoretical backing for the Chinese government's efforts to broadly promote the "double carbon" target, realize enterprise greening, and develop diverse environmental policies. It also serves as a foundation for the implementation of flexible policies.

Green innovation

10.2139/ssrn.4435184

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Transport across a polarized monolayer of Caco-2 cells by transferrin receptor-mediated adenovirus transcytosis

Virology (2004)

Zeng B. Zhu Sharmila Makhija Baogen Lu Minghui Wang Ángel A. Rivera

Transcytosis

Transferrin receptor

10.1016/j.virol.2004.04.021

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Novel Treatments for Pediatric Relapsed or Refractory Acute B-Cell Lineage Lymphoblastic Leukemia: Precision Medicine Era

Frontiers in Pediatrics (2022)

Shang Mengxuan Fen Zhou Runming Jin

With the markedly increased cure rate for children with newly diagnosed pediatric B-cell acute lymphoblastic leukemia (B-ALL), relapse and refractory B-ALL (R/R B-ALL) remain the primary cause of death worldwide due to the limitations of multidrug chemotherapy. As we now have a more profound understanding of R/R ALL, including the mechanism of recurrence and drug resistance, prognostic indicators, genotypic changes and so on, we can use newly emerging technologies to identify operational molecular targets and find sensitive drugs for individualized treatment. In addition, more promising and innovative immunotherapies and molecular targeted drugs that are expected to kill leukemic cells more effectively while maintaining low toxicity to achieve minimal residual disease (MRD) negativity and better bridge hematopoietic stem cell transplantation (HSCT) have also been widely developed. To date, the prognosis of pediatric patients with R/R B-ALL has been enhanced markedly thanks to the development of novel drugs. This article reviews the new advancements of several promising strategies for pediatric R/R B-ALL.

Minimal Residual Disease

Refractory (planetary science)

10.3389/fped.2022.923419

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Allogeneic and Autologous Anti-CD7 CAR-T Cell Therapies in Relapsed or Refractory T Cell Malignancies

Blood (2022)

Yinqiang Zhang Chenggong Li Huiwen Jiang Wenjing Luo Mengyi Du

Cytokine Release Syndrome

10.1182/blood-2022-170819

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Citations (2)

Prognostic significance of steroid response in pediatric acute lymphoblastic leukemia: The CCCG-ALL-2015 study

Frontiers in Oncology (2022)

Jinhua Chu Huaju Cai Jiaoyang Cai Xinni Bian Cheng Yumei

Introduction Whether steroid response is an independent risk factor for acute lymphoblastic leukemia (ALL) is controversial. This study aimed to investigate the relationship between response to dexamethasone and prognosis in children with ALL. Methods We analyzed the data of 5,161 children with ALL who received treatment in accordance with the Chinese Children’s Cancer Group ALL-2015 protocol between January 1, 2015, and December 31, 2018, in China. All patients received dexamethasone for 4 days as upfront window therapy. Based on the peripheral lymphoblast count on day 5, these patients were classified into the dexamethasone good response (DGR) and dexamethasone poor response (DPR) groups. A peripheral lymphoblast count ≥1× 10 9 /L indicated poor response to dexamethasone. Results The age, white blood cell counts, prevalence of the BCR/ABL1 and TCF3/PBX1 fusion genes, and rates of recurrence in the central nervous system were higher in the DPR than in the DGR group ( P <0.001). Compared to the DPR group, the DGR group had a lower recurrence rate (18.6% vs. 11%) and higher 6-year event-free survival (73% vs. 83%) and overall survival (86% vs. 92%) rates; nevertheless, subgroup analysis only showed significant difference in the intermediate-risk group ( P <0.001). Discussion Response to dexamethasone was associated with an early treatment response in our study. In the intermediate-risk group, dexamethasone response added a prognostic value in addition to minimal residual disease, which may direct early intervention to reduce the relapse rate.

Minimal Residual Disease

Lymphoblast

White blood cell

10.3389/fonc.2022.1062065

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Citations (4)

A relapsed B-acute Lymphoblastic Leukemia Patient with Low CD19 Density Achieved Remission with a Low Dose of Blinatumomab After Repeated CAR-T Cell Failure: a case report

Authorea (Authorea) (2023)

Cong Lu Fen Zhou Danying Liao Jine Zheng Li Chengong

Patients were still at a high risk of relapse after achieving complete remission by CAR-T therapy. The mechanisms underlying CD19+ relapse still remain to be further clarified in B-acute lymphoblastic leukemia (B-ALL). We reported a patient with B-ALL who relapsed at nine months after allogeneic stem cell transplantation. After two times of autologous anti-CD19 CAR-T infusion treatment, he recured with CD19 MRD positive the third time. CD19 antigen density was assessed for recurrence after a second CAR- T infusion and was found to be decreasing. The patient obtained MRD-negative (sCR4) on day 7 of treatment with the initial dose of Blinatumomab and remained negative throughout the four courses of maintenance treatment. Our case demonstrates that patients with CD19 + relapsed MRD treated with CD19-targeted CAR-T are still effective with low-dose Blinatumomab. The secondary infusion of CAR-T with 4-1BB domain may reduce the density of CD19 target antigen on the surface of tumor cells, resulting in the short maintenance of PFS. Treatment with Blinatumomab may not depend on CD19 target antigen density. Blinatumomab as a Bispecific T engager may act as an adaptor to improve T cell and CAR-T responses for patients relapsed after CAR-T therapy, which explained one possible cause of relapse after secondary CAR-T infusion and provided reference for salvage treatment strategies after CAR-T relapse.

Blinatumomab

10.22541/au.167523854.48320547/v1

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Influenza-specific effector memory B cells predict long-lived antibody responses to vaccination in humans

bioRxiv (Cold Spring Harbor Laboratory) (2019)

Anoma Nellore Esther Zumaquero Christopher D. Scharer R. Glenn King Christopher M. Tipton

Abstract Seasonal influenza vaccination elicits hemagglutinin (HA)-specific CD27 + memory B cells (Bmem) that differ in expression of T-bet, BACH2 and TCF7. T-bet hi BACH2 lo TCF7 lo Bmem are transcriptionally similar to effector-like memory cells while T-bet lo BACH2 + TCF7 + Bmem exhibit stem-like central memory properties. T-bet hi Bmem do not express plasma cell-specific transcription factors but do exhibit transcriptional, epigenetic, metabolic and functional changes that poise the cells for antibody production. Consistent with these changes, D7 HA + T-bet hi Bmem express intracellular immunoglobulin and T-bet hi Bmem differentiate more rapidly into ASCs in vitro. The T-bet hi Bmem response positively correlates with long-lived humoral immunity and clonotypes from T-bet hi Bmem are represented in the early secondary ASC response to repeat vaccination, suggesting that this effector-like population can be used to predict vaccine durability and recall potential.

10.1101/643973

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Citations (15)