Interleukin-28 and hepatitis C virus genotype-4:Treatment-induced clearance and liver fibrosis

AIM:To investigate the association between interleukin-28B(IL28B) genotype and response to treatment and hepatic fibrosis in patients with hepatitis C virus(HCV) genotype 4.METHODS:Two hundred and one HCV-genotype 4 patients were included.All patients were treated with Peginterferon alph2a/Ribavirin for 48 wk.End of treatment response(ETR) was defined as loss of detectable serum HCV RNA at the end of treatment.Sustained viral response(SVR) was defined as loss of detectable serum HCV RNA at the end of 24 wk follow up.Genotyping of IL28B rs12979860 was performed using the TaqMan assay.We used logistic regression to estimate the adjusted odds ratio(aOR) and 95%CI.RESULTS:The study included 201 HCV-genotype 4 patients.The majority of patients were men(89.6%),with a median age of 47 years,inter-quartile range(40-51).Approximately 62.5% of patients had ETR,and 49.6% had SVR.Individuals who achieved SVR were more likely to be younger(χ 2 = 4.91,P = 0.027),and less likely to have fibrosis(χ 2 = 15.54,P < 0.0001),or inflammation(χ 2 = 7.58,P = 0.006).The genotype distribution of rs12979860 was 36.2%,49.0% and 14.8% for genotypes CC,CT,and TT,respectively.In these participants,rs12979860 genotype distribution did not differ by gender(P = 0.466),pretreatment viral load(P = 0.600),inflammation(P = 0.435),or fibrosis(P = 0.291).The frequencies of IL28B rs12979860 genotypes were TT(14.8%),CT(49.0%),and CC(36.2%).Compared to rs12979860 genotype TT,aORs(95%CI) for ETR and SVR were:CC genotype,[17.55(5.34-57.69) and 5.92(2.09-16.76),respectively];CT genotype,[5.15(1.80-14.78) and 2.48(0.94-6.52),respectively].In the current study,the patients who did not achieve ETR or SVR had a lower prevalence of rs12979860 CC(17.4% and 23.3%,respectively) than individuals who had ETR or SVR(47.9% and 47.2%,respectively).Individuals with rs12979860 CC genotype had approximately 6 times the odds of SVR compared to individuals with TT genotype(aOR = 5.92;95%CI:2.09-16.76).Similarly,patients with CT genotype had SVR more often than patients with TT genotype(aOR = 2.48;95%CI:0.94-6.52).Carrying at least one copy of the C allele(genotypes CT and CC) had almost 8 times the probability of ETR compared to those with genotype rs12979860 TT(aOR = 7.87;95%CI:2.84-21.82),and approximately 3 times the odds of SVR compared to those with genotype rs12979860 TT(aOR = 3.46;95%CI:1.37-8.74).In addition,data were consistent with a significant gene-dose relationship(aOR = 4.05/allele;95%CI:2.27-7.22).The association between rs12979860 genotype and SVR was similar among those who achieved and those who did not achieve SVR.CONCLUSION:In HCV-genotype 4 patients,rs12979860 is a sensitive predictor of viral clearance,independent of viral load,age,gender or fibrosis,with no similar relation to severity of fibrosis.

Impact of Interleukin-28B Polymorphism on Response to Treatment in Chinese Hepatitis C Patients

The candidate polymorphism rs12979860 of interleukin 28B（IL28B） gene was genotyped by means of polymerase chain reaction（PCR） amplification and direct PCR sequencing, and then the role of this single nucleotide polymorphism（SNP） in the response to the treatment of 172 Chinese patients with hepatitis C virus（HCV） chronic infection was analyzed. The results show that the frequencies of major homozygotes（CC） and heterozygotes（CT） of rs12979860 were 0.84 and 0.16, respectively, and the minor homozygotes（TT） wasn’t found in this cohort. A highly significant association was found between the CC genotype and sustained virological response（SVR） in HCV geno type 1 infected patients（P〈0.001） but not in HCV non-genotype 1 infected patients. In addition, a strong association was found between rs12979860 CC genotype and rapid virological response（RVR） in both HCV genotype 1 infected patients（P〈0.001） and non-genotype 1 infected patients（P〈0.001）. Taken together, these results indicate that IL28B polymorphism plays a key role in response to hepatitis C therapy in Chinese patients. Combine assessment of clinical predictors and the IL28B polymorphism may be beneficial to the individualized treatment decision in Asian chronic hepatitis C（CHC） patients.

Interleukin-6 in epilepsy and its neuropsychiatric comorbidities: How to bridge the gap

There is growing evidence that interleukin(IL)-6 plays an important role in neurological and psychiatric disorders.This editorial comments on the study published in the recent issue of the World Journal of Psychiatry,which employed Mendelian randomization to identify a causal relationship between IL-6 receptor blockade and decreased epilepsy incidence.The purpose of this editorial is to highlight the dual effects of IL-6 in epilepsy and its related neuropsychiatric comorbidities.IL-6 plays a critical role in the facilitation of epileptogenesis and maintenance of epileptic seizures and is implicated in neuroinflammatory proce-sses associated with epilepsy.Furthermore,IL-6 significantly influences mood regulation and cognitive dysfunction in patients with epilepsy,highlighting its involvement in neuropsychiatric comorbidities.In summary,IL-6 is not only a pivotal factor in the pathogenesis of epilepsy but also significantly contributes to the emergence of epilepsy-related neuropsychiatric complications.Future resear-ch should prioritize elucidating the specific mechanisms by which IL-6 operates across different subtypes,stages and neuropsychiatric comorbidities of epilepsy,with the aim of developing more precise and effective interventions.Furthermore,the potential of IL-6 as a biomarker for the early diagnosis and prognosis of epile-psy warrants further investigation.

Interleukin-17A facilitates tumor progression via upregulating programmed death ligand-1 expression in hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)is an inflammation-associated tumor with a dismal prognosis.Immunotherapy has become an important treatment strategy for HCC,as immunity is closely related to inflammation in the tumor microenvir-onment.Inflammation regulates the expression of programmed death ligand-1(PD-L1)in the immunosuppressive tumor microenvironment and affects im-munotherapy efficacy.Interleukin-17A(IL-17A)is involved in the remodeling of the tumor microenvironment and plays a protumor or antitumor role in different tumors.We hypothesized that IL-17A participates in tumor progression by affe-cting the level of immune checkpoint molecules in HCC.The upregulation of PD-L1 expression in HCC cells by IL-17A was assessed by reverse transcription PCR,western blotting,and flow cytometry.Mechanistic studies were conducted with gene knockout models and pathway inhibitors.The function of IL-17A in immune evasion was explored through coculture of T cells and HCC cells.The effects of IL-17A on the malignant biological behaviors of HCC cells were evaluated in vitro,and the antitumor effects of an IL-17A inhibitor and its synergistic effects with a PD-L1 inhibitor were studied in vivo.RESULTS IL-17A upregulated PD-L1 expression in HCC cells in a dose-dependent manner,whereas IL-17A receptor knockout or treatment with a small mothers against decapentaplegic 2 inhibitor diminished the PD-L1 expression induced by IL-17A.IL-17A enhanced the survival of HCC cells in the coculture system.IL-17A increased the viability,G2/M ratio,and migration of HCC cells and decreased the apoptotic index.Cyclin D1,VEGF,MMP9,and Bcl-1 expression increased after IL-17A treatment,whereas BAX expression decreased.The combination of IL-17A and PD-L1 inhibitors showed synergistic antitumor efficacy and increased cluster of differentiation 8+T lymphocyte infiltration in an HCC mouse model.CONCLUSION IL-17A upregulates PD-L1 expression via the IL-17A receptor/phosphorylation-small mothers against decapenta-plegic 2 signaling pathway in HCC cells.Blocking IL-17A enhances the therapeutic efficacy of PD-L1 antibodies in HCC in vivo.

Association of interleukin-6 with acute lung injury risk and disease severity in sepsis

Sepsis is a life-threatening condition caused by a dysregulated response of the body in response to an infection that harms its tissues and organs.Interleukin-6(IL-6)is a significant component of the inflammatory response as part of the pa-thogenesis of sepsis.It aids in the development of Acute lung injury and,subse-quently,multiple organ dysfunction syndrome.This letter probes into the corre-lation between plasma IL-6 levels and the risk of developing acute lung injury and multiple organ dysfunction syndrome in critically ill patients with sepsis.While it shows promising results,limitations like its observational study design,a limited sample size,a single center involvement,single-time-point measurement,and a lack of a control group restrain its cogency.The study is a big step in identifying IL-6 as a biomarker to improve patient care.

Gene polymorphisms of interleukin-28, p21-activated protein kinases 4, and response to interferon-α based therapy in Chinese patients with chronic hepatitis B

Background Peg-lnterferon-a treatment is expensive and associated with considerable adverse effects, selection of patients with the highest probability of response is essential for clinical practice. The objective of this study was to assess the relationship between the gene polymorphisms of interleukin-28 （IL-28）, p21-activated protein kinase 4 （PAK4） and the response to interferon treatment in chronic hepatitis B patients. Methods Two hundred and forty interferon-naive treatment HBeAg seropositive chronic hepatitis B patients were enrolled in the present prospective nested case-control study. Peripheral blood samples were collected, including 92 with favorable response and 148 without response to the interferon treatment. Rs8099917, rs12980602, and rs9676717 SNP was genotyped using matrix assisted laser desorption/ionization time of flight mass spectrometry （MALDI-TOF MS）. Results IL-28 genotype was not associated with response to interferon treatment （OR for GT/GG vs. TT, 0.881 （95% CI 0.388-2.002）; P=0.762; OR for CT/CC vs. TT, 0.902 （95% CI 0.458-1.778）; P=-0.766）. Rs9676717 in PAK4 genotype was independently associated with the response （OR for CT/CC vs. TT, 0.524 （95% CI 0.310-0.888）; P=0.016）. When adjusting for age, gender, smoking, drinking, levels of hepatitis B virus DNA, and alanine aminotransferase （ALT）, rs9676717 genotype TT appeared to be associated with a higher probability of response for interferon treatment （OR, 0.155 （95% CI 0.034-0.700）; P=0.015）. Conclusion Genotype TTfor rs9676717 in PAK4 gene and no drinking may be predictive of the interferon-a treatment success.

三联体基序包含蛋白28在胃癌组织中的表达及其对胃癌HGC-27细胞侵袭、迁移、增殖和硼替佐米诱导的细胞凋亡的影响

目的:探讨三联体基序包含蛋白28(TRIM28)在胃癌组织中的表达及其对胃癌HGC-27细胞侵袭、迁移、增殖和硼替佐米(BTZ)诱导的细胞凋亡的影响。方法:收集10例胃癌患者的癌组织和癌旁组织,采用免疫组化和实时荧光定量PCR(RT-qPCR)分别检测TRIM28阳性率及mRNA的表达水平。采用RNA干扰技术敲低人胃癌细胞株HGC-27中的TRIM28表达,采用Transwell和划痕愈合实验探究敲低TRIM28表达对胃癌细胞的侵袭、迁移能力的影响,采用MTT法检测细胞增殖能力,采用流式细胞术检测细胞的凋亡情况。结果:胃癌组织中TRIM28阳性率及其mRNA表达水平高于癌旁组织(均P<0.05)。敲低TRIM28表达可抑制胃癌细胞的侵袭和迁移能力。敲低TRIM28表达显著抑制了胃癌细胞的增殖能力,并显著增强了BTZ诱导的细胞凋亡。结论:TRIM28在胃癌组织过表达,且与胃癌HGC-27细胞的侵袭、迁移、增殖和凋亡有关,同时影响BTZ的抗肿瘤作用。

Ⅰ型自身免疫性肝炎患者IL28RA、PD-L1表达及与肝功能的相关性分析

目的 分析Ⅰ型自身免疫性肝炎(AIH)患者白细胞介素-28受体拮抗剂(IL28RA)、程序性细胞死亡因子配体1(PD-L1)表达及与肝功能的关系。方法 选取2018年2月—2023年3月仙桃市第一人民医院收治的Ⅰ型AIH患者85例,其中活动期53例(重度炎症组8例、中度炎症组12例和轻度炎症组33例)、缓解期32例。在超声引导下通过BARD一次性全自动活检枪实施肝穿刺活检术取得肝组织,另取同期该院收治的27例肝血管瘤患者(经手术取得肝组织)为对照组。采用ABC法测定肝组织PD-L1蛋白含量,荧光实时荧光定量聚合酶链反应检测肝组织IL28RA基因表达,比较肝功能指标[γ-谷氨酰转肽酶(γ-GT)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(TBIL)]水平及肝组织IL28RA、PD-L1表达,分析肝组织IL28RA、PD-L1表达与肝功能指标的相关性。结果 活动期患者IL28RA相对表达量低于缓解期患者(P <0.05),PD-L1高于缓解期患者(P <0.05)。活动期患者TBIL、AST、γ-GT、ALT水平均高于缓解期患者(P <0.05)。AIH组IL28RA基因相对表达量低于对照组(P <0.05),PD-L1蛋白含量高于对照组(P <0.05)。与缓解期患者相比,各炎症组IL28RA基因相对表达量降低(P <0.05),PD-L1、AST、ALT、TBIL、γ-GT、IgG水平均升高(P <0.05)。Ⅰ型AIH患者IL28RA表达与AST、ALT、TBIL均呈负相关(r=-0.567、-0.671和-0.549,均P=0.000);PD-L1表达与AST、ALT、TBIL、血清IgG均呈正相关(r=0.643、0.598、0.552和0.476,均P=0.000)。结论 Ⅰ型AIH患者与IL28RA、PD-L1表达及与肝功能密切相关。Ⅰ型AIH患者IL28RA表达下调,PD-L1表达上调。IL28RA表达与肝功能、肝组织炎症活动度呈负相关,PD-L1表达与肝功能、肝组织炎症活动度及血清IgG水平呈正相关。

持续性血液滤过对中毒性休克合并急性呼吸窘迫综合征患者的预后以及28 d生存率分析

目的探究中毒性休克合并急性呼吸窘迫综合征患者使用持续性血液滤过的治疗效果及对其28 d生存率的影响。方法回顾性选取2018年5月—2023年5月福建省安溪县医院收治的80例中毒性休克合并急性呼吸窘迫综合征患者的临床资料,根据治疗方案不同分为两组,每组40例,对照组开展常规治疗+有创通气,观察组开展常规治疗+持续性血液滤过治疗。比较两组的呼吸功能、血流动力学、预后效果及28 d生存率。结果治疗前,两组氧合指数[血氧分压/吸入氧浓度(partial pressure of oxygen/fraction of inspiration oxygen,PaO_(2)/FiO_(2))]、呼气末正压(positive end-expiratory pressure,PEEP)及pH比较,差异无统计学意义(P均>0.05);治疗后,两组pH比较,差异无统计学意义(P>0.05),观察组PaO_(2)/FIO_(2)高于对照组,PEEP低于对照组,差异有统计学意义(P均<0.05)。治疗后,观察组的心指数(cardiac index,CI)、全身血管阻力指数(systemic vascular resistance index,SVRI)高于对照组,血乳酸(lactic acid,LAC)、去甲肾上腺素(noradrenaline,NE)低于对照组,差异有统计学意义(P均<0.05)。观察组的预后良好率高于对照组,差异有统计学意义(P<0.05)。观察组的28 d生存率为95.00%(38/40),高于对照组80.00%(32/40),差异有统计学意义(χ^(2)=4.114,P<0.05)。结论中毒性休克合并急性呼吸窘迫综合征患者辅助持续性血液滤过,可以稳定血流动力学,改善呼吸功能,预后良好,28 d生存率高。

Ga^(28+)离子1s^(2)np(2≤n≤9)Rydberg态的能级结构

利用全实加关联方法构造了Ga^(28+)离子1s^(2)np(2≤n≤9)Rydberg态的波函数,通过Rayleigh-Ritz变分法计算了1s^(2)np Rydberg态的非相对论能级.在此基础上,充分考虑一阶相对论效应、质量极化效应、高阶相对论效应和量子电动力学效应对能级的影响,计算了Ga^(28+)离子1s^(2)np(2≤n≤9)Rydberg态的精细结构劈裂、激发能和电离能.得到的精细结构劈裂符合Rydberg态的变化规律,激发能和电离能结果与现有实验数据也符合得很好,具有较好的精度.

0.01%28-高芸苔素内酯·吲哚丁酸对寒地水稻生长及产量的影响

为明确0.01%28-高芸苔素内酯·吲哚丁酸对寒地水稻生长调节作用,采用随机区组试验设计,研究不同施药量对寒地水稻生长及产量的影响。结果表明,于分蘖期施用0.01%28-高芸苔素内酯·吲哚丁酸颗粒剂,能明显促进水稻分蘖,缩短始穗期至齐穗期天数,促进干物质积累,增强抗倒伏能力,提高水稻产量,对水稻生长安全。药剂施用量为22.5 kg/hm^(2)时,水稻穗粒数、结实率、千粒重最大,产量最高,是最佳施用量。

ADAM28 shRNA干扰载体对人牙周膜干细胞增殖、分化和凋亡的影响

目的:探讨金属蛋白酶解离素28(ADAM28)shRNA干扰载体对人牙周膜干细胞(HPDLSCs)增殖、分化和凋亡的影响及作用机制。方法:用ADAM28 shRNA干扰载体转染HPDLSCs 48 h后检测转染效率,CCK-8法检测细胞增殖,流式细胞术(FCM)检测细胞周期。酶动力学法检测碱性磷酸酶(ALP)活性,Western blot检测分化相关基因CAP、Pax9蛋白的表达。FCM测定HPDLSCs凋亡率,Western blot检测Bax、Bcl-2蛋白的表达差异。用SPSS 21.0软件包对数据进行统计学分析。结果:重组干扰载体PGPU6/GFP/Neo-ADAM28-shRNA可高效转染HPDLSCs,干扰载体组的细胞增殖活性显著下降,S期、G 2+M期的细胞比例和细胞增殖指数(PI=S+G 2M)明显降低,ALP值明显降低,CAP、Pax9蛋白的表达水平下降,凋亡率显著提高,Bcl-2、Bax蛋白的表达水平上调。结论:ADAM28 shRNA干扰载体抑制HPDLSCs的增殖、分化,诱导HPDLSCs凋亡。其机制可能是干扰载体抑制金属蛋白酶域和类解离素域的催化裂解和类EGF功能域的促细胞增殖作用,阻碍Notch信号传递并参与细胞凋亡负反馈调节机制。

大麦新品种保啤麦28号的选育

保啤麦28号是保山市农业科学研究所选育的啤酒大麦新品种,2023年通过国家非主要农作物品种登记,登记编号:GPD大麦(青稞)(2023)530030。该品种产量高,高抗条纹病、白粉病,抗锈病,千粒重高,高抗倒伏,麦芽品质优,适宜在云南省冬播种植。对保啤麦28号的选育过程、特征特性、产量表现、栽培技术要点进行介绍,并对其选育体会进行总结。

外周血CD8+CD28-CD57+T淋巴细胞对老年脓毒症患者预后的预测价值

目的 探讨外周血CD8+CD28-CD57+T淋巴细胞对老年脓毒症患者预后的预测价值。方法 采用回顾性队列研究,选取2015年2月—2016年8月西安交通大学第二附属医院重症医学科住院的年龄≥60岁的脓毒症患者75例,依据ICU结局分为存活组(n=54)及死亡组(n=21)。收集患者一般资料,诊断脓毒症当天进行急性生理和慢性健康评分Ⅱ(APACHEⅡ)评分及序贯器官衰竭(SOFA)评分,检测外周血液标本TNF-a、IL-10及CD8+CD28-CD57+T淋巴细胞。结果 死亡组平均年龄大于存活组(P<0.05)。死亡组较存活组有更高的APACHEⅡ评分、SOFA评分及休克比例,差异均有统计学意义(P<0.05)。死亡组外周血CD8+CD28-CD57+T淋巴细胞、TNF-a、IL-10较存活组更高(P<0.05)。存活组的耐药菌感染比例低于死亡组,但差异无统计学意义(P>0.05)。无论单因素还是对一系列协变量进行调整的多因素Logistic回归分析均显示,较高的外周血CD8+CD28-CD57+T淋巴细胞比例与高的ICU死亡率相关(OR, 1.21;95%CI, 1.10~1.33)(OR, 1.30;95%CI, 1.07~1.58);APACHEⅡ评分预后预测的AUC为0.78(95%CI 0.67~0.90),将最适诊断界点22.5分作为预测死亡可能的临界点,敏感性和特异性分别为61.9%和75.2%。SOFA评分预后预测的AUC为0.80(95%CI,0.68~0.92),将最适诊断界点9.5分作为预测死亡可能的临界点,敏感性和特异性分别为71.4%和77.8%。外周血CD8+CD28-CD57+T淋巴细胞预后预测的AUC为0.91(95%CI,0.83~0.99),将最适诊断界点60.2%作为预测死亡可能的临界点,敏感性和特异性分别为81.0%和92.6%。结论 老年脓毒症患者外周血高CD8+CD28-CD57+T淋巴细胞比例与ICU死亡率增加相关,一定程度上可用于评估此类人群的病情严重程度及预测预后。

常规糯稻湘糯28的选育及高产栽培技术

湘糯28是湖南湘穗种业有限责任公司用湘晚糯1号与鄂荆糯6号杂交,经系统选育而成的优质高产常规糯稻新品种,于2020年通过湖南省审定。该品种具有适应性广、糯性好、抗倒性强、群体结构理想等优点。笔者介绍了湘糯28的选育过程、特征特性,并详细总结了其高产栽培技术。

大电流KYN28型高压开关柜改善温升解决方法

为解决大电流KYN28型高压开关柜温升发热问题,分析了该开关柜的温升发热机理,确定了主回路内阻、接触电阻、感应电阻3个发热源,并计算了发热的总功率。采用增大配电柜两侧散热面积、增大配电柜通风口面积、强制对流风冷、柜体内风道设计改进等措施,平衡发热功率,使散热功率大于发热的总功率。在实验室使用HZDL-WS-6300/12全自动温升试验系统进行测量,在符合标准规定的环境下,测得温升下降约10%,得到明显改善,总体结果基本符合预期。证明所提措施可以解决温升问题,并认为解决温升问题时需要结合设备运行,实时监视温升情况,以确保设备运行安全。

四川省眉山市爱媛28和春见果实品质分析与评价

【目的】了解眉山市主栽柑橘品种果实品质,对各个区县爱媛28和春见果实品质进行综合评价,为眉山市柑橘品种示范和推广提供理论依据。【方法】以眉山市爱媛28、春见果园采集的共72个果实为材料,测定果实品质,利用主成分分析和聚类分析对来自不同区县的同一品种进行综合评价,计算得分排名并筛选品质评价指标。【结果】各区县爱媛28果实几项外在品质指标(a*、单果质量、纵径、皮厚度)在不同区县间存在显著差异,内在品质指标各区县之间无显著差异;各区县春见果实内外品质指标均存在显著差异。对两品种果实品质指标通过主成分分析提取到4个主成分,累积贡献率分别为75.646%、76.940%。综合评价得分结果表明,爱媛28果实品质综合得分均值排列顺序为东坡区>仁寿县>丹棱县>彭山区;春见果实品质综合得分均值排列顺序为彭山区>东坡区>丹棱县>仁寿县>青神县。【结论】明确了眉山市主栽柑橘品种的品质表现和不同区县间的异同,对优化调整眉山市柑橘品种结构、提高眉山市整体柑橘果实品质具有一定的参考意义。

CD28^(+)、CD56^(+)在多发性骨髓瘤患者中的表达及其对预后的评估价值

目的分析CD28^(+)、CD56^(+)在多发性骨髓瘤(MM)患者中的表达及其对预后的评估价值。方法纳入103例MM患者,于入院时检测其CD28、CD56表达情况。随访2年统计预后结果,比较不同预后(存活、病死)患者资料,通过COX分析MM患者预后相关因素,分析CD28^(+)、CD56^(+)与MM患者国际分期系统(R-ISS)分期、β2微球蛋白(β2-MG)的相关性,绘制DCA曲线分析CD28^(+)、CD56^(+)预测MM患者预后的价值。结果103例MM患者2年内共19例病死,84例存活,2年存活率为81.55%(84/103)。COX分析显示,R-ISS分期Ⅲ期、β2-MG、CD28^(+)、CD56^(+)均为MM患者病死的影响因素(HR>1,P<0.05)。Kendall's tau-b相关性分析显示,CD28^(+)、CD56^(+)均与MM患者R-ISS分期呈正相关(P<0.05);Spearson相关性分析显示,CD28^(+)表达与MM患者β2-MG水平呈正相关(P<0.05),CD56^(+)表达与MM患者β2-MG水平无相关(P>0.05)。DCA曲线分析显示,当高风险阈值为0.0~0.31时,CD28^(+)、CD56^(+)表达预测MM患者预后净受益率大于0,有临床意义,净受益率最大值为0.184。结论CD28^(+)、CD56^(+)在MM患者中表达异常,对预后有一定预测价值。

MiR-28-5p靶向DOK4对口腔鳞状细胞癌细胞增殖的影响

目的探讨微小RNA(miR)-28-5p通过靶向酪氨酸激酶下游蛋白4(DOK4)对口腔鳞状细胞癌细胞增殖的调控作用。方法下载癌症基因组图谱(TCGA)口腔癌数据库,分析miR-28-5p、DOK4与口腔鳞状细胞癌临床表型的关系;转染miR-28-5p模拟物(mimics)、miR-28-5p抑制剂(inhibitor)及对照物(NC)、pcDNA3.1-DOK4及空载体(Vector)、DOK4干扰序列(siDOK4)。CCK-8法和克隆集落形成实验检测口腔鳞状细胞癌的细胞增殖能力;检测各组细胞的抗氧化能力和细胞活性氧(ROS)含量;双荧光素酶报告基因实验验证miR-28-5p与DOK4的靶向关系;观察DOK4过表达对细胞增殖和口腔鳞状细胞癌裸鼠移植瘤生长的影响。结果生物信息学分析显示,相较于癌旁口腔组织,miR-28-5p在口腔鳞状细胞癌组织中表达上调,DOK4 mRNA下调(P<0.05);临床分期Ⅳ期、M 1期、G 3~G 4分级患者miR-28-5p水平高于临床分期Ⅰ~Ⅲ期、M 0期、G 1~G 2分级者(P<0.05);临床分期Ⅳ期、N 1期、G_(3)~G_(4)分级患者DOK4 mRNA水平低于临床分期Ⅰ~Ⅲ期、N 0期、G_(1)~G_(2)分级者(P<0.05);DOK4高表达组无进展生存期和总生存期均高于DOK4低表达组(P<0.05)。与miR-NC组比较,miR-28-5p inhibitor组miR-28-5p水平、细胞活性和集落形成数降低(P<0.05)。与miR-NC组比较,miR-28-5p mimics组DOK4 mRNA和蛋白表达水平降低(P<0.05);与Vector组比较,DOK4过表达组细胞和移植瘤组织中DOK4 mRNA和蛋白表达升高,细胞活性、集落形成数、肿瘤体积及重量降低(P<0.05);与miR-28-5p inhibitor组比较,miR-28-5p inhibitor+siDOK4组的DOK4 mRNA和蛋白表达水平降低,细胞增殖活性、集落形成数、还原型烟酰胺腺嘌呤二核苷酸/烟酰胺腺嘌呤二核苷酸(NADPH/NADP+)、谷胱甘肽/氧化性谷胱甘肽(GSH/GSSG)升高,ROS含量降低(P<0.05)。结论miR-28-5p在口腔鳞状细胞癌中表达上调,通过靶向抑制DOK4表达,降低ROS水平,促进细胞增殖。

CD28在初诊多发性骨髓瘤患者中的表达及其与肿瘤负荷和临床预后的相关性

目的研究CD28在初诊多发性骨髓瘤(MM)患者中的表达及其与肿瘤负荷、临床预后的相关性。方法以回顾性分析为法,观察对象为2021年1月至2023年1月淮南市第一人民医院的89例初诊MM患者。所有患者均经流式细胞术对其骨髓标本予以免疫表型分析,参考CD28表达水平分为CD28^(+)(研究组,n=30)与CD28-(对照组,n=59)。对比两组患者的实验室特征、CD28表达水平、遗传学异常发生率和近期疗效,分析CD28表达对无进展生存期(PFS)的影响。结果两组患者的年龄、性别构成比、白蛋白、乳酸脱氢酶、肌酐、血红蛋白、钙水平比较,差异均无统计学意义(P>0.05);研究组β2微球蛋白表达水平、克隆浆细胞比率、骨髓浆细胞(BMPC)比率、国际分期系统(ISS)-Ⅲ期患者比率分别为(6.61±1.14)mg/L、(21.68±5.82)%、(41.83±8.62)%、73.33%,均明显高于对照组[(5.68±1.07)mg/L、(10.97±4.12)%、(27.01±7.14)%、47.46%],差异均有统计学意义(P<0.05)。研究组患者1q21扩增发生率、≥2个遗传学异常的高危病例发生率分别为40.00%、26.67%,均明显高于对照组(18.64%、8.47%),差异均有统计学意义(P<0.05);两组13q14-、IgH重排、17p-发生率比较,差异均无统计学意义(P>0.05)。化疗4个周期之后,研究组患者的治疗总有效率为60.00%,明显低于对照组(88.14%),差异有统计学意义(P<0.05)。中位随访10个月,研究组患者中位PFS为(10.72±1.23)个月,明显低于对照组[(14.08±1.34)个月],差异有统计学意义(P<0.05)。单因素分析显示,CD28^(+)表达及≥2个遗传学异常、ISSⅢ期、血红蛋白<60 g/L、年龄≥60岁并非影响MM患者PFS的危险因素;多因素分析显示,影响MM患者PFS的独立危险因素为CD28^(+)表达、诱导效果<PR。结论CD28^(+)与初诊MM患者临床特征、肿瘤负荷及预后有着密切联系,CD28^(+)可辅助评估初诊MM患者的预后。