15例非胃黏膜相关淋巴组织淋巴瘤临床特点与疗效分析

目的 探讨非胃黏膜相关淋巴组织(MALT)淋巴瘤的临床特点和治疗方法。方法 回顾性分析安徽省肿瘤医院2011年6月至2015年6月收治的15例非胃MALT淋巴瘤患者临床资料。结果 在一线接受放疗或(和)化疗的15例患者中,总有效率为100.00%。局限期(Ⅰ~Ⅱ期)患者完全缓解率明显高于进展期(Ⅲ~Ⅳ期)患者(P<0.05),原发部位在头颈部患者总生存(OS)率、无疾病进展生存(PFS)率优于原发于肺及小肠患者(P<0.05)。14例化疗患者中,使用利妥昔单抗患者的OS率、PFS率与未使用患者相比,无明显优势。局限期患者OS率、PFS率优于进展期患者,但差异无统计学意义。结论 非胃MALT淋巴瘤疾病进展缓慢,预后良好,临床上可根据患者病变范围和身体状况选择适当治疗。     

地西他滨联合三氧化二砷方案治疗老年中高危骨髓增生异常综合征的应用价值

目的 比较地西他滨联合三氧化二砷方案与地西他滨单药方案治疗老年中高危骨髓增生异常综合征（MDS）的临床疗效及安全性。方法 回顾性分析2016年1月1日至2017年6月30日宣城市人民医院血液科收治的73例初诊老年中高危MDS患者的临床资料,根据治疗方法不同分为观察组（地西他滨联合三氧化二砷化疗组,35例）和对照组（地西他滨单药化疗组,38例）。比较两组患者治疗2个周期、4个周期的近期临床疗效,并比较两组患者治疗4个周期后的无进展生存时间（PFS）和总生存时间（OS）,同时比较治疗过程中两组患者的药物不良反应发生率。结果 治疗2个周期后观察组35例患者中完全缓解（CR）1例,骨髓完全缓解（mCR）4例,部分缓解（PR）5例,血液学改善（HI）9例,临床总有效率（ORR）54.28%,缓解率（RR）28.57%,对照组38例患者中CR 0例,mCR 2例,PR 4例,HI 9例,ORR 39.47%,RR为15.79%,两组患者临床ORR和RR比较,差异无统计学意义（P>0.05）;治疗4个周期后观察组中CR 6例,mCR 9例,PR 5例,HI 3例,ORR 65.71%,RR 57.14%,对照组中CR1例,mCR5例,PR 4例,HI 10例,ORR 52.63%,RR 26.31%,两组患者ORR差异无统计学意义（P>0.05）,但观察组RR高于对照组,差异有统计学意义（P<0.05）;截至随访终点2018年6月30日,观察组PFS 9（5,19）月,对照组PFS 7（3,17）月,观察组患者PFS长于对照组,差异有统计学（P<0.05）。观察组患者OS与对照组相比延长,差异有统计学（χ²=12.179,P=0.001）。两组患者化疗期间均未出现死亡,两组患者不良反应发生率相近,差异无统计学意义（P>0.05）。结论 地西他滨联合三氧化二砷不能提高老年中高危MDS患者ORR,但可提高RR,能够延长患者PFS和OS,同时不会增加患者不良反应发生率,值得进一步临床研究。     

放疗在美罗华时代对局限期原发韦氏环弥漫大B细胞淋巴瘤的治疗价值

目的 分析在美罗华联合化疗背景下,放疗对局限期韦氏环弥漫大B细胞淋巴瘤的治疗价值。方法 收集2010年—2017年收治的93例Ⅰ-Ⅱ期原发韦氏环弥漫大B细胞淋巴瘤患者的临床资料,将仅接受美罗华联合CHOP或CHOP类似方案化疗的38例患者分为单纯化疗组,将接受化疗+巩固放疗的55例患者分为综合治疗组。采用Kaplan-Meier法计算无进展生存（PFS）、总生存（OS）、局部区域控制率（LRC）,并行单因素分析;采用Log-rank法检验两组患者生存差异,并行Cox多因素回归分析。结果 本研究患者随访中位时间47个月,3年存活病例67例。单纯化疗组和综合治疗组患者的3年PFS分别为76.1%和94.2%（P=0.036）,3年OS分别为78.6%和96.0%（P=0.032）,3年LRC分别为83.1%和98.1%（P=0.015）。其中62例化疗后疗效评估为完全缓解（CR）的患者中,单纯化疗组和综合治疗组的3年PFS、OS和LRC分别为87.8%和97.6%（P=0.164）、93.8%和97.4%（P=0.522）、87.8%和100.0%（P=0.028）。进一步单因素分析结果显示,年龄>60岁和化疗疗效未达CR是PFS和OS的不良预后因素,B症状和化疗疗效未达CR是LRC的不良预后因素。多因素分析结果显示,年龄>60岁、B症状、化疗疗效未达CR是患者PFS的不良预后因素,年龄>60岁、化疗疗效未达CR是OS的不良预后因素,B症状、化疗疗效未达CR和未放疗是LRC的不良预后因素。结论 Ⅰ-Ⅱ期原发韦氏环弥漫大B细胞淋巴瘤采用美罗华联合CHOP为主的化疗后的巩固性放疗可显著改善患者的PFS、OS和LRC,但仍需大样本和前瞻性研究进一步证实。     

奈达铂+5-氟尿嘧啶联合放疗对食管鳞癌的临床疗效及其作用机制

目的 探讨奈达铂+5-氟尿嘧啶（5-Fu）联合放疗对食管鳞癌的临床疗效及对患者外周血中热休克蛋白90a（HSP90a）、癌胚抗原（CEA）及CK20蛋白表达的影响。方法 回顾性分析2014年1月至2017年1月在海安医院肿瘤科接受放化疗的130例中晚期食管鳞癌患者的临床资料。按照给药方案不同,分为试验组（67例）和对照组（63例）,试验组采用奈达铂+5-Fu方案化疗联合放疗;对照组采用顺铂+5-Fu方案化疗联合放疗。观察并比较6个疗程后两组患者临床疗效、副反应及患者外周血中热休克蛋白90a、CEA、CK20蛋白水平变化。结果 试验组临床疗效高于对照组,差异有统计学意义（P<0.05）;试验组患者胃肠道反应和肝肾功能损伤发生率（22.00%,5.00%）均低于对照组（43.00%,24.00%）,差异有统计学意义（P<0.05）;试验组治疗后HSP90a、CEA及CK20蛋白水平低于对照组,差异有统计学意义（P<0.05）。结论 奈达铂+5-Fu联合放疗治疗食管癌疗效优于顺铂+5-Fu联合方案,可降低患者外周血HSP90a、CEA及CK20表达水平。     

硼替佐米为基础的治疗方案治疗华氏巨球蛋白血症15例的临床分析

目的 探讨以硼替佐米为基础的方案治疗华氏巨球蛋白血症（Waldenström macroglobulinemia,WM）的临床疗效及安全性。方法 回顾性分析2008年12月至2015年10月收治的15例采用以硼替佐米为基础方案治疗的WM患者的临床资料。其中1例采用硼替佐米+地塞米松（BD）方案,3例采用硼替佐米+地塞米松+美罗华（RBD）方案,11例采用硼替佐米+地塞米松+环磷酰胺（BCD）方案,评价上述三方案的疗效及不良反应,并进行生存分析。结果 治疗的总反应率及主要反应率分别为93.3%和80%[其中完全缓解（CR）1例、非常好的部分缓解（VGPR）2例、部分缓解（PR）9例、微小反应（MR）2例]。不良反应包括胃肠道副作用（53.3%）、白细胞减少（20%）、感染（20%）及外周神经病变（26.7%）。随访时间为3~85个月（中位数21个月）,无进展生存（PFS）时间为3~36个月（中位数21个月）,1年的PFS率分别为83.3%。生存分析显示IPSSWM分级为高危组（P=0.015）及用药后治疗反应小于PR（P=0.024）是影响WM患者PFS的危险因素。结论 以硼替佐米为基础的治疗方案可有效治疗WM患者,IPSSWM分级体系及治疗反应可作为判断以硼替佐米为基础的治疗方案的WM患者疾病进展预后的参考因素。     

局部晚期乳腺癌TEC方案新辅助化疗的临床疗效分析

目的 探讨局部晚期乳腺癌TEC方案新辅助化疗的临床疗效及安全性。方法 回顾性分析2010年6月至2015年10月南京医科大学附属明基医院普外科收治的112例进展期乳腺癌患者的临床资料,根据患者的治疗方案,将接受新辅助化疗的53例患者作为治疗组,未接受新辅助化疗的59例患者作为对照组。比较两组患者肿瘤治疗有效率、不良反应发生率、术后并发症发生率、保乳率及术后复发转移率等指标的差异。结果 治疗组患者治疗有效率为61.15%,对照组为3.39%,治疗组患者手术保乳率为31.19%,对照组为11.86%,差异均有统计学意义（P<0.05）。治疗组5例患者出现病情进展,两组患者术后辅助化疗不良反应、手术相关并发症等进行比较,差异无统计学意义（P>0.05）。术后随访,治疗组患者肿瘤局部复发率（22.64%）高于对照组（8.47%）,差异有统计学意义（P<0.05）,但远处转移率（3.77%vs 5.08%）比较,差异无统计学意义（P>0.05）。结论 局部晚期乳腺癌的新辅助化疗可缩小肿瘤,增加乳腺癌患者保乳率,但增加术后局部复发率,有待进一步临床研究思考及验证。     

塞来昔布联合化疗对转移性或术后复发性晚期胃癌的疗效及药物不良反应

目的 分析塞来昔布联合化疗治疗转移性或术后复发性胃癌的疗效和安全性。方法 收集2010年9月至2016年12月转移性或术后复发性胃癌患者,分为塞来昔布+化疗组和单纯化疗组,治疗6个周期。比较两组患者间临床资料、无进展生存期（PFS）、总生存期（OS）的差异,并进一步分析COX-2阳性亚组的生存情况,评价药物安全性。结果 共纳入患者176例,塞来昔布+化疗组89例,单纯化疗组87例。两组患者客观缓解率、疾病控制率比较,差异均无统计学意义（P>0.05）。两组患者中位OS（P=0.59）和中位PFS（P=0.734）比较,差异均无统计学意义。塞来昔布+化疗组COX-2阳性患者中位OS为14个月,单纯化疗组COX-2阳性患者为10个月,差异有统计学意义（P=0.010）;塞来昔布+化疗组COX-2阳性患者中位PFS为7.5个月,单纯化疗组COX-2阳性患者为5个月,差异有统计学意义（P<0.001）。两组患者的药物不良反应均以恶心最为常见,但差异无统计学意义。结论 塞来昔布联合化疗可延长COX-2阳性晚期胃癌患者的OS和PFS,且不增加药物不良反应。     

灵芪加口服液治疗失眠症（心脾两虚证）临床研究

目的 以灵芝口服液为对照评价灵芪加口服液治疗失眠症（心脾两虚证）临床应用的有效性和安全性。方法 将188例失眠症（心脾两虚证）患者随机分为两组,治疗组141例、对照组47例;治疗组实施灵芪加口服液治疗,对照组实施灵芝口服液治疗,两组均治疗4周。比较两组匹茨堡睡眠质量指数量表（PSQI）评分改善情况、疾病综合疗效、中医证候疗效及不良反应。结果 两组治疗后匹茨堡睡眠质量指数量表（PSQI）评分均低于治疗前,组内比较差异均有统计学意义（P < 0.05）;两组间比较采用秩和检验,差异无统计学意义（P=0.9598）。疾病综合疗效：治疗组愈显率47.52%,总有效率75.18%;对照组愈显率27.66%,总有效率59.57%。两组愈显率治疗组优于对照组（χ²=5.6864,P=0.0171）,两组总有效率治疗组优于对照组（χ²=4.1916,P=0.0406）。中医证候疗效：治疗组愈显率48.23%;对照组愈显率27.66%,两组愈显率比较,治疗组优于对照组（χ²=6.0808,P=0.0137）。"失眠"、"倦怠乏力"、"精神不振"、"食欲不振"单项症状,治疗组优于对照组,差异有统计学意义（P < 0.05）。结论 灵芪加口服液治疗失眠症（心脾两虚证）疗效确切,临床服用安全,具有较好的临床应用前景。     

信迪利单抗联合DA-EPOCH-R方案治疗弥漫大B细胞淋巴瘤的效果及安全性评价

目的 评价信迪利单抗联合环磷酰胺＋表柔比星＋依托泊苷＋长春新碱＋泼尼松、利妥昔单抗无放射治疗（DA-EPOCH-R）方案治疗弥漫大B细胞淋巴瘤（DLBCL）的效果及安全性。方法 回顾性选取2019年3月—2022年2月洛阳市第三人民医院收治的经一线治疗方案治疗后疾病复发或进展的DLBCL患者103例,根据治疗方案分为试验组54例、对照组49例。对照组给予DA-EPOCH-R方案治疗,试验组在对照组基础上加用信迪利单抗治疗。比较两组治疗前后免疫相关指标、血管内皮生长因子（VEGF）、血清胸苷激酶1（TK1）、白细胞介素-2（IL-2）水平,统计疗效和不良反应。结果 试验组客观缓解率（ORR）达72.22%,高于对照组的53.06%,差异有统计学意义（P<0.05）。治疗后,试验组Treg细胞占比及VEGF、TK1水平低于本组治疗前（P<0.05）,Th17细胞占比、IL-2水平高于本组治疗前（P<0.05）;对照组NK细胞占比及VEGF、TK1水平低于本组治疗前（P<0.05）,Treg细胞占比及IL-2水平高于本组治疗前（P<0.05）;两组CD3⁺T、CD3⁺CD4⁺T、CD3⁺CD8⁺T与治疗前比较无统计学意义（P>0.05）。试验组治疗后IL-2水平、NK细胞占比、Th17细胞占比较对照组更高（P<0.05）,Treg细胞占比及VEGF、TK1水平较对照组更低（P<0.05）。试验组和对照组败血症、皮疹、肺部感染、黏膜炎、腹泻、恶心呕吐、脱发、肾功能损伤、肝功能损伤、血小板减少、白细胞减少、贫血、发热、甲状腺功能减退等不良反应方面比较,差异无统计学意义（P>0.05）。结论 信迪利单抗联合DA-EPOCH-R方案治疗DLBCL可改善患者免疫功能,降低VEGF、TK1的表达,加强疗效,安全性良好。     

安罗替尼联合替吉奥二线治疗晚期食管癌的疗效及安全性

目的 探讨安罗替尼联合替吉奥二线治疗晚期食管癌的疗效及安全性。方法 选取2018年6月至2019年9月安徽医科大学附属巢湖医院收治的60例一线化疗后失败或缓解后再进展的晚期食管癌患者,采用随机数字表法分为观察组和对照组,各30例,观察组给予安罗替尼联合替吉奥方案,对照组给予单药替吉奥方案,每2周期进行疗效评价,分析两组有效率（ORR）、疾病控制率（DCR）、中位无进展生存时间（PFS）,同时比较两组乏力、高血压、胃肠道反应、手足皮肤反应、口腔粘膜炎、骨髓抑制、肝功能损害、蛋白尿等不良反应差异。结果 观察组ORR为23.3%（7/30）,对照组ORR为10.0%（3/30）,两组差异无统计学意义（P>0.05）。观察组DCR为76.7%（23/30）,PFS为5.6个月;对照组DCR为46.7%（14/30）,PFS为1.4个月,两组DCR、PFS差异均有统计学意义（P<0.05）。观察组高血压发生率高于对照组（P<0.05）,两组余不良反应发生率差异均无统计学意义（P>0.05）。所有不良反应经对症处理后均缓解。结论 安罗替尼联合替吉奥方案治疗晚期食管癌疗效及安全性尚可,不良反应可耐受,值得临床推广。     

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.     

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.