Prognostic utility of gamma-glutamyl transpeptidase to platelet ratio in patients with solitary hepatitis B virus-related hepatocellular carcinoma after hepatectomy

BACKGROUND The prognostic impact of preoperative gamma-glutamyl transpeptidase to platelet ratio(GPR)levels in patients with solitary hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC)following radical resection has not been established.AIM To examine the clinical utility of GPR for prognosis prediction in solitary HBVrelated HCC patients.METHODS A total of 1167 solitary HBV-related HCC patients were retrospectively analyzed.GPR levels were compared with 908 non-HCC individuals.Overall survival(OS)and recurrence-free survival(RFS)were evaluated,and cox proportional hazard model analyses were performed to identify independent risk factors.Differences in characteristics were adjusted by propensity score matching(PSM).Subgroup and stratified survival analyses for HCC risks were performed,and a linear trend of the hazard ratio(HR)according to GPR levels was constructed.RESULTS GPR levels of patients with solitary HBV-related HCC were higher than those with hepatic hemangiomas,chronic hepatitis B and healthy control(adjusted P<0.05).Variable bias was diminished after the PSM balance test.The low GPR group had improved OS(P<0.001)and RFS(P<0.001)in the PSM analysis and when combined with other variables.Multivariate cox analyses suggested that low GPR levels were associated with a better OS(HR=0.5,95%CI:0.36-0.7,P<0.001)and RFS(HR=0.57,95%CI:0.44-0.73,P<0.001).This same trend was confirmed in subgroup analyses.Prognostic nomograms were constructed and the calibration curves showed that GPR had good survival prediction.Moreover,stratified survival analyses found that GPR>0.6 was associated with a worse OS and higher recurrence rate(P for trend<0.001).CONCLUSION Preoperative GPR can serve as a noninvasive indicator to predict the prognosis of patients with solitary HBVrelated HCC.

迈腾B8L发动机故障诊断与修复

发动机电控系统诊断与修复是汽车技术国赛考核的重点,也是教学的难点。笔者结合自身参赛经历和发动机电控系统诊断与修复的教学经验,总结迈腾B8L1.4T发动机故障诊断与排除流程,对于教师教学备课和技能竞赛备赛具有参考意义。

非洲猪瘟病毒B602L蛋白的原核表达、纯化及多克隆抗体制备

【目的】非洲猪瘟病毒(African swine fever virus,ASFV)是对生猪养殖业危害极大的一种病原体,B602L蛋白作为其重要的非结构蛋白,是衣壳蛋白p72折叠为正确的三级结构的伴侣分子之一,在病毒组装成二十面体结构的过程中发挥着关键作用。特异性抗体对于抗非洲猪瘟免疫应答机制及血清学检测方法研究具有重要意义,本研究旨在获取ASFV B602L蛋白,并制备抗ASFV B602L蛋白的多克隆抗体,为ASFV B602L蛋白功能研究及相关诊断试剂的研发提供材料。【方法】以ASFV China/2018/AnhuiXCGQ株的B 602 L基因为研究对象,应用生物信息学软件对B602L蛋白的理化性质、信号肽、跨膜结构、抗原性和蛋白结构进行分析后,利用同源重组的方法将其克隆至原核表达载体pET-28a(+)中,转化大肠杆菌BL21(DE3)感受态细胞后经诱导表达获得B602L重组蛋白,利用镍柱亲和层析进行蛋白纯化,通过SDS-PAGE和Western blotting对B602L蛋白纯化效果进行验证。将纯化后的B602L蛋白免疫BALB/c小鼠制备多克隆抗体,通过间接ELISA方法测定多克隆抗体效价,通过Western blotting和Dot blotting检测多克隆抗体特异性。【结果】生物信息学分析表明,B602L蛋白属于稳定性亲水蛋白,无跨膜区和信号肽。二级结构主要含有α-螺旋(54.91%)、延伸链(9.81%)和无规则卷曲(32.08%)。成功构建了ASFV B602L重组质粒,SDS-PAGE和Western blotting结果显示,重组菌pET-28a-B602L-BL21在16℃、0.5 mmol/L IPTG诱导下高效表达,获得的重组蛋白主要表达在BL21菌株上清中,大小约为70 ku,且能与ASFV阳性血清特异性结合。间接ELISA检测结果显示,制备的抗B602L鼠源多克隆抗体效价达1∶409600,Western blotting和Dot blotting试验结果表明,抗B602L鼠源多克隆抗体能够特异性识别B602L蛋白。【结论】原核表达的B602L重组蛋白具有良好的免疫原性,能够与ASFV阳性血清特异性结合,制备的鼠抗ASFV B602L蛋白多克隆抗体具备较好的生物学活性。本试验结果可为进一步研究ASFV B602L蛋白的生物学功能和非洲猪瘟诊断方法的建立提供生物材料和理论支撑。

MyD88L265P及CD79B基因突变对原发性中枢神经系统淋巴瘤预后的影响

目的探究MyD88L265P及CD79B基因突变对原发性中枢神经系统淋巴瘤(PCNSL)患者预后的影响。方法收集2018年8月-2020年11月于兰州大学第二医院经开颅手术或立体定位活检术确诊的18例免疫功能正常(无HIV感染及免疫抑制药服用病史)的PCNSL患者临床资料进行回顾性分析。分别采用实时荧光定量PCR和一代基因测序技术检测18例PCNSL患者肿瘤组织中MyD88L265P和CD79B基因突变情况。针对可能与PCNSL首次无疾病进展生存期(PFS)和总生存期相关的指标行单因素分析,并采用Cox回归进行多因素分析。结果18例PCNSL肿瘤组织MyD88L265P突变率为38.9%,CD79B突变率为33.3%,MyD88L265P/CD79B共突变率为27.8%。单因素分析结果显示,病灶多发、病灶深部受累、肿瘤组织CD79B突变患者的PFS时间更短(P<0.05);多因素分析结果显示,病灶深部受累(HR=0.135,95%CI 0.023~0.799,P<0.05)、肿瘤组织CD79B突变(HR=0.149,95%CI 0.028~0.800,P<0.05)是PCNSL患者预后不良的独立危险因素。结论本组PCNSL患者肿瘤组织MyD88L265P、CD79B突变频率较高,这两种基因突变尤其是CD79B突变可能与PCNSL不良预后相关。

汽油车无法发动综合故障快速诊断研究分析——以大众迈腾B8L为例

本文主要分析汽油发动机作为动力主体的燃油车辆无法发动的具体故障现象以及根据故障现象快速判断故障方向的方法。详细阐述以大众迈腾B8L为例的汽油车无法发动的故障现象与原因以及测量方法,总结了汽油车无法发动故障的快速诊断诀窍。内容包含汽油发动机电控系统的全部内容与要点,汽油车仍旧是社会交通工具的主体,本文仍具有一定的研究价值与意义。

Evaluation of the Potential of Araucaria angustifolia Seeds as Source of Oligosaccharides, Resistant Starch and Growth of Probiotic Bacteria

“Pinhão”, the seed of Araucaria angustifolia, is an important food, being part of the eating habits of Indigenous communities. In this study, we evaluated the oligosaccharide content, resistant starch and the growth of probiotic bacteria. GF4 (1-fructofuranosylnystose) was the main fructo-oligosaccharides found, in higher contents compared to other food sources. Maltooligosaccharides (MOS) represented the main part of the oligosaccharides profile of Brazilian pine seeds. In descending order of importance was maltoheptaose (G7), maltohexose (G6) and maltotriose (G3). The starches from the variety Sanct josephi presented the highest amount of resistant starch that could stimulate probiotic strains, mainly B. breve and L. plantarum, and may have a prebiotic effect, potentially promoting health benefits. This study advances the understanding of the chemical composition of the main portion of the “pinhão” enhancing awareness of its potential as a healthy food source, contributing to different uses and indirectly with the species preservation.

大众迈腾B8L轿车启动系统工作过程与故障诊断分析

以大众迈腾B8L轿车发动机启动系统为例,分析启动系统的工作过程以及当启动系统出现故障时的诊断流程和思路。分析认为,维修人员熟悉该车发动机启动系统的工作过程,能够对启动系统工作条件是否正常进行判断,以及可以熟练掌握该车发动机启动系统的诊断流程。

Rhizobium Inoculation and Micronutrient Addition Influence the Growth,Yield,Quality and Nutrient Uptake of Garden Peas(Pisum sativum L.)

Garden pea productivity and qualities are hampered in zinc(Zn),boron(B),and molybdenum(Mo)deficient soil.Thus,the combination of micronutrients(i.e.,Zn,B,and Mo)and rhizobium is necessary to increase the productivity and quality of garden peas,since this management for garden peas is neglected in Bangladesh.Therefore,the present study was made to assess the effectiveness of rhizobium inoculant singly or in combination with the micronutrients(i.e.,Zn,B,and Mo)on growth,yield,nutrient uptake,and quality of garden peas.Treatments were:T_(1)=Control,T_(2)=Rhizobium inoculation at 50 g/kg seed,T_(3)=T_(2)+Zn_(3)Mo1,T_(4)=T_(2)+B_(2)Mo1,T_(5)=T_(2)+Zn_(3)B_(2),T_(6)=T_(2)+Zn_(3)B_(2)Mo1 and T_(7)=Zn_(3)B_(2)Mo1.All treatments were arranged in a randomized complete block design and repeated all treatments in three times.The application of 3 kg Zn,2 kg B,and 1 kg Mo ha^(−1)with inoculation of Rhizobium at 50 g kg^(−1)seed(T_(6))facilitated to increase of 44.8%in the green pod and 29.7%seed yield over control.The same treatment contributed to attaining the maximum nodulation(25.3 plant^(−1)),Vitamin C(43.5 mg 100 g^(−1)),protein content(22.2%),and nutrient uptake as well as accumulation in garden peas.Among all treatment combinations,treatment T_(6)was found superior to others based on microbial activities,soil fertility,and profitability.The results of the study found that the application of 3 kg Zn,2 kg B,and 1 kg Mo ha^(−1)in combination with Rhizobium inoculation(50 g kg^(−1)seed)can improve the yield and quality of garden peas.The results of the study have the potential for the areas,where there is no use of Rhizobium inoculant or Zn,B,and Mo fertilizer for cultivation of garden pea.

迈腾B8L发动机无法启动故障诊断与排除

以高职国赛“汽车故障检修”选用的迈腾B8L为对象,诊断与排除电气系统的典型部件损坏造成发动机无法启动的故障。首先,描述了发动机无法启动的故障现象:全车不上电、起动机无法运转及起动机运转不着车等;其次,介绍迈腾B8L的启动策略:整车上电策略及起动机运转策略;再次,选取点火开关损坏造成的不上电故障,动力总线损坏造成的起动机不运转故障,起动继电器及其线路损坏造成的起动机不运转故障,曲轴位置传感器及其线路损坏造成的不着车故障;最后,对点火开关、动力总线、启动继电器及其线路、曲轴位置传感器及其线路的故障进行了诊断与排除。在不使用故障诊断仪的前提下,为以上四大部件损坏造成的发动机无法启动故障,提供了系统、全面、有效的排除方法,也为诊断与排除其他部件的故障提供了详细的参考依据。

Stochastic modeling and analysis of hepatitis and tuberculosis co-infection dynamics

Several mathematical models have been developed to investigate the dynamics of tuberculosis(TB)and hepatitis B virus(HBV).Numerous current models for TB,HBV,and their co-dynamics fall short in capturing the important and practical aspect of unpredictability.It is crucial to take into account a stochastic co-infection HBV–TB epidemic model since different random elements have a substantial impact on the overall dynamics of these diseases.We provide a novel stochastic co-model for TB and HBV in this study,and we establish criteria on the uniqueness and existence of a nonnegative global solution.We also looked at the persistence of the infections as long its dynamics are governable by the proposed model.To verify the theoretical conclusions,numerical simulations are presented keeping in view the associated analytical results.The infections are found to finally die out and go extinct with certainty when L´evy intensities surpass the specified thresholds and the related stochastic thresholds fall below unity.The findings also demonstrate the impact of noise on the decline in the co-circulation of HBV and TB in a given population.Our results provide insights into effective intervention strategies,ultimately aiming to improve the management and control of TB and HBV co-infections.

IL-6、CRP、NLR和NT-proBNP对老年心力衰竭合并肺炎的诊断价值

目的探讨白细胞介素-6(IL-6)、C-反应蛋白(CRP)、中性粒细胞与淋巴细胞比值(NLR)和N末端前脑钠肽前体(NT-proBNP)对老年心力衰竭(以下简称心衰)合并肺炎的诊断价值。方法选取2022年4月至2023年4月该院收治的165例老年心衰患者作为研究对象,根据是否合并肺炎分为心衰合并肺炎组(78例)和单纯心衰组(87例),根据美国纽约心脏病协会(NYHA)心功能分级标准分为Ⅱ级组(59例)和Ⅲ级+Ⅳ级组(106例)。比较各组IL-6、CRP、NT-proBNP水平和NLR;采用Spearman相关分析IL-6、CRP、NLR与NT-proBNP水平的相关性;采用受试者工作特征(ROC)曲线评估IL-6、CRP、NLR、NT-proBNP单独及联合检测对心衰患者合并肺炎的诊断效能。结果心衰合并肺炎组IL-6、CRP、NT-proBNP水平及NLR明显高于单纯心衰组(P<0.05),Ⅲ级+Ⅳ级组IL-6、CRP、NT-proBNP水平及NLR明显高于Ⅱ级组(P<0.05)。Spearman相关性分析结果显示,NT-proBNP水平与IL-6、CRP、NLR水平呈正相关(r=0.263、0.419、0.468,P<0.001)。IL-6、CRP、NLR和NTproBNP联合诊断心衰合并肺炎的曲线下面积(AUC)为0.726(95%CI:0.650~0.803),灵敏度为67.9%,特异度为71.3%。结论心衰合并肺炎患者IL-6、CRP、NT-proBNP水平和NLR明显高于单纯心衰患者,上述4项指标联合检测对心衰合并肺炎患者有一定的诊断效能。

Bioactive chemical constituents from the marine-derived fungus Cladosporium sp.DLT-5

A new isochromanone,cladosporinisochromanone(1),accompanied by 15 known compounds(2–16)were obtained from secondary metabolites produced by marine-derived fungus Cladosporium sp.DLT-5.NMR and HRESIMS spectra elucidation determined the planar structure of 1.Subsequent electronic circular dichroism(ECD)experiment assigned the absolute configuration of 1.Compounds 1,2,4–6,and 10 displayed different degrees of neuroprotective activities on human neuroblastoma cells SH-SY5Y.Five compounds(1,3–5,and 13)emerged resistance to protein tyrosine phosphatase 1B(PTP1B),further kinetic analysis and molecular docking study indicated that the most potent compound 13(IC50value of 10.74±0.61μmol/L)was found as a noncompetitive inhibitor for PTP1B.Surface plasmon resonance(SPR)and molecular docking studies also demonstrated the interaction between compound 12 and Niemann-Pick C1 Like 1(NPC1L1),which has been identified as significant therapeutic target for hypercholesteremia.In addition,compounds 3,6,and 14 showed attractive inhibitory activity against the phytopathogenic fungi:Colletotrichum capsici.Therefore,library of Cladosporium metabolites is enriched and new active uses of known compounds are explored.

马头山羊羊口疮病毒的分离鉴定及其B2L基因的特征分析

为确定湖北省某马头山羊养殖场发生的疑似羊口疮(Orf)的病原及其分子生物学特征。本试验利用牛睾丸细胞对马头山羊唇部痂皮病料进行病毒分离培养,通过细胞病变观察、病毒滴度测定、PCR扩增和测序等方法对分离毒株进行了鉴定。并采用MegAlign、MEGA 7.0、DNAMAN和Bioedit等软件分析了分离毒株和China Vaccine毒株B2L基因的核苷酸序列相似性,并预测了蛋白二级结构和疏水性。结果显示,接种病料上清液的牛睾丸细胞盲传5代后出现细胞病变,经PCR扩增的分离毒株B2L基因大小为1137 bp;所分离羊口疮病毒(ORFV)病毒滴度可达105.5TCID50/mL;分离毒株与AH1404、FJ-YX和GX-BH毒株B2L基因同源性为99.3%;与China Vaccine毒株同源性为89.5%。分离毒株与China Vaccine毒株B2L基因序列分析显示处在不同分支,两者存在8个位点突变(aa11、aa80、aa101、aa123、aa126、aa294、aa327和aa333);B2L蛋白为稳定的疏水性蛋白;分离毒株和China Vaccine毒株的蛋白二级结构存在差异。结果表明,该养殖场ORFV的B2L基因出现变异,有关部门应当加强对ORFV流行情况的监测。

Crocus sativus L.produces anti-inflammatory effects and regulates the NLRP3–NF-κB pathway

Objective:This study aimed to evaluate the anti-inflammatory effects of petal and stamen extracts of saffron crocus(Crocus sativus)and explore the underlying mechanism.Methods:Local and systemic inflammation models were used to investigate the anti-inflammatory effects of C.sativus.A xyleneinduced inflammation model or lipopolysaccharide(LPS)-induced inflammation model was used in this study.C.sativus petal and stamen extracts were each administered to the mice in the xylene and LPS models by gavage for 14 d at 0.1 and 0.4 g/kg doses,respectively.Enzyme-linked immunosorbent assay(ELISA)was used to measure the concentrations of tumor necrosis factor(TNF)-αand interleukin(IL)-1βin mouse serum.Hematoxylin and eosin(H&E)staining was used to observe the pathological changes in the ear in the xylene-induced inflammation model and in the spleen in the LPS-induced inflammation model.NOD-like receptor thermal protein domain associated protein 3(NLRP3)protein levels within the nuclear factor-kappa B(NF-κB)pathway were assessed using western blotting.RAW264.7 cells were treated with LPS(5μg/mL)and LPS+C.sativus(0.05,0.1,and 0.2 mg/mL)for 24 h,and a Cell Counting Kit-8 was used to measure cell proliferation.Changes in NLRP3 and NF-κB levels were evaluated by western blotting.Results:Petal and stamen extracts of C.sativus attenuated the anti-inflammatory effects in local or systemic inflammatory models and repaired pathological changes in the ear in the xylene-induced inflammation model and spleen in the LPS-induced inflammation model.These extracts also decreased the concentrations of TNF-αand IL-1βin the mouse serum in the LPS-induced inflammation model.C.sativus downregulated NLRP3 protein level through the NF-κB pathway and downregulated LC-3 and BECLIN1 in vivo and in vitro.Carbonyl Cyanide3-ChloroPhenylhydrazone(CCCP)weakened the effects of C.sativus on the NLRP3–NF-κB pathway.Conclusion:C.sativus has anti-inflammatory effects and regulates the NLRP3-NF-κB pathway.

2020款迈腾B8L发动机无法启动故障检修

一辆2020款迈腾B8L轿车,按启动按钮,仪表正常点亮;踩刹车同时按启动按钮,启动机有吸合声音但无法转动,无着车迹象。针对该故障现象,根据故障产生机理,依次对该车发动机启动系统的相关部件及其电路等进行了检测诊断。最终排查出的故障原因是,发动机控制单元J623的P/N挡信号线与启动反馈信号线短路,对其进行修复后,发动机可正常启动,车辆故障排除。

LMR/LDH对弥漫大B细胞淋巴瘤合并乙型病毒性肝炎患者预后的价值

目的探讨外周血淋巴细胞/单核细胞比值(LMR)与乳酸脱氢酶(LDH)的比值(LMR/LDH)对弥漫大B细胞淋巴瘤(DLBCL)合并乙型病毒性肝炎患者预后的价值。方法选取DLBCL合并乙型病毒性肝炎患者77例为研究对象,收集患者的临床资料[性别、年龄、临床分期、B症状、美国东部肿瘤协作组(ECOG)评分、淋巴结外受累数量、国际预后指数(IPI)分级等];抽取治疗前空腹抗凝全血及静脉血,采用电阻抗、高频电导及激光散射联合检测法检测淋巴细胞绝对值和单核细胞绝对值并计算LMR,采用紫外分光光度法和免疫比浊法检测血清乳酸脱氢酶(LDH)和β2-微球蛋白(β2-MG);所有患者出院后随访36个月,记录患者的总生存期(OS)及无进展生存期(PFS);采用患者工作特征(ROC)曲线确定LMR/LDH的临界值,分析LMR/LDH高低对患者OS及PFS的影响;采用COX回归模型分析LMR/LDH与患者临床特征的关系。结果ROC曲线分析显示,LMR/LDH的临界值为0.008,敏感度和特异度分别为0.6607和0.7619,曲线下面积(AUC)为0.7054(95%CI为0.5491~0.8937,P=0.0057);LMR/LDH与临床分期、ECOG评分、淋巴结外受累数量、IPI、LDH、β2-MG相关(P<0.05);单因素分析显示,LMR/LDH、临床分期、ECOG≥2分、淋巴结外受累数量≥2个、IPI、LDH及β2-MG对患者OS及PFS均有影响(P<0.05);多因素分析显示,LMR/LDH是影响DLBCL合并乙型病毒性肝炎患者OS及PFS的独立危险因素(P<0.05);高LMR/LDH组的OS与PFS高于低LMR/LDH组。结论LMR/LDH对DLBCL合并乙型病毒性肝炎患者的预后有一定的临床预测价值。

LMR和CD163^(+)TAM对弥漫大B细胞淋巴瘤患者预后的评估价值

目的:探究淋巴细胞和单核细胞比值(LMR)和CD163^(+)肿瘤相关巨噬细胞(TAM)对弥漫大B细胞淋巴瘤(DLBCL)患者预后的评估价值。方法:收集63例初诊DLBCL患者外周血和淋巴结组织。检测患者血常规,得出淋巴细胞和单核细胞数量,计算出LMR。采用免疫组化方法检测淋巴结组织中CD163^(+)TAM数量。采用ROC曲线确定LMR和CD163^(+)TAM的截断值,分析LMR和CD163^(+)TAM与DLBCL患者预后指标的相关性。结果:63例初诊DLBCL患者的LMR的水平为3.69±1.71,CD163^(+)TAM的中位值为26/HPF。CD163^(+)TAM与LMR呈负相关(r=-0.58),与单核细胞计数呈正相关(r=0.46)。采用ROC曲线确定LMR和CD163^(+)TAM临界值分别为2.95和29/HPF,并以此将患者分为低LMR组和高LMR组以及低CD163^(+)TAM组和高CD163^(+)TAM组。低LMR组临床分期Ⅲ-Ⅳ期、IPI评分3-5分以及存在骨髓浸润的患者比例均明显高于高LMR组(P<0.05)。高CD163^(+)TAM组临床分期Ⅲ-Ⅳ期、IPI评分3-5分、LDH水平升高以及存在骨髓浸润的患者比例均明显高于低CD163^(+)TAM组(P<0.05)。LMR与OS呈正相关(r=0.43),CD163^(+)TAM比例与OS呈负相关(r=-0.65)。低LMR组和高CD163^(+)TAM组的DLBCL患者具有更短的OS(P<0.05)。结论:低LMR和高CD163^(+)TAM可以作为DLBCL患者预后不良的生物学标志。

弥漫大B细胞淋巴瘤中MYD88、NAP1L5基因特征与临床特征及预后的关系

目的 探讨弥漫性大B细胞淋巴瘤(Diffuse Large B-cell Lymphoma, DLBCL)中MYD88和NAP1L5基因的特征,及其与临床表现和预后之间的关系。方法 分析本院2019年1月至2022年12月期间的87例DLBCL患者中MYD88和NAP1L5基因突变的情况,并分析其与临床特征的关系。评估影响DLBCL患者总生存期的相关因素。结果 87例患者中,31例出现MYD88基因异常,35例出现NAP1L5基因异常。两个基因共异常率为26.43%。MYD88和NAP1L5基因异常及共异常主要集中在ABC型DLBCL中,阳性率分别达74.19%、74.28%、73.91%。在Ⅲ~Ⅳ期病例中,MYD88基因异常和两基因共异常的比例(61.29%、65.21%)均高于I~II期的病例(P<0.05)。在IPI指数为3~5的病例中,MYD88基因异常的比例(64.51%)高于IPI指数为0~2的病例(P<0.05)。生存时间的单因素分析显示,病理分型、临床分期、MYD88、NAP1L5基因异常组和两基因共异常是影响因素。生存分析显示,不同病理分型、临床分期、MYD88基因状态、NAP1L5基因状态、MYD88、NAP1L5基因共异常情况患者的生存时间差异显著(P<0.05)。临床分期、MYD88和NAP1L5基因共异常是影响患者总生存期的独立因素(P<0.05)。结论 MYD88、NAP1L5基因异常与DLBCL的临床特征密切相关,临床分期和MYD88和NAP1L5基因的共异常是影响DLBCL患者总生存期的独立因素。

血常规衍生指标与HBV-DNA载量及ALT关系的研究

目的:选择中性粒细胞淋巴细胞比值(NLR)、血小板淋巴细胞比值(PLR)和血清谷丙转氨酶(ALT)、HBV-DNA作为研究指标,通过分析HBV感染者外周血NLR、PLR的表达与疾病进程及HBV-DNA载量和ALT的关系,探讨NLR和PLR在慢性乙型肝炎患者病情发展的临床意义。方法:收集慢性乙型肝炎患者475例外周血标本,检测血常规、肝功能和乙肝DNA水平,按照HBV-DNA载量水平不同分为阴性组(作为对照组)、低拷贝组、中拷贝组、高拷贝组,分别比较HBV-DNA升高组与阴性组外周血NLR、PLR水平,分析其差异性;同时按照ALT升高水平分为轻、中、重度三个观察组和正常对照组,分别比较观察组与正常组对应的外周血NLR、PLR水平,查找规律;对HBV-DNA阳性的患者在进行药物治疗过程中,监测血NLR、PLR水平变化。结果:NLR与疾病的进展有一定的相关性,其中中拷贝组和高拷贝组与阴性组比较,差异有统计学意义(P均<0.05);而PLR与HBV-DNA未发现有显著相关性,但三个升高组与阴性组比较,PLR数值差异有统计学意义(P均<0.05);随着ALT的逐步升高,NLR也随着升高,轻度和中度升高组,NLR变化不大,但重度升高组与正常组比较,差异有统计学意义(P<0.05);而PLR与ALT的关系不大,差异无统计学意义(P均>0.05);在抗病毒治疗的早期,由于淋巴细胞数量的减少,NLR和PLR会一时性升高。结论:NLR和PLR具有评估慢性HBV感染患者肝脏炎症活动度的临床应用价值,持续动态检测这两个指标的变化对慢性乙肝患者的病情预判有一定的指导作用。

Immunogenetic basis of chicken’s heterophil to lymphocyte ratio revealed by genome-wide indel variants analysis

Enhancing host immunity is an effective way to reduce morbidity in chickens.Heterophil to lymphocyte ratio(H/L)is associated with host disease resistance in birds.Chickens with different H/L levels show different disease resistances.However,the utility of the H/L as an indicator of immune function needs to be further analyzed.In this study,a H/L directional breeding chicken line(Jingxing yellow chicken)was constructed,which has been bred for 12 generations.We compared the function of heterophils,and combined statistical analysis to explore the candidate genes and pathways related to H/L.The oxidative burst function of the heterophils isolated from the H/L selection line(G12)was increased(P=0.044)compared to the non-selection line(NS).The 22.44 Mb genomic regions which annotated 300 protein-coding genes were selected in the genome of G9(n=92)compared to NS(n=92)based on a genome-wide selective sweep.Several selective regions were identified containing genes like interferon induced with helicase C domain 1(IFIH1)and moesin(MSN)associated with the intracellular receptor signaling pathway,C–C motif chemokine receptor 6(CCR6),dipeptidyl peptidase 4(DPP4)and hemolytic complement(HC)associated with the negative regulation of leukocyte chemotaxis and tight junction protein 1(TJP1)associated with actin cytoskeleton organization.In addition,45 genome-wide significant indels containing 29 protein-coding genes were also identified as associated with the H/L based on genome-wide association study(GWAS).The expression of protein tyrosine phosphatase non-receptor type 5(PTPN5)(r=0.75,P=0.033)and oxysterol binding protein like 5(OSBPL5)(r=0.89,P=0.0027)were positively correlated with H/L.Compared to the high H/L group,the expressions of PTPN5 and OSBPL5 were decreased(P<0.05)in the low H/L group of Beijing you chicken.The A/A allelic frequency of indel 5_13108985(P=3.85E–06)within OSBPL5 gradually increased from the NS to G5 and G9,and the individuals with A/A exhibited lower H/L than individuals with heterozygote A/ATCT(P=4.28E–04)and homozygous ATCT/ATCT(P=3.40E–05).Above results indicated oxidative burst function of heterophils were enhanced,and 22.44 Mb genomic regions were selected with the directional selection of H/L.In addition,PTPN5 and OSBPL5 genes were identified as H/L-related candidate genes.These findings revealed the complex genetic mechanism of H/L related to immunity and will allow selection for improving chicken immunity based on the H/L.