Publications by authors named "Wen Lei"

274 Publications

Field-Free Improvement of Oxygen Evolution Reaction in Magnetic Two-Dimensional Heterostructures.

Nano Lett 2021 Dec 3. Epub 2021 Dec 3.

Jiangxi Key Laboratory of Nanomaterials and Sensors, School of Physics, Communication and Electronics, Jiangxi Normal University, 99 Ziyang Avenue, Nanchang 330022, Jiangxi, China.

Ferromagnetic (FM) electrocatalysts have been demonstrated to reduce the kinetic barrier of oxygen evolution reaction (OER) by spin-dependent kinetics and thus enhance the efficiency fundamentally. Accordingly, FM two-dimensional (2D) materials with unique physicochemical properties are expected to be promising oxygen-evolution catalysts; however, related research is yet to be reported due to their air-instabilities and low Curie temperatures (). Here, based on the synthesis of 2D air-stable FM CrTe nanosheets with a low around 200 K, room-temperature ferromagnetism is achieved in CrTe by proximity to an antiferromagnetic (AFM) CrOOH, demonstrating the accomplishment of long-ranged FM ordering in CrTe because the magnetic proximity effect stems from paramagnetic (PM)/AFM heterostructure. Therefore, the OER performance can be permanently promoted (without applied magnetic field due to nonvolatile nature of spin) after magnetization. This work demonstrates that a representative PM/AFM 2D heterostructure, CrTe/CrOOH, is expected to be a high-efficient magnetic heterostructure catalysts for oxygen-evolution.
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http://dx.doi.org/10.1021/acs.nanolett.1c03981DOI Listing
December 2021

T cell landscape and dynamics in immunoglobulin light chain amyloidosis before and after daratumumab-based therapy.

Clin Transl Med 2021 11;11(11):e582

Department of Immunology, School of Basic Medical Sciences, Peking University. NHC Key Laboratory of Medical Immunology (Peking University), Beijing, China.

Amyloid light-chain (AL) is characterized by the presence of small, poorly proliferating plasma cell clones with the production and deposition of light chains into tissues. T cell changes within the tumour microenvironment in AL are poorly understood. By sequencing at a single-cell level of CD3 T cells purified from bone marrow (BM) and blood of newly diagnosed AL patients before and after a combination of daratumumab with cyclophosphamide, bortezomib, and dexamethasone (Dara-BCD), we analysed the transcriptomic features of T cells and found an expansion, activation and type I cytokine upregulation in BM and circulating T cells after the treatment. More prominent changes were shown in CD8 T cells. In particular, we found the presence of CD8 BM resident memory T cells (T ) with high expression of inhibitory molecules in AL patients at diagnosis. After Dara-BCD, these T cells were quickly activated with downregulation of suppressive molecules and upregulation of IFNG expression. These data collectively demonstrate that Dara-based therapy in patients with AL amyloidosis promotes anti-tumour T cell responses. The similar transcriptomic features of BM and circulating T cells before and after therapy further provide a less invasive approach for molecular monitoring of T cell response in AL amyloidosis.
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http://dx.doi.org/10.1002/ctm2.582DOI Listing
November 2021

Incidence and prophylaxis of herpes zoster in relapsed or refractory B-cell lymphoma patients after CD19-specific CAR-T cell therapy.

Leuk Lymphoma 2021 Nov 28:1-4. Epub 2021 Nov 28.

Department of Hematology, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China.

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http://dx.doi.org/10.1080/10428194.2021.2010062DOI Listing
November 2021

Prevalence of Echinococcus Species in Wild Foxes and Stray Dogs in Qinghai Province, China.

Am J Trop Med Hyg 2021 Nov 15. Epub 2021 Nov 15.

National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), NHC Key Laboratory of Parasite and Vector Biology, WHO Collaborating Center for Tropical Diseases, National Center for International Research on Tropical Diseases, Shanghai, China.

Echinococcosis is a zoonotic parasitic disease that is highly endemic to the Qinghai province of China. Limited data are available on the prevalence of the causal pathogen, Echinococcus spp., in definitive hosts in this region. Thus, the aim of this study was to evaluate the prevalence of Echinococcus spp. in wild foxes and stray dogs in Qinghai province. Five hundred and twenty-eight feces from wild foxes and 277 from stray dogs were collected from 11 counties in the Golog, Yushu, and Haixi prefectures and screened for Echinococcus spp. using copro-DNA polymerase chain reaction (PCR). In total, 5.5% of wild foxes and 15.2% of stray dogs tested positive for Echinococcus spp. The prevalence rates of Echinococcus spp. in wild foxes in Golog, Yushu, and Haixi were 7.3%, 5.2%, and 1.9%, respectively. In stray dogs, these rates were 13.3%, 17.3%, and 0%, respectively. Sequencing analysis determined that Echinococcus multilocularis was the most prevalent species, occurring in 4.0% and 12.6% of wild foxes and stray dogs, respectively. Echinococcus shiquicus was observed in 1.5% of wild foxes and 0.7% of stray dogs. Echinococcus granulosus was observed only in wild dogs, with a prevalence rate of 1.8%. To our knowledge, this is the first report on the prevalence of E. shiquicus in dogs in Qinghai province. The current results improve our understanding of the transmission and dissemination of human echinococcosis and suggest that exposure to the eggs of E. multilocularis harbored by wild foxes and stray dogs may pose a great risk of alveolar echinococcosis to humans in Qinghai province.
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http://dx.doi.org/10.4269/ajtmh.21-0622DOI Listing
November 2021

A Novel Six Autophagy-Related Genes Signature Associated With Outcomes and Immune Microenvironment in Lower-Grade Glioma.

Front Genet 2021 13;12:698284. Epub 2021 Oct 13.

Department of Neurosurgery, Guangdong Sanjiu Brain Hospital, Guangzhou, China.

Since autophagy and the immune microenvironment are deeply involved in the tumor development and progression of Lower-grade gliomas (LGG), our study aimed to construct an autophagy-related risk model for prognosis prediction and investigate the relationship between the immune microenvironment and risk signature in LGG. Therefore, we identified six autophagy-related genes (BAG1, PTK6, EEF2, PEA15, ITGA6, and MAP1LC3C) to build in the training cohort ( = 305 patients) and verify the prognostic model in the validation cohort ( = 128) and the whole cohort ( = 433), based on the data from The Cancer Genome Atlas (TCGA). The six-gene risk signature could divide LGG patients into high- and low-risk groups with distinct overall survival in multiple cohorts (all < 0.001). The prognostic effect was assessed by area under the time-dependent ROC (t-ROC) analysis in the training, validation, and whole cohorts, in which the AUC value at the survival time of 5 years was 0.837, 0.755, and 0.803, respectively. Cox regression analysis demonstrated that the risk model was an independent risk predictor of OS (HR > 1, < 0.05). A nomogram including the traditional clinical parameters and risk signature was constructed, and t-ROC, C-index, and calibration curves confirmed its robust predictive capacity. KM analysis revealed a significant difference in the subgroup analyses' survival. Functional enrichment analysis revealed that these autophagy-related signatures were mainly involved in the phagosome and immune-related pathways. Besides, we also found significant differences in immune cell infiltration and immunotherapy targets between risk groups. In conclusion, we built a powerful predictive signature and explored immune components (including immune cells and emerging immunotherapy targets) in LGG.
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http://dx.doi.org/10.3389/fgene.2021.698284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8548643PMC
October 2021

Severe fever with thrombocytopenia syndrome virus (SFTSV)-host interactome screen identifies viral nucleoprotein-associated host factors as potential antiviral targets.

Comput Struct Biotechnol J 2021 1;19:5568-5577. Epub 2021 Oct 1.

State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne virus that causes severe infection in humans characterized by an acute febrile illness with thrombocytopenia and hemorrhagic complications, and a mortality rate of up to 30%. Understanding on virus-host protein interactions may facilitate the identification of druggable antiviral targets. Herein, we utilized liquid chromatography-tandem mass spectrometry to characterize the SFTSV interactome in human embryonic kidney-derived permanent culture (HEK-293T) cells. We identified 445 host proteins that co-precipitated with the viral glycoprotein N, glycoprotein C, nucleoprotein, or nonstructural protein. A network of SFTSV-host protein interactions based on reduced viral fitness affected upon host factor down-regulation was then generated. Screening of the DrugBank database revealed numerous drug compounds that inhibited the prioritized host factors in this SFTSV interactome. Among these drug compounds, the clinically approved artenimol (an antimalarial) and omacetaxine mepesuccinate (a cephalotaxine) were found to exhibit anti-SFTSV activity . The higher selectivity of artenimol (71.83) than omacetaxine mepesuccinate (8.00) highlights artenimol's potential for further antiviral development. Mechanistic evaluation showed that artenimol interfered with the interaction between the SFTSV nucleoprotein and the host glucose-6-phosphate isomerase (GPI), and that omacetaxine mepesuccinate interfered with the interaction between the viral nucleoprotein with the host ribosomal protein L3 (RPL3). In summary, the novel interactomic data in this study revealed the virus-host protein interactions in SFTSV infection and facilitated the discovery of potential anti-SFTSV treatments.
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http://dx.doi.org/10.1016/j.csbj.2021.09.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8523828PMC
October 2021

Rational Design of the Lotus-Like N-Co VO -Co Heterostructures with Well-Defined Interfaces in Suppressing the Shuttle Effect and Dendrite Growth in Lithium-Sulfur Batteries.

Small 2021 Oct 27:e2104109. Epub 2021 Oct 27.

New Energy Research Institute, School of Environment and Energy, South China University of Technology, Higher Education Mega Center, 382 East Waihuan Road, Guangzhou, 510006, China.

The shuttle effect caused by soluble lithium polysulfides (LiPSs) and intrinsic slow electrochemical transformation from LiPSs to Li S/Li S will induce undesirable cycling performance, which is the primary obstruct limiting the practical applications of lithium-sulfur (Li-S) batteries. Here a convenient method is designed to fabricate the 2D louts-like N-Co VO -Co heterostructures with well-abundant interfaces and oxygen vacancies (V ), endowing the materials with both "sulfiphilic" and "lithiophilic" features. When employed as the modification layer coated on commercial Celgard 2400 separator, the as-prepared N-Co VO -Co/PP with synergistic adsorption-electrocatalysis effects achieves desirable sulfur electrochemistry, thus showing a high initial discharge capacity of 1466.4 mAh g at 0.1 C and stable cycle life with a fade rate of 0.03% per cycle over 1000 cycle at 3.0 C. Moreover, a superior areal capacity of 12.84 mAh cm is preserved under high sulfur loading of 14.3 mg cm .
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http://dx.doi.org/10.1002/smll.202104109DOI Listing
October 2021

In Silico Structure-Based Design of Antiviral Peptides Targeting the Severe Fever with Thrombocytopenia Syndrome Virus Glycoprotein Gn.

Viruses 2021 Oct 11;13(10). Epub 2021 Oct 11.

State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus in Asia that causes severe disease. Despite its clinical importance, treatment options for SFTSV infection remains limited. The SFTSV glycoprotein Gn plays a major role in mediating virus entry into host cells and is therefore a potential antiviral target. In this study, we employed an in silico structure-based strategy to design novel cyclic antiviral peptides that target the SFTSV glycoprotein Gn. Among the cyclic peptides, HKU-P1 potently neutralizes the SFTSV virion. Combinatorial treatment with HKU-P1 and the broad-spectrum viral RNA-dependent RNA polymerase inhibitor favipiravir exhibited synergistic antiviral effects in vitro. The in silico peptide design platform in this study may facilitate the generation of novel antiviral peptides for other emerging viruses.
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http://dx.doi.org/10.3390/v13102047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8539749PMC
October 2021

Emerging SARS-CoV-2 variants expand species tropism to murines.

EBioMedicine 2021 Nov 21;73:103643. Epub 2021 Oct 21.

State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China; Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China; Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China; Department of Clinical Microbiology and Infection Control, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, China; Department of Microbiology, Queen Mary Hospital, Pokfulam, Hong Kong Special Administrative Region, China; Academician workstation of Hainan Province, Hainan Medical University, and Hainan Medical University-The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China. Electronic address:

Background: Wildtype mice are not susceptible to SARS-CoV-2 infection. Emerging SARS-CoV-2 variants, including B.1.1.7, B.1.351, P.1, and P.3, contain mutations in spike that has been suggested to associate with an increased recognition of mouse ACE2, raising the postulation that these SARS-CoV-2 variants may have evolved to expand species tropism to wildtype mouse and potentially other murines. Our study evaluated this possibility with substantial public health importance.

Methods: We investigated the capacity of wildtype (WT) SARS-CoV-2 and SARS-CoV-2 variants in infecting mice (Mus musculus) and rats (Rattus norvegicus) under in vitro and in vivo settings. Susceptibility to infection was evaluated with RT-qPCR, plaque assays, immunohistological stainings, and neutralization assays.

Findings: Our results reveal that B.1.1.7 and other N501Y-carrying variants but not WT SARS-CoV-2 can infect wildtype mice. High viral genome copies and high infectious virus particle titres are recovered from the nasal turbinate and lung of B.1.1.7-inocluated mice for 4-to-7 days post infection. In agreement with these observations, robust expression of viral nucleocapsid protein and histopathological changes are detected from the nasal turbinate and lung of B.1.1.7-inocluated mice but not that of the WT SARS-CoV-2-inoculated mice. Similarly, B.1.1.7 readily infects wildtype rats with production of infectious virus particles.

Interpretation: Our study provides direct evidence that the SARS-CoV-2 variant, B.1.1.7, as well as other N501Y-carrying variants including B.1.351 and P.3, has gained the capability to expand species tropism to murines and public health measures including stringent murine control should be implemented to facilitate the control of the ongoing pandemic.

Funding: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.
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http://dx.doi.org/10.1016/j.ebiom.2021.103643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8530107PMC
November 2021

Survival outcomes, hematologic complications and growth impairment after sequential chemoradiotherapy in intracranial NGGCTs: a retrospective study.

Strahlenther Onkol 2021 Oct 21. Epub 2021 Oct 21.

Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, 510515, Guangzhou, China.

Purpose: This study aimed to evaluate the clinical features, prognostic factors, and survival outcomes for patients with intracranial nongerminomatous germ cell tumors (NGGCTs), with a particular focus on treatment toxicity for long-term survivors.

Methods: Intracranial NGGCTs treated with platinum-based chemotherapy and craniospinal irradiation (CSI) in our institution were retrospectively analyzed. Hematological complications following sequential chemoradiotherapy as well as height and weight in childhood survivors were evaluated. Plasma growth hormone (GH) concentrations prior to and after radiotherapy were obtained for the comparisons.

Results: A total of 111 intracranial NGGCTs were included. The 3‑year overall survival (OS) and event-free survival (EFS) rates were 83.5% ± 3.9% and 71.0% ± 4.8%, respectively. A combined treatment modality consisting of ≥ 4 cycles of platinum-based chemotherapy and CSI was associated with an improved OS (P = 0.003) and EFS (P < 0.001). Thrombocytopenia of any grade occurred in 35.4% (34/96) of patients, and the threshold age for an increased risk of thrombocytopenia was 14 years (area under the curve AUC = 0.752, P < 0.0001) as derived from receiver operating characteristic (ROC) analysis. Growth impediment was found in 8 of 56 (14%) patients. The age for receiving radiotherapy was found to inversely correlate with height development, revealing a cut-off age of 11.5 years for risking growth impairment (AUC = 0.806, P = 0.004). Consistently, a significant decline in plasma growth hormone after radiotherapy was observed in patients ≤ 11.5 years (P < 0.01) but not patients > 11.5 years. (P > 0.05).

Conclusion: Our study suggested that a combined treatment modality with at least four cycles of chemotherapy and CSI was safe and effective for patients with intracranial NGGCTs. Radiotherapy should be used with caution for patients < 11.5 years due to growth impairment.
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http://dx.doi.org/10.1007/s00066-021-01857-3DOI Listing
October 2021

Histone Deacetylase Inhibitor Trichostatin A Reduces Endothelial Cell Proliferation by Suppressing STAT5A-Related Gene Transcription.

Front Oncol 2021 23;11:746266. Epub 2021 Sep 23.

Department of Clinical Oncology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

Inhibitors of histone deacetylases (HDACi) have shown promising effects in preclinical applications for the treatment of many diseases. Confusedly though, the effects of the HDACi trichostatin A (TSA) on angiogenesis are variable among different diseases. This study investigated the direct effects of TSA on endothelial cells, which plays essential roles in angiogenesis and the underlying molecular events. TSA reduced the viability of human umbilical vein endothelial cells (HUVECs), in which proliferation-related genes including , , and were found to be involved. Furthermore, signal transducer and activator of transcription 5 A (STAT5A) was demonstrated to be reduced by TSA and to mediate TSA-induced downregulation of , , and and HUVEC proliferation. Mechanistically, data showed that STAT5A directly bound to the promoters of , , and and activated their transcription through special DNA sequence sites. Finally, the TSA-STAT5A-, , and axis also worked in a cancerous endothelial cell angiogenesis model. The results of this study revealed novel mechanisms underlying the effects of TSA on endothelial cells and provided insights for angiogenesis-associated diseases.
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http://dx.doi.org/10.3389/fonc.2021.746266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8506210PMC
September 2021

Brain Abscess in a Multiple Myeloma Patient Treated with Proteasome Inhibitor: A Case Report and Review of the Literature.

Brain Sci 2021 Sep 13;11(9). Epub 2021 Sep 13.

Department of Hematology, College of Medicine, The Second Affiliated Hospital, Zhejiang University, Hangzhou 310009, China.

Nocardia brain abscess is relatively rare, accounting for about 1-2% of all brain abscesses, and its mortality rate is three times higher than of other types of bacterial brain abscesses; thus, early diagnosis and treatment are essential. Nocardia brain abscess generally occurs in immunodeficient patients. We report a case of brain abscess in a multiple myeloma patient treated with proteasome inhibitor (bortezomib and ixazomib), cyclophosphamide, and corticosteroid. The patient was treated with ceftriaxone and trimethoprim-sulfamethoxazole, together with drainage of the brain abscess. Regular brain MRI follow-ups showed that intracranial lesions were gradually absorbed and improved.
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http://dx.doi.org/10.3390/brainsci11091204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467943PMC
September 2021

Research Progress on Coating Structure of Silicon Anode Materials for Lithium-Ion Batteries.

ChemSusChem 2021 Sep 17. Epub 2021 Sep 17.

The State Key Laboratory of Refractories and Metallurgy and, Institute of Advanced Materials and Nanotechnology, Wuhan University of Science and Technology, Wuhan, 430081, P. R. China.

Silicon, which has been widely studied by virtue of its extremely high theoretical capacity and abundance, is recognized as one of the most promising anode materials for the next generation of lithium-ion batteries. However, silicon undergoes tremendous volume change during cycling, which leads to the destruction of the electrode structure and irreversible capacity loss, so the promotion of silicon materials in commercial applications is greatly hampered. In recent years, many strategies have been proposed to address these shortcomings of silicon. This Review focused on different coatings materials (e. g., carbon-based materials, metals, oxides, conducting polymers, etc.) for silicon materials. The role of different types of materials in the modification of silicon-based material encapsulation structure was reviewed to confirm the feasibility of the protective layer strategy. Finally, the future research direction of the silicon-based material coating structure design for the next-generation lithium-ion battery was summarized.
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http://dx.doi.org/10.1002/cssc.202101837DOI Listing
September 2021

Crystal phase transition and polyhedron transformation towards the evolution of photoluminescence and the improvement of thermal stability in efficient blue-emitting BaSrAlSiO:Eu.

Dalton Trans 2021 Sep 14;50(35):12147-12158. Epub 2021 Sep 14.

Engineering Research Center of Nano-Geomaterials of Ministry of Education, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan 430074, China.

Investigations into novel single-phase phosphors with outstanding luminescence properties and excellent thermal stability are urgently needed in the lighting field. In this work, a crystal phase transition and polyhedron transformation strategy cation substitution has been proposed. controlling the Sr/Ba ratio, the structural evolution of the phosphor from a monocelsian phase to a hexacelsian or feldspar phase and the variation of the local environments of Eu sites are correspondingly studied in BaSrAlSiO:0.03Eu. Consequently, the optimal BaSrAlSiO:0.03Eu sample exhibits a higher intensity, up to 15.2-fold that of BaAlSiO:0.03Eu. A narrower full-width-at-half-maximum of 73 nm, better color purity of 82.96%, and an internal quantum yield of 82.3% can be realized. With an increase in temperature, the emission intensity losses of samples from = -10.0-47.0% are no more than 10.0% at 473 K. Moreover, a WLED (CCT = 5210 K; CRI = 90.3) fabricated using BaSrAlSiO:0.03Eu displays warmer white light than one fabricated using BaMgAlO:Eu under the same assembly and test conditions. Analysis shows that the structural evolution with reduced polyhedral symmetry and the condensed crystal structure with fortified rigidity are responsible for the improvement in properties. This discovery demonstrates that the utilization of a crystal phase transition and symmetrical coordination is an efficient way to develop novel efficient phosphors and other related materials.
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http://dx.doi.org/10.1039/d1dt01140eDOI Listing
September 2021

Broadband GaAsSb Nanowire Array Photodetectors for Filter-Free Multispectral Imaging.

Nano Lett 2021 09 23;21(17):7388-7395. Epub 2021 Aug 23.

Department of Electronic Materials Engineering, Research School of Physics, The Australian National University, Canberra, ACT 2601, Australia.

Highly compact, filter-free multispectral photodetectors have important applications in biological imaging, face recognition, and remote sensing. In this work, we demonstrate room-temperature wavelength-selective multipixel photodetectors based on GaAsSb nanowire arrays grown by metalorganic vapor phase epitaxy, providing more than 10 light detection channels covering both visible and near-infrared ranges without using any optical filters. The nanowire array geometry-related tunable spectral photoresponse has been demonstrated both theoretically and experimentally and shown to be originated from the strong and tunable resonance modes that are supported in the GaAsSb array nanowires. High responsivity and detectivity (up to 44.9 A/W and 1.2 × 10 cm √Hz/W at 1 V, respectively) were obtained from the array photodetectors, enabling high-resolution RGB color imaging by applying such a nanowire array based single pixel imager. The results indicate that our filter-free wavelength-selective GaAsSb nanowire array photodetectors are promising candidates for the development of future high-quality multispectral imagers.
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http://dx.doi.org/10.1021/acs.nanolett.1c02777DOI Listing
September 2021

Treatment-Related Adverse Events of Chimeric Antigen Receptor T-Cell (CAR T) in Clinical Trials: A Systematic Review and Meta-Analysis.

Cancers (Basel) 2021 Aug 3;13(15). Epub 2021 Aug 3.

Department of Hematology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, China.

Chimeric antigen receptors T (CAR-T) cell therapy of cancer is a rapidly evolving field. It has been shown to be remarkably effective in cases of hematological malignancies, and its approval by the FDA has significantly increased the enthusiasm for wide clinical usage and development of novel CAR-T therapies. However, it has also challenged physicians and investigators to recognize and deal with treatment-associated toxicities. A total of 2592 patients were included from 84 eligible studies that were systematically searched and reviewed from the databases of PubMed, de, the American Society of Hematology and the Cochrane Library. The meta-analysis and subgroup analysis by a Bayesian logistic regression model were used to evaluate the incidences of therapy-related toxicities such as cytokine release syndrome (CRS) and neurological symptoms (NS), and the differences between different targets and cancer types were analyzed. The pooled all-grade CRS rate and grade ≥ 3 CRS rate was 77% and 29%, respectively, with a significantly higher incidence in the hematologic malignancies (all-grade: 81%; grade ≥ 3: 29%) than in solid tumors (all-grade: 37%; grade ≥ 3: 19%). The pooled estimate NS rate from the individual studies were 40% for all-grade and 28% for grade ≥ 3. It was also higher in the hematologic subgroup than in the solid tumors group. The subgroup analysis by cancer type showed that higher incidences of grade ≥ 3 CRS were observed in anti-CD19 CAR-T therapy for ALL and NHL, anti-BCMA CAR-T for MM, and anti-CEA CAR-T for solid tumors, which were between 24-36%, while higher incidences of grade ≥ 3 NS were mainly observed in CD19-ALL/NHL (23-37%) and BCMA-MM (12%). Importantly, subgroup analysis on anti-CD19 CAR-T studies showed that young patients (vs. adult patients), allologous T cell origin (vs. autologous origin), gamma retrovirus vector, and higher doses of CAR-T cells were associated with high-grade CRS. On the other hand, the patients with NHL (vs ALL), administered with higher dose of CAR-T, and adult patients (vs. young patients) had an increased incidence of grade ≥ 3 NS events. This study offers a comprehensive summary of treatment-related toxicity and will guide future clinical trials and therapeutic designs investigating CAR T cell therapy.
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http://dx.doi.org/10.3390/cancers13153912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345443PMC
August 2021

CD70-targeting CAR-T cells have potential activity against CD19-negative B-cell Lymphoma.

Cancer Commun (Lond) 2021 09 27;41(9):925-929. Epub 2021 Jul 27.

Department of Hematology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310009, P. R. China.

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http://dx.doi.org/10.1002/cac2.12201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8441055PMC
September 2021

An efficient and general method for the synthesis of stable isotope deuterium labeled phthalate esters.

J Labelled Comp Radiopharm 2021 08 26;64(10):378-384. Epub 2021 Jun 26.

State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai, China.

An efficient and general synthetic route of deuterium-labeled phthalate esters is described with high isotopic enrichment and excellent chemical purities using inexpensive and readily available o-xylene-D as labeled starting material. The structures and isotope-abundance were confirmed via H NMR and mass spectrometry. These deuterium labeled phthalate esters can be used as analytical reference standards for the detection of plasticizer residues in soil, water, food, plastic products, etc.
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http://dx.doi.org/10.1002/jlcr.3930DOI Listing
August 2021

Targeting highly pathogenic coronavirus-induced apoptosis reduces viral pathogenesis and disease severity.

Sci Adv 2021 06 16;7(25). Epub 2021 Jun 16.

State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.

Infection by highly pathogenic coronaviruses results in substantial apoptosis. However, the physiological relevance of apoptosis in the pathogenesis of coronavirus infections is unknown. Here, with a combination of in vitro, ex vivo, and in vivo models, we demonstrated that protein kinase R-like endoplasmic reticulum kinase (PERK) signaling mediated the proapoptotic signals in Middle East respiratory syndrome coronavirus (MERS-CoV) infection, which converged in the intrinsic apoptosis pathway. Inhibiting PERK signaling or intrinsic apoptosis both alleviated MERS pathogenesis in vivo. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV induced apoptosis through distinct mechanisms but inhibition of intrinsic apoptosis similarly limited SARS-CoV-2- and SARS-CoV-induced apoptosis in vitro and markedly ameliorated the lung damage of SARS-CoV-2-inoculated human angiotensin-converting enzyme 2 (hACE2) mice. Collectively, our study provides the first evidence that virus-induced apoptosis is an important disease determinant of highly pathogenic coronaviruses and demonstrates that this process can be targeted to attenuate disease severity.
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http://dx.doi.org/10.1126/sciadv.abf8577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208716PMC
June 2021

Effects of Rice Straw Powder (RSP) Size and Pretreatment on Properties of FDM 3D-Printed RSP/Poly(Lactic Acid) Biocomposites.

Molecules 2021 May 27;26(11). Epub 2021 May 27.

College of Science, Nanjing Forestry University, Nanjing 210037, China.

To develop a new kind of environment-friendly composite filament for fused deposition modeling (FDM) 3D printing, rice straw powder (RSP)/poly(lactic acid) (PLA) biocomposites were FDM-3D-printed, and the effects of the particle size and pretreatment of RSP on the properties of RSP/PLA biocomposites were investigated. The results indicated that the 120-mesh RSP/PLA biocomposites (named 120#RSP/PLA) showed better performance than RSP/PLA biocomposites prepared with other RSP sizes. Infrared results showed that pretreatment of RSP by different methods was successful, and scanning electron microscopy indicated that composites prepared after pretreatment exhibited good interfacial compatibility due to a preferable binding force between fiber and matrix. When RSP was synergistically pretreated by alkaline and ultrasound, the composite exhibited a high tensile strength, tensile modulus, flexural strength, and flexural modulus of 58.59, 568.68, 90.32, and 3218.12 MPa, respectively, reflecting an increase of 31.19%, 16.48%, 18.75%, and 25.27%, respectively, compared with unmodified 120#RSP/PLA. Pretreatment of RSP also improved the thermal stability and hydrophobic properties, while reducing the water absorption of 120#RSP/PLA. This work is believed to provide highlights of the development of cost-effective biocomposite filaments and improvement of the properties of FDM parts.
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http://dx.doi.org/10.3390/molecules26113234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197895PMC
May 2021

Individualized Nomogram for Predicting Survival in Patients with Brain Metastases After Stereotactic Radiosurgery Utilizing Driver Gene Mutations and Volumetric Surrogates.

Front Oncol 2021 13;11:659538. Epub 2021 May 13.

Department of Oncology, Guangdong Sanjiu Brain Hospital, Guangzhou, China.

It is well-known that genomic mutational analysis plays a significant role in patients with NSCLC for personalized treatment. Given the increasing use of stereotactic radiosurgery (SRS) for brain metastases (BM), there is an emerging need for more precise assessment of survival outcomes after SRS. Patients with BM and treated by SRS were eligible in this study. The primary endpoint was overall survival (OS). Cox regression models were used to identify independent prognostic factors. A survival predictive nomogram was developed and evaluated by Concordance-index (C-index), area under the curve (AUC), and calibration curve. From January 2016 to December 2019, a total of 356 BM patients were eligible. The median OS was 17.7 months [95% confidence interval (CI) 15.5-19.9] and the actual OS at 1- and 2-years measured 63.2 and 37.6%, respectively. A nomogram for OS was developed by incorporating four independent prognostic factors: Karnofsky Performance Score, cumulative tumor volume, gene mutation status, and serum lactate dehydrogenase. The nomogram was validated in a separate cohort and demonstrated good calibration and good discriminative ability (C-index = 0.780, AUC = 0.784). The prognostic accuracy of the nomogram (0.792) was considerably enhanced when compared with classical prognostic indices, including the Graded Prognostic Assessment (0.708), recursive partitioning analysis (0.587), and the SRS (0.536). Kaplan-Meier curves showed significant differences in OS among the stratified low-, median- and high-risk groups ( < 0.001). In conclusion, we developed and validated an individualized prognostic nomogram by integrating physiological, volumetric, clinical chemistry, and molecular biological surrogates. Although this nomogram should be validated by independent external study, it has a potential to facilitate more precise risk-stratifications to guide personalized treatment for BM.
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http://dx.doi.org/10.3389/fonc.2021.659538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158152PMC
May 2021

Enhanced Diffusion Kinetics of Li Ions in Double-Shell Hollow Carbon Fibers.

ACS Appl Mater Interfaces 2021 Jun 24;13(21):24604-24614. Epub 2021 May 24.

The State Key Laboratory of Refractories and Metallurgy, Wuhan University of Science and Technology, Wuhan 430081, China.

The rational design and preparation of hierarchical hollow structures have promising potential in electrochemical energy storage systems. In this paper, double-shell hollow carbon fibers (DSHCFs) with tunable thickness and shell spacing are prepared using hollow electrospun polystyrene fibers as the hard template and in situ coated polypyrrole as the carbon source. The as-prepared DSHCFs with an optimized structure exhibit a submicrometer shell spacing and a nanoscaled shell thickness, which guarantees sufficient contact area with the electrolyte and provides abundant electrochemical active sites for Li storage. Owing to the unique structural advantages, a DSHCF-based anode shows favorable transport kinetics for both Li ions and electrons during the lithiation/delithiation process, and a high reversible capacity of 348 mAh g at 5.0 A g is well maintained even after 500 cycles with no obvious capacity attenuation. Particular emphasis is given to kinetic Li storage mechanisms in DSHCFs that are discussed in detail, providing a new avenue for developing high-performance carbon materials for the practical application of energy storage devices.
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http://dx.doi.org/10.1021/acsami.1c01222DOI Listing
June 2021

A non-small cell lung cancer (NSCLC) patient with leptomeningeal metastasis harboring rare epidermal growth factor receptor (EGFR) mutations G719S and L861Q benefited from doubling dosage of osimertinib: a case report.

Ann Palliat Med 2021 May 8;10(5):5897-5901. Epub 2021 May 8.

Department of Neuro-Oncology, Guangdong Sanjiu Brain Hospital, Guangzhou, China.

Leptomeningeal metastasis (LM) is a rare but lethal complication of advanced non-small cell lung cancer (NSCLC) that has a devastating impact on patient survival and quality of life. Osimertinib, an irreversible tyrosine kinase inhibitor, is approved as a therapy for advanced NSCLC with epidermal growth factor receptor (EGFR) mutation. However, the efficacy and optimal dosage of osimertinib in the treatment of NSCLC patients with LM who harbor uncommon EGFR mutations have yet to be fully investigated. Herein, we report a case of an advanced NSCLC patient with LM carrying EGFR G719S and L861Q, who was successfully treated by osimertinib at 160 mg. The patient initially presented with clear cell renal carcinoma and renal metastatic adenocarcinoma, and underwent right nephrectomy. At 2 months after nephrectomy, he developed a disturbance of consciousness and was subsequently diagnosed with NSCLC with LM by meningeal biopsy pathology and cerebrospinal fluid (CSF) cytology. Next-generation sequencing detected the rare EGFR mutations G719S and L861R in the meningeal biopsy tissues. The patient was then administered osimertinib at 80 mg quaque die (QD); after 1 month of treatment, his symptoms were alleviated. However, two months later, he experienced epileptic episode. Subsequently, the osimertinib dosage was doubled to 160 mg QD. After 1 month of treatment, the patient achieved central nervous system (CNS) response, and at the time of this manuscript's submission, he had maintained stable disease (SD) for more than 1 year. To our knowledge, this study provides the first clinical evidence that the administration of osimertinib at 160 mg once daily can achieve an encouraging, durable response in an NSCLC patient with LM carrying EGFR G719S and L861Q.
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http://dx.doi.org/10.21037/apm-20-2556DOI Listing
May 2021

structure-based discovery of a SARS-CoV-2 main protease inhibitor.

Int J Biol Sci 2021 10;17(6):1555-1564. Epub 2021 Apr 10.

Department of Clinical Microbiology and Infection Control, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong Province, China.

The Coronavirus Disease 2019 (COVID-19) pandemic caused by the novel lineage B betacoroanvirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in significant mortality, morbidity, and socioeconomic disruptions worldwide. Effective antivirals are urgently needed for COVID-19. The main protease (M) of SARS-CoV-2 is an attractive antiviral target because of its essential role in the cleavage of the viral polypeptide. In this study, we performed an structure-based screening of a large chemical library to identify potential SARS-CoV-2 M inhibitors. Among 8,820 compounds in the library, our screening identified trichostatin A, a histone deacetylase inhibitor and an antifungal compound, as an inhibitor of SARS-CoV-2 M activity and replication. The half maximal effective concentration of trichostatin A against SARS-CoV-2 replication was 1.5 to 2.7µM, which was markedly below its 50% effective cytotoxic concentration (75.7µM) and peak serum concentration (132µM). Further drug compound optimization to develop more stable analogues with longer half-lives should be performed. This structure-based drug discovery platform should facilitate the identification of additional enzyme inhibitors of SARS-CoV-2.
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http://dx.doi.org/10.7150/ijbs.59191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071767PMC
May 2021

Multimodal investigation of rat hepatitis E virus antigenicity: Implications for infection, diagnostics, and vaccine efficacy.

J Hepatol 2021 06 9;74(6):1315-1324. Epub 2021 Apr 9.

Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong; Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong; The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong, Hong Kong. Electronic address:

Background & Aims: Rat hepatitis E virus (Orthohepevirus species C; HEV-C1) is an emerging cause of viral hepatitis in humans. HEV-C1 is divergent from other HEV variants infecting humans that belong to Orthohepevirus species A (HEV-A). This study assessed HEV-C1 antigenic divergence from HEV-A and investigated the impact of this divergence on infection susceptibility, serological test sensitivity, and vaccine efficacy.

Methods: Immunodominant E2s peptide sequences of HEV-A and HEV-C1 were aligned. Interactions of HEV-C1 E2s and anti-HEV-A monoclonal antibodies (mAbs) were modeled. Recombinant peptides incorporating E2s of HEV-A (HEV-A4 p239) and HEV-C1 (HEV-C1 p241) were expressed. HEV-A and HEV-C1 patient sera were tested using antibody enzymatic immunoassays (EIA), antigen EIAs, and HEV-A4 p239/HEV-C1 p241 immunoblots. Rats immunized with HEV-A1 p239 vaccine (Hecolin), HEV-A4 p239 or HEV-C1 p241 peptides were challenged with a HEV-C1 strain.

Results: E2s sequence identity between HEV-A and HEV-C1 was only 48%. There was low conservation at E2s residues (23/53; 43.4%) involved in mAb binding. Anti-HEV-A mAbs bound HEV-C1 poorly in homology modeling and antigen EIAs. Divergence resulted in low sensitivity of commercial antigen (0%) and antibody EIAs (10-70%) for HEV-C1 diagnosis. Species-specific HEV-A4 p239/HEV-C1 p241 immunoblots accurately differentiated HEV-A and HEV-C1 serological profiles in immunized rats (18/18; 100%) and infected-patient sera (32/36; 88.9%). Immunization with Hecolin and HEV-A4 p239 was partially protective while HEV-C1 p241 was fully protective against HEV-C1 infection in rats.

Conclusions: Antigenic divergence significantly decreases sensitivity of hepatitis E serodiagnostic assays for HEV-C1 infection. Species-specific immunoblots are useful for diagnosing HEV-C1 and for differentiating the serological profiles of HEV-A and HEV-C1. Prior HEV-A exposure is not protective against HEV-C1. HEV-C1 p241 is an immunogenic vaccine candidate against HEV-C1.

Lay Summary: Rat hepatitis E virus (HEV-C1) is a new cause of hepatitis in humans. Using a combination of methods, we showed that HEV-C1 is highly divergent from the usual cause of human hepatitis (HEV-A). This divergence reduces the capacity of existing tests to diagnose HEV-C1 and also indicates that prior exposure to HEV-A (via infection or vaccination) is not protective against HEV-C1.
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http://dx.doi.org/10.1016/j.jhep.2020.12.028DOI Listing
June 2021

Risk stratification by long non-coding RNAs profiling in COVID-19 patients.

J Cell Mol Med 2021 05 23;25(10):4753-4764. Epub 2021 Mar 23.

Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic worldwide. Long non-coding RNAs (lncRNAs) are a subclass of endogenous, non-protein-coding RNA, which lacks an open reading frame and is more than 200 nucleotides in length. However, the functions for lncRNAs in COVID-19 have not been unravelled. The present study aimed at identifying the related lncRNAs based on RNA sequencing of peripheral blood mononuclear cells from patients with SARS-CoV-2 infection as well as health individuals. Overall, 17 severe, 12 non-severe patients and 10 healthy controls were enrolled in this study. Firstly, we reported some altered lncRNAs between severe, non-severe COVID-19 patients and healthy controls. Next, we developed a 7-lncRNA panel with a good differential ability between severe and non-severe COVID-19 patients using least absolute shrinkage and selection operator regression. Finally, we observed that COVID-19 is a heterogeneous disease among which severe COVID-19 patients have two subtypes with similar risk score and immune score based on lncRNA panel using iCluster algorithm. As the roles of lncRNAs in COVID-19 have not yet been fully identified and understood, our analysis should provide valuable resource and information for the future studies.
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http://dx.doi.org/10.1111/jcmm.16444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107096PMC
May 2021

CD19 CAR-T expressing PD-1/CD28 chimeric switch receptor as a salvage therapy for DLBCL patients treated with different CD19-directed CAR T-cell therapies.

J Hematol Oncol 2021 02 16;14(1):26. Epub 2021 Feb 16.

Department of Hematology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.

CD19-targeted chimeric antigen receptor T (CAR T) cell therapy is a promising option to treat relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). However, the majority of CAR T-treated patients will eventually progress and require salvage treatment, for which there is no current standard. In this study, we analyzed data from 6 patients with R/R DLBCL who experienced progression following CD19-CAR T therapy, and then received CD19-specific CAR T cells that express a PD-1/CD28 chimeric switch-receptor (CD19-PD-1/CD28-CAR T) as salvage therapy at our institution. After the second infusion of CAR T cells, 3 of 6 patients achieved complete remissions and the duration of the response of responsive patients ranged from 8 to 25 months. One patient showed a stable disease. In contrast, 2/6 patients died on 60 days because of progression disease. Importantly, no severe neurologic toxicity or cytokine release syndrome was observed. These data suggest that CD19-PD-1/CD28-CAR-T cells, a novel anti-CD19 CAR-T cell therapy, elicit a potent and durable anticancer response, and can be used in the post-CD19-CAR T failure setting.
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http://dx.doi.org/10.1186/s13045-021-01044-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885572PMC
February 2021

Bevacizumab as a treatment for radiation necrosis following stereotactic radiosurgery for brain metastases: clinical and radiation dosimetric impacts.

Ann Palliat Med 2021 Feb 3;10(2):2018-2026. Epub 2021 Feb 3.

Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Background: Brain necrosis (RN) is a common radiotherapy sequela for brain metastases. Bevacizumab is identified as a therapeutic strategy for RN. This study aimed to study the clinical and radiobiological impacts on the efficacy of Bevacizumab in treating RN following stereotactic radiosurgery (SRS) for brain metastases.

Methods: From April 2011 to November 2019, 40 patients diagnosed with RN after SRS for brain metastases were retrospectively analyzed. Patients were treated with Bevacizumab for RN and follow-up for 6 months using MR imaging at different timepoints. Linear regression was performed to evaluate the relationship between these variables.

Results: The median time course from the end of radiotherapy to the onset of RN was 11 months (range, 7-35 months). No significant difference was found in the edema volume between the chemotherapy group and non-chemotherapy group (P>0.05). Patients received with SRS + WBRT exhibited relatively larger edema volumes post radiotherapy than those without WBRT (P<0.05). Interestingly, the ratio of BED/GTV (Gy/cm3 ) correlated positively with the severity (time for half-reduction dose of corticosteroids) (r2 =0.13, P<0.05), and negatively with the latency period (time course for development of radiation-induced brain necrosis) (r2 =0.21, P<0.01). A new radiation doses volume index, BED × GTV (Gy·cm3 ), was proposed to facilitate the risk stratifications of patients for radiation-induced brain necrosis. Furthermore, no significant difference was found in alleviating brain edema between different regimens of Bevacizumab, i.e., 5 vs. 10 mg/kg, 2 vs. >2 cycles (both P>0.05).

Conclusions: Bevacizumab is a feasible and favorable salvage treatment of BN after SRS for patients with BM. The efficacy is mainly manifested in radiological improvement and symptoms alleviation. The development of RN was found to be largely associated with radiation dose and gross tumor volume, and thus we proposed two new indexes, i.e., BED/GTV (Gy/cm3 ) for quantitative assessment of the severity and latency time, and BED × GTV (Gy·cm3 ) for risk stratifications for BN. A low dose with two cycles of Bevacizumab is recommended.
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http://dx.doi.org/10.21037/apm-20-2417DOI Listing
February 2021

Stereotactic radiosurgery for treatment of large cerebellum metastases from lung cancer.

Ann Palliat Med 2021 Jan;10(1):220-228

Department of Neuro-Oncology, Guangdong Sanjiu Brain Hospital, Guangzhou, China. Email:

Background: Stereotactic radiosurgery (SRS) is an important treatment option. This report evaluated the efficacy and safety of SRS in patients with large cerebellum metastases from lung cancer.

Methods: Between September 2016 and January 2020, a total of 44 patients with large cerebellum metastases >2 cm from lung cancer were evaluated. A median dose of 20 Gy (range, 8-24 Gy) was delivered in 1 to 3 fractions for SRS treatment. The survival rate was analyzed with SPSS software 21.0 and compared by log-rank test using the Kaplan-Meier method.

Results: The median overall survival (OS) and neurological progression-free survival (PFS) were 10.5 months (range, 1-32 months) and 9.0 months (range, 1-32 months), respectively. The median diameter and volume of the metastases were 3.5 cm (range, 2.1-5.7 cm) and 12.5 cc (range, 1.8-39.7 cc), respectively. The median volume of peritumoral edema was 36.3 cc (range, 3.7-100.3 cc). The median ratio of tumor volume to cerebellum volume was 8.7% (range, 1.3-27.0%). The median ratio of peritumoral edema volume to cerebellum volume was 25.0% (range, 2.5-68.6%). Neurological symptoms were present in 97.7% (43/44) of patients. After SRS treatment, symptoms improved in 83.7% (36/44) patients, stabilized in 11.6% (5/44) patients, whilst two patients experienced symptomatic progression. Of the latter, one patient accepted emergency surgery and the other accepted palliative care.

Conclusions: Large cerebellum metastases are amongst the most severe forms of brain tumors. Increased tumor volume and peritumoral edema volume correlate with the most severe symptoms. SRS may be an effective alternative treatment for large cerebellum metastases from lung cancer and may preserve neurological function.
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http://dx.doi.org/10.21037/apm-20-2237DOI Listing
January 2021
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