阿扎胞苷与地西他滨治疗骨髓增生异常综合征有效性和安全性比较及疗效影响因素分析

目的 比较阿扎胞苷和地西他滨治疗骨髓增生异常综合征的有效性和安全性，并探讨影响2种药物疗效的相关因素。方法 回顾性分析南京鼓楼医院2013年7月—2022年12月收治的63例骨髓增生异常综合征患者，根据不同治疗方案分为阿扎胞苷组（n＝37）和地西他滨组（n＝26）。阿扎胞苷组：sc注射用阿扎胞苷50 mg·m^-2·d^-1×10 d或75 mg·m^-2·d^-1×7 d，28 d为1个疗程。地西他滨组：sc注射用地西他滨20 mg·m^-2·d^-1×5 d或25 mg·m^-2·d^-1×4 d，每4周为1个疗程。对两组患者进行疗效和安全性评估，并对影响临床疗效的因素进行单因素及多因素Logistic回归分析。结果 阿扎胞苷组的总反应率（ORR）及骨髓完全缓解率高于地西他滨组（ORR：73.0% vs 42.3%，P=0.014；骨髓完全缓解率：40.5% vs 11.5%，P=0.012），但两组的完全缓解率和血液学改善率均无显著差异。单因素分析结果发现，患者年龄、疗程、基线血红蛋白与临床疗效相关（P< 0.05）；多因素分析结果显示，疗程≥4个［比值比（OR）＝5.439，P=0.007］和基线血红蛋白≥80 g·L^-1 （OR＝4.788，P=0.027）是影响临床疗效的独立保护因素。地西他滨组骨髓抑制及发热的发生率高于阿扎胞苷组（骨髓抑制： 65.4% vs 32.4%，P= 0.012；发热：53.8% vs 24.3%，P=0.017）。结论 阿扎胞苷治疗骨髓增生异常综合征的临床疗效优于地西他滨，疗程及基线血红蛋白水平均可影响二者的疗效。阿扎胞苷在血液学方面的安全性高于地西他滨。     

宽郁舒气方联合乳清蛋白改善乳腺癌患者术后生存状况的作用

目的 研究乳腺癌患者术后使用宽郁舒气方和乳清蛋白的作用。方法 将我院收治的90例乳腺癌患者按随机数字表法分为对照组和观察组，各45例。两组患者均行乳腺癌根治术，术后采用不同的营养支持方案进行干预，对照组给予常规营养+乳清蛋白，观察组在对照组的基础上加用宽郁舒气方。比较两组患者营养状况、生活质量、心理负面情绪等方面的差异。结果 干预后，观察组患者体质指数（BMI）、上臂肌围（MAMC）、血清血红蛋白（Hb）水平、白蛋白（ALB）水平分别为（18.4±2.8） kg·m^-2、（28.7±4.5） cm、（40.5±4.2） g·L^-1、（46.4±4.1） g·L^-1，改善程度均优于对照组，差异有统计学意义（P<0.05）；观察组患者SAS评分和SDS评分［（37.68±2.16）、（38.68±1.65）］均低于对照组［（57.75±2.15）、（42.58±2.89）］，差异有统计学意义（P<0.05），情绪改善效果更为明显；观察组患者生活质量评分亦明显高于对照组（P<0.05）。结论 宽郁舒气方联合乳清蛋白可改善乳腺癌患者术后生存状况，值得临床推广应用。     

复方苦参注射液联合SOX化疗方案治疗晚期胃癌的临床研究

目的 探讨复方苦参注射液联合SOX方案治疗晚期胃癌患者的临床疗效。方法 选择2018年3月—2022年2月成都市第五人民医院收治的128例晚期胃癌患者，随机将患者分为对照组和治疗组，每组各64例。对照组给予SOX化疗方案治疗，其中静脉滴注奥沙利铂注射液，130 mg/m²加入250 mL 5%葡萄糖溶液中，第1天持续2 h；同时口服替吉奥胶囊，40 mg/次，2次/d，第1～14天。21 d为1个疗程。治疗组在对照组基础上静脉滴注复方苦参注射液，20 mL/次，用药14 d、停药7 d，3周为1个疗程。两组患者均治疗4个疗程。观察两组患者临床疗效，比较治疗前后两组患者血清肿瘤标志物癌胚抗原（CEA）、糖类抗原19-9（CA19-9）和糖类抗原724（CA724）水平，及T淋巴细胞亚群CD3^＋、CD4^＋、CD8^＋、CD4^＋/CD8^＋水平。结果 治疗后，治疗组的客观缓解率、疾病控制率分别是为78.13%、92.19%，明显高对照组56.25%、79.69%，两组比较差异具有统计学意义（P＜0.05）。治疗后，两组患者CEA、CA19-9、CA724和CD8^＋水平较治疗前均明显降低，而CD3^＋、CD4^＋和CD4^＋/CD8^＋水平明显升高（P＜0.05），且治疗组这些指标明显好于对照组（P＜0.05）结论 复方苦参注射液联合SOX方案治疗晚期胃癌临床疗效较好，能有效降低血清中的肿瘤标志物水平，提升患者的免疫功能。     

疏肝健脾益肾汤联合化疗对晚期肝郁脾虚型乳腺癌患者血清炎性因子及肿瘤标志物的影响

目的 探讨疏肝健脾益肾汤联合化疗对晚期肝郁脾虚型乳腺癌患者血清炎性因子及肿瘤标志物的影响。方法 选择2017年7月—2018年6月烟台市烟台山医院收治的晚期肝郁脾虚型乳腺癌患者120例为研究对象,采用随机数字表法分为观察组62例、对照组58例。对照组采用GP方案（吉西他滨+顺铂）化疗,观察组在对照组的基础上联合疏肝健脾益肾汤,两组均治疗18周。比较两组患者中医症状临床疗效、实体瘤临床疗效、血清炎性因子、肿瘤标志物、毒副反应等指标。结果 治疗后,观察组中医证候积分（8.43±1.35）显著低于对照组（12.52±2.45）（P<0.05）,有效率（82.86%）明显高于对照组（60.34%）（P<0.05）,缓解率（58.06%）明显高于对照组（39.66%）（P<0.05）;观察组血清白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、超敏C反应蛋白（hs-CRP）水平均显著低于对照组［（28.32±4.34） μg·L^-1 vs. （35.45±5.12） μg·L^-1、（76.45±9.21） pg·L^-1 vs. （82.35±9.54） pg·L^-1、（5.45±0.78） mg·L^-1 vs. （7.12±1.24） mg·L^-1; P<0.05］;观察组血清癌胚抗原（CEA）、糖类抗原125（CA125）、CA15-3水平均显著低于对照组［（6.45±1.12） ng·mL^-1 vs. （10.24±1.4） ng·mL^-1、（22.32±4.12） U·mL^-1 vs. （28.65±5.20） U·mL^-1、（18.45±3.65） U·mL^-1 vs. （24.74±4.32） U·mL^-1; P<0.05］;观察组Ⅲ-Ⅳ级白细胞减少、血小板减少、恶心呕吐的发生率（15.52%、9.68%、11.29%）均明显低于对照组（31.03%、24.14%、53.45%）（P<0.05）。结论 疏肝健脾益肾汤联合化疗有助于提高晚期肝郁脾虚型乳腺癌患者的临床疗效,减轻毒副反应,可能与抑制炎症反应、降低血清肿瘤标志物水平等因素有关。     

间硝苯地平对DOCA-satl 高血压大鼠心肌膜碎片二氢吡啶结合位点的影响

用 DOCA-salt 高血压大鼠心肌肥厚模型，观察间硝苯地平（m-Nif）对肥厚心肌膜碎片二氢吡啶（DHP）结合位点的影响。结果显示：预防或治疗性给予m-Nif（20 mg·kg^-1·d^-1）12 或 9 周，血压降低，心室重和心肌线粒体钙含量减少，且肥厚心肌DHP结合位点密度显著降低（450±25, 462±36 fmol·mg^-1 vs 836±47 fmol·mg^-1 protein, P<0.001）。提示：m-Nif预防和逆转DOCA-salt 高血压大鼠心肌肥厚的作用可能与其减少肥厚心肌DHP 结合位点密度和血压降低有关。     

膜性肾病患者他克莫司血浓度与给药剂量的相关性研究

摘 要 目的： 研究他克莫司治疗膜性肾病的有效血药浓度与给药剂量的相关性。 方法: 41例膜性肾病患者给予他克莫司联合小剂量激素治疗,采用均相酶扩大免疫分析法测定他克莫司全血谷浓度,根据患者24h尿蛋白、血浆白蛋白及肾功能变化进行临床疗效评价,分析他克莫司治疗膜性肾病的疗效与血药浓度及给药剂量的相关性。结果:完全缓解组患者他克莫司血药浓度为（7.47±2.74）ng·ml^-1,给药剂量为（0.047±0.007）mg·kg^-1·d^-1;部分缓解组血药浓度为（5.72±1.19）ng·ml^-1,给药剂量为（0.049±0.008）mg·kg^-1·d^-1;无缓解组血药浓度为（3.30±1.08）ng·ml^-1,给药剂量为（0.052±0.01）mg·kg^-1·d^-1。结论: 他克莫司血药浓度在（5.10～9.32）ng·ml^-1时有较好治疗效果,部分患者血药浓度不随给药剂量的增加而提高。     

HPLC法检测人血浆中百草枯的浓度

摘 要 目的:建立检测人血浆百草枯浓度的高效液相色谱方法。方法: 流动相为乙腈-3 mmol·L^-1 SDS-0.2％TFA（35∶28∶37）,流速为1.0 ml·min^-1,检测波长258 nm,柱温35℃,内标为卡马西平。用乙腈沉淀血浆蛋白处理后,进行高效液相色谱分析。结果:血浆百草枯在0.5～100.0 mg·L^-1范围内线性关系良好（r=0.999 8）。高、中、低三个浓度（1.00,10.00,50.00 mg·L^-1 ）的相对回收率分别为（103.06±4.04）％,（100.20±3.00）％和（99.33±2.26）％;日内RSD分别为4.85％,5.97％和4.91％;日间RSD分别为6.60％,5.98％和4.10％。结论:本方法准确可靠,简便快速,适用于百草枯中毒患者的血药浓度检测。     

复方苦参注射液联合TP方案治疗局部晚期宫颈癌的疗效观察

目的 探讨复方苦参注射液联合TP方案化疗治疗局部晚期宫颈癌的临床疗效。方法 选择郑州市第三人民医院2016年9月-2022年10月收治的82例局部晚期宫颈癌患者，随机分为对照组和治疗组，每组各41例。对照组静脉滴注紫杉醇注射液，135~175 mg/m²，1次/3周；同时静脉滴注顺铂注射液，75 mg/m²。治疗组在对照组治疗基础上静脉滴注复方苦参注射液，30 mL加入生理盐水250 mL，1次/d，连用14 d。21 d为1个化疗疗程，两组均连续治疗3个疗程。观察两组患者临床疗效，比较治疗前后两组患者中医证候积分和不良反应。结果 治疗后，治疗组的客观缓解率（87.80%）与对照组客观缓解率（70.73%）相比明显升高（P<0.05）。治疗后，两组患者阴道出血、带下量、带下色、带下质评分均低于治疗前（P<0.05），且治疗组明显低于对照组（P<0.05）。治疗后，治疗组不良反应发生率明显低于对照组（P<0.05）。结论 复方苦参注射液联合TP方案化疗治疗局部晚期宫颈鳞状细胞癌的临床疗效较好，安全性和可靠性较高。     

UPLC-MS/MS测定大鼠血浆中香附烯酮和α-香附酮浓度及其药动学研究

目的 建立UPLC-MS/MS测定大鼠血浆中香附烯酮和α-香附酮的方法，并研究其药动学。方法 采用Phenomennex C₁₈(150 mm×2.0 mm，3 μm)色谱柱，以乙腈-水为流动相进行梯度洗脱，柱温30 ℃，进样量1 μL，蛇床子素为内标，采用电喷雾离子源，正离子模式，香附烯酮m/z为219.1/135.1，α-香附酮m/z为219.1/111.0，蛇床子素m/z为245.0/123.0。检测大鼠血浆中香附烯酮、α-香附酮的浓度，应用DAS 2.0软件拟合主要的药动学参数。结果 香附烯酮在10~500 ng·mL^-1内线性关系良好(r=0.991 0)，α-香附酮在2.5~300 ng·mL^-1内线性关系良好(r=0.994 1)，日内精密度RSD＜9.45%，日间精密度RSD＜9.09%，加样回收率＞86.79%。SD大鼠灌胃给予香附挥发油提取物(20 mg·kg^-1)后，香附烯酮和α-香附酮C_max、AUC_0-∞、MRT_(0-∞)分别为(8 862.59±1 106.81)ng·L^-1，(7 060.94±774.25)ng·L^-1·h，(3.21±0.72)h和(934.69±106.81)ng·L^-1，(792.26±74.52)ng·L^-1·h，(4.94±0.82)h。结论 建立的方法能够快速、准确测定血浆中香附烯酮和α-香附酮的浓度，可用于香附烯酮和α-香附酮在大鼠体内的药动学研究。     

平消胶囊联合SOX方案治疗晚期胃癌的疗效及其对外周血TGF-α、ARK5水平的影响

目的 探讨平消胶囊联合SOX方案治疗晚期胃癌的疗效。方法 选取2018年6月—2020年2月北京航天总医院收治的102例晚期胃癌患者作为研究对象,将所有患者按照治疗方法分为对照组与观察组,每组各51例。对照组患者给予SOX方案化疗,即口服替吉奥胶囊,初始剂量根据体表面积确定：体表面积<1.25 m²者40 mg/次,1.25～1.5 m²者50 mg/次,>1.5 m²者60 mg/次,均为2次/d,分别于早晚饭后服用,连续服用2周后停药1周;第1天奥沙利铂注射液,130 mg/m²,静脉滴注3 h。观察组在对照组治疗的基础上口服平消胶囊,5粒/次,3次/d,于化疗1周后开始服用。治疗4周后观察各指标变化情况。观察两组患者的临床疗效,同时比较两组的血清糖类抗原242（CA242）、糖类抗原125（CA125）、糖类抗原199（CA199）和癌胚抗原（CEA）水平,外周血转化生长因子-α（TGF-α）和腺苷酸活化蛋白激酶5（ARK5）水平;CD4+T淋巴细胞亚型Th17细胞、CD4⁺CD25⁺调节性T淋巴细胞（Treg）及Th17/Treg比值;观察并记录两组无进展生存期（PFS）和总生存期（OS）。结果 治疗后,观察组疾病控制率为73.47%,显著高于对照组的54.00%,两组比较差异有统计学意义（P<0.05）。治疗后,两组CA242、CA125、CA199、CEA水平显著低于治疗前（P<0.05）,观察组CA242、CA125、CA199、CEA水平显著低于对照组（P<0.05）。治疗后,两组Th17、Treg、Th17/Treg均值低于治疗前（P<0.05）;治疗后,观察组Th17、Treg、Th17/Treg值显著低于对照组（P<0.05）。治疗后,观察组患者PFS和OS为均长于对照组,差异有统计学意义（P<0.05）。治疗后,两组外周血TGF-α、ARK5水平均显著低于治疗前（P<0.05）;且观察组治疗后外周血TGF-α、ARK5水平显著低于对照组（P<0.05）。结论 平消胶囊联合SOX方案治疗晚期胃癌疗效显著,可有效降低肿瘤标志物水平,抑制肿瘤生长,改善患者的免疫功能,延长生存期,改善预后,降低TGF-α、ARK5水平,抑制肿瘤转移,促进肿瘤细胞凋亡,同时还能降低毒副反应的发生率,安全性较高。     

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.     

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.     

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.