非小细胞肺癌组织蛋白酶D表达分析

目的:探讨非小细胞肺癌(nonsmall-cell lung cancer,NSCLC)组织蛋白酶D(cathepsin D,Cath-D)表达与NSCLC发生、发展及浸润转移的关系。方法:肺癌组56例肿瘤组织保存蜡块,其中临床分期Ⅰ期15例,Ⅱ期28例,Ⅲ期13例。病理分级高分化16例,中分化22例,低分化18例。另选择18例癌旁组织作对照。采用免疫组织化学染色法和原位杂交法检测Cath-D表达和mRNA水平。结果:NSCLC组Cath-D定位于癌细胞胞浆,阳性率(41/56,73.2%)显著高于癌旁组(2/18,11.1%),淋巴转移NSCLC中的阳性率显著高于无转移NSCLC的,不同临床分期、不同病理分化程度的NSCLC Cath-D蛋白阳性表达率有显著区别。Cath-D mRNA阳性率(39/56,69.6%)显著高于癌旁组(1/18,5.6%),不同临床分期、不同病理分化程度的NSCLC Cath-D mRNA阳性表达率有显著区别。结论:NSCLC组织中Cath-D和mRNA均有较高水平表达,Cath-D表达与NSCLC的发生、发展及浸润转移有关。     

NSCLC乙酰肝素酶及C—erbB-2表达分析

目的:探讨非小细胞肺癌(nonsmall-cell lung cancer,NSCLC)乙酰肝素酶(HPA)和C-erbB-2表达与NSCLC发生发展和浸润转移的关系。方法:NSCLC组为56例非小细胞肺癌保存蜡块,其中临床分期Ⅰ期15例、Ⅱ期28例、Ⅲ期13例。病理分级高分化16例、中分化22例、低分化18例,对照组为18例癌旁组织。采用免疫组织化学染色法检测两组HPA和C-erbB-2蛋白表达情况。结果:NSCLC组HPA表达阳性率(43/56例,76.8%)显著高于对照组(2/18例,11.1%),淋巴结转移NSCLC组显著高于无淋巴结转移NSCLC组,不同临床分期、不同病理分化程度NSCLC组HPA阳性表达率差异有显著性。NSCLC组C-erbB-2阳性率(40/56例,71.4%)显著高于对照组(2/18例,11.1%),NSCLC组不同临床分期、不同病理分化程度的C-erbB-2阳性表达率差异有显著性。结论:HPA和C-erbB-2高表达与NSCLC的发生、发展及浸润转移有显著关系。     

Panx1在非小细胞肺癌组织中的表达及临床意义

目的 研究Panx1（Pannexin1）在人非小细胞肺癌（NSCLC）中的表达情况,并分析其临床意义。方法 应用实时荧光定量PCR法检测25例非小细胞肺癌组织及配对的癌旁组织中Panx1 mRNA的表达。应用免疫组织化学染色法检测30例非小细胞肺癌组织、配对的癌旁组织及10例正常肺组织中Panx1蛋白的表达,分析其表达与临床病理特征的关系。结果 NSCLC中Panx1 mRNA和Panx1蛋白的表达水平均高于癌旁组织,差异有统计学意义（P＜0.05）。不同年龄、性别、胸膜侵袭情况、病理分级分组的NSCLC患者组织中Panx1蛋白阳性表达率比较差异无统计学意义（P＞0.05）,TNM临床分期Ⅲ~Ⅳ期组的Panx1阳性表达率高于Ⅰ~Ⅱ期组,有淋巴结转移组的Panx1阳性表达率高于无淋巴结转移组,差异均有统计学意义（P＜0.05）。结论 Panx1在NSCLC组织中显著高表达,而在癌旁组织中低表达,提示Panx1可能在NSCLC的发生、发展及转移侵袭中起重要作用。     

环氧化酶-2和P53蛋白在非小细胞肺癌中的表达及意义

目的研究环氧化酶-2（COX-2）和P53蛋白在非小细胞肺癌（NSCLC）组织和癌旁组织中表达情况,探讨其在NSCLC的发生、发展中的作用。方法应用免疫组化SP方法,检测NSCLC组织（40例）和癌旁组织（40例）中COX-2及P53蛋白表达情况。结果COX-2及P53蛋白在NSCLC组织中的表达显著高于癌旁组织。COX-2在NSCLC组织中的表达与组织类型、分化程度、肿瘤大小、临床分期及淋巴结转移密切相关;在腺癌中的表达明显高于鳞癌,且随着肿瘤分化程度越低、肿瘤体积增大、分期越高及淋巴结转移增多,COX-2表达阳性率越高。P53蛋白在NSCLC组织中的表达与淋巴结转移密切相关,随着肿瘤淋巴结转移增多,P53蛋白表达阳性率越高。P53的表达与COX-2正相关,P〈0．01。结论COX-2及P53蛋白在NSCLC组织中呈高表达,它们在非小细胞肺癌的发生、发展过程中起重要作用,有助于判断NSCLC的发展、淋巴结转移及其预后。     

肺癌及其癌旁组织、良性病变 survivin 的表达意义

目的探讨survivin在肺癌及其癌旁组织、良性病变的表达与肺癌发生、发展、预后的关系。方法以免疫组织化学法检测肺癌标本60例、癌旁组织15例、良性病变10例中survivin蛋白表达情况,用SPSS软件分析数据。结果 （1）survivin在肺癌高表达、在癌旁组织低表达、良性病变无表达。（2）survivin阳性染色主要位于细胞质,部分位于胞核,部分胞质胞核均表达。（3）survivin胞质表达与肺癌患者年龄、肿瘤大小、组织类型、分化程度、病理分期无关（P〉0.05）,与淋巴结转移有关,（P〈0.05）。（4）Kaplan-Meier生存分析显示：survivin胞质阳性生存率高于阴性表达者,有统计学差异（P〈0.05）。（5）Cox多因素分析显示：淋巴结转移和survivin胞质表达是肺癌预后的高危因素,危险度为：18.882、3.546。结论 （1）survivin表达与肺癌的发生有关。（2）survivin胞质表达与肺癌淋巴结转移有关而与其他病理特征无关。（3）survivin胞质表达和淋巴结转移是肺癌患者独立预后因素。     

WWOX蛋白与突变型P53蛋白在非小细胞肺癌中的表达及意义

目的 探讨WWOX与突变型P53蛋白在非小细胞肺癌(NSCLC)及癌旁组织中的表达与肿瘤临床病理参数的关系及两者表达的相关性.方法 用免疫组化elivision法分别检测WWOX及突变型P53蛋白在51例NSCLC及20例癌旁正常组织中表达情况.结果 WWOX蛋白在NSCLC组织中与癌旁正常组织中表达的阳性率分别为25.49％(13/51)和85.0％(17/20).突变型P53蛋白在NSCLC组织中与癌旁正常组织中表达的阳性率分别为58.82％(30/51)和10.0％(2/20).WWOX蛋白的阳性率与NSCLC的组织分化程度、病理类型、吸烟、有无淋巴结转移的表达差异有统计学意义(P＜0.05),而与患者的年龄、性别及肿瘤TNM分期无关(P＞0.05).突变型P53的阳性率与NSCLC的分化程度、肿瘤TNM分期、有无淋巴结转移有关(P＜0.05),而与患者的年龄、性别、吸烟、病理类型无关(P＞0.05).WWOX蛋白、突变型P53在NSCLC中的阳性表达呈负相关(r=-3.33,P＜0.05).结论 WWOX蛋白和突变型P53在NSCLC及癌旁组织的表达有显著差异.WWOX与突变型P53蛋白与NSCLC的发生、发展密切相关,并可能起协同作用,其综合检测对肺癌的病情判断和预后评价具有一定价值.     

TTF-1、CDK4、EGFR在非小细胞肺癌组织中的表达及与临床病理特征的相关分析

目的 探讨甲状腺转录因子1(TTF-1)、细胞周期蛋白依赖性激酶4(CDK4)、表皮生长因子受体(EGFR)在非小细胞肺癌(NSCLC)组织中的表达,并分析其与临床病理特征的关系。方法 选取2021年1月—2022年10月在驻马店市中心医院诊治的NSCLC患者115例,检测癌组织和癌旁组织TTF-1、CDK4、EGFR表达,并分析癌组织TTF-1、CDK4、EGFR表达与年龄、性别、肿瘤直径、肿瘤位置、肿瘤分期、分化程度、淋巴结转移、吸烟等临床病理特征的关系。结果 NSCLC患者癌组织TTF-1阳性率(58.26%vs 10.43%)、CDK4阳性率(92.17%vs 84.35%)、EGFR阳性率(64.35%vs 6.09%)明显高于癌旁组织(P<0.05)。NSCLC患者癌组织TTF-1阳性表达与年龄、性别、肿瘤直径、肿瘤位置、吸烟无关(P>0.05),与肿瘤分期、分化程度、淋巴结转移有关(P<0.05);NSCLC患者癌组织EGFR阳性表达与年龄、性别、肿瘤直径、肿瘤位置、吸烟无关(P>0.05),与肿瘤分期、分化程度、淋巴结转移有关(P<0.05...     

自噬基因 pULK、 PI3KC3 在非小细胞肺癌中的表达及相关性研究

目的 探讨自噬基因 pULK、 PI3KC3 在非小细胞肺癌（NSCLC）中的表达及相关性。方法 随机抽取NSCLC 患者 （肺癌组） 77 例 （鳞癌 31 例、 腺癌 31 例、 大细胞未分化癌 15 例） 及其癌旁正常组织 21 例作为对照。采用免疫组织化学染色及免疫印迹方法定性、 定量检测 pULK、 PI3KC3 在 NSCLC 和癌旁正常肺组织中的表达情况, 并采用 SPSS 13.0 统计软件进行病理因素及相关性分析。结果 免疫组化结果显示 pULK 和 PI3KC3 阳性表达定位于细胞质。pULK 和 PI3KC3 在肺癌组中的阳性表达(35.1%、 40.3%)显著低于癌旁正常肺组织(81.0%、 76.2%, P＜0.01)。NSCLC 中无淋巴结转移、 TNM 分期的Ⅰ～Ⅱ期和中高分化患者的 pULK 和 PI3KC3 蛋白表达阳性率均较高（P＜0.01）, 而不同年龄、 性别、 肿瘤直径大小的 NSCLC 的表达差异无统计学意义。相关性分析显示 pULK 与 PI3KC3 表达呈正相关关系。结论 pULK、 PI3KC3 在 NSCLC 中呈低表达。其表达与患者的临床分期、 分化程度及淋巴结转移有关, 而与患者年龄、 性别、 肿瘤组织学类型及大小无关。     

RRM1蛋白在NSCLC组织中的表达及其临床意义

目的 探讨核糖核苷酸还原酶M1蛋白(RRM1)在非小细胞肺癌(NSCLC)组织中的表达及其临床意义.方法 选取2015年10月至2016年12月我院手术后经病理学证实的NSCLC组织及其癌旁组织100例,采用免疫组化染色观察两种组织标本中RRM1蛋白的表达水平,并分析其与患者临床病理特征的关系.结果 肺癌组织中RRM1蛋白阳性表达率68.00%,其中阴性表达32例、弱阳性38例、阳性表达20例、强阳性表达10例,癌旁组织中的RRM1蛋白阳性表达率36.00%,其中阴性表达率64例、弱阳性36例,两组比较差异具有统计学意义(P<0.05);肺癌组织中RRM1蛋白阳性表达与NSCLC患者的TNM分期、组织分化程度、发生淋巴结转移具有显著的相关性(P<0.05).RRM1蛋白阴性表达与NSCLC患者的2年生存率55.88%高于阳性表达患者的34.38%(P<0.05).结论 RRM1蛋白在NSCLC组织中高表达,并且与患者的预后有关.     

VEGF-D及MMP-12蛋白的表达与非小细胞肺癌纵隔淋巴结转移的相关性研究

目的通过对血管内皮细胞生长因子-D(VEGF-D)及基质金属蛋白酶-12(MMP-12)在非小细胞肺癌(NSCLC)组织及癌旁组织中的表达特点进行检测,探讨VEGF-D及MMP-12 2种蛋白的表达与NSCLC纵隔淋巴结转移的相关性。方法采集60例NSCLC组织及其癌旁组织,应用免疫组织化学方法检测VEGF-D及MMP-12蛋白在这2种组织中的表达情况,分析其与临床病理因素之间的关系,以及与纵隔淋巴结转移的相关性。结果 VEGF-D及MMP-12蛋白在NSCLC组织中呈高表达[均为93.3%(56/60)],显著高于癌旁组织[51.7%(31/60),63.3%(38/60)](P<0.01)。在有纵隔淋巴结转移的癌组织中的表达显著高于无纵隔淋巴结转移的癌组织(P<0.05)。在NSCLC组织中,2种蛋白的高表达与性别、年龄、分化程度以及组织学类型无关(P>0.05),但与肿瘤病理学分期有关(P<0.05)。在有纵隔淋巴结转移的癌组织中,VEGF-D与MMP-12蛋白的表达存在相关性(c=0.274,P=0.041)。结论 VEGF-D及MMP-12蛋白在NSCLC组织及癌旁组织中的高表达现象与NSCLC的淋巴结转移密切相关,抑制VEGF-D及MMP-12蛋白的表达有可能为NSCLC的治疗提供新的治疗靶点。     

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.     

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.     

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     

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.     

Isolation and characterization of glycosylated and non-glycosylated prolactins from alligator and crocodile

Two molecular forms of prolactin (PRL). glycosylated and non-glycosylated, were isolated from pituitary glands of two reptiles, alligator and crocodile. The reptilian PRLs were extracted under alkaline conditions from the precipitate obtained after pituitaries were first extracted with 0.25 m sucrose, 1 mM NH₄HCO₃, pH 6.3. Purification was performed by ion exchange chromatography on DE-52, gel filtration on Sephadex G-75 superfine, and reversed phase high performance liquid chromatography. Two forms of both alligator and crocodile PRL, designated PRLI and PRLII, with molecular weights of 26000 and 24000 were isolated. Alligator and crocodile PRLI and PRLII were stained specifically in immunoblots with anti-sea turtle PRL and anti-ostrich PRL. Sequence analysis revealed that both forms of alligator and crocodile PRLs consisted of 199 amino acid residues with a glycosylation consensus sequence (Asn-Ala-Ser) at position 60 in alligator and crocodile PRLs with a molecular weight of 26000 (PRLI). In contrast, Thr was substituted for Asn at position 60 in the PRLs with a molecular weight of 24000 (PRLII). The sequences of alligator PRLs differed from crocodile PRLs only in position 134: Val for alligator PRLs and He for crocodile PRLs. There is a high degree of structural conservation between the reptilian PRLs isolated in this study and avian PRL; each showed 92% sequence identity with chicken PRL and 89% with turkey PRL.