Research Progress in Biological Control of Soft Rot of Amorphophallus konjac

In this paper,the main control methods of soft rot of Amorphophallus konjac are reviewed,with a focus on the current research status of using plant growth promoting rhizobacteria for biological control of soft rot of A.konjac,and future research directions are looked forward to.

Prognostic value of interim ^(18)F-FDG PET/CT in diffuse large B-cell lymphoma

Objective： Diffuse large B-cell lymphoma （DLBCL） is a heterogeneous disease. The prognostic factor currently used is not accurate enough to predict the outcomes of patients with DLBCL. The prognostic significance of interim PET/CT in DLBCL remains controversial. The aim of this study is to determine the predictive value of interim 18F-FDG PET/CT after first-line treatment in patients with DLBCL. Methods： Thirty-two patients with DLBCL underwent baseline, interim and post-treatment lSF-FDG PET/CT scans. Imaging results were analyzed for the survival of patients via software SPSS 13.0, retrospectively. Results： Thirty-one of the 32 patients were treated with R-CHOP regimen, and interim 18F-FDG PET/CT of 24 patients was performed after 2 cycles of treatment. After a median follow-up period of 16.7 months, the 2-year progression-free survival （PFS） rates were significantly different between the groups above and below SUVmax CUt-Off value of 2.5 （P=0.039）. No significant differences were found in the 2-year PFS rates if SUVm, cut-offvalues were set as 2.0 and 3.0, respectively （P=0.360; P=0.113）. Conclusions： Interim PET/CT could predict the prognosis of DLBCL patients with the SUVmax cut-off value of 2.5, but more clinical data should be concluded to confirm this conclusion.

弥漫性大B细胞淋巴瘤继发中枢神经系统侵犯的诊疗进展

弥漫性大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)继发中枢神经系统(central nervous system,CNS)侵犯是一种严重的临床并发症,治疗方法有限,预后普遍较差。随着利妥昔单抗的广泛应用,其发生率呈降低趋势,但是脑实质受累越发多见,病理活检在诊断中则越发重要。在高危因素鉴定方面需要结合临床与分子生物学因素综合评估。以大剂量甲氨蝶呤为主的全身化疗作为主流的预防策略,其作用尚存争议。伊布替尼等新药、新疗法的治疗价值得到进一步探索。本文旨在对近年来DLBCL继发CNS侵犯的诊疗进展予以综述。

Prognostic value of ^(18)F-fluorodeoxyglucose positron emission tomography using Deauville criteria in diffuse large B cell lymphoma treated with autologous hematopoietic stem cell transplantation

Objective: High-dose chemotherapy(HDC) followed by autologous hematopoietic stem cell transplantation(auto-HSCT) plays an important role in improving outcomes of diffuse large B cell lymphoma(DLBCL) patients.18 F-fluorodeoxyglucose(18 F-FDG) positron emission tomography(PET)/computed tomography(CT) has been widely accepted in response assessment and prediction of prognosis in DLBCL. Here, we report the value of 18 FFDG PET/CT pre-and post-HSCT in predicting outcomes of patients with DLBCL.Methods: DLBCL patients who had PET/CT scan before and after HSCT were included. PET results were interpreted based upon Deauville criteria. The prognostic value of 18 F-FDG PET/CT in auto-HSCT was evaluated.Results: Eighty-four patients were enrolled. In univariate analysis, pre-and post-HSCT PET findings were correlated with 3-year progression-free survival(PFS) [hazard ratio(HR)=4.391, P=0.001; HR=7.607, P<0.001] and overall survival(OS)(HR=4.792, P=0.008; HR=26.138, P<0.001). Patients receiving upfront auto-HSCT after firstline treatment had better outcomes than relapsed/refractory DLBCL patients(3-year PFS, P<0.001; 3-year OS,P<0.001). In the relapsed/refractory patients, pre-and post-HSCT PET findings were also associated with 3-year PFS(P=0.003 vs. P<0.001) and OS(P=0.027 vs. P<0.001). A significant correlation was observed between clinical response to chemotherapy before auto-HSCT and outcomes of patients in the entire cohort(3-year PFS, P<0.001;3-year OS, P<0.001) and in the subgroup of 21 patients with positive pre-HSCT PET(3-year PFS, P=0.084; 3-year OS, P=0.240). A significant association between survival and post-HSCT PET findings was observed in multivariate analysis(HR=5.168, P<0.001).Conclusions: PET results before and after HSCT are useful prognostic factors for DLBCL patients receiving HSCT. Patients who responded to chemotherapy, even those with positive pre-HSCT PET, are appropriate candidates for auto-HSCT.

A durable 4-1BB-based CD19 CAR-T cell for treatment of relapsed or refractory non-Hodgkin lymphoma

Objective:Previous studies reported that 4-1BB-based CD19 chimeric antigen receptor(CAR)-T cells were more beneficial for the clinical outcomes than CD28-based CAR-T cells,especially the lower incidence rate of severe adverse events.However,the median progression-free survival(mPFS)of 4-1BB-based product Kymriah was shorter than that of CD28-based Yescarta(2.9 months vs.5.9 months),suggesting that Kymriah was limited in the long-term efficacy.Thus,a safe and durable 4-1BB-based CD19 CAR-T needs to be developed.Methods:We designed a CD19-targeted CAR-T(named as IM19)which consisted of an FMC63 scFv,4-1BB and CD3ζintracellular domain and was manufactured into a memory T-enriched formulation.A phase I/II clinical trial was launched to evaluate the clinical outcomes of IM19 in relapsed or refractory(r/r)B cell non-Hodgkin lymphoma(B-NHL).Dose-escalation investigation(at a dose of 5×10^(5)/kg,1×10^(6)/kg and 3×106/kg)was performed in 22 r/r B-NHL patients.All patients received a single infusion of IM19 after 3-day conditional regimen.Results:At month 3,the overall response rate(ORR)was 59.1%,the complete response rate(CRR)was 50.0%.The mPFS was 6 months and the 1-year overall survival rate was 77.8%.Cytokine release syndrome(CRS)occurred in 13 patients(59.1%),with 54.5%of grade 1−2 CRS.Only one patient(4.5%)experienced grade 3 CRS and grade 3 neurotoxicity.Conclusions:These results demonstrated the safety and durable efficacy of a 4-1BB-based CD19 CAR-T,IM19,which is promising for further development and clinical investigation.

PEG-asparaginase in BFM-90 regimen improves outcomes in adults with newly diagnosed lymphoblastic lymphoma

Objective： Although L-asparaginase（L-ASP） is a standard treatment for lymphoblastic lymphoma（LBL）,hypersensitivity reactions by some patients limit its application. Polyethylene glycol-conjugated asparaginase（PEGASP） has a lower immunogenicity and is a standard treatment in all pediatric acute lymphoblastic leukemia（ALL）.In this study, we investigated the efficacy and toxicity of PEG-ASP instead of L-ASP as used in the BFM-90regimen（PEG-ASP-BFM-90） for adult LBL.Methods： Between June 2012 and July 2015, we treated 30 adult patients with newly diagnosed LBL, using PEGASP-BFM-90 in a prospective, multicenter and single-arm clinical study at 5 participating institutions in China.Results： All the 30 patients, including 19 males and 11 females with a median age of 30（range： 18–62） years,completed 128 times of the PEG-ASP, with the median of 4（range： 2–6） times. Patients did not receive radiotherapy at this time. The overall response rate was 86.7%（26/30）, with 50.0%（15/30） complete response and36.7%（11/30） partial response. The 3-year overall survival was 46.0% [95% confidence interval（95% CI）,28.2%–64.8%], and the 3-year progression-free survival was 43.0%（95% CI, 25.7%–62.0%）. Major adverse events were myelosuppression, reduced fibrinogen, liver dysfunction and digestive tract toxicities. No allergic reaction and no treatment-related mortality or severe complications were recorded.Conclusions： Our clinical data and observed outcomes indicate that 1 dose of PEG-ASP can replace multiple doses of native L-ASP in BFM-90, with predominantly grade 3–4 neutropenia for adult LBL, and no therapyrelated deaths. The effect is similar to previous reports of PEG-ASP-containing regimens for adult ALL. Major advantages include less serious allergic reactions, 2–3 weeks of action duration, and convenience for patients and physicians.

Network-pharmacology and molecular docking-based investigation of mechanism of Sophora flavescens on cancer and inflammation

Objective:In order to explore the systematical regulatory mechanism of Kushen(Sophora flavescens,SF)on inflammation and cancer,we analyzed inter-molecular interactions between herbal ingredients of SF and human inflammation and cancer through network-pharmacology and molecular docking-based approaches.Methods:Firstly,ingredients and potential targets were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,GeneCards database,Therapeutic Targets Database and Online Mendelian Inheritance in Man database.Then,protein-protein interaction network and medicine-ingredient-target-disease network were established and analyzed via STRING and Cytoscape.Surflex-dock was performed by SybylX-2.0.Finally,functional enrichment and pathway enrichment were achieved by Gene Ontology database and Kyoto Encyclopedia of Genes and Genomes database.Results:The results showed that 113 components of SF and 53 potential targets were related in the study.SF exerts anti-inflammatory and anti-cancer mechanism through key targets located in nucleus,such as JUN,MYC,RELA,NCOA,PPARG which may trigger the NF-κB pathway,the Bcl-2/Bax pathway and other pathways to effect DNA transcriptional activity.Conclusions:The study predicted the mechanism of SF on cancer and inflammation.According to the results,we suggest that the ingredients of SF effect on DNA bingding and transcription in nuclear receptors-like JUN,MYC,RELA,NCOA,PPARG.the receptors trigger several pathways including NF-κB pathway,the Bcl-2/Bax pathway and others.Eventually,it regulats inflammatory factors and cell proliferation,senescence and apoptosis.

Targeting FAPα-positive lymph node metastatic tumor cells suppresses colorectal cancer metastasis

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer(LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha(FAPα) expression in LNM-CRC cells. Gain-or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis(CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

Functionalization of small black phosphorus nanoparticles for targeted imaging and photothermal therapy of cancer

Black phosphorus(BP) nanomaterials have attracted extensive attention due to their unique physical,chemical, and biological properties. In this study, small BP nanoparticles were synthesized and modified with dextran and poly(ethyleneimine) for functionalization with folic acid and cyanine 7. The functionalized BP nanoparticles exhibit excellent biocompatibility, stability, and near infrared optical properties for targeted imaging of tumors through photoacoustic imaging and near-infrared fluorescence imaging.They also display high photothermal conversion efficiency for photothermal therapy of cancer. This work demonstrates the potential of functionalized small BP nanoparticles as an emerging nanotheranostic agent for the diagnosis and treatment of cancer.

Smoothed particle hydrodynamics for coarse-grained modeling of rapid granular flow

We simulated rapid flow in transient plane Couette flows of granular particles using the smoothed particle hydrodynamics （SPH） solutions of a set of continuum equations, This simulation was performed to test the viability of SPH in solving the equations for the solid phase of the two-fluid model associated with fluidization. We found that SPH requires the handling of fewer particles in simulating the collective behavior of rapid granular flow, thereby bolstering expectations of solving the equations for the solid phase in the two-fluid modeling of fluidization. Further work is needed to investigate the effect of terms describing pressure and viscous stress of solids on stability in simulations.

Deletion of Gab2 in mice protects against hepatic steatosis and steatohepatitis:a novel therapeutic target for fatty liver disease

Fatty liver disease is a serious health problem worldwide and is the most common cause for chronic liver disease and metabolic disorders.The major challenge in the prevention and intervention of this disease is the incomplete understanding of the underlying mechanism and thus lack of potent therapeutic targets due to multifaceted and interdependent disease factors.In this study,we investigated the role of a signaling adaptor protein,GRB2-associated-binding protein 2(Gab2),in fatty liver using an animal disease model.Gab2 expression in hepatocytes responded to various disease factor stimulations,and Gab2 knockout mice exhibited resistance to fat-induced obesity,fat-or alcohol-stimulated hepatic steatosis,as well as methionine and choline deficiency-induced steatohepatitis.Concordantly,the forced expression or knockdown of Gab2 enhanced or diminished oleic acid(OA)-or ethanol-induced lipid production in hepatocytes in vitro,respectively.During lipid accumulation in hepatocytes,both fat and alcohol induced the recruitment of PI3K or Socs3 by Gab2 and the activation of their downstream signaling proteins AKT,ERK,and Stat3.Therefore,Gab2 may be a disease-associated protein that is induced by pathogenic factors to amplify and coordinate multifactor-induced signals to govern disease development in the liver.Our research provides a novel potential target for the prevention and intervention of fatty liver disease.