Expression of alpha-methylacyl-CoA racemase (P504s) in various malignant neoplasms and normal tissues: astudy of 761 cases

Alpha-methylacyl CoA racemase (AMACR), also known as P504S, plays an important role in peroxisomal beta-oxidation of branched-chain fatty acids. It has recently been shown that AMACR is highly expressed in prostate cancer and that it may be an important diagnostic marker for prostate carcinoma. However, little is known about expression of AMACR in normal tissues and other malignant tumors. In this study, we investigated expression of AMACR in 539 malignant tumors and 222 normal human tissues of various types by immunohistochemical analysis. mRNA levels of AMACR in normal organs and in selected tumors were assessed by real time PCR. In normal tissue, high expression of AMACR mRNA was identified in liver, kidney and salivary gland, while AMACR protein was detected in liver (hepatocytes), kidney (tubular epithelial cells), lung (only bronchial epithelial cells), and gallbladder (only mucosal epithelial cells). High expression of AMACR mRNA was found in prostate, liver, and kidney cancers but rarely in stomach and bladder cancers. A high percent of adenocarcinomas arising from these organs express AMACR, including 17 of 21 (81%) of hepatocellular carcinomas and 18 of 24 (75%) of renal cell carcinomas. In addition, carcinomas arising from tissues normally not expressing AMACR were also positive for the antigen, including 17 of 18 (94%) prostate carcinomas, 9 of 29 (31%) of urothelial carcinomas, and 4 of 15 (27%) of gastric adenocarcinomas. Two hundred and fifty cases of adenocarcinomas from lung, breast, pancreas, bile duct, adrenal gland, salivary gland, ovary, thyroid and endometrium were negative or rarely positive for AMACR. Neuroendocrine carcinomas rarely expressed AMACR. Melanomas, squamous cell carcinomas, basal cell carcinomas, soft tissue tumors (including epithelioid sarcomas and synovial sarcoma), thymomas, and germ cell tumors were negative for AMACR. Our data provide important baseline information for using AMACR in clinical practice and also are valuable in furthering understanding of the pathogenic role of AMACR in malignant neoplasms.     

Expression of TNFalpha by muscle fibers in biopsies from children with untreated juvenile dermatomyositis: association with the TNFalpha-308A allele

Juvenile dermatomyositis (JDM) is the most common pediatric inflammatory myopathy. In patients with JDM, the A --> G polymorphism in the tumor necrosis factor alpha (TNFalpha)-308 promoter region (TNFalpha-308A) is associated with prolonged disease course and increased production of TNFalpha by peripheral blood mononuclear cells (Arthritis Rheum. 43, 2368-2377, 2000). Magnetic resonance imaging directed biopsies from 21 white children with untreated JDM were evaluated for TNFalpha expression. Using monoclonal antibody to TNFalpha, fresh frozen sections were processed by the standard immunohistochemical technique. We investigated the association among the expression of TNFalpha by muscle fibers, disease activity, duration of untreated disease, and the TNFalpha-308 polymorphism. Untreated children with JDM who had the TNFalpha-308A allele had an increased number of TNFalpha stained muscle fibers than children with the TNFalpha-308G allele (P = 0.001). There was no association with disease activity or duration of untreated disease. We speculate that muscle fiber production of TNFalpha provides a microenvironment in which TNFalpha acts synergistically with other mediators to prolong muscle fiber damage.     

肾综合征出血热患者血清炎性细胞因子与疾病进程及预后的相关性

目的分析肾综合征出血热患者不同临床分期及不同临床分型血清中C反应蛋白、白细胞介素-1、白细胞介素-6、肿瘤坏死因子-α水平与疾病的相关性,为HFRS临床诊治提供依据。方法以2018年6月至2020年1月在锦州医科大学附属第一医院住院的37例HFRS患者和15例健康体检者(对照组)为研究对象,用ELISA法分别检测患者血清炎性细胞因子CRP、IL-1、IL-6和TNF-α水平,并分析其与临床分期、临床分型的相关性。结果临床分期为急性期和恢复期的患者血清中CRP、IL-1、IL-6和TNF-α水平均高于正常组(P<0.01),且急性期各细胞因子显著高于恢复期(P<0.01);临床分型轻型、中型、重型、危重型患者血清CRP、IL-1、IL-6和TNF-α水平较比对照组有不同程度的增加(P<0.05)。Spearman相关分析显示,CRP、IL-1、IL-6和TNF-α水平与不同临床分期呈负相关(r=-0.48,P<0.01;r=-0.59,P<0.01;r=-0.33,P=0.03;r=-0.47,P<0.01);与不同临床分型呈正相关(r=0.42,P=0.01;r=0.56,P<0.01;r=0.52,P<0.01;r=0.34,P=0.04);与预后(存活)呈负相关(r=-0.32,P=0.02;r=-0.46,P<0.01;r=-0.40,P<0.01;r=-0.37,P=0.01)。结论HFRS患者血清炎性细胞因子水平与疾病严重程度及预后密切相关。     

恩替卡韦序贯聚乙二醇化干扰素-α与单用恩替卡韦治疗慢性乙型肝炎的临床疗效比较:系统评价与分析

 目的 系统评价与分析恩替卡韦(ETV)序贯聚乙二醇化干扰素-α(Peg-IFN-α)与单用ETV在治疗慢性乙型肝炎患者中的临床疗效。方法 计算机检索PubMed、Embase、Cochrane Library、中国知网、万方数据库,搜索有关ETV及ETV序贯Peg-IFN-α治疗慢性乙型肝炎的随机对照试验研究,应用Stata 16.0软件对符合纳入条件的临床研究进行系统评价与分析。结果 共纳入10篇文献,1 250例患者,其中553例患者采用ETV序贯Peg-IFN-α治疗,697例患者单用ETV治疗,两组患者组间基线特征比较,差异均无统计学意义(均P＞0.05)。ETV序贯Peg-IFN-α试验组的HBsAg转换率、HBsAg清除率、HBeAg转换率、HBeAg清除率均高于ETV对照组,差异均有统计学意义(均P＜0.05)。结论 在慢性乙型肝炎抗病毒治疗中,总体上ETV序贯Peg-IFN-α治疗疗效优于单用ETV。     

重组人干扰素α2b雾化吸入联合远红外止咳贴治疗小儿毛细支气管炎的临床效果

目的观察重组人干扰素α2b雾化吸入联合远红外止咳贴治疗毛细支气管炎的效果。方法选取2018年3月至2020年3月玉林市妇幼保健院收治的80例毛细支气管炎患儿,采用随机数字表法分为观察组与对照组,每组各40例。对照组给予常规综合治疗,观察组在常规综合治疗的基础上给予氧气驱动雾化吸入α2b干扰素联合远红外止咳贴治疗。比较两组治疗后的临床疗效、临床症状消失时间、住院时间以及肺部功能。结果观察组临床总有效率高于对照组,差异有统计学意义(P<0.05);观察组喘憋消失时间、咳嗽消失时间、肺部啰音消失时间、体温恢复正常时间、住院时间均短于对照组,差异有统计学意义(P<0.05);观察组治疗后潮气量、达峰时间比、达峰容积比均高于对照组,差异有统计学意义(P<0.05)。结论雾化吸入干扰素α2b联合远红外止咳贴治疗毛细支气管炎对提高治疗有效率,缩短临床症状消失时间、住院时间,改善肺功能具有重要作用,值得临床推广使用。     

Directional screening and identification of potential cytotoxic components from Achnatherum inebrians by a combination of surface palsmon resonance and chromatography

Objective: To establish a method for directional screening of the cytotoxic components from the medicinal herb of Achnatherum inebrians by a combination of surface plasmon resonance (SPR) biosensor and chromatographic isolation technology. Methods: Under the guidance of bioactive assessment based on binding abilities between objects and the α-Mannosidase (α-Man) target, the active components from different solvents extracts, different polar extraction parts and fractions were screened orderly and directionally using SPR. Components with a high binding ability to α-Man can be precisely oriented in a narrower fractions range and are easy to isolate. Three human cancer cells were used to evaluate the cytotoxic activity of component with the highest affinity to α-Man. Results: Eight compounds were isolated and identificated from A. inebrians for the first time. Deoxyvasicinone possessed the highest affinity to α-Man among them. Moreover, deoxyvasicinone showed good effects on inhibited proliferation of human hepatoma cells HepG2 (IC50 = 5.7 μmol/L), human breast cancer cells MCF7 (IC50 = 7.21 μmol/L) and human lung cancer cells HCC827 (IC50 = 0.75 μmol/L), respectively. In particular, its inhibitory effect on HCC827 was stronger than the positive drug gefitinib (IC50 = 1.65 μmol/L). Conclusion: A comprehensive strategy of directional screening potential cytotoxic components from herb based on biomolecular interaction and chromatography was established. Deoxyvasicinone as an effective anti-cancer component was initially isolated from A. inebrians. It is expected that this screening strategy could provide new perspectives for rapid screening and identification of active components from natural plants with the complex matrix.     

降糖方对糖耐量异常大鼠糖脂代谢及骨骼肌组织IκB-α和NF-κBp65的影响

目的:探讨降糖方对糖耐量异常大鼠糖脂代谢及骨骼肌组织κB抑制蛋白α(IκB-α)、核转录因子肽p65(NF-κBp65)的影响。方法:SD大鼠随机分为正常组、模型组、盐酸二甲双胍组、降糖方低、高剂量组,采用高脂饮食喂养4周,链脲佐菌素(STZ)腹膜内注射建立糖耐量异常大鼠模型,治疗8周后,观察骨骼肌组织病理变化,测定空腹血糖(FPG)、血清胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白(LDL-C)、骨骼肌组织IκB-α mRNA、NF-κBp65 mRNA水平、骨骼肌组织白细胞介素-4(IL-4)、白细胞介素-12(IL-12)、肿瘤坏死因子-α(TNF-α)蛋白水平。结果:正常组大鼠骨骼肌组织结构正常,模型组骨骼肌排列紊乱、肌纤维断裂、可见明显炎症细胞浸润;盐酸二甲双胍及降糖方干预后,骨骼肌炎症细胞浸润减少,肌纤维排列趋于整齐。模型组大鼠FPG、FINS、HOMA-IR水平、血清TG、TC、LDL-C水平、骨骼肌IκB-α mRNA、NF-κBp65 mRNA和蛋白水平、骨骼肌组织IL-4、IL-12、TNF-α蛋白水平高于对...     

当归通痹汤联合中药热敷治疗膝关节骨性关节炎的疗效及对IL-1β、MMP-3和TNF-α水平的影响

目的:探讨当归通痹汤联合中药热敷治疗膝关节骨性关节炎的疗效及对白细胞介素(IL)-1β、基质金属酶(MMP)-3和肿瘤坏死因子(TNF)-α水平的影响。方法:选取我院收治的膝关节骨性关节炎患者140例,随机分为两组各70例。对照组给予中药热敷治疗,治疗组在对照组基础上给予当归通痹汤,对比两组治疗后的临床疗效、VAS评分、WOMAC指数和ADL评分,以及IL-1β、MMP-3和TNF-α水平。结果:治疗后,治疗组的总有效率为94.29%,高于对照组的81.43%,差异有统计学意义(P<0.05);两组ADL评分明显升高,WOMAC指数、VAS评分明显降低(P<0.05);且治疗组比对照组明显改善(P<0.05);两组患者治疗后的IL-1β、MMP-3和TNF-α水平均显著低于治疗前(P<0.05);且治疗组低于对照组,差异有统计学意义(P<0.05)。两组患者不良反应发生率差异无统计学意义(P>0.05)。结论:膝关节骨性关节炎患者采用当归通痹汤联合中药热敷治疗,具有较好的临床疗效,能够改善患者膝关节功能,值得在临床上推广应用。     

补气活血止痛汤配合硫辛酸注射液对糖尿病周围神经病变 患者炎症反应和下肢神经功能的影响

目的:探讨补气活血止痛汤配合硫辛酸注射液对糖尿病周围神经病变(DPN)患者的炎症反应和下肢神经功能的影响。方法:选取2018年1月—2019年12月在上海市静安区江宁路街道社区卫生服务中心收治的DPN患者148例,按照随机对照的方法,随机分为对照组(n=74)和观察组(n=74),对照组给予硫辛酸注射液治疗,观察组在对照组的基础上给予补气活血止痛汤治疗,4周为1个疗程,连续用药2个疗程后比较临床疗效。结果:观察组治疗后患者IL-6、IL-1β、TNF-α及CRP水平较对照组显著下降(P<0.05);观察组治疗后左胫神经、右胫神经、左腓总神经和右腓总神经传导速度较对照组显著提高(P<0.05);观察组治疗后TCSS、TSS和NRS评分较对照组临床症状评分下降更明显(P<0.05)。结论:补气活血止痛汤配合硫辛酸注射液可显著降低炎症反应、促进神经传导功能,从而改善DPN患者的临床症状。