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论著

血浆细胞周期依赖性激酶9水平与急性大动脉粥样硬化型脑梗死病情进展及预后的相关性

Correlation between plasma cyclin-dependent kinase 9 level and disease progression and prognosis in patients with acute large artery atherosclerotic cerebral infarction

:625-632
 
       目的 探讨血浆细胞周期依赖性激酶9(CDK9)水平与大动脉粥样硬化(LAA)型脑梗死病情进展及预后的相关性,评估其作为疾病风险分层及预后评估生物标志物的临床价值。方法 选取2020年1月—2024年12月期间于本院就诊的400例急性LAA型脑梗死患者作为观察组,并同期纳入100名健康体检者作为对照组。发病90 d后,采用改良Rankin量表(mRS)对所有患者进行预后评估。根据评估结果,将观察组进一步划分为预后不良组(152例)与预后良好组(248例)。检测患者血浆CDK9水平并收集临床资料。分析CDK9水平与美国国立卫生研究院卒中量表(NIHSS)评分、梗死灶体积的相关性;分析预后不良的影响因素。结果 观察组CDK9水平高于对照组[(185.6±42.3) pg/mL vs (62.4±18.5) pg/mL,P<0.001],且与梗死体积(r=0.586)、NIHSS评分(r=0.628)、高敏C反应蛋白(r=0.452)及白介素6(r=0.418)呈正相关(均P<0.001)。多因素Logistic回归分析显示,CDK9升高是90天预后不良的独立危险因素。受试者工作特征曲线(ROC)曲线分析显示,CDK9预测预后不良的曲线下面积(AUC)为0.854(最佳截断值为198.6 pg/mL,灵敏度为78.3%,特异度为82.5%),联合NIHSS评分及梗死体积后AUC提升至0.912(P<0.001)。结论 血浆CDK9水平可作为急性LAA型脑梗死病情进展及预后的独立预测标志物,联合传统指标可提高预后评估效能。

      Objective To investigate the correlation between plasma cyclin-dependent kinase 9(CDK9)level and disease progression and prognosis in patients with acute large artery atherosclerosis(LAA)cerebral infarction,and to evaluate its clinical value as a biomarker for disease risk stratification and prognostic assessment.Methods This study enrolled 400 patients with acute LAA-type cerebral infarction who visited our hospital between January 2020 and December 2024 as the observation group,along with 100 healthy individuals as the control group during the same period.After 90 days of symptom onset,all patients were assessed using the modified Rankin Scale(mRS)for prognostic evaluation.Based on the assessment results,the observation group was further divided into two subgroups:the poor prognosis group(152 cases)and the good prognosis group(248 cases).Plasma CDK9 levels were measured,and clinical data were collected.The correlation between CDK9 level and National Institutes of Health Stroke Scale(NIHSS)score and infarct volume,and the factors affecting poor prognosis were analyzed.Results Plasma CDK9 levels in the observation group were higher than those in the control group([185.6±42.3] pg/mL vs [62.4±18.5] pg/mL,P<0.001),and were positively correlated with infarct volume(r=0.586),NIHSS score(r=0.628),high-sensitivity C-reactive protein(r=0.452),and interleukin-6(r=0.418)(all P<0.001).Multivariate Logistic regression analysis showed that elevated CDK9 level was an independent risk factor for poor prognosis at 90 d.Receiver Operating Characteristic(ROC)curve analysis revealed that the area under the curve(AUC)of CDK9 for predicting poor prognosis was 0.854(optimal cut-off value:198.6 pg/mL,sensitivity:78.3%,specificity:82.5%),and the AUC increased to 0.912 when combined with NIHSS score and infarct volume(P<0.001).Conclusions Plasma CDK9 level may serve as an independent predictive biomarker for disease progression and prognosis in acute LAA cerebral infarction,and combining it with traditional indicators can improve the efficacy of prognostic assessment.

论著

血清乳酸脱氢酶在中晚期肝细胞癌靶向及免疫治疗中的预后预测价值研究

The prognostic value of serum lactate dehydrogenase level as a predictor of prognosis in targeted therapy and immunotherapy for advanced hepatocellular carcinoma

:446-452
 
      目的 探讨血清乳酸脱氢酶(LDH)在中晚期肝癌患者接受靶向联合免疫治疗后的预后预测价值。方法 选取2022年1月—2024年8月在莆田学院附属医院肿瘤内科经病理和影像学检查确诊的中晚期肝癌患者作为研究对象。从医院的电子病历系统中收集患者的基线资料,随访截止2025年8月,并记录随访结果,包括患者的疾病缓解情况和死亡情况,以及无疾病进展生存期(PFS)、总生存期(OS)。采用Kaplan-Meier方法绘制不同基线LDH水平患者的OS生存曲线,并通过Log-rank检验比较生存曲线。同时,运用多因素Cox比例风险回归分析探讨影响中晚期肝癌患者在接受靶向联合免疫治疗后OS的相关因素。结果 结果显示,在50例肝癌患者中,基线LDH低于200 U/L的有15例,而高于200 U/L的有35例。与基线LDH<200 U/L组相比,基线 LDH≥200 U/L患者PFS、OS更短,差异均有统计学意义(χ2分别为5.51、15.6,P值分别为0.019、0.017)。治疗8周后,与LDH降低患者相比,LDH升高患者OS更短,差异有统计学意义(χ2=13.2,P=0.04)。多因素Cox比例风险回归分析结果表明,基线LDH水平超过200 U/L是中晚期肝癌患者接受靶向联合免疫治疗后OS的影响因素[P=0.035,HR(95%CI)=5.03(1.12,22.54)]。结论 基线LDH水平较低的患者表现出更好的OS。基线LDH水平可以作为预测中晚期肝癌患者在接受靶向联合免疫治疗时预后的指标。 
   Objective To evaluate the prognostic significance of serum lactate dehydrogenase(LDH)levels in patients with advanced hepatocellular carcinoma(HCC)undergoing targeted therapy combined immunotherapy.Methods Patients diagnosed with advanced HCC were selected in Putian College Affiliated Hospital from January 2022 to August 2024,diagnosed with pathological and imaging examinations results.Patient baseline data were collected from the hospital’s electronic medical records,with follow-up extending until August 2025.We documented outcomes such as disease response and mortality,along with progression-free survival(PFS)and overall survival(OS).Kaplan-Meier survival curves were constructed based on baseline LDH levels,and the Log-rank test was employed for comparison.Additionally,multivariate Cox proportional hazards regression analysis was conducted to identify factors influencing OS in patients receiving targeted therapy combined immunotherapy.Results Among the 50 patients,15 had baseline LDH levels below 200 U/L,while 35 had levels above.Patients with baseline LDH≥200 U/L had significantly shorter PFS and OS than those with baseline LDH <200 U/L(χ2=5.51 and 15.6 for PFS and OS,respectively;P=0.019 and 0.017,respectively).After 8 weeks of treatment,patients with increased LDH had significantly shorter OS compared with patients with decreased LDH(χ2=13.2,P=0.04).Multivariate Cox proportional hazards regression analysis indicated that a baseline LDH level exceeding 200 U/L is an independent prognostic factor for OS in patients with intermediate to advanced HCC receiving targeted therapy combined with immunotherapy(P=0.035,HR 5.03[1.12,22.54]).Conclusions Patients with lower baseline LDH levels demonstrated better OS,suggesting that baseline LDH can serve as an important prognostic indicator for advanced HCC patients undergoing targeted combined immunotherapy.
专家述评

造血干细胞治疗多囊肾的机制及治疗前景

Mechanisms and therapeutic prospects of hematopoietic stem cells in polycystic kidney disease

:545-553
 
       常染色体显性多囊肾病(ADPKD)是导致遗传性肾衰竭的主要病因之一,目前仍缺乏有效的手段来逆转其疾病进展。干细胞疗法因其在组织修复和免疫调节方面的潜力,成为研究的热点领域。本研究系统阐述了造血干细胞(HSCs)通过旁分泌作用、代谢重塑及免疫调控干预ADPKD病理进程的机制,并总结了其在急性肾损伤和慢性肾病中的临床转化证据。此外,文章比较分析了间充质干细胞(MSCs)和诱导多能干细胞(iPSCs)在ADPKD治疗中的独特优势与面临的挑战,为多模态干细胞疗法的开发提供理论支持。
    Autosomal dominant polycystic kidney disease(ADPKD)stands as a leading cause of inherited renal failure,with current therapeutic strategies lacking effective means to reverse disease progression.Stem cell therapy,owing to its potential in tissue repair and immunomodulation,has emerged as a focal point of research.This review systematically elucidates the mechanisms by which hematopoietic stem cells(HSCs)intervene in ADPKD pathology through paracrine effects,metabolic reprogramming,and immune regulation.Furthermore,it summarizes clinical translational evidence of HSCs in both acute kidney injury and chronic kidney disease.This article also comparatively analyzes the unique advantages and challenges of mesenchymal stem cells(MSCs)and induced pluripotent stem cells(iPSCs)in the context of ADPKD treatment,thereby providing theoretical support for the development of multimodal stem cell therapies.

专家述评

细胞外囊泡来源异质性在乳腺癌转移中的机制及临床转化潜力

Research progress on heterogeneity of extracellular vesicle origins,metastatic mechanisms and clinical translational potential in breast cancer

:798-810
 
       乳腺癌(BC)发病率持续上升,已成为严重威胁公共健康的重大挑战,转移仍是导致患者死亡的主要原因。目前,切除肿瘤并辅以放化疗后仍有较大几率发生转移。此外,早期转移隐匿性强,干预措施不完善及耐药发生迅速均是预后不良的重要因素。细胞外囊泡(EVs)是由细胞释放的、具有膜结构的纳米级颗粒,是细胞间通讯的重要介质。EVs通过转运膜性组分、胞质蛋白及核酸等,调控乳腺癌的发生、进展及转移定植,其来源异质性决定了其在乳腺癌转移中发挥独特作用。本文重点总结了不同来源EVs作为液体活检标志物在转移预警中的价值,以及靶向EVs分泌或阻断其通讯网络在克服免疫治疗耐药中的潜在临床应用,以期为临床医生提供有价值的诊疗参考。
     The incidence of breast cancer(BC) continues to rise and has become a major public health challenge.Metastasis remains the principal cause of BC-related mortality.Currently,there remains a high probability of metastasis even after surgical tumor resection followed by radiotherapy and chemotherapy.The insidious nature of early metastasis,inadequate intervention strategies,and rapid development of drug resistance are all critical factors contributing to poor prognosis.Extracellular vesicles(EVs) are membrane-enclosed,nanoscale particles released by cells.As mediators of intercellular communication,EVs transfer membrane components,cytosolic proteins,and nucleic acids to recipient cells,thereby modulating BC initiation,progression,and metastatic dissemination.The heterogeneity of EV origins determines their distinct roles in breast cancer metastasis.This review focuses on summarizing the value of EVs from different sources as liquid biopsy biomarkers for metastasis warning,as well as their potential clinical applications in targeting EV secretion or blocking their communication networks to overcome immunotherapy resistance,aiming to provide valuable diagnostic and therapeutic references for clinicians.

论著

远志皂苷元通过 Nrf2/HO-1 通路抑制脑出血体外细胞模型 BV2 小胶质细胞炎症的机制研究

Tenuigenin suppresses inflammation via the Nrf2/HO-1 pathway in BV2 microglia within an in vitro model of intracerebral hemorrhage

:729-737
 
       目的 探索Nrf2/HO-1通路是否参与远志皂苷元(远志)在脑出血体外细胞模型中对BV2小胶质细胞炎症反应的调控作用。方法 采用红细胞与BV2小鼠小胶质细胞共培养构建体外脑出血模型。分别给予远志单独处理、远志联合Nrf2抑制剂ML385处理,检测炎症因子水平。收集细胞上清制备条件培养基,用于培养SH-SY5Y人神经母细胞瘤细胞,并检测其铁死亡水平。结果 模型组BV2细胞炎症因子(IL-1β,IL-6,TNF-α)水平较对照组显著升高(P<0.001);高浓度远志(20 μM)可降低炎症因子水平,并上调Nrf2/HO-1通路蛋白表达,而ML385能逆转该作用。模型组条件培养基可诱导SH-SY5Y细胞铁死亡,而经远志处理的BV2细胞条件培养基则减轻该现象;ML385预处理可削弱远志对SH-SY5Y细胞的保护作用,远志组铁离子、丙二醛、转铁蛋白受体1水平低于远志联合ML385组(P<0.05),铁转运蛋白、谷胱甘肽和谷胱甘肽过氧化物酶水平高于远志联合ML385组(P<0.05)。结论 远志皂苷元通过激活Nrf2/HO-1通路抑制BV2小胶质细胞炎症反应,并在脑出血体外模型中发挥神经保护作用。

     Objective To investigate whether the Nrf2/HO1 signaling pathway is involved in the regulatory effect of tenuigenin(TEN)on the inflammatory response of BV2 microglial cells in an in vitro intracerebral hemorrhage(ICH)model.Methods An in vitro ICH model was established by coculturing BV2 murine microglial cells with red blood cells.Cells were treated with TEN alone or in combination with the Nrf2 inhibitor ML385,and the levels of inflammatory factors were measured.The conditioned medium collected from the cell supernatant was used to culture SHSY5Y human neuroblastoma cells,and ferroptosis levels were assessed.Results The levels of inflammatory factors(IL-1β,IL-6,TNF-α)in BV2 cells of the model group were significantly higher than those in the control group(P<0.001).High concentration of TEN(20 μM)could reduce the levels of inflammatory factors and up-regulate the expression of Nrf2/HO-1 pathway proteins,while ML385 could reverse this effect.The conditioned medium of the model group could induce ferroptosis in SH-SY5Y cells,while the conditioned medium of BV2 cells treated with TEN could alleviate this phenomenon.Pretreatment with ML385 could weaken the protective effect of TEN on SH-SY5Y cells.The levels of iron ions,malondialdehyde and transferrin receptor protein 1 in the TEN group were lower than those in the TEN combined with ML385 group(P<0.05),while the levels of ferroportin glutathione and glutathione peroxidase 4 were higher than those in the TEN combined with ML385 group(P<0.05).Conclusions TEN inhibits the inflammatory response of BV2 microglial cells by activating the Nrf2/HO1 pathway and exerts a neuroprotective effect in the in vitro ICH model.
论著

α-突触核蛋白对THP-1巨噬细胞源性泡沫细胞胆固醇蓄积和LOX-1表达的影响

Effects of α-synuclein on cholesterol accumulation and LOX-1 expression in THP-1 macrophage-derived foam cells

:176-181
 
       目的 探索α-突触核蛋白(α-Syn)干预对人单核细胞白血病细胞系(THP-1)巨噬细胞源性泡沫细胞的影响。方法 通过佛波酯(PMA)和氧化型低密度脂蛋白(ox-LDL)构建THP-1巨噬细胞源性泡沫细胞模型,使用不同浓度(33、66、100、133 nmol/L)α-Syn处理泡沫细胞,随后检测细胞胆固醇含量和炎症因子白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)及白细胞介素-8(IL-8)的mRNA表达以及核因子κB(NF-κB)和凝集素样氧化低密度脂蛋白受体-1(LOX-1)的蛋白表达变化。结果 高剂量(100和133 nmol/L)α-Syn处理可以减少THP-1巨噬细胞源性泡沫细胞内胆固醇的含量(P<0.05),并且减少IL-1β、IL-6和IL-8的mRNA表达(P<0.05)。进一步发现(100 nmol/L和133 nmol/L)α-Syn可以降低THP-1巨噬细胞源性泡沫细胞p-NF-κB和LOX-1的蛋白表达(P<0.05)。结论 α-Syn可以降低THP-1源性巨噬细胞泡沫细胞胆固醇蓄积和炎症反应,可能是通过下调p-NF-κB和LOX-1蛋白表达。
      Objective To explore the effects of α-synuclein(α-Syn)intervention on human monocytic leukemia cell(THP-1)macrophage-derived foam cells.Methods The THP-1 macrophage-derived foam cell model was constructed by phorbol 12-myristate 13-acetate(PMA)and oxidized low-density lipoprotein(ox-LDL).Foam cells were treated with different concentrations(33, 66, 100, and 133 nmol/L)of α-Syn, and the cellular cholesterol contents, as well as the mRNA expression of IL-1β、IL-6 and IL-8 were detected.Subsequently,alternation in protein expression of NF-κB and LOX-1 was measured.Results High-dose(100 and 133nmol/L)α-Syn treatment significantly reduced the levels of intracellular cholesterol in THP-1-derived macrophage foam cells(P<0.05)and decreased the mRNA expression of IL-1β、IL-6 and IL-8(P<0.05).It was further found that(100 nmol/L and 133 nmol/L)α-Syn decreased the protein expression of p-NF-κB and LOX-1 in THP-1 macrophage-derived foam cells(P<0.05).Conclusions The results of the present study suggest that α-Syn reduces cholesterol accumulation and inflammatory response in THP-1-derived macrophage foam cells, possibly by down-regulating p-NF-κB and LOX-1 protein expression.
综述

中医药调控 CD4+ T 细胞亚群防治动脉粥样硬化的研究进展

Research progress on the regulation of CD4+ T cell subsets by traditional Chinese medicine for the prevention and treatment of atherosclerosis

:24-29
 
       动脉粥样硬化(AS)是一种起始于炎症介导的内皮损伤的慢性血管疾病,其本质是免疫炎症驱动的病理过程,是众多心血管疾病的病理基础。CD4+  T细胞亚群[包括辅助性T细胞1型(T helper 1 cell,Th1)、Th2、Th17、调节性T细胞等]通过分泌特异性细胞因子参与AS的炎症反应,其中促炎性CD4+  T细胞与抗炎性CD4+  T细胞的抗炎功能失衡是推动斑块进展的关键环节,在AS斑块形成与发展中起关键作用。近年来,多项研究表明某些中药单体、经典复方及其有效成分,具有多靶点、多层次机制调控CD4+  T细胞分化及功能,这些作用共同减轻血管内皮炎症反应、抑制巨噬细胞泡沫化及平滑肌细胞迁移等,延缓AS斑块形成与发展,为AS防治提供了新思路,展现了中医药在该领域的研究展现出独特优势与广阔前景,本文综述了中医药通过干预CD4+  T细胞亚群平衡防治AS的最新研究进展,及其影响相关细胞因子网络及关键信号通路的作用机制,为开发具有多靶点协同优势的创新中药与中西医结合治疗方案提供了关键理论依据与实践方向。
       Atherosclerosis(AS)is a chronic vascular disease that originates from inflammation mediated endothelial 
damage.Its essence is a pathological process driven by immune inflammation,and it is the pathological basis of many cardiovascular diseases.CD4+  T cell subsets(including Th1,Th2,Th17,Treg,etc.)participate in the inflammatory response of AS by secreting specific cytokines.The imbalance of anti-inflammatory function between pro-inflammatory CD4+  T cells and anti-inflammatory CD4+T cells is a key link in promoting plaque progression and playing a crucial role in the formation and development of AS plaques.In recent years,a number of studies have shown that the monomers,classic prescriptions and their effective ingredients of Chinese herbs have the effect of multi-target,multi-level mechanism to regulate the differentiation and function of CD4+  T cells.These effects together reduce the inflammatory reaction of vascular endothelium,inhibit the foam formation of macrophages and smooth muscle cell migration,delay the formation and development of AS plaque,provide new ideas for the prevention and treatment of AS,and make the research of Chinese medicine show unique advantages and broad prospects in this field.This article  reviews the latest  research progress of Chinese medicine in the prevention and treatment of AS by intervening in the balance of CD4+  T cell subsets,as well as the mechanism of its effects on related cytokine networks and key signal pathways.This provides a key theoretical basis and practical direction for the development of innovative traditional Chinese medicine and integrated traditional Chinese and Western medicine treatment plans with multi-target synergistic advantages.
论著

慢性阻塞性肺疾病急性加重期血嗜酸性粒细胞比例、血清IL-5 水平与肺功能的相关性

Correlation between blood eosinophils ratio,serum IL-5 levels,and pulmonary function during acute exacerbation of chronic obstructive pulmonary disease

:1684-1692
 
       目的   探讨慢性阻塞性肺疾病急性加重期血嗜酸性粒细胞(EOS)、血清白细胞介素-5(IL-5)水平与第一秒用力呼气容积(FEV1)、第一秒用力呼气容积与用力肺活量的比值(FEV1/FVC)、用力肺活量(FVC)的相关性。方法   纳入2023年3月—2024年3月于佛山市顺德区第五人民医院住院的73例慢性阻塞性肺疾病急性加重期患者,以2%作为外周血EOS比例(EOS%)截断值分为两组,研究组(EOS%≥2%)34例,对照组(EOS%<2%)39例,收集两组患者的一般临床资料、实验室检查结果、肺功能检查结果(FEV1、FVC、FEV1/FVC),比较组间差异,分析指标间的相关性。结果   对照组与实验组患者EOS%分别为0.5(0.1,0.9)%、5.15(2.60,10.05)%,两组患者EOS%差异有统计学意义(P<0.05)。对照组与实验组患者IL-5水平分别为0.98(0.56,1.78)ng/L、3.6(1.73,6.77)ng/L,两组IL-5水平差异有统计学意义(P<0.05)。对照组FEV1(L)、FVC(L)、FEV1/FVC水平分别为1.32(1.18,1.58)、2.07(1.92,2.62)、0.62(0.57,0.67);实验组分别为1.24(1.00,1.52)、2.22(1.94,2.56)、0.58(0.47,0.67),两组FEV1、FVC、FEV1/FVC水平差异均无统计学意义(P>0.05)。Spearman等级相关检验结果显示,EOS%与IL-5水平呈正相关(rs=0.870,P<0.001);按组别进行分层后结果显示,对照组、试验组EOS%与IL-5水平均呈正相关(rs=0.820,P<0.001;rs=0.938,P<0.001)。EOS%、IL-5水平与FEV1、FEV1/FVC呈负相关(P<0.05),与FVC不相关(rs=0.039,P>0.05)。对照组EOS%、IL-5水平与FEV1、FEV1/FVC、FVC不相关(P>0.05);实验组EOS%、IL-5水平与FEV1、FEV1/FVC呈负相关(P<0.05),与FVC不相关(P>0.05)。结论 慢性阻塞性肺疾病急性加重期血EOS%与血清IL-5水平呈正相关,外周血EOS%≥2%时血EOS%、血清IL-5与FEV1、FEV1/FVC呈负相关,与FVC无关。
       Objective  To explore the correlation among blood eosinophil levels,serum interleukin-5(IL-5)levels,and forced expiratory volume in one second(FEV1),the ratio of forced expiratory volume in one second to forced vital capacity(FEV1/FVC),and forced vital capacity(FVC)during the acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Methods  From March 2023 to March 2024,73 patients hospitalized for AECOPD at Shunde District Fifth People’s Hospital of Foshan City were included,and divided into two groups based on a cutoff value of 2% for peripheral blood eosinophil(EOS%).The experimental group(EOS%≥2%)included 34 patients,while the control group(EOS%<2%)included 39 patients.General clinical data,laboratory test results,and pulmonary function test results(FEV1,FVC,FEV1/FVC)were collected from both groups.Results  The median quartiles of EOS% for the control group and experimental group were 0.5(0.10.9)% and 5.15(2.60,10.05)%,respectively.There was a statistically significant difference between the EOS% of two groups(P0.05).The median quartiles of IL-5 levels for the control group and experimental group were 0.98(0.56,1.78)ng/L and 3.6(1.73,6.77)ng/L,respectively.There was also a statistically significant difference in IL-5 levels between the two groups(P0.05).For the control group,the median quartiles of FEV1,FVC,and FEV1/FVC were 1.32(1.18,1.58),2.07(1.92,2.62)and 0.62(0.57,0.67),respectively.For the experimental group,they were 1.24(1.00,1.52),2.22(1.94,2.56)and 0.58(0.47,0.67)respectively.There was no statistically significant difference between the two groups in FEV1,FVC and FEV1/FVC levels(P<0.05).Spearman rank correlation analysis showed a positive correlation between EOS% and IL-5 level (rs=0.870,P<0.001).Stratified by group,both the control and experimental groups showed a positive correlation between EOS% and IL-5 level (rs=0.820,P0.001;rs=0.938,P<0.001).There was a negative correlation between EOS%,IL-5 level,and FEV1,FEV1/FVC(P<0.05),but no correlation with FVC(P>0.05).In the control group,there was no correlation between EOS%,IL-5 level,and FEV1,FEV1/FVC,or FVCP>0.05).In the experimental group,there was a negative correlation between EOS%,IL-5 level,and FEV1,FEV1/FVC(P<0.05),but no correlation with FVC(P>0.05).Conclusions  During AECOPD,blood EOS% is positivelycorrelated with serum IL-5 levels.When peripheral blood eosinophils are ≥2%,blood EOS%,serum IL-5,and FEV1,FEV1/FVC are negatively correlated,while there is no correlation with FVC.
论著

非小细胞肺癌干细胞靶点筛选及 NDC80 临床意义分析

Screening of stem cell targets for non-small cell lung cancer and analysis of clinical significance of NDC80

:1638-1650
 
      目的   通过生物信息学手段筛选非小细胞肺癌(NSCLC)中的关键靶点基因,识别预后标志物NDC80,并探讨其在NSCLC中的表达意义,进而分析NDC80作为NSCLC基因治疗靶点的可行性。方法   采用癌症基因组图谱(TCGA)TCGA数据库检索NSCLC相关数据,进行加权基因共表达网络分析(WGCNA)以识别关键基因,并进行差异表达分析、相关性分析和蛋白互作网络构建。对筛选出的关键基因进行功能分析。利用免疫组化染色法检测癌组织及癌旁组织中NDC80蛋白的表达水平,并进一步探究其与临床病理特征的关系。采用Kaplan-Meier法分析NDC80表达与NSCLC患者无进展生存时间(PFS)的关系。结果   共筛选出20个与NSCLC高度关联的关键基因,包括CDC20、CDK1、MCM4、CDC6、MCM2、PLK1、NDC80、CCNB1、CDC45、AURKA、MCM8、BUB1、CDT1、ORC1、CCNA2、CASC5、MAD2L1、BUB1B、CENPA、AURKB。免疫组化验证显示,NDC80蛋白在NSCLC组织中高表达,其在NSCLC组(阳性表达率88.6%)显著高于癌旁组(50.0%)(P<0.05)。NDC80蛋白的阳性表达率在TNM分期(Ⅲ期+Ⅳ期)、低分化、淋巴结转移的NSCLC组高于TNM分期(Ⅰ期+Ⅱ期)、高分化及中分化以及未发生淋巴结转移的NSCLC组(P<0.05)。NDC80蛋白的阳性表达率在不同性别、年龄、病灶大小分类的NSCLC组织中无显著差异(P>0.05)。Kaplan-Meier分析显示,NDC80蛋白高表达组的PFS中位数为(9.00±0.27)个月,明显低于低表达组(11.00±0.79)个月(P<0.05)。结论   本研究发现的关键基因在NSCLC干细胞的维持中发挥重要作用。免疫组化结果显示,NDC80蛋白在NSCLC组织中高表达,且与肿瘤分化、TNM分期及淋巴结转移密切相关。NDC80蛋白高表达组的PFS明显低于低表达组,提示NDC80可能成为NSCLC筛查、治疗和预后评估的潜在生物标志物。
      Objective  To screen the key target genes in non-small cell lung cancer(NSCLC)by bioinformatics,identify the prognostic marker NDC80,and explore its expression significance in NSCLC,so as to analyze the feasibility of NDC80 as a gene therapy target for NSCLC.Methods  TCGA database was used to retrieve NSCLC-related data,and weighted gene co-expression network analysis(WGCNA)was used to identify key genes,and differential expression analysis,correlation analysis and protein-protein interaction network construction were carried out.The function of the selected key genes was analyzed.Immunohistochemical staining was used to detect the expression level of NDC80 protein in cancer tissues and adjacent tissues,and to further explore its relationship with clinicopathological features.Kaplan-Meier method was used to analyze the relationship between NDC80 expression and progression-free survival (PFS)of NSCLC patients.Results  A total of 20 key genes highly associated with NSCLC were screened out,which were CDC20,CDK1,MCM4,CDC6,MCM2,PLK1,NDC80,CCNB1,CDC45,AURKA,MCM8,BUB1,CDT1,ORC1,CCNA2,CASC5,MAD2L1,BUB1B and CENPA.Immunohistochemical  verification  showed that NDC80 protein was highly expressed in NSCLC tissue,and its positive expression rate in NSCLC group(88.6%)was significantly higher than that in adjacent cancer group(50.0%,P<0.05).The positive expression rate of NDC80 protein in NSCLC with TNM staging(Ⅲ+Ⅳ),low differentiation and lymph node metastasis was higher than that in NSCLC with TNM staging(Ⅰ+Ⅱ),high differentiation and moderate differentiation and no lymph node metastasis(P<0.05).There was no significant difference in the positive expression rate of NDC80 protein among NSCLC tissues with different gender,age and lesion size(P>0.05).Kaplan-Meier analysis showed that the median PFS of high expression group of NDC80 protein was(9.00±0.27)months,which was significantly lower than that of low expression group(11.00±0.79)months(P<0.05).Conclusions  The key genes found in this study play an important role in the maintenance of NSCLC stem cells.Immunohistochemical results showed that NDC80 protein was highly expressed in NSCLC,and it was closely related to tumor differentiation,TNM staging and lymph node metastasis.The PFS of high expression group of NDC80 protein was significantly lower than that of low expression group,suggesting that NDC80 may become a potential biomarker for screening,treatment and prognosis evaluation of NSCLC.
论著

基于红细胞膜修饰的聚合物载体搭载的纳米靶向药物在骨再生和血管生成中的作用

Bone-targeted nanomedicine based on red blood cell membrane-coated polymeric carriers for bone regeneration and vascularization

:1621-1629
 
       目的   开发一种多功能纳米颗粒输送系统来刺激骨再生和血管形成,用于逆转骨质疏松症。方法   通过制备基于外消旋聚乳酸 Poly(D,L-lactide)即PLA的纳米颗粒来封装淫羊藿苷。随后,通过红细胞膜包被这些纳米颗粒以增强生物相容性。为了提高靶向特异性,进一步合成了由阿仑膦酸盐修饰的聚乙二醇-磷脂酰乙醇胺(PEG-DSPE) 组成的骨靶向聚合物脂质,并将其掺入细胞膜涂层中。结果   多功能纳米颗粒输送系统可通过调节骨髓间充质干细胞 (BMSC)功能,从而增强成骨和血管生成能力。结论   本研究结果表明,多功能纳米颗粒输送系统可以在体外刺激骨形成和血管形成,表明其有成为骨质疏松症先进治疗策略的潜力。
       Objective  To developed a multifunctional nanoparticle system to stimulate bone regeneration and vascularization as a therapeutics strategy for osteopovost.Methods  Poly(D,L-lactide)(PLA)-based nanoparticles were fabricated to encapsulate the icariin,which is renowned for its osteogenic potential.These nanoparticles were then coated with  red blood cell membranes to enhance biocompatibility.To further improve targeting specificity,a bone-targeted polymer-lipid consisting of alendronate-modified PEG-DSPE was synthesized and incorporated into the cell membrane coating.Results  The delivery system was designed to modulate the function of bone marrow mesenchymal stem cells,thereby enhancing both osteogenesis and angiogenesis.Conclusions  Our findings demonstrated that the therapeutic system could enhance bone formation and vascularization in vitro,indicating its potential as an advanced treatment strategy for osteoporosis.
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