2022 Chinese expert consensus and guidelines on clinical management of toxicity in anti-CD19 chimeric antigen receptor T-cell therapy for B-cell non-Hodgkin lymphoma

Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-cell products and advances in CAR T cell therapy,CAR T cells are expected to be used in a growing number of cases.However,CAR T-cell-associated toxicities can be severe or even fatal,thus compromising the survival benefit from this therapy.Standardizing and studying the clinical management of these toxicities are imperative.In contrast to other hematological malignancies,such as acute lymphoblastic leukemia and multiple myeloma,anti-CD19 CAR T-cell-associated toxicities in B-NHL have several distinctive features,most notably local cytokine-release syndrome(CRS).However,previously published guidelines have provided few specific recommendations for the grading and management of toxicities associated with CAR T-cell treatment for B-NHL.Consequently,we developed this consensus for the prevention,recognition,and management of these toxicities,on the basis of published literature regarding the management of anti-CD19 CAR T-cell-associated toxicities and the clinical experience of multiple Chinese institutions.This consensus refines a grading system and classification of CRS in B-NHL and corresponding measures for CRS management,and delineates comprehensive principles and exploratory recommendations for managing anti-CD19 CAR T-cell-associated toxicities in addition to CRS.

Comparative assessment of nitrogen fixation rate by ^(15)N_(2) tracer assays in the South China Sea

Nitrogen fixation is one of the most important sources of new nitrogen in the ocean and thus profoundly affects the nitrogen and carbon biogeochemical processes.The distribution,controlling factors,and flux of N2 fixation in the global ocean remain uncertain,partly because of the lack of methodological uniformity.The^(15)N_(2)tracer assay(the original bubble method→the^(15)N_(2)-enriched seawater method→the modified bubble method)is the mainstream method for field measurements of N2 fixation rates(NFRs),among which the original bubble method is the most frequently used.However,accumulating evidence has suggested an underestimation of NFRs when using this method.To improve the availability of previous data,we compared NFRs measured by three^(15)N_(2)tracer assays in the South China Sea.Our results indicate that the relationship between NFRs measured by the original bubble method and the^(15)N_(2)-enriched seawater method varies obviously with area and season,which may be influenced by incubation time,diazotrophic composition,and environmental factors.In comparison,the relationship between NFRs measured by the original bubble method and the modified bubble method is more stable,indicating that the N2 fixation rates based on the original bubble methods may be underestimated by approximately 50%.Based on this result,we revised the flux of N2 fixation in the South China Sea to 40 mmol/(m2·a).Our results improve the availability and comparability of literature NFR data in the South China Sea.The comparison of the^(15)N_(2)tracer assay for NFRs measurements on a larger scale is urgently necessary over the global ocean for a more robust understanding of the role of N2 fixation in the marine nitrogen cycle.

The combination of chidamide with the CHOEP regimen in previously untreated patients with peripheral T-cell lymphoma: a prospective, multicenter, single arm, phase 1b/2 study

Objective:To assess the efficacy and safety of the novel histone deacetylase inhibitor,chidamide,in combination with cyclophosphamide,doxorubicin,vincristine,etoposide,and prednisone(Chi-CHOEP)for untreated peripheral T-cell lymphoma(PTCL).Methods:A prospective,multicenter,single arm,phase 1 b/2 study was conducted.A total of 128 patients with untreated PTCL(18–70 years of age)were enrolled between March 2016 and November 2019,and treated with up to 6 cycles with the Chi-CHOEP regimen.In the phase 1 b study,3 dose levels of chidamide were evaluated and the primary endpoint was determination of the maximumtolerated dose and recommended phase 2 dose(RP2 D).The primary endpoint of the phase 2 study was 2-year progression-free survival(PFS).Results:Fifteen patients were enrolled in the phase 1 b study and the RP2 D for chidamide was determined to be 20 mg,twice a week.A total of 113 patients were treated at the RP2 D in the phase 2 study,and the overall response rate was 60.2%,with a complete response rate of 40.7%.At a median follow-up of 36 months,the median PFS was 10.7 months,with 1-,2-,and 3-year PFS rates of 49.9%,38.0%,and 32.8%,respectively.The Chi-CHOEP regimen was well-tolerated,with grade 3/4 neutropenia occurring in approximately two-thirds of the patients.No unexpected adverse events(AEs)were reported and the observed AEs were manageable.Conclusions:This large cohort phase 1 b/2 study showed that Chi-CHOEP was well-tolerated with modest efficacy in previously untreated PTCL patients.

Effect of river plume on phytoplankton community structure in Zhujiang River estuary

To examine the phytoplankton assemblages and the effect of diluted waters on them,a research cruise was conducted from July 19 to August 7,2015 in the Zhujiang(Pearl)River estuary in the northern South China Sea(21°N–23.5°N,111°E–117°E).Samples were collected from 65 stations including one for time-series sampling.A total of 212 phytoplankton taxa were identified from 61 genera belonging to 4 phyla.Among them,122 species identified from 42 genera of Bacillariophyta and 83 species from 15 genera of Pyrrophyta.Chain-forming diatoms dominated the phytoplankton community where Pseudonitzschia delicatissima,Guinardia striata,Thalassionema nitzschioides,and P.pungens comprised about 52%of the total abundance.However,higher cell abundances concentrated on both sides of the estuary,because of low salinity and high nutrients brought by diluted water.In addition,Canonical Correspondence Analysis revealed that salinity and dissolved inorganic nitrogen shaped the species composition in the study area.Furthermore,the Jaccard similarity index showed prevailing high similarity in the distribution of species in low-salinity diluted waters,and the Bray-Curtis similarity depicted distinguished grouping for phytoplankton assemblages along the salinity gradient.However,phytoplankton diel vertical cycles showed maximum abundance occurred at 2:00 am,which was mainly contributed by benthic phytoplankton species Pseudo-nitzschia spp.and T.nitzschioides.

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

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

Clinical features and prognostic analysis of the blastoid variant of mantle cell lymphoma: An analysis of 20 patients from two centers

Managing Editor:Peng Lyu Mantle cell lymphoma(MCL),a relatively uncommon subtype of non-Hodgkin's lymphoma(NHL),constitutes approximately 2%-10%of NHL cases.Characterized by its inertness,aggressiveness,and incurability,MCL has a median overall survival(OS)of approximately 3-5 years.

Controllable growth of type-II Dirac semimetal PtTe2 atomic layer on Au substrate for sensitive room temperature terahertz photodetection

Platinum telluride(PtTe_(2)),a member of metallic transition metal dichalcogenides,provides a new platform for investigating various properties such as type-II Dirac fermions,topological superconductivity,and wide-band photodetection.However,the study of PtTe_(2)is largely limited to exfoliated flakes,and its direct synthesis remains challenging.Herein,we report the controllable synthesis of highly crystalline 2D PtTe_(2)crystals with tunable morphology and thickness via chemical vapor deposition(CVD)growth on Au substrate.By adjusting Te amount and substrate temperature,anisotropic and isotropic growth modes of PtTe_(2)were realized on the solid and molten Au substrates,respectively.The domain size of PtTe_(2)crystal was achieved up to 30μm,and its thickness can be tuned from 5.6 to 50 nm via controlling the growth time.Furthermore,a metal–PtTe_(2)–metal structural device was fabricated to validate the wide-band terahertz(THz)photodetection from 0.04 to 0.3 THz at room temperature.Owing to the high crystallinity of PtTe_(2)crystal,the photodetector acquires high responsivity(30–250 mA W-1 from 0.12 to 0.3 THz),fast response rate(rise time:7μs,decay time:8μs),and high-quality imaging ability.Our work demonstrates the feasibility for realistic exploitation of high-performing photodetection system at THz band based on the CVDgrown 2D Dirac semimetal materials.

Thermodynamic instability of 3D Einstein-Born-Infeld AdS black holes

Super-entropic black holes possess finite-area but noncompact event horizons and violate the reverse iso-perimetric inequality.It has been conjectured that such black holes always have negative specific heat at constant volume C_(V)or negative specific heat at constant pressure C_(p)whenever Cy>0,making them unstable in extended thermodynamics.In this paper,we describe a test of this instability conjecture with a family of nonlinear electro-dynamic black holes,namely 3D Einstein-Bom-Infeld(EBI)AdS black holes.Our results show that when nonlinear electrodynamics effects are weak,the instability conjecture is valid.However,the conjecture can be violated in some parameter region when nonlinear electrodynamics effects are strong enough.This observation thus provides a counter example to the instability conjecture,which suggests that super-entropic black holes may be thermodynamically stable.

Phase structures and transitions of quintessence surrounding RN black holes in a grand canonical ensemble

Considering a grand canonical ensemble,we study the phase structures and transitions of RN black holes surrounded by quintessence dark energy on two different boundary conditions,namely AdS space and a Dirichlet wall.For AdS space,under the condition of fixed temperature and potential,as the temperature increases for lower potential,the black hole undergoes a first-order phase transition,while for higher potential,no phase transition occurs.There are two different regions in the parameter space.For the Dirichlet wall,on which the temperature and potential are fixed,the state parameter of quintessenceω=-2/3 is analyzed in detail.Then,three different physically allowed regions in the parameter space of the black hole are well studied.As the temperature rises,first-order and second-order phase transitions may occur.In this case,there are nine regions in the parameter space,which is evidently distinct from the case of AdS space.

Theoretical Simulation on a Nonlinear Photonics Process of Er(1%)Yb(8%):FOV Oxyfluoride Nanophase Vitroceramics

We numerically simulate a photonics phenomenon of what we call intensity inversion between red and green fluorescence in oxyfluoride nanophase vitroceramics Er(1%)Yb(8%):FOV through the integration of whole fluorescence’s theories.We found that it is essential to introduce a coefficient presenting the difference between the Stokes energy transfer and anti-Stokes energy transfer processes in nano-material when calculating the energy transfer rate.Under this consideration,and with the total crystallized volume ratio set to be 17.6%,the simulation results of the population probabilities values of all energy levels of Er^(3+) ion are coincident with the experimental result perfectly.

Geology, environment, and life in the deepest part of the world’s oceans

The hadal zone,mostly comprising of deep trenches and constituting of the deepest part of the world’s oceans,represents the least explored habitat but one of the last frontiers on our planet.The present scientific understanding of the hadal environment is still relatively rudimentary,particularly in comparison with that of shallower marine environments.In the last 30 years,continuous efforts have been launched in deepening our knowledge regarding the ecology of the hadal trench.However,the geological and environmental processes that potentially affect the sedimentary,geochemical and biological processes in hadal trenches have received less attention.Here,we review recent advances in the geology,biology,and environment of hadal trenches and offer a perspective of the hadal science involved therein.For the first time,we release highdefinition images taken by a new full-ocean-depth manned submersible Fendouzhe that reveal novel species with an unexpectedly high density,outcrops of mantle and basaltic rocks,and anthropogenic pollutants at the deepest point of the world’s ocean.We advocate that the hydration of the hadal lithosphere is a driving force that influences a variety of sedimentary,geochemical,and biological processes in the hadal trench.Hadal lithosphere might host the Earth’s deepest subsurface microbial ecosystem.Future research,combined with technological advances and international cooperation,should focus on establishing the intrinsic linkage of the geology,biology,and environment of the hadal trenches.