Apogossypolone, a novel inhibitor of anfiapoptotic Bcl-2 family proteins, induces autophagy of PC-3 and LNCaP prostate cancer cells in vitro

Limited treatment options are available for aggressive prostate cancer. Gossypol has been reported to have a potent anticancer activity in many types of cancer. It can increase the sensitivity of cancer cells to alkylating agents, diminish multidrug resistance and decrease metastasis. Whether or not it can induce autophagy in cancer cells has not yet been determined. Here we investigated the antiproliferative activity of apogossypolone （ApoG2） and （-）-gossypol on the human prostate cancer cell line PC3 and LNCaP in vitro. Exposure of PC-3 and LNCaP cells to ApoG2 resulted in several specific features characteristic of autophagy, including the appearance of membranous vacuoles in the cytoplasm and formation of acidic vesicular organelles. Expression of autophagy-associated LC3-Ⅱ and beclin-1 increased in both cell lines after treatment. Inhibition of autophagy with 3-methyladenine promoted apoptosis of both cell types. Taken together, these data demonstrated that induction of autophagy could represent a defense mechanism against apoptosis in human prostate cancer cells.     

Functional urinary and fecal incontinence in neurologically normal children: symptoms of one 'functional elimination disorder'?

OBJECTIVE: To clarify the relationship between disordered defecation and non-neuropathic bladder-sphincter dysfunction (NNBSD) by comparing the prevalence of symptoms of disordered defecation in children with NNBSD before and after treatment for urinary incontinence (UI), and assessing the effect of such symptoms on the cure rate for UI. PATIENTS AND METHODS: In the European Bladder Dysfunction Study, a prospective multicentre study comparing treatment plans for children with NNBSD, 202 children completed questionnaires on voiding and on defecation, at entry and after treatment for UI. Four symptoms of disordered defecation were evaluated; low defecation frequency, painful defecation, fecal soiling, and encopresis. RESULTS: At entry, 17 of the 179 children with complete data sets had low defecation frequency and/or painful defecation (9%), classified as functional constipation (FC). Of the 179 children, 57 had either isolated fecal soiling or soiling with encopresis (32%), classified as functional fecal incontinence (FFI). After treatment for UI, FFI decreased to 38/179 (21%) (statistically significant, P = 0.035); for FC there were too few children for analysis. After treatment for UI, 19 of the 179 children (11%) reported de novo FFI. Symptoms of disordered defecation did not influence the cure rate of treatment for UI. CONCLUSIONS: FFI improved significantly after treatment for UI only, but not in relation to the outcome of such treatment. FFI did not influence the cure rate for UI. There was little to support a causal relation between disordered defecation and NNBDS ('functional elimination syndrome').     

肛瘘肛周脓肿术后应用复方角菜酸脂乳膏的效果分析

目的:观察复方角菜酸脂乳膏对肛瘘和肛周脓肿术后治疗的效果,寻找一种安全有效的术后换药药物.方法:将188例后位单纯性肛瘘或肛周脓肿一次性根治术后患者,分为复方角菜酸脂乳膏治疗组和中药换药对照组,对其愈合时间和并发症进行对比观察.结果:复方角菜酸脂乳膏在肛瘘或肛周脓肿术后伤口的促进愈合和减低并发症发生等方面优于传统中药换药(P＜0.01).结论:复方角菜酸脂乳膏是一种安全、有效的肛瘘和肛周脓肿术后换药药物,尤其在纤维增殖期(中期)、上皮覆盖期(后期)作用明显,具有明显的镇痛、促进愈合作用,并有效防止湿疹的出现.     

17 β雌二醇通过丝裂原活化蛋白激酶抑制前列腺癌细胞系PC3增殖

目的探讨丝裂原活化蛋白激酶在17β雌二醇(E2)抑制前列腺癌PC3细胞生长中的作用。方法检测不同浓度E2作用不同时间后PC3细胞生长抑制率。流式细胞仪分析细胞周期分布,TUNEL染色检测凋亡。Western blot检测ERK1/2,JNK和p38活性。RT-PCR法检测雌激素受体(ER)α、ERβ、P21WAF1和cyclinD1的表达。结果E2抑制PC3细胞增殖,并且可以激活ERK1/2、JNK和p38。处理因素作用48h后,对照组、E2、E2 PD98059、E2 SP600125、E2 SB203580组细胞的凋亡率分别为(0.9±0.1)%;(23.0±1.4)%;(30.0±1.2)%;(10.6±0.8)%和(14.6±0.7)%,(P<0.05)。E2使细胞阻滞在G1期,PD98059、SP600125、SB203580分别预处理1h后细胞分别进一步阻滞在G1期;轻度阻滞在G1期和进入S期。RT-PCR发现PC3细胞表达ERα和ERβ,E2、E2 PD98059、E2 SP600125、E2 SB203580组中cyclinD1、P21WAF1基因表达分别为对照组的(0.42±0.03)、(3.13±0.02)倍;(0.21±0.03)、(3.08±0.05)倍;(0.43±0.01)、(1.31±0.04)倍;(2.81±0.02)、(3.14±0.02)倍(P<0.05)。结论E2激活JNK增加P21WAF1基因表达,并激活p38抑制cyclinD1表达,使细胞阻滞在G1期,JNK和p38通路还介导E2引起PC3细胞凋亡。同时E2又可激活ERK1/2,轻度拮抗上述作用。     

术中B超辅助切除脑动静脉畸形

目的:探讨术中实时超声在脑动静脉畸形(AVM)外科治疗中的应用价值。方法:15例脑AVM患者接受显微外科治疗,术中病变切除前行超声检查,以定位AVM边界与周围脑组织结构关系;辨别供血动脉和引流静脉;确定血肿与AVM的关系。病变切除后重复超声检查AVM残留与否,并与术后血管造影结果对比。结果:15例患者病变均在实时超声导航下获得全切除。畸形血管团可被准确定位和界定范围,血肿区为高回声无血流信号,供血动脉血流动力学有别于正常血管,术中超声影像上病变的全切除为血管造影所证实。结论:术中实时超声能对脑AVM进行准确定位,并可判定脑AVM的全切除;AVM术中定位可为术前MRI、DSA起到有价值的补充。     

Prognostic value of 1H-MRS in neonatal encephalopathy

The aim of this study was to determine the prognostic value of proton magnetic resonance spectroscopy in neonatal encephalopathy. Studies were carried out in 11 consecutive term newborns with encephalopathy probably caused by hypoxic-ischemic injury. The clinical evaluation included pregnancy data, labor conditions, encephalopathy grade, presence of seizures, and necessity of antiepileptic drug therapy. Polygraphic recordings were obtained in all cases. Interest areas evaluated by spectroscopy were the basal ganglia and thalami. Among the cases, N-acetylaspartate/creatine, choline/creatine, and lactate/creatine ratios were calculated and related to the clinical variables, polygraphic recordings, and 6-month neurodevelopmental outcome. Abnormal follow-up occurred in 5 of 11 patients (45.4%) and was clearly related to an Apgar score <5 at 5 minutes (P = 0.003), encephalopathy grade (P = 0.02), early neonatal seizures (P = 0.02), and antiepileptic therapy (P = 0.01). No relationship was observed between spectroscopy results and polygraphic recordings profile. The lowest mean N-acetylaspartate/creatine ratio was observed in four of five patients with an adverse outcome and, although not statistically significant, demonstrated a clear trend to unfavorable follow-up (t test = 0.06). The choline/creatine ratios could not be related to follow-up in our sample. The most consistently observed abnormality on the spectra was the presence of the lactate peak in four of five patients with unfavorable outcome, with a high relative risk to determine evolution in the sample, relative risk 7.0 (chi2 = 0.01, 95% confidence interval = 1.1-42.9).     

Impact of Alzheimer's pathology on cognitive trajectories in nondemented elderly

OBJECTIVE: Some individuals who are asymptomatic for dementia while alive have substantial Alzheimer's disease (AD) neuropathology at autopsy. We investigated whether cognitive trajectories differ between clinically normal elderly individuals with and without AD neuropathology and how they compare with trajectories of clinically impaired individuals before dementia diagnosis. METHODS: Eighty-one elderly participants in the Baltimore Longitudinal Study of Aging (BLSA) were followed prospectively with neurological and neuropsychological assessments before autopsy evaluation at death. Trajectories of cognitive change were estimated for a number of domains using cognitive data before a clinical diagnosis of dementia. RESULTS: Clinically normal elderly individuals with and without AD-type neuropathology have similar cognitive trajectories across different cognitive domains. In contrast, individuals with mild cognitive impairment/AD show steeper rates of longitudinal decline in several aspects of cognition compared with clinically normal elderly individuals regardless of whether the latter have AD neuropathology. Moreover, the cognitive differences between impaired and unimpaired groups can be detected years before a diagnosis of dementia. INTERPRETATION: Clinically normal individuals with and without AD neuropathology do not differ in rates of cognitive decline across a number of cognitive domains. Understanding the factors that protect some individuals with AD pathology from cognitive impairment may contribute to the maintenance of cognitive health in the elderly.     

国产微螺钉种植体支抗稳定性的临床分析

目的：统计国产微螺钉种植体的脱落率,分析不同加载时机对种植体稳定性的影响。寻找临床上的最佳加载时机。方法：采用回顾性分析的方法,对39例就诊于西安交通大学口腔医院正畸科的患者植入的微螺钉种植体支抗资料进行回顾,分类并统计,根据不同加载情况将种植体归为即刻加载组,两周加载组和不加载组3组,分别对3组种植体临床脱落情况进行统计,得出各组种植体脱落率;根据实验研究的结果,分析影响稳定性的因素。比较不同加载状态对种植体稳定性的影响以及可能影响脱落率的因素。结果：两周后加载的种植体脱落率表现得最低为10%,即刻加载组脱落率为50%;而不加力组脱落率最高为79%。结论：种植体植入后两周加载对于种植体稳定性比不加载稳定性要高;即刻加力的种植体稳定性比不加力的种植体稳定性差。     

Plain Radiograph Fails to Reflect the Alignment and Advantages of Navigation in Total Knee Arthroplasty

The study purposed to determine if a navigation in total knee arthroplasty (TKA) leads to accurate limb alignment and component position than the conventional technique as measured by full length standing radiographs and to evaluate the correlation between navigation and radiographic measurements. A total of 160 knees underwent navigation (n = 80) or conventional (n = 80) TKAs. The frontal femoral alignment was more accurate in navigation TKAs, whereas mechanical axis and frontal tibial alignment were similar in both techniques. Although the intraoperative navigation alignment showed no outliers, postoperative radiographic measure resulted as much as 20% of outliers, and there was no correlation between the two measurements. This lack of correlation and inherent limitations in measuring TKA alignment may bring to question if plain radiograph are useful to determine if alignment achieved by navigation is accurate.     

克罗米芬联合己酮可可碱治疗特发性少、弱精子症的临床研究

目的探讨克罗米芬＋己酮可可碱治疗特发性少、弱精子症的临床效果。方法选取门诊少、弱精子症患者300例,随机分为两组,A组（n=156）口服克罗米芬（50mg,q.d）＋己酮可可碱缓释片（400mg,b.i.d）＋VitE（100mg,t.i.d）;B组（n=144）只服用VitE（100mg,t.i.d）,共3个月,比较两组间各自用药前后的精液参数。进一步将A组患者分成少精子症（n=69）和弱精子症（n=87）2组,比较两者联合药物治疗前后精液各参数。结果（1）联合药物治疗3个月后,A组的精子活率、a级活动精子率、（a＋b）级活动精子率等参数明显增加（P〈0.05）,但精液量、精子密度和活动精子总数无明显差异（P〉0.05）;B组精液各参数没有明显变化。（2）少精子症组联合药物治疗后精子密度、精子活率、活动精子总数明显提高（P〈0.05）;而弱精子症组仅精子活率明显提高（P〈0.05）,精子密度和活动精子总数没有明显变化（P〉0.05）。结论克罗米芬＋已酮可可碱能显著提高特发性少精子症患者的精子密度、精子活率、活动精子总数,以及特发性弱精子症的精子活率。