Morphine reverses the effects of 1-methyl-4-phenylpyridinium in PC12 cells through activating PI3K/Akt

Aim of the study: Parkinson’s disease (PD) is a neurodegenerative disorder. It is caused by the degeneration of dopaminergic neurons and the dopamine (DA) deletion in the substantia nigra pars compacta (SNpc). Morphine elevates the level of dopamine in the mesolimbic dopamine system and plays a role in alleviating PD symptoms. However, the molecular mechanism is still unclear. The aim of the study is to investigate the mechanism on morphine alleviating PD symptoms.

Materials and methods: The viability of PC12 cells was measured by using MTT assay. The expressions of tyrosine hydroxylase (TH), thioredoxin-1 (Trx-1), CyclinD1 and Cyclin-dependent kinase5 (Cdk5) were detected by Western Blot.

Results: In present study, we found that morphine increased the cell viability in PC12 cells. 1-methyl-4-phenylpyridi-nium (MPP+) reduced the cell viability and TH expression, which were reversed by morphine. MPP+ decreased the expressions of Trx-1, CyclinD1, Cdk5, which were restored by morphine. Moreover, the role of morphine in restoring the expressions of Trx-1, CyclinD1 and Cdk5 decreased by MPP+ was abolished by LY294002, phosphatidylinositol-3-kinase (PI3K)/Akt inhibitor.

Conclusions: These results suggest that morphine reverses effects induced by MPP þ through activating PI3K/Akt pathway.     

补骨脂素抗增生性瘢痕作用机制研究

目的探讨补骨脂素抗增生性瘢痕的作用机制。方法体外培养成纤维细胞,按随机数字表法分为正常组(培养正常成纤维细胞)、瘢痕组(培养增生性瘢痕成纤维细胞)、TGF-β1组(10 ng/ml TGF-β1处理增生性瘢痕成纤维细胞5 min^12 h)、Smurf2 RNA干扰组[Smad泛素化调节因子2(Smad ubiquitin regulatory factor2,Smurf2)siRNA转染增生性瘢痕成纤维细胞72 h]、补骨脂素组(10μmol/L补骨脂素处理增生性瘢痕成纤维细胞继续培养72 h)、补骨脂素+TGF-β1组(增生性瘢痕成纤维细胞加入补骨脂素培养72 h后加入TGF-β1培养6 h)。采用Western blot法检测Smurf2、α-平滑肌肌动蛋白(α-actin SMA,α-SMA)蛋白表达;RT-PCR法检测Ⅰ型胶原蛋白mRNA表达;ELISA法检测TGF-β1蛋白分泌。结果与正常组比较,瘢痕组Smurf2蛋白[(0.83±0.08)比(0.38±0.07)]表达增加(P<0.05);与瘢痕组比较,Smurf2 RNA干扰组TGF-β1[(2.2±0.18)比(4.2±0.47)]表达降低(P<0.05);TGF-β1组Smurf2[(0.71±0.06)比(0.42±0.04)]、α-SMA[(1.42±0.12)比(0.91±0.09)]蛋白表达增加(P<0.05),Ⅰ型胶原蛋白mRNA[(0.72±0.09)比(0.41±0.07)]表达增加(P<0.05);补骨脂素组Smurf2[(0.05±0.01)比(0.42±0.04)]、α-SMA[(0.71±0.07)比(0.91±0.09)]蛋白表达降低(P<0.05),Ⅰ型胶原蛋白mRNA表达[(0.12±0.04)比(0.41±0.07)]降低(P<0.05)。结论补骨脂素可能通过TGF-β1/Smurf2信号通路抑制α-SMA蛋白表达,从而降低Ⅰ型胶原蛋白表达,起到抑制瘢痕形成的作用。     

极速实时荧光聚合酶链反应与常规方法对新型布尼亚病毒检测的评价

目的探讨极速实时荧光聚合酶链反应(polymerase chain reaction,PCR)、实时荧光PCR、酶联免疫吸附测定(enzyme-linked immunosorbent assay,ELISA)和胶体金免疫层析法(gold immunochromatography assay,GICA)4种方法检测新型布尼亚病毒的特异度和灵敏度,为发热伴血小板减少综合征的早期诊断提供依据。方法采集2017年6月1日至9月30日山东大学附属济南市传染病医院86例临床诊断为发热伴血小板减少综合征患者的血清样本,分别应用极速实时荧光PCR、实时荧光PCR、ELISA和GICA 4种方法进行检测。统计学分析采用χ^2检验。结果86份患者血清标本中,极速实时荧光PCR、实时荧光PCR、IgM-ELISA、IgG-ELISA、IgM-GICA、IgG-GICA的新型布尼亚病毒阳性分别为82份(95.34%)、79份(91.86%)、41份(47.67%)、8份(9.3%)、19份(22.09%)和3份(3.49%)。极速实时荧光PCR特异度为100%,灵敏度达到1×103拷贝/mL,3次重复扩增试验显示其Ct值变异系数均<2%。在发热伴血小板减少综合征进展的1期、2期、3期病程中,极速实时荧光PCR的阳性检出率为41份(97.62%)、34份(94.44%)、7份(87.50%),实时荧光PCR的阳性检出率为39份(92.86%)、33份(91.67%)、7份(87.50%),在1期和2期两个病程,极速实时荧光PCR阳性检出率略高;IgM-ELISA阳性检出率从1期(28.57%)到3期(87.50%)显著增高,2期、3期与1期相比,差异均有统计学意义(χ^2=8.347、7.561,均P<0.01);IgM-GICA的阳性检出率从1期(14.29%)到2期(33.33%)也有增高,差异有统计学意义(χ^2=3.962,P<0.05),但与其他方法相比,其检出率偏低。1期,实时荧光PCR阳性检出率显著高于ELISA(IgM和IgG)和GICA(IgM和IgG),差异均有统计学意义(χ^2=33.740、55.080、49.010、64.340,均P<0.01)。2期,实时荧光PCR的阳性检出率高于ELISA(IgM和IgG)和GICA(IgM和IgG),差异均有统计学意义(χ^2=7.700、46.720、23.700、50.630,均P<0.01)。3期,极速实时荧光PCR、实时荧光PCR和IgM-ELISA表现出同样高的阳性检出率,远高于IgG-ELISA和GICA(IgM和IgG)。实时荧光PCR阳性检出率和IgG-ELISA、IgM-GICA、IgG-GICA之间差异均有统计学意义(均χ^2=6.250,P<0.05)。结论极速实时荧光PCR在新型布尼亚病毒的早期检测中有更高的灵敏度和特异度,且重复性好、稳定度高,与传统实时荧光PCR相比大大缩短了扩增时间,对发热伴血小板减少综合征的早期快速诊断具有重要价值。     

红参发酵产物联合长春瑞滨及顺铂化疗方案治疗晚期非小细胞肺癌患者的疗效

目的探讨红参发酵产物联合长春瑞滨及顺铂化疗方案治疗晚期非小细胞肺癌患者的疗效。方法将104例晚期非小细胞肺癌患者随机分为治疗组及对照组,每组52例。对照组患者给予单纯长春瑞滨^+顺铂化疗方案,治疗组患者在对照组基础上联合应用红参发酵产物。分别在治疗前后采用疲劳症状量表(FSI)、肺癌治疗功能评价量表(FACT-L)评价两组患者疲劳症状及生活质量,并比较治疗前后两组患者血清肿瘤标志物水平、免疫功能指标水平、药物不良反应及生存情况。结果治疗前,两组患者FSI各维度评分及总分,FACT-L各维度评分及总分,细胞角质蛋白19片段抗原21-1(CYFRA21-1)、神经元特异性烯醇化酶(NSE)、癌胚抗原(CEA)、自然杀伤(NK)细胞、CD3^+、CD4^+、CD8^+、CD4^+/CD8^+水平比较,差异均无统计学意义(P﹥0.05)。治疗后,对照组患者FSI各维度评分及总分均高于治疗前及治疗组;治疗组患者生理状态、情绪状态、对疾病关注度评分及总分均高于治疗前,且生理状态、社会家庭状态、情绪状态、功能状态、对疾病关注度评分及总分均高于对照组;两组患者CEA、CYFRA21-1及NSE水平均较治疗前下降,且治疗组患者均低于对照组患者;治疗组患者NK细胞、CD3^+、CD4^+及CD4^+/CD8^+水平均较治疗前上升,且均高于对照组患者,差异均有统计学意义(P﹤0.05)。治疗组患者血液学不良反应发生例数少于对照组,差异有统计学意义(P﹤0.05)。结论红参发酵产物联合长春瑞滨及顺铂化疗方案能够有效提高晚期非小细胞肺癌患者的免疫功能及生活质量,降低血清肿瘤标志物水平,并减轻血液学不良反应。     

Prevalence of hereditary breast and ovarian cancer (HBOC) predisposition gene mutations among 882 HBOC high‐risk Chinese individuals

Identification of deleterious variants in hereditary breast and ovarian cancer (HBOC) susceptibility genes allows for increased clinical surveillance and early detection, and could predict the response to poly (ADP‐ribose) polymerase (PARP) inhibitor in patients with advanced ovarian carcinomas. To determine the prevalence and clinical prediction factors for HBOC syndrome, 882 selected individuals underwent multigene panel testing for HBOC risk assessment during the period from January 2015 to March 2018. Overall, 176 deleterious mutations were observed in 19.50% (n = 172) of individuals. Twenty‐six of 176 mutations could not be retrieved in related public databases and were considered to be novel. Among patients with ovarian cancer, 115 deleterious mutations were identified in 429 patients (48.6%) with significant enrichment for a family history of breast or ovarian cancer syndrome (P < .05). In the breast cancer subgroup, 31 deleterious mutations were identified in 261 patients. Besides BRCA1 (8; 25.8%) and BRCA2 (11; 35.5%), the most frequently occurring genes, an additional 12 deleterious mutations (38.7%) were found in seven other susceptibility genes. Higher mutation incidence (57.9%) was observed in subjects with histories of breast and ovarian cancer. Our results highlighted the genetic heterogeneity of HBOC and the efficiency of a multigene panel in carrying out risk assessment.     

乳腺癌X线表现分析

目的分析乳腺癌典型及不典型X线征象,提高对乳腺癌不典型X线表现的认识。方法对61例经手术病理证实的乳腺癌资料进行回顾性分析。结果61例乳腺癌主要X线征象:肿块39例;微小钙化30例;不伴肿块及微小钙化的乳腺局部结构紊乱4例、星芒征3例、非对称性密度增高3例。结论肿块及微小钙化是乳腺癌最主要、最直接的X线征象,但部分乳腺癌X线上缺乏上述2种表现,单纯以结构紊乱、非对称性密度增高或星芒征为主要表现。提高对此类乳腺癌不典型X线表现的认识,有利于防止误、漏诊。     

广东高校贫困大学生心理健康状况调查与思考

目的了解广东高校贫困生心理健康状况并提出相应建议。方法用康奈尔医学指数（CMI）及社会支持评定量表，对广东省5所高校500名学生进行了问卷调查，并采用SPSS11．0进行相关统计和分析。结果贫困大学生的心理健康状况在某些方面存在不足，在性别、地域来源等有差异。结论高校应重视贫困大学生的心理健康状况，加强情感引导，尤其不能忽视对女贫困大学生的关注和帮助。     

原发性肾上腺皮质腺癌的CT诊断价值

目的分析原发性肾上腺皮质腺癌（ACC）的CT表现及其动态增强特征，以提高其诊断准确性。方法回顾性分析经手术病理证实的ACC11例，术前均经CT平扫、动脉期（30S）和门静脉期（70—80S）扫描，复习CT扫描表现并和手术病理作对照。结果11例ACC中，右侧5例，左侧6例。直径4．1—16．0cm，其中，〈5．0cm者2例，5．0—10．0cm者4例，〉10．0cm5例；肿瘤境界清楚3例，邻近脂肪间隙见条索状异常密度影3例，邻近实质脏器受侵犯5例。肿瘤实质成分平扫、动脉期和门静脉期CT值分别为21．9～46．7HU（平均35．3HU）、30．5～65．8HU（平均47．1HU）和52．6～97．0HU（平均74．2HU）。肿瘤中央坏死形成假囊肿4例，网络状改变6例，实质为主伴小囊变1例；6例网络状改变者动脉期可见显著强化的不规则肿瘤血管：结论ACC具有较明显的形态学和血液动力学特征，动态增强扫描尤其是动脉期扫描有明显的诊断价值。