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.

Manipulating oxygenate adsorption on N-doped carbon by coupling with CoSn alloy for bifunctional oxygen electrocatalyst

Highly active bifunctional oxygen electrocatalysts accelerate the development of high-performance Zn-air battery,but suffer from the mismatched activities of oxygen evolution reaction(OER)and oxygen reduced reaction(ORR).Herein,highly integrated bifunctional oxygen electrocatalysts,cobalt-tin alloys coated by nitrogen doped carbon(CoSn@NC)are prepared by MOFs-derived method.In this hybrid catalyst,the binary CoSn nanoalloys mainly contribute to highly active OER process while the Co(or Sn)-N-C serves as ORR active sites.Rational interaction between CoSn and NC donates more rapid reaction kinetics than Pt/C(ORR)and IrO_(2)(OER).Such CoSn@NC holds a promise as air-cathode electrocatalyst in Zn-air battery,superior to Pt/C+IrO_(2)catalyst.First-principles calculations predict that CoSn alloys can upgrade charge redistribution on NC and promote the transfer to reactants,thus optimizing the adsorption strength of oxygen-containing intermediates to boost the overall reactivity.The tuning of oxygenate adsorption by interactions between alloy and heteroatom-doped carbon can guide the design of bifunctional oxygen electrocatalysts.

Influence of Wind Turbine Structural Parameters on Wind Shear and Tower Shadow Effect

To overcome the problems of natural decreases in power quality,and to eliminate wind speed fluctuation due to wind shear and tower shadow effect arising from wind turbine structural parameters,an improved prediction model accounting for the dual effect of wind shear and tower shadow is,in this paper,built.Compared to the conventional prediction model,the proposed model contains a new constraint condition,which makes the disturbance term caused by the tower shadow effect always negative so that the prediction result is closer to the actual situation.Furthermore,wind turbine structural parameters such as hub height,rotor diameter,the diameter of the tower top,and rotor overhang on wind shear and tower shadow effect are also explored in detail.The results show that the wind shear effect became weaker with the increase in hub height.The hub height is independent of the tower shadow effect.The rotor diameter is positively correlated with the wind shear and tower shadow effect.The tower shadow effect is positively correlated with the diameter of the tower top and negatively correlated with the rotor overhang.

Topical application of glycyrrhizin preparation ameliorates experimentally induced colitis in rats

AIM:To examine the efficacy of glycyrrhizin preparation(GL-p) in the treatment of a rat model of ulcerative colitis(UC).METHODS:Experimental colitis was induced by oral administration of dextran sodium sulfate.Rats with colitis were intrarectally administered GL-p or saline.The extent of colitis was evaluated based on body weight gain,colon wet weight,and macroscopic damage score.The expression levels of pro-inflammatory cytokines and chemokines in the inflamed mucosa were measured by cytokine antibody array analysis.The effect of GL-p on myeloperoxidase(MPO) activity in the inflamed mucosa and purified enzyme was assayed.RESULTS:GL-p treatment significantly ameliorated the extent of colitis compared to sham treatment with saline.Cytokine antibody array analysis showed that GL-p treatment significantly decreased the expression levels of pro-inflammatory cytokines and chemokines,including interleukin(IL)-1β,IL-6,tumor necrosis factor-α,cytokine-induced neutrophil chemoattractant-2,and monocyte chemoattractant protein-1 in the inflamed mucosa.Furthermore,GL-p inhibited the oxidative activity of mucosal and purified MPO.CONCLUSION:GL-p enema has a therapeutic effect on experimental colitis in rats and may be useful in the treatment of UC.

The effect of Tai Chi exercise on motor function and sleep quality in patients with stroke:A meta-analysis

Objective:The meta-analysis is to objectively evaluate the efficacy of Tai Chi exercise for motor function and sleep quality in patients with stroke.Methods:Randomized controlled trials(RCTs)about the effects of Tai Chi versus a non-exercise or conventional rehabilitation exercise control group on motor function and sleep quality in patients with stroke were searched from multiple electronic databases(PubMed,Web of Science,the Cochrane Library,EMBASE,AMED,CBM,CNKI,Wanfang and VIP)until August 2016.Two investigators independently screened eligible studies,extracted data,and assessed the methodological quality by using the quality evaluation criteria for RCTs recommended by Cochrane Handbook.Then meta-analysis was performed by RevMan5.3 software.Results:A total of 17 RCTs with 1209 participants were included.The meta-analysis indicated that there was a significant difference on improving the balance function(P<0.001)and ability of daily activity(P=0.0003)of patients with stroke between Tai Chi group and control group.However,no significant effect was found on Tai Chi for walking function and sleep quality(P>0.05).Conclusion:Tai Chi exercise can significantly improve the balance function and ability of daily activities of patients with stroke,and there are no significant differences in walking function and sleep quality.Therefore,lots of multicenter,large-sample,higher quality randomized controlled trials are needed to verify the effects of Tai Chi exercise in improving walking function and sleep quality for patients with stroke.

Density functional theory study of formaldehyde adsorption and decomposition on Co-doped defective CeO_(2) (110) surface

Formaldehyde as an air pollutant to adverse health effects for humanity has been getting attention.The adsorption and dissociation of formaldehyde(HCHO)on the CoxCe1−xO_(2)−δ(110)surface were investigated by the density functional theory(DFT)calculations.We calculated the oxygen vacancy formation energy as the function of its site around dopant Co in detail.The results showed that Co doping was accompanied by compensating oxygen hole spontaneous formation.The adsorption configurations and bindings of HCHO at different locations on the CoxCe1−xO_(2)(110)were presented.Four possible pathways of oxidation of formaldehyde on the catalytic surface were explored.The results suggested that formaldehyde dissociation at different adsorption sites on the doped CeO_(2)(110)—first forming dioxymethylene(CH2O_(2))intermediate,and then decomposing into H2O,H2,CO_(2),and CO molecules.It was found that the presence of cobalt and oxygen vacancy significantly prompted the surface activity of CeO_(2).

Synthesis, Structure and Magnetic Properties of CoNi Submicrospherical Chains

High-purity magnetic CoNi submicrospherical chains, each of length 20 μm - 30 μm and self-assembled from fcc-phase CoNi submicrospheres of average diameter 800 nm, are synthesized via a surfactant-assisted solvothermal route without the aid of nucleation agent. The effects of surfactant and reducing agent on the morphology and size of the CoNi chains are studied, and a possible growth mechanism for the CoNi chains is proposed. The CoNi chains show ferromagnetic characteristics with a similarly small saturation magnetization of 104.1 emu/g and a larger coercivity of 150 Oe at room temperature compared to the monodispersed CoNi submicrospheres of 105 emu/g and 34 Oe as a result of the increased shape anisotropy.

农产品产地准出与市场准入运行机制探讨

本文阐述了为建立农产品产地准出与市场准入运行机制,农业农村主管部门在农产品法规和政策制定、生产主体建设、开展产地准出与市场准入基础性工作、试行农产品合格证等"四证"制度、构建农产品检测体系等取得的进展基础上,指出了农产品相关法律法规制度建设、生产经营主体准入门槛、农产品生产标准化、农产品准出准入的大市场氛围等方面存在的问题,提出了从法律层面做好农产品准出准入顶层设计、增加农产品产地准出和市场准入机制的内容、制定农产品市场运行技术规范的解决途径。

ESTIMATES FOR EXTREMAL VALUES FOR A CRITICAL FRACTIONAL EQUATION WITH CONCAVE-CONVEX NONLINEARITIES

In this paper we study the critical fractional equation with a parameter λ and establish uniform lower bounds for Λ, which is the supremum of the set of λ, related to the existence of positive solutions of the critical fractional equation.

De novo Transcriptome Analysis in Leymus mollis to Unveil Genes Involved in Salt Stress Response

Leymus mollis,a wild relative of wheat,is very tolerant to salt stress,and has been considered as a valuable genetic resource for wheat breeding.However,the genetic basis for salt tolerance of this species is still largely unknown.In this study,de novo sequencing,assembly and analysis of L.mollis transcriptome in response to salt stress was performed.A total of 110,323 and 112,846 unigenes were generated for the NaCl-free(CK)and 180 mM NaCl-treated(CT)library,respectively.For the two libraries,73,414 unigenes were successfully annotated in five common protein databases,and 7521 differentially expressed genes(DEGs)between CK and CT libraries were identified.GO enrichment analysis of the DEGs showed that the significantly enriched GO terms were predominantly involved in environmental adaptation(including“response to abiotic stimulus”,“response to water deprivation”),regulation of signaling pathway(such as“regulation of abscisic acid mediated signaling pathway”,“regulation of cell communication”),and photosynthesis(including“response to light stimulus”,“photosynthesis,light harvesting”and“chlorophyll metabolic process”).KEGG pathway enrichment analysis showed that“mRNA surveillance pathway”,“RNA transport”and“plant hormone signal transduction”were predominantly enriched pathways,followed by several secondary metabolic pathways,photosynthesis,carbohydrate metabolism and lipid metabolism.In addition,DEGs related to osmotic stress,ion homeostasis and oxidative stress,including four dehydrins,five aquaporins,an LmNHX2 and several antioxidant enzymes or proteins genes,were found to be up-regulated in response to salt stress.These results will be helpful for further studies on the molecular mechanisms of salt responses in L.mollis.

Initial research of cord blood leptin, adiponectin and IGF-I with fetus growth and development

Objective:In order to reveal the relationship between cord blood leptin,adiponectin and insulin-like growth factor-I(IGF-I)and the fetus growth and development,and discuss the interaction and clinical significance on fetus growth and development.Methods:The levels of cord blood leptin,adiponectin,IGF-I in 86 newborns were examined by radio immunoassay,according to gestation age and birth weight percentile relation,the objects were divided into the SGA group(n=16),the AGA group(n=41),the LGA group(n=29),meanwhile,neonatal birth weight,body length,head circumference,foot length,and placental weight were measured,and body mass index(BMI)was computed.Dependability analysis was taken.Results:The levels of cord blood leptin,adiponectin and IGF-I were as follows:LGA group>AGA group>SGA group.The level of cord blood adiponectin was positively correlated with birth weight,placental weight and BMI(p<.05).Cord blood leptin and IGF-I concentrations were positively correlated with their birth weight,body length,head circumference,foot length,placental weight and BMI,respectively(p<.01),cord blood leptin was positively correlated with adiponectin and IGF-I(p<.01).The levels of cord blood leptin and adiponectin had no statistical significance with neonatal sexuality and deliver style(p>.05);the levels of cord blood IGF-I had no statistical significance with neonatal sexuality(p>.05),but had statistical significance with deliver style(p<.05).Conclusions:Cord blood leptin,adiponectin and IGF-I played an important part in adjusting fetus growth and development as well as participating in the process of fetus growth and development,and could be regarded as one of the clinical indexes to evaluate fetus growth and development or state of nutrition.The abnormal level of cord blood leptin and IGF-I might be one of the reasons to cause intrauterine growth retardation and fetal macrosomia.

C3 glomerulonephritis

A case of rapidly progressive glomerulonephritis with pathological changes to the crescent glomerulonephritis“C3 glomerulonephritis”in the Third Affiliated Hospital of Inner Mongolia Medical University was collected and its diagnosis,clinical manifestation,and pathological characteristics were explored.The experts analyzed the disease from the perspective of its causes,diagnosis,complications and treatment.Timely renal biopsy is required to clarify pathological diagnosis as the primary glomerular disease was newly recognized with a lower incidence.So misdiagnosis and delayed healing is more frequent.The paper aims to enhance the clinician’s understanding of“C3 glomerulonephritis”.

Tyrosinemia

A case of pediatric tyrosinemia in the Third Affiliated Hospital of Inner Mongolia Medical University was collected and analyzed on the basis of diagnosis,physical examination and treatment.Misdiagnosis of tyrosinemia is very common due to the low incidence,rare clinical cases and diagnosis difficulty.So this paper aims to arouse the doctors’awareness of tyrosinemia during clinical practice.

Hemophagocytic lymphohistiocytosis

A case of hemophagocytic lymphohistiocytosis in the Third Affiliated Hospital of Inner Mongolia Medical University was collected and analyzed on the basis of diagnosis,physical examination and treatment.Misdiagnosis of hemophagocytic syndrome is very common since it is a rare disease.So this paper aims to enhance the doctors’awareness of hemophagocytic syndrome during clinical practice.

Yiwu Wholesale Delight

Foran insight into what makes China's foreign trade tick,plus the best international food on offer,head to Yiwu where traders have been flocking for centuries.Iyou think Santa Claus comes from the North Pole,you may want to think twice.He also has another home-Yiwu,where more than 60 percent of the world's Christmas decorations are made.If you're a shopaholic,there's no more interesting place to visit than the world's largest small commodity market.

Revolutionary Rocks

The striking red soil,soaring cliffs and plunging waterfalls are the main attractions of Chishui,but its connections to the founding of modern Chinese history provide a deeper backdrop。Iyou're trying to figure out which parts of China are the reddest,you should jot Chishui down on your list.The city boasts red land,red water and red history.The red history comes from the Battle of Chishui River,when Communist forces on the Long March in early 1935 outmaneuvered their Nationalist foes by crossing the river,recrossing the river,and then recrossing the river two more times.

Challenges and optimal strategies of CAR T therapy for hematological malignancies

Remarkable improvement relative to traditional approaches in the treatment of hematological malignancies by chimeric antigen receptor (CAR) T-cell therapy has promoted sequential approvals of eight commercial CAR T products within last 5 years. Although CAR T cells’ productization is now rapidly boosting their extensive clinical application in real-world patients, the limitation of their clinical efficacy and related toxicities inspire further optimization of CAR structure and substantial development of innovative trials in various scenarios. Herein, we first summarized the current status and major progress in CAR T therapy for hematological malignancies, then described crucial factors which possibly compromise the clinical efficacies of CAR T cells, such as CAR T cell exhaustion and loss of antigen, and finally, we discussed the potential optimization strategies to tackle the challenges in the field of CAR T therapy.

Enter the Kung-Foodies

Kick off a visit to this southern Chinese city by paying homage to iconic martial artists and historic temples,before eating your fll in a uNEsco-isted center of gastronomy.

Recombinant rabies virus expressing IL-15 enhances immunogenicity through promoting the activation of dendritic cells in mice

Rabies remains a public health threat that kills approximately 59,000 people worldwide each year,most of which are from the developing countries of Africa and Asia where dog rabies are endemic.Therefore, developing an affordable and efficacious vaccine is crucial for rabies control in these countries. Interleukin(IL)-15, an immunoregulatory cytokine, is a pluripotent molecule with therapeutic potential, which targets many cell types and links the innate and adaptive immune system. In this study, IL-15 gene was cloned and inserted into the genome of a recombinant rabies virus(RABV) strain LBNSE(designated as LBNSE-IL15), and the effect of over-expression of IL-15 on the immunogenicity of RABV was investigated. It was found that mice vaccinated with LBNSEIL15 could induce significantly higher level of virus-neutralizing antibody(VNA) than those immunized with LBNSE, resulting in the higher protection after challenge. Further investigation was performed to find out the possible role of IL-15 plays in the process of antibody induction, and it was found that LBNSE-IL15 could enhance the maturation of dendritic cells(DCs) in immunized mice. Furthermore, the mice immunized with LBNSE-IL15 could promote the T_(FH) cells differentiation and the generation of germinal center B cells and plasma cells. Together, these data indicated that IL-15 could be a potential adjuvant in enhancing the immunogenicity of RABV, contributing to the development of more-efficacious rabies vaccines.

The model of cytokine release syndrome in CAR T-cell treatment for B-cell non-Hodgkin lymphoma

Chimeric antigen receptor T(CAR T)cell therapy has demonstrated efficacy in the treatment of haematologic malignancies.However,the accompanying adverse events,the most common of which is cytokine release syndrome(CRS),substantially limit its wide application.Due to its unique physiological characteristics,CRS in CAR T-cell treatment for B-cell non-Hodgkin lymphoma(BNHL)may exhibit some special features.Although existing guidelines had greatly promoted the recognition and management of CRS,many recommendations are not fully applicable to B-NHL.Therefore,it is imperative to identify responses that are specific to CRS observed following CAR T treatment for B-NHL.Based on underlying biological processes and known pathophysiological mechanisms,we tentatively propose a new model to illustrate the occurrence and evolution of CAR T-cell-therapy-related CRS in BNHL.In this model,tumour burden and bone marrow suppression are considered determinants of CRS.Novel phenomena after CAR T-cell infusion(such as local inflammatory response)are further identified.The proposed model will help us better understand the basic biology of CRS and recognize and manage it more rationally.