Expressions of chromogranin A and cathepsin D in human primary hepatocellular carcinoma

AIM To determine the expression and clinicalsignificance of chromogranin A and cathepsin Din hepatocellular carcinoma(HCC).METHODS Double immunofluorescence stain-ing techniques combined with laser confocalscanning microscopy(LSCM)was used toinvestigate chromogranin A and cathepsin Dexpressions in 85 HCC patients.RESULTS Cathepsin D was expressed in :3normal liver tissues,while in HCC the stainingshowed regional variation and the fraction ofstrongly stained cells increased as the tumorsbecame less differentiated and usually clinicallymore malignant.Cells which showed strongpositivity for cathepsin D were present in 71/85(83.5%)cases.Strong expression of cathepsinD in cancer cells was related tohistopathological features.They were morecommon in grade 3-4(26/28,92.9%)and grade2(46/53,86.8%)tumors than in grade 1 tumors(1/4,25.0%)(P【0.01).No significantcorrelation was found between age andcathepsin D expression.In patients with positivecathepsin D reaction,the mean age was 52.1±2.8 years(range 32-68 years)and in the groupwith negative reaction,the mean age was 51.3±4.5 years(range 28-71 years).No obvious relationship was observed between CgAexpression in cancer cells and thehistopathological features.The CgA positiverate was 75.0%(3/4)in grade 1,71.7%(38/53)in grade 2,and 71.4%(20/28)in grade 3-4(P】0.05)tumors.The coexpression of CgA andcathepsin D was found by double labeledimmunofluorescence staining techniques.Theprocessing of cathepsin D was disturbed in HCCcells and accumulated in the cells.Cathepsin Dhad proteolytic activity and autocrine mitogeniceffect,suggesting their functions in invasion.These findings demonstrated that the expressionof cathepsin D in HCC had prognostic value.CONCLUSION Chromogranin A and cathepsin Dare expressed in a high proportion of HCC andthe existence of cathepsin D in HCC might berelated to processing of CgA.This is clearly asubject for further studies because of itspotential clinical applications.

Salivary levels of cortisol and chromogranin A in patients with burning mouth syndrome: A case-control study

Burning mouth syndrome (BMS) is a poorly understood oral pain disorder characterized by a painful burning sensation in the oral cavity without any mucosal abnormalities. In this study, we evaluated the salivary cortisol and chromogranin A (CgA) levels of patients with BMS in comparison with age-matched controls. Subjects (n = 114) included 81 BMS patients and 33 controls. Patients with BMS were further classified into a subgroup of subjects who occasionally feel a burning sensation (BMS 1), and a subgroup of subjects who always feel a burning sensation (BMS 2). Salivary cortisol and CgA levels were measured using ELISA kits. All individuals with BMS had significantly higher cortisol and CgA levels than the controls did. Furthermore, when comparing the controls with each BMS subgroup, salivary levels of cortisol were significantly higher in both subgroups than controls. In contrast, the level of CgA was significantly higher in the BMS 2 subgroup only. Multiple regression analysis revealed a significant independent association between salivary levels of cortisol and BMS even after adjustment for gender, antidepressant or antianxiety drug use and hypertension (drug-treated). The study revealed that a significant association was observed between salivary cortisol levels and BMS.

Chromogranin A as a valid marker in oncology: Clinical application or false hopes?

Chromogranin A, due to its primary expression throughout the neuroendocrine system, is a widely accepted biomarker for the assessment of neuro-endocrine tumors. It has been traditionally used in the management of patients with tumors of gastro-enteropancreatic origin. Lately, it has also been implicated in various conditions and diseases, both benign and malignant. However, the paucity of data of adequate strength, as well as its relation with common physiologic conditions and its interaction with commonly prescribed medications, limit its clinical use in only a narrow spectrum. Herein, we present a thorough review to the most frequent conditions where its levels are affected, focusing specifically on its potential use as a prognostic and predictive biomarker in oncology.

Qinghua decoction(清化饮)improves chronic nonbacterial prostatitis possibly via regulating the chromogranin A/nerve growth factor/tyrosine kinase A signaling pathway mediated by inflammatory factors

OBJECTIVE:To explore the mechanism by which Qinghua decoction(清化饮)regulates neuroendocrine inflammation in chronic nonbacterial prostatitis(CNP)model rats and provide an experimental basis for clinical treatment.METHODS:The rats were randomly divided into six groups:normal control,model,Qianlie Tongyu capsule,low-dose Qinghua decoction,medium-dose Qinghua decoction,and high-dose Qinghua decoction group with six rats in each group.Rats in each group were sacrificed on the 29th day of treatment,and blood and prostate tissues were collected.Serum levels of tumor necrosis factor-alpha and interleukins 1-beta,6,8,and 10(TNF-αand IL-1β,-6,-8,and-10,respectively)were measured using enzyme-linked immunosorbent assay.The pathological changes in the rat prostate tissue in each group were observed under a light microscope.The expression levels of chromogranin A(CgA),nerve growth factor(NGF),and tyrosine kinase A(TrkA)were detected using reverse transcription quantitative polymerase chain reaction.Western blotting was used to detect protein expression of CgA,NGF,and TrkA.RESULTS:In the model group,the prostate capsule membrane and stroma were significantly dilated with more inflammatory cells infiltrating the stroma and perivessels.TNF-α,IL-1β,-6,and-8,CgA,NGF,and TrkA levels increased,whereas the content of IL-10 decreased,which was statistically significant compared to that in the normal control group(P<0.05).Prostate tissue cells in the high-dose group were neatly arranged with no obvious inflammatory cell infiltration.When compared with the model group,the high-dose Qinghua decoction group showed a significant improvement in these indices(P<0.05).CONCLUSION:Qinghua decoction led to inhibition of pathological changes in the prostate tissue of rats with CNP,regulation of inflammatory cytokine expression,and inhibition in the expression of CgA,NGF,and TrkA.This mechanism may be primarily related to regulation of the CgA/NGF/TrkA signaling pathway mediated by various inflammatory factors.

老年慢性心力衰竭患者嗜铬粒蛋白A和热休克转录因子1与心脏损伤的关系

目的探讨老年慢性心力衰竭(CHF)患者血清嗜铬粒蛋白A(CgA)和热休克转录因子1(HSF1)的水平变化与心肌重构及心肌损伤的关系。方法选择2019年1月至2022年5月太原市中心医院收治的老年CHF患者165例(疾病组),其中纽约心脏病协会心功能分级Ⅰ级28例,Ⅱ级29例,Ⅲ级65例和Ⅳ级43例。收集同期本院健康志愿者80例(对照组)。检测2组入院血清CgA和HSF1水平,心肌重构和心肌损伤指标,用Pearson分析血清CgA和HSF1与心肌重构及心肌损伤的相关性。随访1年,失访6例,根据是否发生主要不良心血管事件(MACE)分为MACE组51例和非MACE组108例。用单因素和多因素logistic回归分析,使用ROC曲线分析血清CgA和HSF1对MACE的预测价值。结果疾病组血清CgA、左心室质量指数(LVMI)、左心室收缩末期容积(LVESV)、左心室后壁厚度(LVPWT)、肌钙蛋白I(cTnI)、肌酸激酶同工酶(CK-MB)和N末端B型钠尿肽前体(NT-proBNP)水平显著高于对照组,HSF1和左心室射血分数(LVEF)显著低于对照组,差异有统计学意义(P<0.01)。Pearson相关性分析显示,血清CgA与LVEF呈负相关,与LVMI、LVESV、LVPWT、cTnI、CK-MB和NT-proBNP呈正相关(P<0.01);血清HSF1与LVEF呈正相关,与LVMI、LVESV、LVPWT、cTnI、CK-MB和NT-proBNP呈负相关(P<0.01)。多因素logistic回归分析显示,CgA、HSF1、LVEF、LVMI、LVESV、LVPWT和cTnI是老年CHF患者MACE发生的影响因素(P<0.05,P<0.01)。ROC曲线分析显示,血清CgA截断值为387.55μg/L,敏感性为74.51%,特异性为71.30%,曲线下面积为0.802(95%CI:0.751~0.855);血清HSF1截断值为2.34 ng/L,敏感性为74.51%,特异性为69.44%,曲线下面积为0.760(95%CI:0.707~0.812)。结论老年CHF患者血清CgA和HSF1水平与心肌重构及心肌损伤有密切关联,可作为预测MACE的有力工具。

CgA、TNF-α、IL-6联合改良qSOFA评分在儿童脓毒症预后评估中的应用价值

目的探究嗜铬粒蛋白A(chromogranin A,CgA)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin-6,IL-6)联合改良快速序贯器官衰竭评分(qSOFA)在儿童脓毒症预后评估中的应用价值。方法选取2020年3月至2023年4月收治的脓毒症患儿的临床资料,共188例。根据患儿的病情严重程度将其分为脓毒症组(n=113)和严重脓毒症组(n=75)。比较两组患儿的CgA、TNF-α、IL-6水平。分析CgA、TNF-α、IL-6水平及改良qSOFA评分与患儿预后的关系,探究其对患儿预后的预测价值。结果严重脓毒症组患儿的CgA、TNF-α、IL-6及改良qSOFA评分高于脓毒症组(P<0.05)。死亡组患儿的CgA、TNF-α、IL-6及改良qSOFA评分比生存组更高(P<0.05)。以患儿的预后情况为自变量(生存=0,死亡=1),对患儿的CgA、TNF-α、IL-6及改良qSOFA评分进行多因素logistic回归分析,可知上述指标均会对患儿的预后情况产生影响(P<0.05)。采用受试者工作特征(ROC)曲线探究CgA、TNF-α、IL-6及改良qSOFA评分对患者预后不良的预测价值,其AUC值分别为0.926、0.875、0.863、0.862,联合应用的AUC值为0.994,高于各指标分别预测(P<0.05)。结论CgA、TNF-α、IL-6联合改良qSOFA评分在严重脓毒症患儿及死亡患儿中显著升高,且其联合应用对患儿预后不良的预测价值较高,可以辅助患儿的临床治疗。

Prognostic role of chromogranin A in ：astration-resistant prostate cancer： a meta-analysis

We aimed to investigate the prognostic value of chromogranin A （CgA） in castration-resistant prostate cancer （CRPC）. We conducted a systematic literature search of PubMed, Web of Science, and EMBASE for citations published prior to September 2017 that described CgA and CRPC and performed a standard meta-analysis on survival outcomes. Our meta-analysis included eight eligible studies with 686 patients. The results were as follows： progression-free survival （PFS） was associated with CgA level （hazard ratio [HR] = 2.47, 95% confidence interval [CI]： 1.47-4.14, P = 0.0006）; PFS was relative to CgA change （HR = 9.22, 95% Ch 3.03-28.05, P〈 0.0001）; and overall survival （OS） was relative to CgA level （HR = 1.47, 95% Ch 1.15-1.87, P= 0.002）. When we divided the patients into two groups according to therapy status, the result for OS relative to CgA level was an HR of 1.26 （95% CI： 1.09-1.45, P = 0.001） in the first-line hormonal therapy group, and an HR of 2.33 （95% Ch 1.40-3.89, P = 0.001） in the second-line hormonal therapy or chemotherapy group. This meta-analysis indicated that a high CgA level had a negative influence on OS and PFS in CRPC patients. In addition, CRPC patients with a rising CgA had a shorter PFS. Further studies are needed to verify the prognostic value of CgA in CRPC.

保留NAC皮下腺体切除加包裹假体结合TiLoop 补片重建术治疗乳腺癌疗效分析

目的探讨保留乳头乳晕复合体(NAC)皮下腺体切除加包裹假体结合TiLoop补片重建治疗方案治疗乳腺癌的优势。方法选取南阳市中心医院乳腺外科2021年5月~2022年12月收治的70例乳腺癌患者,随机分为观察组和对照组,35例,观察组采用保留NAC切除加包裹假体结合TiLoop补片重建治疗方案,对照组采用切除乳房组织及其周围正常组织的改良根治术治疗方案,比较两组患者的临床效果、术后并发症、手术指标、神经降压素受体1(NTSR1)、嗜铬粒蛋白A(CgA)水平。结果观察组总有效率为94.29%,高于对照组(74.29%);术后并发症发生率为5.71%,明显低于对照组(25.71%),差异均有统计学意义(P<0.05);观察组术中出血量、手术时间、术后拔管时间、住院时间均优于对照组(P<0.05),而前哨淋巴结阳性率和住院时间两组比较无统计学差别。观察组患者术后6个月NTSR1(15.9±3.4)ng/mL、CgA(27.3±4.0)ng/mL,对照组分别为(13.8±2.6)ng/mL、(35.1±6.2)ng/mL,差异有统计学意义(P<0.05)。结论保留NAC皮下腺体切除加包裹假体结合TiLoop补片重建治疗方案是一种安全有效的乳腺癌手术方式,能够提高患者的临床效果,减少术后并发症,改善神经内分泌功能,值得临床推广应用。

Combination of insulin-like growth factor-1, IGF binding protein-3, chromogranin A and prostate specific antigen can improve the detection of prostate cancer

Aim:Prostate cancer(PCa)is the second most prevalent male cancer worldwide and designated the sixth most frequent male cancer in Arab countries.Although prostate specific antigen(PSA)has become the best and most valuable biomarker for screening of PCa,elevated levels of PSA can reflect the presence of malignant cells but can overlap with benign prostatic diseases.There is a necessity to develop and improve current tools for early detection and diagnosis of PCa.This study was done to evaluate the validation of serum insulin-like growth factor-1(IGF-1),IGF binding protein-3(IGFBP-3),chromogranin A(CgA)and combination with PSA in treatment of benign prostatic hyperplasia(BPH)and PCa patients.Methods:The study included 72 patients with PCa,70 BPH patients and 56 healthy male subjects of matched age.Full history and clinical data were recorded for all subjects.Results:Serum PSA attained sensitivity of 84%at 82%specificity with an accuracy of 83%,although IGF-1,IGFBP-3 and CgA did not recognize PCa patients.Conclusion:Combinations of IGF-1 and IGFBP-3 biomarkers with PSA were effectively differentiated between PCa and control groups as well as improving the overall value of sensitivity,specificity and diagnostic accuracy of PCa to 85%and 86%for IGF-1/PSA and IGFP-3/PSA respectively.

t-PA、CgA、LP-PLA2对经皮冠状动脉介入术后发生MACE的预测价值

目的探讨血清中组织型纤溶酶原激活剂(t-PA)、嗜铬粒蛋白A(CgA)、脂蛋白相关磷脂酶A2(LP-PLA2)对经皮冠状动脉介入术(PCI)后发生主要不良心血管事件(MACE)的预测价值。方法将2020年8月至2022年8月于该院行PCI治疗的120例冠心病患者纳入研究。根据PCI术后1年内是否发生MACE,将患者分为MACE组(33例)和非MACE组(87例)。比较MACE组和非MACE组血清t-PA、CgA、LP-PLA2水平及临床资料。采用多因素Logistic回归分析PCI术后发生MACE的危险因素。采用受试者工作特征(ROC)曲线分析t-PA、CgA、LP-PLA2单项或联合对PCI术后发生MACE的预测价值。结果MACE组有吸烟史者占比、NT-proBNP、CgA、LP-PLA2、合并高血压者占比均高于非MACE组(P<0.05),而积左心室射血分数(LVEF)、t-PA低于非MACE组(P<0.05)。两组年龄、性别构成、血肌酐、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、饮酒史、NYHA心功能分级、合并糖尿病情况、应用阿司匹林、应用氯吡格雷情况比较,差异均无统计学意义(P>0.05)。多因素Logistic回归分析显示,吸烟史、NT-proBNP升高、合并高血压、LVEF降低、t-PA降低、CgA升高、LP-PLA2升高是PCI术后发生MACE的危险因素(P<0.05)。ROC曲线分析显示,血清t-PA、CgA、LP-PLA2单项或联合预测PCI术后发生MACE的曲线下面积(AUC)分别为0.785(95%CI:0.693~0.877)、0.678(95%CI:0.564~0.791)、0.730(95%CI:0.636~0.824)、0.888(95%CI:0.830~0.946),联合预测的效能优于单项检测(P<0.05)。结论血清t-PA水平越低及CgA、LP-PLA2水平越高者PCI术后MACE发生风险越大,3项指标联合预测PCI术后MACE的价值较高。

Mutual relationships between contents of chromogranin A, cholecys-tokinin octapeptide and serotonin in individual EC cells

Chromogranin A (CgA) is a kind of acidic protein originally isolated from the chromaffin cells of the ox adrenal gland medulla. It was found that the CgA was also widely distributed in the neuroendocrine cells besides the adrenal medulla. The physiological function of the CgA is not yet elucidated, but it was presumed to be involved in organizing the granule matrix and regulating the processing of the prohormones. Besides, CgA is also the precursor of some peptide hormones such

内镜黏膜下剥离术治疗胃肠神经内分泌肿瘤的效果及对血清IL-6、CgA的影响

目的分析内镜黏膜下剥离术(ESD)治疗胃肠神经内分泌肿瘤(GI-NENs)的效果,并探讨其对患者血清白介素-6(IL-6)、嗜铬粒蛋白A(CgA)的影响。方法回顾性分析2017年1月至2018年10月期间榆林市第一医院消化内科收治的85例GI-NENs患者的临床资料,按照手术方式不同分为EDS组41例和EMR组44例,ESD组患者给予ESD治疗,EMR组患者给予内镜下黏膜切除术(EMR)治疗。比较两组患者手术相关指标、病变切除情况,检测并比较两组患者手术前、手术后1周的血清IL-6、CgA水平,记录两组患者手术并发症发生情况,随访3年,统计两组患者病灶残留和复发情况。结果ESD组患者的手术时间、住院时间分别为(39.01±4.74)min、(6.72±1.12)d,明显长于EMR组的(14.85±2.35)min、(5.46±0.79)d,手术费用为(1.02±0.15)万元,明显多于EMR组的(0.31±0.06)万元,差异均有统计学意义(P<0.05);ESD组切除病灶大小为(1.85±0.42)cm,明显大于EMR组的(1.34±0.27)cm,病灶整块切除率、完全切除率分别为92.68%、85.37%,明显高于EMR组的65.91%、61.36%,差异均有统计学意义(P<0.05);ESD组术后迟发性出血、穿孔以及皮下气肿或气腹手术并发症发生率分别为4.88%、9.76%、7.32%,与EMR组的2.27%、0、2.27%比较差异无统计学意义(P>0.05),ESD组并发症总发生率为21.95%,明显高于EMR组的4.55%,差异有统计学意义(P<0.05);手术后,ESD组血清IL-6、CgA水平分别为(6.13±0.89)ng/L、(54.72±6.01)μg/L,明显低于EMR组的(7.82±1.01)ng/L、(67.13±6.94)μg/L,差异均有统计学意义(P<0.05);随访3年,ESD组残留率9.76%与EMR组的22.73%比较差异无统计学意义(P>0.05),ESD组复发率为4.88%,明显低于EMR组的20.45%,差异有统计学意义(P<0.05)。结论ESD治疗GI-NENs可有效切除病灶,提高病灶切除效率,降低血清IL-6、CgA水平,减少患者复发风险,但手术并发症较多,手术花销较大。

Investigation of possible relationship between atopic dermatitis and salivary biomarkers,stress,and sleep disorders

Atopic dermatitis(AD)is a chronic,relapsing,multifactorial inflammatory disease with genetic,environmental,and immunological characteristics.The quality of life and sleep of patients and their families are affected by AD,which triggers stress,described as one of the factors that worsens AD.Salivary biomarkers such as cortisol,alpha-amylase,chromogranin A,and melatonin have been associated with stress and sleep disturbances.Therefore,the evaluation of stress and sleep disorders using salivary biomarkers in AD patients is important.This review aims to describe the possible relationship between atopic dermatitis and stress,sleep disorders,and salivary biomarkers,seeking to contribute to better understanding and clinical management of AD.This descriptive study is characterized as a narrative literature review.A literature search was conducted of studies published in English and Portuguese between January 2012 and October 2022 that are available in electronic media from various databases,such as Scientific Electronic Library Online,Latin American and Caribbean Literature on Health Sciences,and PubMed.AD is associated with different degrees of impact on the lives of individuals who present with the disease.Psychological stress may induce changes in saliva composition and worsen AD;at the same time,the severity of the disease may be associated with emotional impact.Further studies are needed to assess and correlate AD severity,stress,and sleep disturbances with salivary biomarkers in order to better understand this association.

Duodenal neuroendocrine tumor-tertiary care centre experience:A case report

BACKGROUND Neuroendocrine neoplasms(NENs)are a heterogeneous group of neoplasms arising from neuroendocrine cells,which contribute a small fraction of gastrointestinal malignancies.Duodenal neuroendocrine tumors(dNETs)represent 2%of all gastroenteropancreatic NENs.NENs are heterogeneous in terms of clinical symptoms,location,and prognosis.Non-functional NETs are mostly asymptomatic and need a high degree of clinical suspicion.Diagnosis of NETs is by endoscopic,endosonographic biopsy,and histopathological examination with immunohistochemistry staining for synaptophysin and chromogranin A.CASE SUMMARY We present case reports of 5 patients obtained over a period of 10 years in our center with dNETs.One patient had moderately differentiated NET and the remaining four had well-differentiated NET.Surveillance endoscopy was recommended in all the patients and is kept under regular follow-up after performing endoscopic therapy using endoscopic mucosal resection in 4 of them and one patient was advised to undergo a Whipple procedure.CONCLUSION Recently,the number of reported cases of NETs has increased due to advancements in diagnostic modalities and prevalence because of longer survival duration.The management differs based on the site,size,proliferation grade,and locally invasive pattern.They are slow-growing tumors with a good overall prognosis.The prognosis correlates with local lymph node status and metastasis.

高分化直肠神经内分泌肿瘤的临床病理特征及预后分析

目的 探讨高分化直肠神经内分泌肿瘤(RNET)的临床病理特征及预后。方法 回顾性分析2017年8月-2021年12月在该院住院治疗的83例高分化RNET患者的临床资料,包括:临床表现、内镜检查、内镜下治疗、术后并发症、术后病理、随访情况和预后。以2019年世界卫生组织(WHO)确定的消化系统肿瘤分类为标准,根据病理分期,将83例患者分为G1期组(72例)和G2期组(11例);根据患者瘤体数,将83例患者分为单发RNET组(77例)和多发RNET组(6例);比较两种分组之间嗜铬粒蛋白A(CgA)、突触素(Syn)和CD56的表达情况。结果 根据病理结果分组时,G1期组CgA阳性率明显高于G2期组,差异有统计学意义(χ^(2)=4.23,P=0.040);根据瘤体数分组时,多发RNET组CgA阳性率明显高于单发RNET组,差异有统计学意义(χ^(2)=5.74,P=0.017);Syn和CD56在以上两种分组中比较,差异均无统计学意义(P> 0.05)。结论 高分化RNET常无特异性临床表现,多为单发直肠G1期,ESD切除安全性高,预后良好,G1期患者中CgA阳性率较高,多发RNET患者中CgA阳性率较高。

CGA 衍生多肽 CHR 抑制 TNF -α引起的血管内皮细胞高通透性的研究

目的：观察嗜铬粒蛋白 A （ chromogranin A ， CGA ）的衍生多肽 CGA47-66（chromogranin， CHR）对TNF-α引起血管内皮细胞（EA．hy926）高通透性的影响和初步机制。方法分别用 CHR、TNF -α作用人血管内皮细胞系 EA．hy926，应用 Transwell 小室法、PCR、Western-blot检测单层内皮细胞通透性的改变，血管内皮钙黏蛋白VE-cadherin mRNA和蛋白的表达，以及磷酸化p38丝裂素活化蛋白激酶（ p38 mitogen activated protien kinase ， p38 MAPK）和总p38 MAPK等渗透性相关蛋白的表达。结果与空白对照组比较，TNF-α组EA．hy926细胞的通透性显著增高（2．479±0．117比1．769±0．554，t＝3．543，P＝0．008），VE-cadherin mRNA的表达显著降低（1．145±0．035比1．593±0．161， t＝-4．707， P＝0．035），而CHR （1 nM、10 nM、100 nM）组中EA．hy926细胞的VE-cadherin mRNA的表达较空白对照组有显著增加（1．512±0．04、1.615±0．170、1．918±0．355比1．162±0．189，P＜0．05），同时CHR（1 nM、10 nM、100 nM、1000 nM）能够缓解TNF-α组引起的高渗透性改变（1．954±0．379、1．835±0．090、1．430±0．349、1.559±0．447比2．479±0．117，P＜0．05）和 VE -cadherin mRNA 的低表达（1．541±0．149、1．529±0．098、2．087±0．437、1．640±0．160比1．145±0．035，P＜0．05），并且在1～100 nM范围内，上述作用呈剂量依赖性；Western-blot检测到TNF-α组EA．hy926细胞的VE-cadherin蛋白表达明显低于空白对照组，磷酸化p38 MAPK蛋白表达明显高于空白对照组；TNF-α组＋CHR组与TNF-α组相比，TNF-α组＋CHR组中VE -cadherin 蛋白的表达明显增加，磷酸化p38 MAPK蛋白明显降低。结论 CGA衍生多肽CHR能改善TNF-α引起的血管内皮细胞高通透性，这一作用在一定剂量范围内呈剂量依赖性，并且可能与p38 MAPK信号通路相关。

Role and function of granin proteins in diabetes mellitus

The granin glycoprotein family consists of nine acidic proteins;chromogranin A(CgA),chromogranin B(CgB),and secretogranin II–VIII.They are produced by a wide range of neuronal,neuroendocrine,and endocrine cells throughout the human body.Their major intracellular function is to sort peptides and proteins into secretory granules,but their cleavage products also take part in the extracellular regulation of diverse biological processes.The contribution of granins to carbohydrate metabolism and diabetes mellitus is a recent research area.CgA is associated with glucose homeostasis and the progression of type 1 diabetes.WE-14,CgA10-19,and CgA43-52 are peptide derivates of CgA,and act as CD4+or CD8+autoantigens in type 1 diabetes,whereas pancreastatin(PST)and catestatin have regulatory effects in carbohydrate metabolism.Furthermore,PST is related to gestational and type 2 diabetes.CgB has a crucial role in physiological insulin secretion.Secretogranins II and III have angiogenic activity in diabetic retinopathy(DR),and are novel targets in recent DR studies.Ongoing studies are beginning to investigate the potential use of granin derivatives as drugs to treat diabetes based on the divergent relationships between granins and different types of diabetes.

乳腺癌伴神经内分泌分化与预后因素的相关性

目的:通过观察雌激素受体(ER)、孕激素受体(PR)、Her-2、Ki67在乳腺癌伴神经内分泌分化(nueroendocrine differen-tiation,NED)中的表达,探讨乳腺癌伴NED的预后。方法:选取2000年1月至2009年8月温岭市第一人民医院乳腺癌根治术或改良根治术确诊病例55例,2008年8月-2009年8月温州医学院附属第一医院乳腺癌改良根治术确诊病例35例,根据CgA和Syn免疫组织化学染色结果,分为乳腺癌伴NED阳性和阴性两组。分析两组患者发病年龄、肿块大小、组织学分级、淋巴结转移状态、ER、PR、Her-2、Ki67的表达情况之间的差异。结果:90例患者中NED阳性组33例(占36.67%)。NED阳性组ER、PR阳性表达分别为24例(占72.73%)、21例(占63.64%),明显高于阴性组(P<0.05)。NED阳性组Her-2、Ki67阳性表达分别为11例(占33.33%)、15例(占45.45%),与NED阴性组比差异有统计学意义(P<0.05)。NED阳性组组织学分级为II～III级的患者比例为78.79%,低于NED阴性组92.98%(P<0.05)。NED阳性组淋巴结转移≥1枚的为7例(21.21%),明显低于NED阴性组24例(42.11%,P<0.05)。NED阳性组与NED阴性组间发病年龄及肿块大小的差异无统计学意义(P>0.05)。结论:与不伴NED的乳腺癌相比,乳腺癌伴NED的侵袭性较小,预后好。

嗜铬粒蛋白N区抗真菌活性片段研究

为寻找高效低毒的抗真菌药物,利用PCR技术扩增了编码人嗜铬粒蛋白N端18-76、18-66和31-76位氨基酸(CGA18-76、CGA18-66和CGA31-76)的DNA片段,将之克隆进枯草杆菌诱导型表达载体pSBPTQ,获得3种重组质粒pSC18-76、pSC18-66和pSC31-76,转化枯草杆菌DB1342。SDS-PAGE分析结果显示:经蔗糖诱导后,CGA18-76、CGA18-66和CGA31-76片段分别在枯草杆菌工程菌中获得表达,产物分泌到细胞外。表达量分别为5.6 mg/L、5.3 mg/L和5.6 mg/L。利用孔穴琼脂扩散法检测表达产物的抗真菌活性,并与CGA1-76进行比较,发现CGA18-76、CGA18-66和CGA31-76对烟曲霉菌、黄曲霉菌、石膏样小孢子菌和白念珠菌均有抑制作用,并以CGA31-76对白念珠菌的抑制作用为最强,CGA18-66对除白念珠菌之外的另3种测试真菌的抑制作用较强,而CGA18-76对测试真菌的抑制作用最弱。

老年血液透析合并心力衰竭患者血清嗜铬粒蛋白A与B型钠尿肽和心功能分级的关系

目的探讨老年血液透析合并心力衰竭患者血清嗜铬粒蛋白A(CGA)与B型钠尿肽(BNP)和心功能分级的关系。方法选择2012年11月～2018年2月大连大学附属中山医院血液透析中心治疗的老年慢性肾功能衰竭患者86例,根据心功能(NYHA)分级分为心功能Ⅰ级组23例,心功能Ⅱ级组20例,心功能Ⅲ级组19例,心功能Ⅳ级组24例,同期选择健康体检者20例为对照组,检测血清CGA、BNP水平,并行心脏彩色超声检查,测量LVEF、左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)、左心房内径(LAD)等相关指标。用Pearson相关性分析CGA与心脏超声指标的关系。结果各组CGA和BNP水平比较,差异有统计学意义(P<0.01)。心功能Ⅰ级组、心功能Ⅱ级组、心功能Ⅲ级组和心功能Ⅳ级组CGA和BNP水平较对照组明显增高,差异有统计学意义(P<0.01)。心功能Ⅱ级组CGA和BNP水平较心功能Ⅰ级组明显升高,心功能Ⅲ级组CGA和BNP水平较心功能Ⅰ级组和心功能Ⅱ级组明显增高,心功能Ⅳ级组CGA和BNP水平较心功能Ⅰ级组、心功能Ⅱ级组和心功能Ⅲ级组明显增高,差异有统计学意义(P<0.01)。相关性分析显示,血清CGA与LVEF呈负相关(r=-0.702,P=0.016),与LVEDD、LVESD和LAD呈正相关(r=0.616,P=0.028;r=0.683,P=0.019;r=0.631,P=0.021)。结论检测CGA水平有助于判断老年血液透析合并慢性心力衰竭患者心力衰竭的严重程度。