二次电切联合盐酸吡柔比星膀胱灌注治疗高危非肌层浸润性膀胱尿路上皮癌疗效观察

目的探讨经尿道二次气化电切联合盐酸吡柔比星（THP）膀胱灌注治疗高危非肌层浸润性膀胱尿路上皮癌的疗效。方法选取2007年6月至2012年3月该院收治的已行第1次经尿道膀胱肿瘤电切术的高危非肌层浸润性膀胱尿路上皮癌患者68例,所有患者术后1周内给予盐酸THP 30 mg膀胱灌注,每周1次,连续10周。术后6周将患者随机分为对照组和治疗组,各34例。对照组患者继续采用盐酸THP膀胱灌注化疗,治疗组患者行第2次经尿道气化电切术,术后采用盐酸THP膀胱灌注。随访2年,观察比较两组患者肿瘤复发率。结果治疗组患者膀胱肿瘤的复发率[14.71%（5/34）]较对照组[35.29%（12/34）]显著降低,差异有统计学意义（P〈0.05）。至随访截止时,治疗组继续随访肿瘤复发率[27.27%（9/33）]显著低于对照组[71.88%（23/32）],差异有统计学意义（P〈0.05）,但两组进展为肌层浸润肿瘤的发生率比较,差异无统计学意义（P〉0.05）。结论经尿道二次气化电切联合THP膀胱灌注治疗高危非肌层浸润性膀胱尿路上皮癌,可显著降低肿瘤复发率,改善患者预后。     

膀胱尿路上皮癌组织Livin和BCL-2的表达及其相关性研究

目的 探讨Livin与BCL-2在膀胱尿路上皮癌及癌旁组织中的蛋白表达水平及二者在膀胱尿路上皮癌中的相关关系,分析其致癌机制,为膀胱尿路上皮癌的诊断及临床治疗提供理论依据.方法 用流式细胞分析技术检测90例膀胱尿路上皮癌及对应的90例癌旁组织,及20例正常膀胱粘膜移行上皮组织中的Livin、BCL-2蛋白的表达.90例膀胱尿路上皮癌中,男66例,女24例,年龄26~68(平均50.24±9.87)岁.按照WHO病理分级:G124例,G240例,G326例;TNM临床分期诊断标准:非浸润性癌(Ta-1期)38例,浸润性癌(T2-4期)52例;单发48例,多发42例;初发54例,复发36例;20例正常对照为前列腺增生症、膀胱结石患者经膀胱手术所取膀胱黏膜组织,均经病理检查证实为正常膀胱黏膜组织.将表达结果进行分析.结果 Livin在正常膀胱组织中不表达.于癌旁组织中亦无表达.Livin在膀胱尿路上皮癌组织中阳性率为71.11%,其中阳性64例,阴性26例.Livin的蛋白表达与细胞的凋亡率呈负相关.BCL-2阳性表达结果 膀胱癌癌组织(51.11%)与癌旁组织(73.33)BCL-2的表达差异有显著性 (P<0.05).90例膀胱尿路上皮癌中46例BCL-2蛋白表达阳性,阳性率为51.11%,与正常膀胱粘膜阳性表达率10%比较,阳性率明显上升(P<0.05).Bcl-2的蛋白表达与细胞的凋亡率呈负相关.在膀胱尿路上皮癌中Livin与BCL-2表达有密切关系 ,在膀胱癌BCL-2的表达随着膀胱肿瘤的分化程度越差阳性表达就增加 ,而 Livin蛋白的表达亦明显增加 ,呈现正相关 (P<0.05).结论 细胞凋亡抑制因子Livin在膀胱尿路上皮癌组织中表达上调,并且与凋亡率呈负相关,提示Livin可能通过抑制细胞凋亡,对膀胱尿路上皮癌的发生、发展起重要作用,有望成为一种有效、敏感的肿肿瘤标志物志物,并为膀胱尿路上皮癌的基因治疗提供新的靶点.Livin与BCL-2在膀胱尿路上皮癌细胞凋亡的调控方面可能起着协同作用.     

吡柔比星及卡介苗膀胱灌注预防膀胱癌术后复发的临床观察

目的评价吡柔比星(THP)膀胱灌注及卡介苗(BCG)膀胱灌注预防膀胱癌术后复发的效果。方法患者随机分成两组,一组患者膀胱灌注THP(58例),另一组膀胱灌注卡介苗(54例),各组均灌注6-48个月,期间观察复发情况及不良反应。结果THP膀胱灌注组复发率为12.3%,18.96%出现不良反应症状;卡介苗膀胱灌注组复发率为9.25%,31.48%患者出现不良反应症状,两组比较BCG组疗效高于THP组,而BCG膀胱刺激症状亦高于THP组。结论THP及卡介苗均是有效的预防膀胱癌术后复发的药物,卡介苗膀胱灌注后患者1年内复发率明显低于THP组,但局部反应较大,可根据病患的具体情况应用药物。     

吡柔比星及卡介苗膀胱灌注预防膀胱癌术后复发的临床观察

目的评价吡柔比星(THP)膀胱灌注及卡介苗(BCG)膀胱灌注预防膀胱癌术后复发的效果.方法患者随机分成两组,一组患者膀胱灌注THP(52例),另一组膀胱灌注卡介苗(47例),各组均灌注6～48个月,期间观察复发情况及不良反应.结果THP膀胱灌注组复发率为11.5%,无全身不良反应例子;卡介苗膀胱灌注组复发率为21.2%,68.1%患者出现膀胱刺激症状,两组比较THP组略好于.结论THP及卡介苗均是有效的预防膀胱癌术后复发的药物,THP膀胱灌注操作简单,全身不良反应小,是一种安全有效的膀胱局部化疗药物.     

肿瘤电切术后联合吡柔比星和丝裂霉素C膀胱灌注疗效对比

目的观察经尿道膀胱肿瘤电切术（TuRBT）术后分别应用吡柔比星（THP）或丝裂霉素C（MMC）膀胱内灌注预防浅表性膀胱癌复发的效果。方法抽取62例浅表性膀胱肿瘤TURBT术后患者,其中32例行THP膀胱内灌注治疗,3O例行MMC膀胱内灌注治疗。定期作血、尿常规、肝肾功能检查,每3个月复查膀胱镜,2年后每6个月检查1次。结果随访时间18～93个月,平均56个月,THP组无肿瘤复发26例,6例复发,复发率18.8%,32例均可完成治疗;MMC组无肿瘤复发24例,6例复发,复发率25%,30例可完成治疗,2例不能耐受。结论THP膀胱灌注化疗预防浅表性膀胱癌复发,较MMC疗效满意,患者耐受性好,不良反应小,是目前较为理想的膀胱癌术后预防复发的腔内化疗药物。     

S6K1和4EBP-1蛋白在膀胱尿路上皮癌中的表达及意义

目的探讨S6K1和4EBP-1蛋白在膀胱尿路上皮癌中的表达及意义。方法使用免疫印迹法(Western-blot)检测S6K1和4EBP-1蛋白在80例膀胱尿路上皮癌及20例正常膀胱黏膜中的表达。结果膀胱尿路上皮癌中S6K1蛋白表达率(64%)高于正常膀胱黏膜(10%),4EBP-1蛋白表达率(71%)高于正常膀胱黏膜(15%)。S6K1和4EBP-1蛋白在低分级膀胱癌中的表达率显著高于高分级膀胱癌中的表达率。复发肿瘤的S6K1和4EBP-1蛋白表达率高于初发肿瘤。而S6K1和4EBP-1蛋白表达率在不同性别患者、不同肿瘤分期和是否吸烟患者中差异无统计学意义。结论膀胱尿路上皮癌中S6K1和4EBP-1蛋白与膀胱癌的分级和复发相关,可能成为肿瘤诊断治疗的新靶点。     

二次电切联合吉西他滨即刻灌注治疗非肌层浸润性膀胱癌的临床效果

目的 研究二次电切联合吉西他滨即刻膀胱灌注治疗非肌层浸润性膀胱癌的临床效果。方法 选择2011年10月至2014年10月在中国人民解放军联勤保障部队第901医院行经尿道膀胱肿瘤切除术（TURB-t）治疗的52例非肌层浸润性膀胱癌患者,将仅行TURB-t的24例患者为对照组,TURB-t术后且行二次电切的28例患者为观察组,两组患者均使用吉西他滨即刻灌注治疗。分析两组患者肿瘤病灶残留、肿瘤的复发率及进展率情况。结果 对照组患者首次TURB-t术后残留率为8.33%,观察组为14.29%,两组差异无统计学意义（χ²=0.055,P=0.815）。对照组患者12个月内肿瘤复发率为33.33%,观察组为7.14%,两组差异有统计学意义（χ²=4.145,P=0.042）;对照组患者24个月内复发率为50.00%,观察组为17.86%,两组差异有统计学意义（χ²=6.068,P=0.014）。对照组患者24个月内肿瘤进展率为33.33%,观察组为7.14%,两组差异有统计学意义（χ²=4.145,P=0.042）。结论 二次电切能减少肿瘤病灶残留,二次电切联合吉西他滨即刻膀胱灌注治疗能够降低非肌层浸润性膀胱癌的复发率。     

卡介菌多糖核酸膀胱灌注防治膀胱癌术后复发的临床研究

目的评价卡介菌多糖核酸(BCG-PSN)膀胱灌注预防膀胱癌术后复发的疗效与安全性。方法将74例患者随机分为BCG-PSN组38例和吡柔比星(THP)组36例。两组定期进行膀胱灌注,随访12-36个月,观察复发情况及不良反应。结果 BCG-PSN组膀胱癌术后复发率为18.4%(7/38),出现不良反应9例(23.7%);THP组复发率为19.4%(7/36),出现不良反应24例(66.7%)。两组复发率比较,差异无统计学意义(P>0.05),BCG-PSN组不良反应明显低于THP组,差异有统计学意义(P<0.01)。结论 BCG-PSN及THP都是有效预防膀胱癌术后复发的药物,但BCG-PSN膀胱灌注后不良反应明显小于THP组,是理想的膀胱灌注治疗药物。     

吉西他滨与吡柔比星序贯膀胱灌注治疗行尿道膀胱肿瘤切除术的非肌层浸润性膀胱癌患者的临床疗效

目的 探讨吉西他滨与吡柔比星序贯膀胱灌注治疗行尿道膀胱肿瘤切除术（TURBT）的非肌层浸润性膀胱癌（NMIBC）患者的临床疗效以及对患者尿液肿瘤标志物和外周血中性粒细胞与淋巴细胞比值（NLR）、T淋巴细胞亚群水平的影响。方法 回顾性收集濮阳市油田总医院2018年1月—2021年2月收治的80例NMIBC患者为研究对象,按治疗方案不同将患者分为对照组和试验组,每组各40例。两组均行相同的TURBT治疗,术后均即刻开始膀胱灌注化疗。试验组给予吉西他滨与吡柔比星序贯膀胱灌注治疗,首次膀胱灌注使用注射用盐酸吡柔比星30 mg＋5%葡萄糖注射液,稀释至质量浓度为1 mg·mL^-1的溶液,通过导尿管注入膀胱内,夹闭导尿管,保留1 h;第2次使用注射用盐酸吉西他滨1 000 mg＋0.9%氯化钠注射液50 mL,经导尿管注入膀胱内,夹闭导尿管,保留1 h;两种药物交替使用。对照组单用注射用盐酸吡柔比星膀胱灌注治疗,每次用法用量同试验组。两组均规律膀胱灌注治疗,开始时每周1次,持续8周,随后每月1次,共计10次。治疗后对所有患者进行至少12个月的追踪随访,比较两组肿瘤复发情况。治疗前和治疗后12个月测定两组患者尿液肿瘤标志物［细胞角蛋白19片段抗原（CYFRA21-1）、癌胚抗原（CEA）、糖类抗原125（CA125）］水平;检查血常规,计算外周血NLR;采用流式细胞仪检测外周血T淋巴细胞亚群分布情况。并统计两组治疗期间不良反应发生情况。结果 试验组治疗后12个月内肿瘤复发率为5.0%,显著低于对照组的20.0%（P<0.05）。两组治疗后12个月尿液CYFRA21-1、CEA和CA125水平均较治疗前显著降低（P<0.05）,且均以试验组的下降更显著（P<0.05）。两组治疗后12个月外周血NLR和外周血CD8⁺T细胞水平均较治疗前显著降低（P<0.05）,外周血CD4⁺T细胞水平、CD4⁺/CD8⁺均较治疗前显著升高（P<0.05）;且与同期对照组相比,试验组治疗后12个月外周血NLR和外周血CD8⁺T细胞水平均显著降低（P<0.05）,外周血CD4⁺T细胞水平、CD4⁺/CD8⁺均显著升高（P<0.05）。治疗期间,两组膀胱刺激症状、血尿、发热、胃肠道反应及肝肾功能异常的总发生率比较,差异均无统计学意义（P>0.05）。结论 吉西他滨与吡柔比星序贯膀胱灌注联合TURBT能有效降低NMIBC患者外周血NLR,改善T淋巴细胞亚群水平,下调尿液肿瘤标志物表达水平,降低术后复发风险,且不加重不良反应。     

吡柔比星灌注预防膀胱癌术后复发的临床研究

目的：探讨膀胱灌注吡柔比星（THP）预防浅表性膀胱癌术后复发的疗效及安全性。方法：对97例浅表性膀胱癌患者行经尿道膀胱肿瘤电切术（AURBt）或膀胱部分切除术，术后1周开始用THP（30mg／40ml）进行膀胱内定期灌注．每次药物在膀胱内保留30-60分钟，每周1次。连续8次，以后每月1次。连续10次，并随访17-92个月。结果：97侧患者均未见全身性药物不良反应，仅9例出现轻微膀胱刺激症状。复发16倒，复发率16．49％。结论：膀胱灌注THP预防浅表性膀胱癌术后复发的疗效确切，不良反应小。安全性好，长期疗效待进一步观察。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.