Loss-of-function mutations of microRNA-142-3p promote ASH1L expression to induce immune evasion and hepatocellular carcinoma progression

BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact molecular mechanisms leading to the progression of HCC are still unclear.Research has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor tissues.In this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between them.AIM To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC patients.METHODS In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC patients.Furthermore,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,etc.The statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank test.RESULTS In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival rate.ASH1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated region.Furthermore,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via ASH1L.For the exploration mechanism,we found ASH1L may promote an immunosuppressive microenvironment in HCC and ASH1L affects the expression of the cell junction protein zonula occludens-1,which is potentially relevant to the immune system.CONCLUSION Loss function of microRNA-142-3p induces cancer progression and immune evasion through upregulation of ASH1L in HCC.Both microRNA-142-3p and ASH1L can feature as new biomarker for HCC in the future.

Microscopic experimental study on the effects of NaCl concentration on the self-preservation effect of methane hydrates under 268.15 K

It is known that salt ions are abundant in the natural environment where natural gas hydrates are located;thus,it is essential to investigate the self-preservation effect of salt ions on methane hydrates.The dissociation behaviors of gas hydrates formed from various NaCl concentration solutions in a quartz sand system at 268.15 K were investigated to reveal the microscopic mechanism of the self-preservation effect under different salt concentrations.Results showed that as the salt concentration rises,the initial rate of hydrate decomposition quickens.Methane hydrate hardly shows self-preservation ability in the 3.35%(mass)NaCl and seawater systems at 268.15 K.Combined the morphology of hydrate observed by the confocal microscope with results obtained from in situ Raman spectroscopy,it was found that during the initial decomposition stage of gas hydrate below the ice point,gas hydrate firstly converts into liquid water and gas molecules,then turns from water to solid ice rather than directly transforming into solid ice and gas molecules.The presence of salt ions interferes with the ability of liquid water to condense into solid ice.The results of this study provide an important guide for the mechanism and application of the self-preservation effect on the storage and transport of gas and the exploitation of natural gas hydrates.

The dual action of N_(2)on morphology regulation and mass-transfer acceleration of CO_(2)hydrate film

The morphology characteristics of CH_(4),CO_(2),and CO_(2)+N_(2)hydrate film forming on the suspending gas bubbles are studied using microscopic visual method at supercooling conditions from 1.0 to 3.0 K.The hydrate film vertical growth rate and thickness along the planar gas-water interface are measured to study the hydrate formation kinetics and mass transfer process.Adding N_(2)in the gas mixture plays the same role as lowering the supercooling conditions,both retarding the crystal nucleation and growth rates,which results in larger single crystal size and rough hydrate morphology.N_(2)in the gas mixture helps to delay the secondary nucleation on the hydrate film,which is beneficial to maintain the porethroat structure and enhance the mass transfer.The vertical growth rate of hydrate film mainly depends on the supercooling conditions and gas compositions but has weak dependence on the experimental temperature and pressure.Under the same gas composition condition,the final film thickness shows a linear relationship with the supercooling conditions.The mass transfer coefficient of CH_(4)molecules in hydrates ranges from 4.54×10^(-8)to 7.54×10^(-8)mol·cm^(-2)·s^(-1)·MPa^(-1).The maximum mass transfer coefficient for CO_(2)t N_(2)hydrate occurs at the composition of 60%CO_(2)t 40%N_(2),which is 3.98×10^(-8)mol·cm^(-2)·s^(-1)·MPa^(-1).

The Role of ZNF207 in Liver Hepatocellular Carcinoma:Expression Analysis and Prognostic Implications

Objective:To analyze the expression and clinical significance of the zinc finger protein ZNF207 gene in liver hepatocellular carcinoma(LIHC)based on The Cancer Genome Atlas(TCGA)database.Methods:The mRNA sequencing data of 371 cases of primary liver cancer,50 cases of normal tissues,and 3 cases of recurrent liver cancer were downloaded from the TCGA database.The corresponding clinical information of the 371 cases of hepatocellular carcinoma was subsequently analyzed.The difference in ZNF207 expression between normal and tumor tissues was analyzed using the UALCAN online database.The impact of ZNF207 expression on survival prognosis was assessed using the Kaplan-Meier method in R software.The GO and KEGG pathways of ZNF207 were analyzed.The Cox proportional hazards model was used to evaluate the prognostic factors of patients with LIHC.RT-qPCR was employed to verify the expression of ZNF207 in LIHC cells.Results:ZNF207 was highly expressed in LIHC tissues and HepG2 cells,with a significant difference(P<0.05).Multivariate Cox regression analysis revealed that patients with high ZNF207 expression had a significantly shorter overall survival time compared to those with low ZNF207 expression(HR=1.466,95%CI:1.011-2.126,P<0.05).GO enrichment analysis suggested that ZNF207 may influence the onset and progression of hepatocellular carcinoma by regulating mRNA splicing and mRNA transcription processing through the spliceosome.KEGG pathway enrichment analysis indicated that ZNF207 might affect the onset and progression of hepatocellular carcinoma through mitophagy,mRNA surveillance,homologous recombination,spliceosome,and nuclear-cytoplasmic transport.Conclusion:The expression of ZNF207 may be an independent predictor of the prognosis of patients with LIHC and could influence the development of hepatocellular carcinoma through various gene functions and pathways.It has the potential to serve as a novel molecular marker for predicting the prognosis of hepatocellular carcinoma.

卵母细胞成熟比例对卵胞浆内单精子注射助孕疗效的影响

目的探讨卵母细胞成熟比例对卵胞浆内单精子注射(ICSI)助孕患者疗效的影响。方法本研究纳入194例需行ICSI助孕治疗的患者,根据不同卵母细胞成熟的比例将患者分为A、B组,对两组患者ICSI受精率、卵裂率、可利用胚胎数、优质胚胎数、胚胎着床率、临床妊娠率及早期流产率等进行比较。结果两组患者大卵泡数、获卵率、促性腺激素(Gn)使用天数、Gn总剂量、人绒毛膜促性腺激素日子宫内膜厚度、可利用胚胎数、优质胚胎数、移植胚胎数、临床妊娠率、胚胎着床率及自然流产率比较,差异无统计学意义(P>0.05);两组患者小卵泡数、平均获卵数、ICSI受精率及卵裂率比较,差异有统计学意义(P <0.05)。结论卵母细胞成熟比例过低可能影响受精率及卵裂率,降低卵母细胞利用率。

理工专业课程的思政元素挖掘与应用

科学思维具有客观性、抽象性和逻辑性,决定了理工科课程内容是超越意识形态的,理工类课程的思政元素构架是新工科教学工作的一项重要任务。理工专业课程也应充分挖掘蕴含在课程中的时政热点、职业素养、工匠精神、舆论导向等思政元素,详细分析授课要点、思政映射与融入点、授课形式与教学方法、预期成效等,并进一步落实专业课程思政教育具体实施要点,以期能够达到专业课程“立德树人”的德育目的。

Detection of <i>Acinetobacter baumannii</i>in the Oropharynx of Long-Term Hospitalized Patients and the Expression of <i>IntI</i>Gene Induced by Different Antibiotics

Acinetobacter baumannii is the main drug resistant bacteria in clinic at present, and its drug resistance is still rising rapidly. Integrons play an important role in bacterial acquisition of exogenous drug resistance genes. This study investigated A. baumannii colonization in oropharynx and the integron gene carrying, and the expressions of integrase gene were determined when exposed to the different concentrations of antibiotics. 64 hospitalized patients were collected during January 2019 to June in respiratory department of our hospital (the hospitalized time more than 14 days) in our experiment. All throat swab collections were used for DNA extraction, and A. baumannii identification and integron gene detection were done by PCR assay. A. baumannii strains isolated from the oropharynx were identified by MALD-TOF-MS technology and the drug resistance was also analyzed. When expose to a series of ceftazidime and imipenem (10 μg/mL, 5 μg/mL, 1 μg/mL, 0.1 μg/mL, 0.01 μg/mL), the expressions of integron gene in the strains originated from oropharynx were determined by qRT-PCR assay. The results of the PCR showed that 60 patients had detected the A. baumannii Ab-ITS gene and rA gene in throat swabs, wherein 43 patients with symptoms of infection and 17 without symptoms of infection. There was no significant difference in Ab-ITS gene and rA gene detection rates in the symptoms of infection and no symptoms of infection (P > 0.05). In total 60 cases of samples, 29 cases had detected the IntI genes. 6 strains of A. baumannii isolated from the throat swabs of hospitalized patients were multi-drug resistant bacteria with IntI gene and variable region genes. Gene sequencing analysis revealed that the variable region gene cassettes were aacA4-catB8-aadA1-qacEdelta1. When exposed to the concentration of 1 μg/mL and 5 μg/mL ceftazidime, the mRNA expression of IntI had significantly increase compared to the negative control (P < 0.05). When exposed to the concentration of 0.1 μg/mL, 1 μg/mL and 5 μg/mL imipenem, the mRNA expression of IntI had significantly increase compared to the negative control (P < 0.05). The results indicated that oropharyngeal microflora includes multidrug-resistant A. baumannii and carries ingegron genes in long-term hospitalized patients. The improper use of ceftazidime and imipenem might also contribute to the up-regulation of the integrase genes expression and the enhancement of bacterial resistance, which requires more attention in clinical work.

聚多巴胺包覆对立构复合聚乳酸支架性能的影响

采用溶液浇铸和粒子沥滤的方法制备立构复合聚乳酸支架,研究了盐酸聚多巴胺溶液浸泡处理不同时间的聚多巴胺包覆立构复合聚乳酸支架的结构与性能。利用差示扫描量热、场发射电子显微镜、X射线光电子能谱分析、液滴形状分析和动态热机械分析研究了盐酸聚多巴胺溶液处理时间对立构复合聚乳酸支架的熔融行为、孔结构、表面元素组成、润湿性和储能模量的影响。结果表明,利用聚多巴胺包覆立构复合聚乳酸支架可以有效提高支架表面的亲水性,当处理时间为20h时,聚多巴胺包覆立构复合聚乳酸支架的水接触角为0°,吸水率为421.8%;同时,在121℃高温下储能模量依然保持在155.3 MPa。

Simultaneous partial splenectomy during liver transplantation for advanced cirrhosis patients combined with severe splenomegaly and hypersplenism

BACKGROUND The most effective treatment for advanced cirrhosis and portal hypertension is liver transplantation(LT).However,splenomegaly and hypersplenism can persist even after LT in patients with massive splenomegaly.AIM To examine the feasibility of performing partial splenectomy during LT in patients with advanced cirrhosis combined with severe splenomegaly and hypersplenism.METHODS Between October 2015 and February 2019,762 orthotopic LTs were performed for patients with end-stage liver diseases in Tianjin First Center Hospital.Eighty-four cases had advanced cirrhosis combined with severe splenomegaly and hypersplenism.Among these patients,41 received partial splenectomy during LT(PSLT group),and 43 received only LT(LT group).Patient characteristics,intraoperative parameters,and postoperative outcomes were retrospectively analyzed and compared between the two groups.RESULTS The incidence of postoperative hypersplenism(2/41,4.8%)and recurrent ascites(1/41,2.4%)in the PSLT group was significantly lower than that in the LT group(22/43,51.2%;8/43,18.6%,respectively).Seventeen patients(17/43,39.5%)in the LT group required two-stage splenic embolization,and further splenectomy was required in 6 of them.The operation time and intraoperative blood loss in the PSLT group(8.6±1.3 h;640.8±347.3 mL)were relatively increased compared with the LT group(6.8±0.9 h;349.4±116.1 mL).The incidence of postoperative bleeding,pulmonary infection,thrombosis and splenic arterial steal syndrome in the PSLT group was not different to that in the LT group,respectively.CONCLUSION Simultaneous PSLT is an effective treatment and should be performed in patients with advanced cirrhosis combined with severe splenomegaly and hypersplenism to prevent postoperative persistent hypersplenism.

The clinical features, therapeutic responses, and prognosis of the patients with mantle cell lymphoma

Mantle cell lymphoma(MCL), a special type of non-Hodgkin's lymphoma, is incurable through conventional treatment. This study aimed to analyze the clinical features, therapeutic responses, and prognosis of patients with MCL. Clinical data of 30 patients with MCL treated in our hospital between April 2006 and July 2011 were analyzed. Eighteen patients were treated with CHOP plus rituximab (R-CHOP) regimen, 12 underwent conventional chemotherapy. The median age of the 30 patients was 58 years, 23 were men, all patients had Cyclin D1 overexpression, 29 (96.7%) had advanced disease, 11 (36.7%) had bone marrow involvement, 9 (30.0%) had gastrointestinal involvement, and 15 (50.0%) had splenomegaly. The complete response(CR) rate and overall response rate(ORR) were significantly higher in patients undergoing R-CHOP immunochemotherapy than in those undergoing conventional chemotherapy (38.9% vs. 16.7%, P = 0.187; 72.2% vs. 41.4%, P = 0.098). The difference of 2-year overall survival rate between the two groups was not significant (P = 0.807) due to the short follow-up time. The 2-year progression-free survival (PFS) rate was higher in R-CHOP group than in conventional chemotherapy group (53% vs. 25%, P = 0.083), and was higher in patients with a lower mantle cell lymphoma international prognostic index (MIPI) (51% for MIPI 0-3, 33% for MIPI 4-5, and 0% for MIPI 6-11, P = 0.059). Most patients with MCL were elderly; in an advanced stage; showed a male predominance; and usually had bone marrow involvement, gastrointestinal involvement, or splenomegaly. R-CHOP regimen could improve the CR rate and ORR of MCL patients. MIPI can be a new prognostic index for predicting the prognosis of advanced MCL.

宫腔镜窄带成像技术诊断不同类型子宫内膜增生性病变的价值

目的探讨宫腔镜窄带成像技术(NBI)诊断不同类型子宫内膜增生性病变的价值。方法选取148例异常子宫出血患者行宫腔镜检查,分别于白光和NBI模式下观察子宫内膜,对可疑病灶行靶向活检,送病理组织学检查。以病理诊断为金标准,比较白光与NBI模式对不同分类子宫内膜增生性病变的诊断价值。结果低危型子宫内膜增生性病变表现以Ⅱ型微血管为主,高危型子宫内膜增生性病变以Ⅲ~Ⅳ型微血管为主。宫腔镜白光及NBI模式诊断低危型子宫内膜增生性病变的敏感性分别为65.52%及86.21%,差异有统计学意义(χ~2=6.78,P=0.009);NBI模式诊断低危型子宫内膜增生性病变与病理学诊断一致性中等(Kappa值为0.617)。宫腔镜白光、NBI模式诊断高危型子宫内膜增生性病变的准确率分别为81.08%及89.86%(χ~2=4.60,P=0.032),敏感性分别为57.14%及92.86%(χ~2=14.29,P=0.000),阴性预测值分别为84.21%及96.91%(χ~2=9.43,P=0.002),差异均有统计学意义;特异性分别为90.57%及88.68%(χ~2=0.20,P=0.652),阳性预测值分别为70.59%及76.47%(χ~2=0.37,P=0.544),差异均无统计学意义;NBI模式诊断高危型子宫内膜增生性病变与病理学诊断有较好的一致性(Kappa值为0.766)。结论宫腔镜NBI可清晰地观察子宫内膜表面及深层的微血管形态变化,有助于减少低危型子宫内膜增生性病变的漏诊,提高诊断高危型子宫内膜增生性病变的准确率。NBI在诊断不同分类子宫内膜病变中具有一定临床应用价值。

Early Permian Sunidyouqi suprasubduction-zone ophiolites in the central Solonker suture zone(Inner Mongolia, China)

Different final closing ages have been proposed for the evolution of the Paleo-Asian Ocean(PAO),including Late Silurian, pre-Late Devonian, Early Permian, Late-Permian and Late Permian-Early Triassic.Ophiolites represent fragments of ancient oceanic crust and play an important role in identifying the suture zone and unveiling the evolutionary history of fossil oceans. Our detailed geological, geochemical and geochronological investigations argue for the existence of Early Permian(297 Ma) SSZ type ophiolites in the Sunidyouqi area of central Inner Mongolia, China. The gabbros and basalts show LREE depleted REE patterns and left-leaning primitive mantle-normalized spider diagrams with variable negative Nb-Ta anomalies(Nb~*= 0.24-1.28 and 0.29-0.55, respectively). The Sunidyouqi ophiolites were generated in a mature back-arc basin. The Sunidyouqi ophiolites share the same petrological,geochemical and geochronological characteristics with the other ophiolites along the Solonker suture zone, delineating a Late Paleozoic ocean and arc-trench system. This Late Paleozoic ocean and arc-trench system coincides with a Permian paleobiogeographical boundary, i.e. the boundary between the northern cold climate(Boreal faunal-Angaraland floral realm), and a southern warm climate(Tethys faunal-Cathaysian floral realm). A tectonic scenario was proposed at last for the closure of the SE PAO involving(1) Late Ordovician to Middle Permian continuous southward subduction beneath the northern margin of North China;(2) Carboniferous to Middle Permian continuous northward subduction the forming the Northern Accretionary Orogen;(3) Late Permian final closure of the SE PAO.

Local inhibition of GABA affects precedence effect in the inferior colliculus

The precedence effect is a prerequisite for faithful sound localization in a complex auditory environment, and is a physiological phenomenon in which the auditory system selectively suppresses the directional information from echoes. Here we investigated how neurons in the inferior colliculus respond to the paired sounds that produce precedence-effect illusions, and whether their firing behavior can be modulated through inhibition with gamma-aminobutyric acid （GABA）. We recorded extracellularly from 36 neurons in rat inferior colliculus under three conditions： no injection, injection with saline, and injection with gamma-aminobutyric acid. The paired sounds that produced precedence effects were two identical 4-ms noise bursts, which were delivered contralaterally or ipsilaterally to the recording site. The normalized neural responses were measured as a function of different inter-stimulus delays and half-maximal interstimulus delays were acquired. Neuronal responses to the lagging sounds were weak when the inter-stimulus delay was short, but increased gradually as the delay was lengthened. Saline injection produced no changes in neural responses, but after local gamma-arninobutyric acid application, responses to the lagging stimulus were suppressed. Application of gamma-aminobutyric acid affected the normalized response to lagging sounds, independently of whether they or the paired sounds were contralateral or ipsilateral to the recording site. These observations suggest that local inhibition by gamma-aminobutyric acid in the rat inferior colliculus shapes the neural responses to lagging sounds, and modulates the precedence effect.

Response of leaf carbon metabolism and dry matter accumulation to density and row spacing in two rapeseed(Brassica napus L.)genotypes with differing plant architectures

Biological yield indicates the potential for increasing yield.Leaf carbon metabolism plays an important role in the biomass accumulation of rapeseed(Brassica napus L.).Field experiments with the hybrid HZ62(with a conventional plant architecture)grown in 2016–2017,and HZ62 and accession 1301(with a compact plant architecture)grown in 2017–2018 were conducted to characterize the physiological and proteomic responses of leaf photosynthetic carbon metabolism to density and row spacing configurations.The densities were set at 15×10;ha^(-1)(D1),30×10^(4)ha^(-1)(D2),and 45×10^(4)ha^(-1)(D3)(main plot),with row spacings of 15 cm(R15),25 cm(R25),and 35 cm(R35)(subplot).Individual and plant population biomass accumulation was greatest at R25,R15,and R15 for D1,D2,and D3,respectively,for both genotypes.In comparison with D1 R25,the individual aboveground biomass of HZ62 decreased by60.2%,whereas the population biomass increased by 31.9%,and the individual biomass of genotype1301 decreased by 54.0%and the population biomass increased by 53.9%at D3 R15.Leaf carbon metabolic enzymes varied between genotypes at flowering stage.In contrast to D1 R25,at D3 R15 the activities of ribulose-1,5-bisphosphate carboxylase/oxygenase(Rubisco)and sucrose phosphate synthase(SPS)and the contents of starch,sucrose and soluble sugars in leaves were significantly decreased in HZ62 and increased in genotype 1301.The activities of fructose-1,6-bisphosphatase(FBPase)decreased,in consistency with the abundance of fructose-bisphosphate aldolase in HZ62.In contrast,sucrose synthase(Su Sy)activity appeared to decrease in both genotypes,but a significant increase in abundance of a protein with sucrose synthase was found in the 1301 genotype by proteomic analysis.With increased density and reduced row spacing,the expression of most key proteins involved in carbon metabolism was elevated,and enzyme activity and carbon assimilate content were increased in 1301,whereas HZ62 showed the opposite trend,indicating that the compact plant type can accumulate more population biomass with denser planting.

In Silico search and biological validation of MicroR171 family related to abiotic stress response in mulberry(Morus alba)

miR171 belongs to a highly conserved and ubiquitously expressed micro RNA gene family across species that play a critical role in controlling plant growth and development through the regulation of the miR171-SCL(scarecrow-like proteins)module.There is limited research available on the evolutionary relationship and functional diversification of miR171 members.In this study,we identified eight miR171 genes in the mulberry genome by bioinformatics analysis that were subsequently used to compare the evolutionary levels and explore abiotic stress mechanisms mediated by mno-miR171s(Morus notabilis miR171s).The results of phylogenetic analysis showed that the mature mno-miR171 sequences have strong sequence conservation,but their critical sites also exhibit high variation leading to functional diversification.Through quantitative real-time PCR,the expression profile of each mno-miR171 was analyzed under different stress treatments.All mno-miR171s,apart from mnomiR171h,were found to be significantly up-regulated under salt and drought stress conditions.The target genes of mno-miR171a namely,Morus020885 and Morus011800,were predicted and verified using the plural RNA method.5-rapid amplification of complementary DNA ends assays further to reveal that the target genes could be degraded by mno-miR171a post-transcriptionally.Overexpression of mno-miR171a in Arabidopsis improved the percentage of seed germination when the seeds were grown in NaCl-and mannitol-containing media.Transgenic plants were observed to grow better under drought conditions.The expression of various stress genes was significantly higher in transgenic plants than in wild type,except ERF11.Taken together,our study confirmed that mno-miR171a enhanced plant resistance to adverse stress environments via the regulation of the SCL targets.

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.

Prognostic value of pre-and post-transplantation 18F-fluorodeoxyglucose positron emission tomography results in non-Hodgkin lymphoma patients receiving autologous stem cell transplantation

Objective： High-dose chemotherapy （HDC） followed by autologous stem cell transplantation （ASCT） is the standard of care in the upfront or relapsed/refractory setting in some patients with non-Hodgkin lymphoma （NHL）. However, a proportion of patients do not respond to ASCT. lSF-fluorodeoxyglueose （FDG） positron emission tomography （PET）/computed tomography （CT） has been widely used for staging, response evaluation, and prognosis prediction. Here, we investigated the prognostic role of PET/CT in NHL patients before and after ASCT. Methods： A retrospective study was conducted at Peking University Cancer Hospital. All NHL patients who underwent ASCT between March 2010 and July 2016 were identified. Patients who had PET/CT scan before and after ASCT were included. Deauville criteria （5-point scale） were used to interpret PET scans. Univariate and multivariate survival analyses were performed using Cox regression. The predictive value of PET scanning was estimated by comparing the area under the receiver operating characteristic （ROC） curve. Results： In total, 79 patients were enrolled in this study. In univariate analysis, pre- and post-ASCT PET result was identified as prognostic factors for 3-year progression-free survival （PFS） and overall survival （OS）. Patients with negative pre-ASCT PET result demonstrated significantly better PFS （84.2% vs. 54.2%） and OS （89.2% vs. 63.6%） than patients with positive pre-ASCT PET result. PFS （91.6% vs. 25.3%） and OS （96.5% vs. 36.8%） were also significantly different between patients with negative and positive post-ASCT PET result. Multivariate analysis also showed a significant association between survival and post-ASCT PET result. ROC analysis revealed that the predictive value of post-ASCT PET result was superior to that of pre-ASCT PET result alone. Combined pre- and post-ASCT PET result is better for predicting outcomes in patients with NHL receiving transplantation. Deauville criteria score 〉3 was identified as the best cutoffvalue for post-ASCT PET. Conclusions： Post-ASCT PET result was more important than pre-ASCT PET result in predicting outcomes for NHL patients who underwent ASCT. The prognostic significance can be improved when combining pre- ASCT PET result with post-ASCT PET result. Deauville criteria can be used for interpreting PET scans in this scenario.

血常规分析对胃癌的早期诊断价值及与幽门螺旋杆菌感染的相关性

目的探究血常规中各个指标对胃癌(gastric cancer,GC)早期诊断的价值,并研究幽门螺旋杆菌(Helicobacter pylori,H.pylori)感染对血常规各指标的影响.方法选取2016-09/2017-09行胃镜检查的门诊及住院患者共223例,并依据胃镜及病理结果分为4组,其中慢性浅表性胃炎(chronic superficial gastritis,CSG)组58例,慢性萎缩性胃炎(chronic atrophic gastritis,CAG)组56例,高级别内瘤变(high-grade intraepithelial neoplasia,HIN)组52例,GC组57例做回顾性分析,比较各组红细胞分布宽度(red blood cell distribution width,RDW)、血小板计数(platelet count,PLT)、血小板体积(mean platelet volume,MPV)、血小板分布宽度(platelet distribution width,PDW)、白细胞计数(white blood cell count,WBC)、淋巴细胞计数(lymphocyte count,LYMP)、中性粒细胞计数(neutrophil counts,NR)、中性粒细胞计数/淋巴细胞计数(neutrophil count to lymphocyte ratio,NLR)、血小板计数/淋巴细胞计数(platelet count to lymphocyte ratio,PLR)指标差异,并比较各指标诊断GC的灵敏度、特异性.与此同时根据H.pylori抗体结果将各组分成H.pylori阳性和H.pylori阴性两个亚组,分别比较各亚组H.pylori感染率及血常规指标变化.结果在CSG组、CAG组、HIN组、GC组中,MPV、LYMP的中位值逐渐下降,RDW、NLR、PLR的中位值逐渐上升.RDW、MPV、LYMP、NLR、PLR均在CSG组与GC组间存在差异(P<0.05).RDW、MPV、LYM P、NLR、PLR、NR各指标检测G C的敏感性分别为82.5%、80.7%、84.2%、84.2%、71.9%、45.6%,特异性分别为72.4%、55.2%、82.8%、91.0%、89.7%、89.7%;CSG组中H.pylori阳性患者的PLT、WBC、NR较H.pylori阴性患者高,差异具有统计学意义(P<0.05).CAG组、HIN组及GC组中H.pylori阳性患者血常规各指标与H.pylori阴性患者相比,差异均无统计学意义(P>0.05).结论 RDW、MPV、LYMP、NLR、PLR对于GC的早期诊断具有重要提示作用;H.pylori感染可以导致全身炎性反应,阻止GC的发生、发展需早期根除H.pylori.

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.

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.