磁共振扫描评价米诺环素对大鼠局灶性脑缺血损伤的保护作用

目的 探讨米诺环素对局灶性脑缺血再灌注损伤后的脑保护作用.方法 30只SD大鼠随机分为假手术组、生理盐水组,预处理组,30 min组,4 h组,每组6只.采用线栓法制作大脑中动脉缺血再灌注模型.用DWI,T<,2>WI,T<,1>WI增强扫描评估各组大鼠脑缺血体积,细胞毒性水肿,血管性水肿和血脑屏障破坏情况.结果 预处理组及30 min组能明显缩小脑梗死体积,减轻细胞毒性水肿,血管源性水肿及血脑屏障破坏程度,4 h组亦能减小脑梗死的体积,减轻血管源性脑水肿及血脑屏障破坏程度,但对细胞毒性水肿效果不明显.结论 米诺环素能减轻局灶性脑缺血损伤后细胞毒性、血管源性脑水肿及血脑屏障破坏程度,缩小脑梗死体积,起到神经保护作用.     

盐酸米诺环素在2型糖尿病并牙周病中的价值探讨及对患者生活质量的改善分析

目的 分析盐酸米诺环素在2型糖尿病并牙周病中的价值及对患者生活质量的改善作用.方法 根据抽签法,将2019年8月—2020年9月在该院救治的2型糖尿病并牙周病90例患者分为观察组和对照组,每组各45例.对照组采用常规治疗,观察组在对照组基础上加入盐酸米诺环素治疗.比较两组牙周相关指标、生活质量、临床指标以及临床疗效.结...     

盐酸米诺环素缓释剂治疗老年牙周炎的疗效

目的 评价盐酸米诺环素缓释剂对老年牙周炎的疗效.方法 用随机、单盲、自身对照的方法将60例牙周炎患者共120个牙周袋分成盐酸米诺环素缓释剂试验组和对照组,观察用药前后临床症状菌斑指数,牙周袋深度、附着水平、龈沟出血指数的变化.试验组和对照组全部进行牙周洁治、刮治和根面平整,试验组用盐酸米诺环素缓释剂牙周袋内上药,1次/w,共4次.结果 试验组显效率为76.7％,对照组中显效率为43.3％,组间比较差异有统计学意义(P＜0.01).盐酸米诺环素缓释剂治疗老年牙周炎的疗效明显高于对照组.结论 盐酸米诺环素缓释剂能较长时间保持局部较高浓度,发挥其抑菌作用,可作为治疗老年中、重度牙周炎的一种有效局部辅助用药.     

米诺环素对衰老痴呆大鼠脑组织eNOS、iNOS表达的影响

目的 观察米诺环素(minocycline)对衰老痴呆大鼠学习记忆和脑组织eNOS、iNOS表达的影响,探讨米诺环素对衰老痴呆脑保护作用机制.方法 Wistar大鼠随机分组:假手术组(S组)、痴呆模型组(M组)、米诺环素治疗组(MT组).酶联免疫吸附法和免疫组织化学法检测大鼠脑组织eNOS、iNOS的含量,行为学检测大鼠记忆学习改变.结果 MT、M组与S组大鼠前后两次跳台实验、水迷宫实验的结果有显著性差异(P＜0.01),MT组与M组大鼠前后两次跳台实验、水迷宫实验的检测结果有显著性差异(P＜0.01).MT组iNOS表达较M组降低(P＜0.01),MT组eNOS表达较M组增高(P＜0.01);MT组eNOS、iNOS表达较S组增高(P＜0.01);M组eNOS、iNOS表达较S组显著增高(P＜0.01).结论 米诺环素能降低衰老痴呆大鼠脑组织iNOS、增强eNOS表达抑制氧化应激反应发挥脑保护作用.     

米诺环素可以改善脑卒中预后

米诺环素是一个半合成的第2代四环素抗菌素，在多发性硬化、巴金森氏病、肌萎缩侧索硬化、脑卒中动物模型中已证明有明显保护作用，作用机制并不是抗菌作用，而是抗炎，减少神经胶质活化，减少基质金属蛋白酶，增加NO、抑制细胞凋亡。研究者收治152名急性脑卒中病人，74名服用米诺环素，77名服用安慰剂，以发病后90天神经功能检查（NIHSS）评分为首要终点，以第7天，第30天NIHSS评分，以及第7、30、90天Barthel指数（BI）与修订Rankin评分（mRS）为次要终点，比较两组差别。     

米诺环素抗兔动脉粥样硬化作用及机制

目的 观察米诺环素对动脉粥样硬化斑块干预治疗后基质金属蛋白酶的分子病理学改变,评价该药对动脉粥样硬化的治疗效果,并分析其作用机制.方法 40只新西兰兔,随机取5只设为正常对照组.另35只建立动脉粥样硬化斑块兔模型(经腹主动脉使用兔气囊致动脉去上皮化损伤,并连续用高脂饲料喂养3个月)后,除在实验过程死亡或患病5只兔外,其余随机分4组,即动脉粥样硬化模型组(8只,继续高脂喂养1个月)、普食恢复组(7只,改用常规饲料喂养1个月)、氟伐他汀组[7只,给予氟伐他汀1mg/(kg·d)连续干预治疗1个月]和米诺环素组[8只,连续给予米诺环素3mg/(kg·d)治疗1个月].各组动物分别麻醉后处死并切取腹主动脉,按常规石蜡包埋切片,以Masson染色法观察动脉粥样硬化斑块病理形态学变化,免疫组织化学法检测动脉粥样硬化斑块内炎症细胞及基质金属蛋白酶表达水平,原位杂交Tunel染色法检测细胞凋亡.结果 动脉管壁组织经Masson染色观察显示,正常对照组未见异常病理变化,模型组和普食恢复组均呈现典型动脉粥样硬化病变特征,而米诺环素和氟伐他汀两治疗组病变明显减轻,尤以前者改善突出.各组动脉粥样硬化斑块巨噬细胞含量及基质金属蛋白酶3和9的表达水平与病变程度相一致,前三者间在各组动物中的表达水平均呈正相关关系(P<0.001).斑块内巨噬细胞含量、基质金属蛋白酶3和9的水平在米诺环素组均显著低于模型组和普食恢复组(P<0.05),且在米诺环素组可见平滑肌细胞明显增加.结论 米诺环素具有改善动脉粥样硬化病变程度和稳定动脉粥样硬化斑块的作用.     

米诺环素对黑质急性炎症的保护作用及与自噬相关性研究

目的观察米诺环素对脂多糖(Lipopolysaccharide,LPS)模型小鼠黑质急性炎症的保护作用,并探讨其作用机制。方法选取3月龄C57BL雄性小鼠,设立对照组、LPS组、中剂量米诺环素组(50 mg M组)、高剂量米诺环素组(75 mg M组)及75 mg M+LPS组、50 mg M+LPS组、25 mg M+LPS组,其中LPS组为单次腹腔注射LPS(5 mg/kg)。随后进行爬杆试验的行为学检测;并采用免疫组化法观察黑质部位小胶质细胞数量,免疫印迹法检测小鼠黑质部位α-突触核蛋白(α-synuclein)、LC3-Ⅱ、P62和HDAC6蛋白表达量。结果与LPS组相比,75mg M+LPS组小鼠爬杆速度下降更显著(P0. 05),25 mg M+LPS组及50 mg M+LPS组小鼠爬杆速度则较LPS组明显加快(P0. 01); 25 mg M+LPS组及50 mg M+LPS组小鼠黑质部位小胶质细胞的活化数量减少,且α-synuclein、LC3-Ⅱ、p62、HDAC6蛋白水平下降(P0. 01),而75 mg M+LPS组α-synuclein、LC3-Ⅱ、p62、HDAC6蛋白水平有所增加(P0. 05)。结论低、中剂量米诺环素不仅能减轻LPS单次腹腔注射造成的小鼠黑质部位急性炎症反应,而且能缓解该部位出现的自噬功能障碍,减少p62和α-synuclein黑质部位的积聚,改善小鼠的运动能力。     

耐亚胺培南鲍曼不动杆菌的体外联合药物敏感试验

目的 了解体外联合药物敏感试验对耐亚胺培南鲍曼不动杆菌的效果,为临床抗感染治疗提供依据.方法 收集自2007年3月至2008年2月耐亚胺培南鲍曼不动杆菌27株标本,以E test法和琼脂稀释法测定7种常用抗菌药物的最低抑菌浓度(MIC),以肉汤稀释棋盘法进行联合药物敏感试验,用时间杀菌试验检测米诺环素和头孢哌酮-舒巴坦的协同率.结果 肉汤稀释棋盘法结果提示,米诺环素与头孢哌酮-舒巴坦、阿米卡星、环丙沙星的协同率分别为74.1%、28.0%、48.1%,阿米卡星与头孢哌酮-舒巴坦、环丙沙星的协同率分别为23.1%、37.0%,头孢哌酮-舒巴坦与环丙沙星的协同率为7.1%.米诺环素与头孢哌酮-舒巴坦联合后药物浓度均降至非耐药范围内.时间杀菌试验结果提示,米诺环素和头孢哌酮-舒巴坦的协同率为100%.结论 针对临床上多重耐药鲍曼不动杆菌的感染,推荐使用米诺环素加头孢哌酮-舒巴坦进行联合治疗.     

盐酸米诺环素对2型糖尿病牙周病的治疗效果分析

目的研究在2型糖尿病牙周病患者的治疗过程中,应用盐酸米诺环素辅助治疗的效果。方法选取牙周炎伴2型糖尿病患者共46例,将其按照就诊时间平均分成研究组(n=23)和参照组(n=23),研究组患者行盐酸米诺环素辅助治疗,参照组行基础治疗,对两组患者治疗后的牙周指数以及总有效率指标进行统计评价。结果加行盐酸米诺环素的研究组其治疗总有效率以及牙周指数显著优于参照组患者,两组数据对比呈现为差异有统计学意义(P0.05)。结论将盐酸米诺环素应用于2型糖尿病牙周病患者的治疗中,具有积极的临床诊治意义,患者恢复情况良好,这对于临床研究具有重要作用。     

本院53株呼吸道嗜麦芽窄食单胞菌体外药敏结果分析

目的 分析嗜麦芽窄食单胞菌的药敏结果.方法 分析从临床标本中分离的53株嗜麦芽窄食单胞菌药敏资料.结果 嗜麦芽窄食单胞菌体外对左氧氟沙星敏感性最高,达90.6％;对复方新诺明、米诺环素和头孢哌酮/舒巴坦等敏感性占第2位,达84.9％.对哌拉西林、头孢噻肟、头孢他啶、头孢吡肟和环丙沙星等敏感性均不超过50％.中介率最高者为头孢他啶,为40.0％.耐药率最低为米诺环素(5.7％),其次为左氧氟沙星和头孢哌酮/舒巴坦(均9.4％),复方新诺明排第3位(15.1％).结论 对嗜麦芽窄食单胞菌敏感性较高的抗菌药为左氧氟沙星、复方新诺明、米诺环素.耐药性较低者包括米诺环素、左氧氟沙星、头孢哌酮/舒巴坦及复方新诺明等.     

Potential role of neuroprotective agents in the treatment of patients with acute ischemic stroke

Opinion statement Currently, intravenous recombinant tissue plasminogen activator is the only US Food and Drug Administration-approved therapy for acute ischemic stroke. Although efficacious, its usefulness is limited, mainly because of the very limited time window for its administration. Neuroprotective treatments are therapies that block the cellular, biochemical, and metabolic elaboration of injury during or after exposure to ischemia, and have a potential role in ameliorating brain injury in patients with acute ischemic stroke. More than 50 neuroprotective agents have reached randomized human clinical trials in focal ischemic stroke, but none have been unequivocally proven efficacious, despite successful preceding animal studies. The failed neuroprotective trials of the past have greatly increased understanding of the fundamental biology of ischemic brain injury and have laid a strong foundation for future advance. Moreover, the recent favorable results of human clinical trials of hypothermia in human cardiac arrest and global brain ischemia have validated the general concept of neuroprotection for ischemic brain injury. Recent innovations in strategies of preclinical drug development and clinical trial design that rectify past defects hold great promise for neuroprotective investigation, including novel approaches to accelerating time to initiation of experimental treatment, use of outcome measures sensitive to treatment effects, and trial testing of combination therapies rather than single agents alone. Although no neuroprotective agent is of proven benefit for focal ischemic stroke, several currently available interventions have shown promising results in preliminary trials and may be considered for cautious, off-label use in acute stroke, including hypothermia, magnesium sulfate, citicoline, albumin, and erythropoietin. Overall, the prospects for safe and effective neuroprotective therapies to improve stroke outcome remain promising.     

Hormonal replacement therapy and Alzheimer's disease. All quiet on the western front?

Although there are plausible biological mechanisms for a neuroprotective effect of estrogens, most therapeutic trials conducted to date have been unable to conclude that hormone replacement therapy (HRT) could significantly slow down the progression of Alzheimer's disease or decrease the severity of dementia. On the other hand, four meta-analyses of the principal epidemiological studies conducted to date suggested a 29 to 44% decreased risk of developing Alzheimer's disease among HRT users. Nevertheless, the results of the recent blind controlled trial, "Women's health initiative memory study" (WHIMS) including 4532 postmenopausal women indicate a two-fold increase in dementia after 4.2 years of treatment. These results do not allow to definitively conclude as to whether HRT could prevent or not the risk of developing dementia. There are several reasons for that, including the heterogeneity of the population studied and of the HRT protocols and also the presence of several methodological limitations. Furthermore, most therapeutic trials could probably not be adapted to detect a neuroprotective effect of HRT (if any). It is also probably the case for the WHIMS considering (i) the population studied (women at cardiovascular risk, aged 65 years and older, very far from the menopause and thus from both the usual clinical situation and the critical period where one might expect a neuroprotective effect to occur), and (ii) the duration and the type of HRT (oral Premarin + medroxyprogesterone, whose side-effects could be extensive, whose neuroprotective properties are not recognized) which is not representative of the clinical practice relating to HRT in France (generally natural steroids, e.g. estradiol [transdermal] + progesterone). On the basis of the data of the literature, there is currently no reason to propose HRT for the prevention of Alzheimer's disease.     

雌激素神经保护作用研究进展

多数流行病学调查和基础研究都表明,雌激素具有神经保护作用,对其在脑血管病中的应用也持肯定态度.然而,大型临床试验却显示雌激素的应用弊大于利,甚至有导致卒中的风险.文章就近年来有关雌激素神经保护作用的正反两方面相关研究做了综述.     

缺血性卒中的神经保护药:现状与挑战

作为缺血性卒中的一种治疗策略,神经保护药被用于拮抗脑缺血时的一系列有害分子生物学事件.文章综述了神经保护药治疗急性缺血性卒中的现状,以及从临床前研究证据向临床试验转化所面临的挑战.应将血管内皮细胞-胶质细胞-神经元作为一个整体进行研究.     

自由基清除剂依达拉奉对脑缺血的治疗作用

自由基在各种缺血性损伤中起重要作用。自由基清除剂依达拉奉打破了神经保护治疗无效的悲观现状。动物实验和临床试验表明 ,依达拉奉在治疗缺血再灌注损伤中的有效。     

脑缺血的神经保护治疗研究现状

目前,在时间窗内进行溶栓治疗是FDA推荐的唯一有效的脑缺血急性期治疗方案,但溶栓时间窗限制了其临床应用,而神经保护则具有更为广泛的适应证,成为脑缺血治疗的研究热点之一.文章综述了目前国内外尚处于实验阶段和已应用于临床的神经保护治疗方法.     

Nonulcer dyspepsia

Nonulcer dyspepsia is a common condition in clinical practice. It is a heterogeneous disorder, and no single therapeutic agent is effective in all patients. The treatment of nonulcer dyspepsia is still dissatisfactory. Eradication of Helicobacter pylori organisms has a limited role and little effect. Antisecretory therapy has a modest effect in alleviating symptoms. Prokinetic agents may be effective, but selection bias in the trials performed to date may exaggerate their benefit. Partial 5-HT₄ agonists stimulate gastric emptying and may also affect gastric accommodation. They are promising but need further study. Data are limited on 5-HT₃ antagonists and hypnotherapy. New treatment approaches are necessary for this common and often chronic condition.     

The effectiveness of mindfulness-based stress reduction intervention on alleviating anxiety and depression in postoperative patients with cervical cancer: A protocol for systematic review and meta-analysis

Background:Surgical treatment for cervical cancer, as a stressor, largely leads to strong psychological reactions to stress like anxiety and depression. Whether mindfulness-based stress reduction (MBSR) can alleviate anxiety and depression in patients after cervical cancer surgery is controversial. Therefore, we aim to perform a meta-analysis involving randomized controlled trials analyzing the effect of MBSR on alleviating anxiety and depression in patients after cervical cancer surgery, thus providing evidence-based medical evidences for nonpharmacological interventions.Methods:Randomized controlled trials analyzing the effect of MBSR on alleviating anxiety and depression in patients after cervical cancer surgery will be searched in online databases, including Cochrane Central Register of Controlled Trials Repositories, PubMed, Embase, Web of Science, Chinese Science Citation Database, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientific Journal Database, and Wan Fang Data. After screening eligible studies, we will perform a meta-analysis on the effect of MBSR on alleviating anxiety and depression in patients after cervical cancer surgery.Results:The results of this meta-analysis will be submitted to a peer-reviewed journal for publication.Conclusion:This study will provide reliable evidence-based evidences for the effects of MBSR on alleviating anxiety and depression in patients after cervical cancer surgery.Ethics and dissemination:Ethical approval was not required for this study. The systematic review will be published in a peer-reviewed journal, presented at conferences, and shared on social media platforms.OSF Registration number:DOI 10.17605/OSF.IO/EXUM3.     

Report of an international working group to standardize response criteria for myelodysplastic syndromes

Standardized criteria for assessing response are essential to ensure comparability among clinical trials for patients with myelodysplastic syndromes (MDS). An international working group of experienced clinicians involved in the management of patients with MDS reviewed currently used response definitions and developed a uniform set of guidelines for future clinical trials in MDS. The MDS differ from many other hematologic malignancies in their chronicity and the morbidity and mortality caused by chronic cytopenias, often without disease progression to acute myeloid leukemia. Whereas response rates may be an important endpoint for phase 2 studies of new agents and may assist regulatory agencies in their evaluation and approval processes, an important goal of clinical trials in MDS should be to prolong patient survival. Therefore, these response criteria reflected 2 sets of goals in MDS: altering the natural history of the disease and alleviating disease-related complications with improved quality of life. It is anticipated that the recommendations presented will require modification as more is learned about the molecular biology and genetics of these disorders. Until then, it is hoped these guidelines will serve to improve communication among investigators and to ensure comparability among clinical trials. (Blood. 2000;96:3671-3674)