骨巨细胞瘤缺氧诱导因子1α和VEGF表达及与肿瘤血管密度关系探讨

目的：探讨缺氧诱导因子-1α（hypoxia inducible factor-1α,HIF-1α）和血管内皮细胞生长因子（vascular endothelial cell growth factor,VEGF）在骨巨细胞瘤中的表达规律及与肿瘤血管密度的关系。方法：选用2003—2007年经手术切除并经病理证实为骨巨细胞瘤的51例患者的组织石蜡包块,病理分级（Jaffe标准）Ⅰ级15例,Ⅱ级17例,Ⅲ级19例,应用免疫组织化学方法。检测骨巨细胞瘤中HIF-1α、VEGF和CD34的表达,统计肿瘤微血管密度（microvessel density,MVD）,检测骨巨细胞瘤HIF-1α、VEGF阳性与阴性标本中MVD并进行组间统计分析。结果：骨巨细胞瘤HIF-1α和ⅦGF总阳性率分别为62．7％（32／51）和71．4％（35／51）,Ⅲ级骨巨细胞瘤HIF-1α和VEGF阳性表达率均显著高于Ⅰ级和Ⅱ级骨巨细胞瘤。HIF-1α与VEGF表达均阳性者28例。HIF-1α与VEGF表达均阴性者12例,HIF-1α与VEGF表达分布有相关一致性。骨巨细胞瘤MVD为25．7±4．2／高倍视野,Ⅲ级骨巨细胞瘤MVD（37．3±3．6／高倍视野）显著高于Ⅰ级骨巨细胞瘤（18．2±3．4／高倍视野）和Ⅱ级骨巨细胞瘤（19．4±2．6／高倍视野）。HIF-1α阳性骨巨细胞瘤MVD（32．2±4．2,高倍视野）显著高于HIF-1α阴性骨巨细胞瘤（14．7±2．5／高倍视野）,VEGF阳性骨巨细胞瘤MVD（30．6±3．7／高倍视野）显著高于VEGF阴性骨巨细胞瘤（14．9±2．6／高倍视野）。结论：HIF-1α和VEGF表达与骨巨细胞瘤的病理分级相关,呈肿瘤特异性表达,与肿瘤血管生成密切相关。     

靶血管栓塞后手术治疗骶骨肿瘤的康复指导

骶骨肿瘤手术困难、出血多、易损伤脏器,患者功能恢复较差[1].作者自1993年7月～2004年10月对采用靶血管栓塞后再手术切除的58例骶骨肿瘤患者进行康复指导,取得满意疗效. 资料与方法 1.一般资料 本组58例,男23例,女35例,年龄23～74岁.病理诊断:脊索瘤28例,骨巨细胞瘤10例,恶性淋巴瘤5例,骨肉瘤及软骨肉瘤各2例,滑膜肉瘤1例,转移性肿瘤3例.术后复发7例(脊索瘤4例,骨巨细胞瘤3例).     

p63和S-100蛋白在骨巨细胞瘤鉴别诊断中的作用

目的：研究p63和S-100在骨巨细胞瘤的表达情况,从而探讨这两种抗体是否可在骨巨细胞瘤的鉴别诊断中起辅助作用从而应用于临床病理诊断。方法通过免疫组化的方法,对骨巨细胞瘤和其他一些富于巨细胞的骨肿瘤进行p63和S-100染色比较。结果 p63在骨巨细胞瘤和软骨母细胞瘤中表达阳性（P＞0.05）,在动脉瘤样骨囊肿,骨的纤维组织细胞瘤和骨肉瘤中表达阴性（P＜0.05）。S-100在骨巨细胞瘤中表达阴性,在软骨母细胞瘤中表达阳性（P＜0.05）,而在动脉瘤样骨囊肿等其他富于巨细胞肿瘤中表达阴性（P＞0.05）。结论联合应用p63和S-100或许在骨巨细胞瘤的鉴别诊断中有辅助作用。     

原发性骨胸壁肿瘤的诊断与治疗

原发性骨胸壁肿瘤临床上较少见，我院1975年11月至1995年10月手术切除并经病理证实为原发性骨胸壁肿瘤63例，现分析如下。临床资料63例中男37例，女26例。年龄7～61岁。良性组平均年龄34．3岁，恶性组平均年龄45．2岁。病程14天～20年，其中良性组病程平均23．8个月，恶性组平均7．6个月。主诉胸痛34例，胸壁肿块36例，二者均有18例。本组肋骨肿瘤58例，胸骨肿瘤5例。按病理分类良性肋骨肿瘤52例中软骨瘤20例，骨纤维结构不良14例，骨软骨瘤5例，骨囊肿4例，骨嗜伊红性肉芽肿4例，巨细胞瘤2例，骨纤维瘤、血管瘤和黄色瘤各1例；恶性肋骨肿瘤…     

良恶性骨肿瘤P27蛋白表达与DNA含量研究

目的：探讨良恶性骨肿瘤细胞P27蛋白表达与DNA含量的关系及意义。方法：取骨肿瘤新鲜标本52例（骨软骨瘤10例,骨巨细胞瘤10例,骨肉瘤20例,其他恶性肿瘤12例）,运用流式细胞术、单克隆抗体技术和定量免疫荧光技术,检测瘤细胞P27蛋白表达、S或细胞百分数（SPF）及DNA含量（DI）,分析三者之间的关系。结果：52例骨肿瘤P27蛋白表达的平均FI值为1．37（骨软骨瘤2．24±0．38,骨巨细胞瘤1．79±0．36,骨肉瘤1.06±039,其他恶性骨肿瘤1．01±0．45）;P27＜1．37组25例,均为恶性骨肿瘤;P27＜1．37组的DI、SPF均明显高于P27≥1．37组（P＜0．001）。结论：P27蛋白表达减少,导致细胞周期失调,S期细胞增多,DNA合成增强,细胞过度增生、恶度,可能是骨肿瘤发生发展的原因之一。     

骶骨原发性肿瘤的外科治疗

目的 探讨骶骨原发性肿瘤的临床特征、诊断及治疗方法。方法 分析18例骶骨原发性肿瘤患者临床资料，其中脊索瘤12例，骨巨细胞瘤5例，骨肉瘤1例。均行肿瘤切除，术后放疗或化疗，随访4～8年。结果 本组18例除1例脊索瘤及2例骨巨细胞瘤患者术后局部复发，再次手术切除，其他患者经随访术后无复发。结论 脊索瘤在原发性骶骨肿瘤中的发病率居首，应采取以手术为主的综合治疗。     

腓骨远端骨肿瘤及肿瘤样病变病例分析

目的探讨腓骨远端骨肿瘤及肿瘤样病变的病种、发病比率及其影像表现。方法对河北医科大学第三医院统计的4172例骨肿瘤及肿瘤样病变中的28例腓骨远端病例进行分析。结果腓骨远端骨肿瘤发病率为0．67％,良性居多,按发病比率由高至低排在前7位的依次为骨软骨瘤、骨囊肿、骨肉瘤、Ewing肉瘤、骨纤维异常增殖症、软骨粘液样纤维瘤和骨巨细胞瘤,其部位及影像表现均有一些各自的特点。结论腓骨远端骨肿瘤及肿瘤样改变,结合其部位特点、影像表现,并运用病种的发病比率的高低顺序综合考虑,对其诊断会有所帮助。     

X线、CT、核磁共振成像检查对骨肿瘤诊断价值比较

目的评价X线、CT、核磁共振成像（MRI）影像学检查方法对骨肿瘤的诊断价值。方法42例骨肿瘤患者均行X线检查,CT检查39例,MRI检查12例,并与手术病理结果相对照,比较三种影像学方法的诊断价值。结果42例中良性骨肿瘤11例（骨巨细胞瘤6例,骨软骨瘤5例）,恶性骨肿瘤18例（骨肉瘤14例,软骨肉瘤4例）,骨转移瘤13例。X线、CT和MRI诊断正确率分别为76．2％、92．3％和100．0％。结论三种影像学检查均可早期发现、早期诊断骨肿瘤,为临床提供可靠治疗依据。     

跟骨恶性肿瘤的影像诊断

目的总结跟骨恶性肿瘤的病理类型和影像特点,提高跟骨恶性肿瘤影像学诊断正确率。方法经手术病理证实的跟骨恶性肿瘤27例,男19例,女8例。年龄9～72岁,中位年龄45岁。全部患者均行X线照片检查;CT检查20例,其中12例行增强扫描;MRI平扫+增强扫描18例,其中16行DWI检查。将全部影像检查资料进行回顾性分析。结果骨肉瘤8例,软骨肉瘤5例,纤维肉瘤及淋巴瘤和恶性骨巨细胞瘤各3例,尤文肉瘤和浆细胞瘤各2例,转移瘤1例。影像学表现为跟骨骨质破坏、瘤骨形成、骨膜异常、钙化、病理骨折及软组织肿块。结论①跟骨恶性肿瘤中骨肉瘤最常见。②跟骨恶性肿瘤影像学表现中以骨质破坏为主,瘤骨形成及骨膜异常、软组织肿块程度轻。③跟骨恶性肿瘤中,病理骨折多见且发生早,易合并出血。④跟骨恶性肿瘤的增强扫描中,跟骨内肿块与跟骨外软组织肿块强化程度一致。     

应用人工关节置换治疗骨肿瘤

目的探讨人工关节置换在骨肿瘤保肢术中的应用价值。方法应用瘤段切除加人工关节置换重建骨缺损治疗骨肿瘤15例，其中骨巨细胞瘤6例，骨肉瘤4例，恶性纤维组织细胞瘤1例，恶性骨巨细胞瘤1例，转移癌1例，家族遗传性骨软骨瘤恶变1例，骨巨细胞瘤铰链式膝关节置换术后假体断裂1例。股骨远端7例，胫骨近端4例，股骨近端2例，肱骨近端2例。铰链式膝关节5例，旋转-铰链式膝关节4例，大段同种异体骨 旋转铰链式膝关节2例，全髋关节2例，人工肱骨头2例。结果随访5～69个月，平均38个月；死于原发病灶1例，死于远处转移2例；局部复发1例；感染2例，其中1例行截肢术，1例窦道形成。参照Enneking评定标准进行功能评定，优：5例，良：6例，尚可：2例，差：2例。优良率达73．3％。结论人工关节置换保技术是骨肿瘤治疗的有效方法。     

Affective and Anxiety Disorders and Alcohol and Drug Dependence:

Depression and anxiety frequently coexist in patients with substance use disorders. This clinically-oriented article examiens the relationship between these conditions and emphasizes data showing that substances of abuse can cause signs and symptoms of both depression and anxiety. These substance-related syndromes appear to have a different course and prognosis than uncomplicated, independent anxiety and major depressive disorders, and clinicians should consider the role of alcohol and other drugs in all patients presenting with these complaints. The authors will also outline an approach for diagnosing and managing patients with the combination of a substance use and depressive or anxiety disorder.     

Modelling and simulation of variability and uncertainty in toxicokinetics and pharmacokinetics

Two important methodological issues within the framework of the variability and uncertainty analysis of toxicokinetic and pharmacokinetic systems are discussed: (i) modelling and simulation of the existing physiologic variability in a population; and (ii) modelling and simulation of variability and uncertainty when there is insufficient or not well defined (e.g. small sample, semiquantitative, qualitative and vague) information available. Physiologically based pharmacokinetic models are especially suited for separating and characterising the physiologic variability from the overall variability and uncertainty in the system. Monte Carlo sampling should draw from multivariate distributions, which reflect all levels of existing dependencies in the intact organism. The population characteristics should be taken into account. A fuzzy simulation approach is proposed to model variability and uncertainty when there is semiquantitative, qualitative and vague information about the model parameters and their statistical distributions cannot be defined reliably.     

Acamprosate and naltrexone treatment effects on ethanol and sucrose seeking and intake in ethanol-dependent and nondependent rats

Rationale  Two pharmacotherapies are approved for treating alcohol craving (acamprosate and naltrexone), but both have shown mixed findings in animals and humans. Objectives  The present experiments utilized a “reinforcer blocking” approach (i.e., rats were able to consume ethanol during treatment) to better understand the efficacy of these treatments for ethanol seeking and drinking using ethanol-dependent and nondependent rats. Materials and methods  In “nondependent” experiments, drugs (acamprosate 50, 100, and 200 mg/kg; naltrexone 0.1, 0.3, and 1.0 mg/kg) were administered over 3-week periods prior to operant sessions with a low response requirement to gain access to reinforcers for 20 min. For “dependent” experiments, rats were made dependent in vapor/inhalation chambers. Results  Acamprosate and naltrexone had similar effects on intake in nondependent and dependent rats; neither drug was selective for ethanol over sucrose drinking. In nondependent animals, naltrexone was more efficacious at more doses than acamprosate, and acamprosate’s effects were limited to a dose that also had adverse effects on body weight. Both pharmacotherapies showed more selectivity when examining reinforcer seeking. In nondependent rats, acamprosate and naltrexone had response-attenuating effects in ethanol, but not sucrose, groups. In dependent animals, acamprosate had selective effects limited to a decrease in sucrose seeking. Naltrexone, however, selectively decreased ethanol-seeking in nondependent rats. Conclusions  The naltrexone-induced decreases in seeking suggested a change in incentive motivation which was selective for ethanol in nondependent rats. The “nondependent” paradigm may model early stages of “problem drinking” in humans, and the findings suggest that naltrexone could be a good intervention for this level of alcohol abuse and relapse prevention.     

成骨细胞的功能与损伤和骨质疏松的防治

骨质疏松是一种全身性骨骼疾病,导致骨折风险增加。成人的骨量通过破骨细胞的骨吸收和成骨细胞的骨形成作用来维持动态平衡,治疗骨质疏松症的理想策略是抑制破骨细胞的骨吸收和/或增强成骨细胞的骨形成功能。目前针对保护成骨细胞及增强其功能的骨质疏松疗法相对较少。因此,本文针对成骨细胞相关功能蛋白、各种细胞损伤机制（内质网应激、氧化应激、机械过载、微小RNA和长链非编码RNA的影响等）及骨质疏松的治疗与预防作一综述,以期为针对增强成骨细胞功能的骨质疏松治疗策略提供新思路。     

Antiinfective and encrustation-inhibiting materials--myth and facts

Catheters, urethral and ureteral stents and other urological implants are frequently affected by encrustration and infection due to their permanent contact with urine. Indwelling urinary catheters provide a haven for microorganisms and thus require extensive monitoring. Several surface modification techniques have been proposed to improve the performance of devices including the immobilization of biomolecules, the incorporation of hydrophilic grafts to reduce protein adsorption, the creation of hydrophobic surfaces, the creation of microdomains to regulate cellular and protein adhesion, new polymers and antimicrobial coatings. Physico-chemical explanation to elucidate the mechanism of such encrustation or infection inhibiting materials is still not available. Our series of experiments showed a marked decrease of silver-activity in biological fluids which corresponds with the controversial clinical results obtained with silver coated urinary catheters. Rifampicin/minocycline coated catheters had very low activity against Gram-negative rods, enterococci and Candida spp., the main causing organisms of urinary catheter infection. Surface engineered materials and antimicrobial drug delivery systems will be the next generation of sophisticated urinary catheters and stents, if both efficacy as well as efficiency has been proved clinically.     

Synthesis and anti-nociceptive and anti-inflammatory effects of gaultherin and its analogs

The synthesis of gaultherin (1) and its analogs was carried out to provide 11 glycosides under phase-transfer catalytic conditions. The activities of all synthesized compounds were evaluated by nitric oxide production inhibitory assay in vitro. Methyl 2-O-(4-O-β-d-galactopyranosyl)-β-d-glucopyranosylbenzoate (5f) showed significantly anti-nociceptive and anti-inflammatory effects by the evaluation in vivo. Structure–activity relationships within these compounds were discussed.     

益生菌与肿瘤防治

益生菌广泛存在于自然界中,通过维持宿主体内菌群平衡、影响肠屏障功能和调节免疫应答等作用,提高宿主健康水平,被公认为"肠道健康卫士".一些益生菌可以增强机体的免疫功能,抑制致癌物质,影响肿瘤细胞的基因表达,对肿瘤具有拮抗作用.大量研究表明,益生菌在未来的肿瘤防治中有很好的应用和发展前景.     

Synthesis and anti-inflammatory and analgesic activities of pyridyloxy- and phenoxyalkanoic acid derivatives

Synthesis of pyridyloxy-, pyridyloxyphenoxy- and phenoxylphenoxyalkanate derivatives and their anti-inflammatory and analgesic activities were investigated. Analysis of structure-activity relationships showed that in pyridyloxyalkanoic acid derivatives anti-edematous potency was associated with the presence of chlorophenoxypropionic acid moiety and 2-nitrated methyl propionates contributed to the analgesic activity.     

Interaction of estrone and estradiol with DNA and protein of liver and kidney in rat and hamster in vivo and in vitro

[6,7-³H] Estrone (E) and [6,7-³H]estradiol-17 (E₂) have been synthesized by reduction of 6-dehydroestrone and 6-dehydroestradiol with tritium gas. Tritiated E and E₂ were administered by oral gavage to female rats and to male and female hamsters on a dose level of about 300 g/kg (54 mCi/kg). After 8 h, the liver was excised from the rats; liver and kidneys were taken from the hamsters. DNA was purified either directly from an organ homogenate or via chromatin. The radioactivity in the DNA was expressed in the units of the Covalent Binding Index, CBI = (mol chemical bound per mol DNA-P)/(mmol chemical administered per kg b.w.). Rat liver DNA isolated via chromatin exhibited the very low values of 0.08 and 0.09 for E and E₂, respectively. The respective figures in hamster liver were 0.08 and 0.11 in females and 0.21 and 0.18 in the males. DNA isolated from the kidney revealed a detectable radioactivity only in the female, with values of 0.03 and 0.05 for E and E₂, respectively. The values for male hamster kidney were < 0.01 for both hormones. The minute radioactivity detectable in the DNA samples does not represent covalent binding to DNA, however, as indicated by two sets of control experiments. (A) Analysis by HPLC of the nucleosides prepared by enzyme digest of liver DNA isolated directly or via chromatin did not reveal any consistent peak which could have been attributed to a nucleoside-steroid adduct. (B) All DNA radioactivity could be due to protein contaminations, because the specific activity of chromatin protein was determined to be more than 3,000 times higher than of DNA. The high affinity of the hormone to protein was also demonstrated by in vitro incubations, where it could be shown that the specific activity of DNA and protein was essentially proportional to the concentration of radiolabelled hormone in the organ homogenate, regardless of whether the animal was treated or whether the hormone was added in vitro to the homogenate.Carcinogens acting by covalent DNA binding can be classified according to potency on the basis of the Covalent Binding Index. Values of 10³–10⁴ have been found for potent, 10² for moderate, and 1–10 for weak carcinogens. Since estrone is moderately carcinogenic for the kidney of the male hamster, a CBI of about 100 would be expected. The actually measured limit of detection of 0.01 places covalent DNA binding among the highly unlikely mechanisms of action. Similar considerations can be made for the liver where any true covalent DNA binding must be below a level of 0.01. It is concluded that an observable tumor induction by estrone or estradiol is unlikely to be due to DNA binding.Paper presented at the Satellite Symposium of the European Society of Toxicology, Rome, March 29, 1983