Proteolytic processing of the Alzheimer disease-associated presenilin-1 generates an in vivo substrate for protein kinase C

The majority of familial Alzheimer disease mutations are linked to the recently cloned presenilin (PS) genes, which encode two highly homologous proteins (PS-1 and PS-2). It was shown that the full-length PS-2 protein is phosphorylated constitutively within its N-terminal domain by casein kinases, whereas the PS-1 protein is not. Full-length PS proteins undergo endoproteolytic cleavage within their hydrophilic loop domain resulting in the formation of ≈20-kDa C-terminal fragments (CTF) and ≈30-kDa N-terminal fragments [Thinakaran, G., et al. (1996) Neuron 17, 181–190]. Here we describe the surprising finding that the CTF of PS-1 is phosphorylated by protein kinase C (PKC). Stimulation of PKC causes a 4- to 5-fold increase of the phosphorylation of the ≈20-kDa CTF of PS-1 resulting in reduced mobility in SDS gels. PKC-stimulated phosphorylation occurs predominantly on serine residues and can be induced either by direct stimulation of PKC with phorbol-12,13-dibutyrate or by activation of the m1 acetylcholine receptor-signaling pathway with the muscarinic agonist carbachol. However, phosphorylation of full-length PS-1 and PS-2 is not altered upon PKC stimulation. In addition, a mutant form of PS-1 lacking exon 10, which does not undergo endoproteolytic cleavage [Thinakaran, G., et al. (1996) Neuron 17, 181–190] is not phosphorylated by PKC, although it still contains all PKC phosphorylation sites conserved between different species. These results show that PKC phosphorylates the PS-1 CTF. Therefore, endoproteolytic cleavage of full-length PS-1 results in the generation of an in vivo substrate for PKC. The selective phosphorylation of the PS-1 CTF indicates that the physiological and/or pathological properties of the CTF are regulated by PKC activity.     

Prospective trial comparing the use of sulphasalazine and auranofin as second line drugs in patients with rheumatoid arthritis.

Two hundred patients with rheumatoid arthritis were studied in a prospective open trial comparing treatment with sulphasalazine and auranofin in patients with active disease over 12 months. The two drugs improved many parameters of disease activity at 12, 24, and 48 weeks. At 12 weeks, the group treated with sulphasalazine had a lower platelet count (Mann-Whitney U test), erythrocyte sedimentation rate, and articular index, with a greater decrease in erythrocyte sedimentation rate (Students t test) and C reactive protein between 0 and 12 weeks. There were no significant differences between sulphasalazine and auranofin treatment after 24 and 48 weeks. Life table analysis showed no significant differences in the rate of side effects which caused treatment to be stopped. Sulphasalazine works more rapidly, may be a more effective disease modifying antirheumatic drug, and is as well tolerated as auranofin.     

Rapid prenatal diagnosis of beta thalassemia using DNA amplification and nonradioactive probes

We used in vitro DNA amplification by the polymerase chain reaction and nonradioactive probes for prenatal diagnosis of beta thalassemia in Chinese from the Guangdong province. Exact molecular diagnoses were made in all 20 fetuses studied over a 6-month period. We conclude that this method of prenatal diagnosis for beta thalassemia is a viable approach in many parts of the world where this disease is common.     

A double blind, randomised, multicentre comparison of two doses of intravenous iloprost in the treatment of Raynaud''s phenomenon secondary to connective tissue diseases.

OBJECTIVE--To compare low (0.5 ng/kg/min) and standard dose (2 ng/kg/min) iloprost (a stable carbacyclin analogue of prostacyclin) in patients with Raynaud''s phenomenon secondary to connective tissue disorders. DESIGN--Double blind, random allocation, three six hour infusions on consecutive days. Follow up period eight weeks. SETTING--Rheumatology units, five teaching hospitals. PATIENTS--55 Patients with Raynaud''s phenomenon (greater than seven attacks per week), 32 secondary to well documented classical progressive systemic sclerosis (American Rheumatism Association criteria), 11 CREST syndrome, 5 mixed connective tissue disease, 1 rheumatoid arthritis, 1 Sjögren''s syndrome, 1 childhood dermatomyositis, and 4 abnormal nailfold capillaroscopy and antibody profiles but no definite diagnosis. INTERVENTIONS--All other treatment for Raynaud''s phenomenon was discontinued two weeks before entry. 28 Patients were randomly allocated to receive the low dose, 27 the standard dose. Differing dilutions allowed infusion rates to be started at 10 ml/h with increments of 10 ml/h every 15 minutes until infusion rates reached 0.5 ng/kg/min and 2 ng/kg/min respectively. MAIN OUTCOME MEASURE(s)--Reduction in frequency, duration, and severity of attacks of Raynaud''s phenomenon. Assessment of ulcer and ischaemic lesion healing. RESULTS--Both dosage regimens were equally effective in reducing severity, frequency, and duration of Raynaud''s attacks. Ulcer healing occurred to similar degree in both treatment groups (standard dose 44%, low dose 39%). Low dose was associated with significantly fewer side effects. CONCLUSIONS--Both dosage regimens reduce severity of Raynaud''s phenomenon and encourage ulcer healing. Low dose was associated with fewer side effects and was better tolerated by the patients.     

鞍山市铁东区公共场所使用化妆品存在的主要卫生问题及对策

目的了解鞍山市铁东区公共场所使用化妆品卫生问题,保障使用者身体健康。方法对2013年度鞍山市铁东区卫生防疫站辖区内监管的公共场所随机抽检化妆品,对公共场所使用化妆品单位数及比例,化妆品标签标识卫生问题等进行描述。结果住宿业化妆品使用情况为56%,其他三种场所100%使用。化妆品标签标识检查住宿业合格率最低,仅为50%。国产特殊用途化妆品持有效证件率仅为65%,普通的仅为62%。标签标识问题突出,进货渠道复杂。化妆品抽检合格率低。结论公共场所的化妆品卫生质量令人担忧。     

鞍山市铁东区公共场所卫生基层问题及解决建议

笔者作为基层卫生监督工作人员经过十多年的公共场所卫生监督工作,通过对鞍山市铁东区公共场所卫生监督情况进行分析。发现当前存在许多公共场所卫生监督执法困难和难题,主要表现为卫生监督队伍薄弱,新兴公共场所剧增,公共场所执法依据不确定性（无法可依）等问题。笔者提出相应的解决建议,应转变卫生监督观念,提高监督管理质量。     

肝细胞生长因子对人脐带间充质干细胞增殖、黏附及迁移影响的体外研究

目的：探讨肝细胞生长因子( HGF)对人脐带间充质干细胞( hUCMSCs)增殖、黏附及迁移能力的影响。方法按照不同腺病毒感染 hUCMSCs 分为实验组( Ad-GFP-HGF )和对照组( Ad-GFP )。以最佳感染复数转染hUCMSCs,观察细胞形态变化以及GFP蛋白的表达。比较各组细胞增殖能力、黏附能力及迁移能力。 Western Bolt检测各组细胞HGF的表达水平。结果对照组和实验组均出现了GFP的表达,实验组hUCMSCs的增殖、黏附及迁移能力均较对照组增强(P<0．05)。实验组细胞HGF的表达水平显著高于对照组(P<0．05)。结论 HGF的高表达能明显促进hUCMSCs的增殖、黏附和迁移。     

改良头皮冠状切口在颧骨复合体骨折中的应用

目的:探讨改良头皮冠状切口在各类颧骨复合体骨折坚固内固定术中的应用。方法:将87例颧骨复合体骨折病例分为改良组和传统组,分别应用改良冠状切口(42例)与传统切口(45例)进行复位和固定,对比分析改良冠状切口的优越性、可能并发症及预防措施。结果:改良组切口均Ⅰ期愈合,随访3⁶个月,面部瘢痕不明显,开口度恢复理想,咬合关系正常,术后秃发率及颞部凹陷率较低,无1例出现面神经功能障碍。传统组中,2例术后第5天出现创区感染,切口延期愈合,术后肿胀反应明显;4例患者术后3月时仍存在面神经功能障碍,术后秃发率及颞部凹陷率较高。结论:改良冠状切口较传统切口具有切口隐蔽、术野暴露好、复位精确、美观效果好、面神经损伤率低等优点,值得推广应用。     

连花清瘟制剂治疗社区获得性肺炎疗效及安全性的系统评价和Meta分析

目的 探究连花清瘟制剂治疗社区获得性肺炎的疗效和安全性。方法 系统检索PubMed、Embase、Cochrane Collaboration、中国知网、维普、万方医学网数据库中所有口服连花清瘟制剂治疗社区获得性肺炎的临床随机对照试验,时间为从建库至2023年2月,制订纳排标准并对检索结果进行筛选,采用风险评估工具（ROB）量表对最终纳入研究的方法学质量进行评价,使用R软件进行数据合并及Meta分析。结果 共纳入30篇文献,包含2 800例患者,在使用抗生素等常规治疗的基础上联合使用连花清瘟,结果显示加用连花清瘟可以提高治愈率［相对危险度（RR）=1.32,95%置信区间（95%CI）［1.23,1.42］,P<0.000 1］并缩短退热时间［均数差（MD）=-1.45,95%CI［-1.93,-0.97］,P<0.000 1］,以患者群体将退热时间分为普通人群及特殊人群亚组,结果均显示加用连花清瘟可以缩短退热时间（普通人群MD=-1.51,95%CI［-2.07,-0.94］,P<0.000 1,特殊人群MD=-1.22,95%CI［-2.16,-0.29］,P=0.010 6）,且不会增加不良反应发生率（RR=0.85,95%CI［0.62,1.15］,P<0.000 1）。使用剪补法补充9篇阴性结果虚拟文献后,加用连花清瘟仍然可以提高CAP的治愈率（RR=1.20,95%CI［1.13,1.29］,P<0.000 1）,结果稳定。结论 CAP治疗中使用抗生素的基础上加用连花清瘟可以提高治愈率并缩短退热时间。