加味半夏泻心汤联合亮菌混合液保留灌肠治疗 伊立替康肠黏膜损伤的疗效观察

目的 观察加味半夏泻心汤联合亮菌混合液保留灌肠治疗伊立替康(CPT-11)肠黏膜损伤的临床疗效。方法 将2016年10月至2018年5月安徽医科大学第一附属医院及安徽省立医院收治的接受过CPT-11单药或联合方案化疗,并出现急性或迟发性腹泻的病人40例,按照随机数字表法随机分为两组,治疗组(20例)和对照组(20例),治疗组采用加味半夏泻心汤联合亮菌混合液保留灌肠治疗,对照组采用亮菌混合液保留灌肠治疗,2周为一疗程,2周后分别观察两组病人的总有效率、症状和体征、生活质量及不良反应等。结果 治疗组和对照组的总有效率分别为90%和70%,两组比较差异有统计学意义(χ²=9.668,P=0.022);治疗后治疗组的腹痛及大便性状改变均较对照组下降明显,分别P=0.039, P=0.029,治疗组优于对照组;经治疗后,治疗组卡氏评分提升较对照组大(两组卡氏评分均数的方差分析:F=6.066,P=0.018);两组在治疗过程中均未见明显不良反应。结论 加味半夏泻心汤联合亮菌混合液保留灌肠治疗CPT-11肠黏膜损伤疗效优于单纯亮菌混合液灌肠。     

半夏泻心汤治疗慢性胃炎的Meta分析

目的：分析半夏泻心汤治疗慢性胃炎的效果。方法采用R软件对符合纳入标准的文献资料进行Meta分析。查阅了近年符合相关标准的40篇文献，共4048例患者，其中治疗组有2139例，对照组有1909例，通过分析两者的疗效差别了解半夏泻心汤治疗慢性胃炎的效果。结果半夏泻心汤及其加味与常规治疗的总有效率差异有统计学意义（P<0.01），合并OR=4.7406，95%CI为3.8963~5.7678（Z=15.5507，P<0.01）。结论半夏泻心汤及其加味可有效治疗慢性胃炎。     

半夏泻心汤治疗慢性胃炎的临床价值

目的：研究雷贝拉唑与莫沙比利联合半夏泻心汤治疗慢性胃炎的临床效果。方法：选取本院2021年7月至2022年1月收治的慢性胃炎门诊患者60例,对照组(30例)和观察组(30例),对照组采用雷贝拉唑+莫沙必利治疗,观察组采用雷贝拉唑+莫沙必利+半夏泻心汤治疗。结果：观察组临床治疗总有效率和Hp根除率高于对照组(P<0.05)。观察组恶心呕吐、上腹疼痛、嗳气、胃灼热临床症状缓解时间低于对照组(P<0.05)。观察组胃泌素水平低于对照组,胃蛋白酶原Ⅰ、胃蛋白酶原Ⅱ高于对照组(P<0.05)。观察组腹部疼痛、嗳气饱胀、食欲不振中医证候积分低于对照组(P<0.05)。观察组恶心呕吐、头晕、腹泻总发生率低于对照组(P<0.05)。结论：雷贝拉唑与莫沙比利联合半夏泻心汤治疗慢性胃炎,临床效果较好,且安全性尚可。     

沙利度胺预防含顺铂方案化疗诱导的延迟性恶心呕吐的临床研究

目的:探讨沙利度胺在预防含顺铂方案化疗引起的延迟性恶心呕吐的作用。方法:80例非小细胞肺癌患者随机分为A、B组,在含顺铂化疗基础上分别加用沙利度胺、甲氧氯普胺治疗延迟性恶心呕吐,观察2组对其控制情况。结果:2组对延迟性恶心呕吐的有效率、完全控制率差异均有统计学意义,但对急性恶心呕吐预防差异无统计学意义。结论:沙利度胺预防延迟性恶心呕吐疗效肯定,安全性较好。     

加味半夏泻心汤治疗慢性结肠炎

加味半夏泻心汤治疗慢性结肠炎曹德瑚慢性结肠炎属祖国医学“泄泻”范畴。以往采用解肌、清利、消导、温补等方法治疗，但对临床常见的寒热错杂、虚实并见之泄泻疗效欠佳。据此，笔者采用寒热并用、补泻兼施的加味半夏泻心汤治疗９５例慢性给肠炎，获得满意的效果。临床资...     

盐酸伊立替康的不良反应及其预防处理

伊立替康(irinotecan,CPT-11)是喜树碱的半合成衍生物,是选择性拓扑异构酶Ⅰ抑制剂,本品及其体内代谢物SN-38可诱导单链DNA损伤,从而阻断DNA复制,产生细胞毒作用。CPT-11于1998年获FDA批准用于标准化疗方案治疗后转移性结肠直肠癌复发和恶化的二线治疗;于2000年3月获FDA批准联合氟尿嘧啶(5-FU)和亚叶酸钙(CF)用于转移性结肠直肠癌的一线治疗。本品单药有效率在18%左右,联合5-FU和CF的有效率约为50%。CPT-11主要不良反应有迟发性腹泻、恶心、呕吐、中性粒细胞减少症、急性胆碱能综合征等,现就其不良反应的表现类型及预防处理方法进行概述。     

艾灸结合穴位按摩预防顺铂化疗后所致恶心呕吐的疗效观察

目的：观察艾灸结合穴位按摩合谷、内关、中脘和足三里对预防顺铂化疗后所致恶心呕吐的疗效。方法将112例接受顺铂化疗方案的患者随机分为实验组(n=54)和对照组(n =58)。两组化疗前予以盐酸托烷司琼注射液4 mg 静脉滴注,实验组在对照组的基础上增加艾灸和穴位按摩。观察顺铂化疗后两组患者恶心、急性呕吐、延迟性呕吐发生率、严重程度和持续的时间。结果实验组在恶心的控制率及延迟性呕吐的治疗有效率均明显高于对照组(P<0.05);实验组和对照组在急性呕吐的预防中无统计学差异(P>0.05)。结论艾灸结合穴位按摩合谷、内关、中脘和足三里等四穴能有效减轻顺铂化疗所致恶心及延迟性呕吐的发生。     

加味半夏泻心汤治疗慢性萎缩性胃炎35例体会

目的：观察加味半夏泻心汤治疗慢性萎缩性胃炎的临床疗效。方法：将69例门诊慢性萎缩性胃炎患者随机分为治疗组35例,对照组34例,治疗组应用加味半夏泻心汤煎服,对照组应用奥美拉唑胶囊加用铝碳酸镁咀嚼片口服。结果：治疗组总有效率77．14％,对照组总有效率58．82％。两组疗效比较有统计学意义（P〈0．05）。结论：加味半夏泻心汤治疗慢性萎缩性胃炎有比较满意的临床疗效。     

托烷司琼加镇吐合剂控制肺癌含铂方案化疗所致恶心、呕吐的临床观察

目的：观察托烷司琼加镇吐合剂预防肺癌含铂方案化疗所致的急性及延迟恶心、呕吐作用，并与单用托烷司琼比较。方法：采用随机、交叉、对照法，观察24h（急性）及5d内（延迟性）恶心、呕吐发生情况。结果：托烷司琼加镇吐合剂预防肺癌含铂方案化疗所致的急性及延迟恶心、呕吐作用的有效率均高于单用托烷司琼，差异有显著性（P〈0．05），2组不良反应无明显差异。结论：托烷司琼加镇吐合剂可以作为预防和控制肺癌含铂方案联合化疗所致恶心、呕吐的一线方案。     

加味半夏泻心汤对伊立替康所致迟发性腹泻模型血清IL-15的影响

目的探讨中药加味半夏泻心汤对伊立替康致迟发性腹泻模型小鼠血清IL-15的影响。方法30只雄性小鼠随机分为5组,模型组腹腔注射伊立替康制备迟发性腹泻模型,正常组等量生理盐水代替,中药高、中、低剂量组在腹腔注射伊立替康前1d,分别按剂量灌胃中药,qd,连续用药7d,同时模型组和正常组予等体积蒸馏水灌胃,观察腹泻情况,第8天测定血清IL-15的含量。结果中药高、中、低剂量组腹泻指数较模型组显著下降（P〈0．01）;中药高、中剂量组血清IL-15含量显著高于模型组（P〈0．01）,而低剂量组差异不明显。结论加味半夏泻心汤预防伊立替康迟发性腹泻的机制可能与上调血清IL-15有关。     

Baicalein,a component of banxia xiexin decoction,alleviates CPT-11-induced gastrointestinal dysfunction by inhibiting ALOX15-mediated ferroptosis

Baicalein, one of the active ingredients of banxia xiexin decoction, has good therapeutic efficacy in treating diarrhea and improving gastrointestinal dysfunction. The role and mechanism of Baicalein on irinotecan (CPT-11)-induced gastrointestinal dysfunction are the focus of this study. Concretely, CPT-11 induced delayed diarrhea rat model and intestinal epithelial cell (IEC)-6 cell injury model with Baicalein treatment as needed. Colonic pathological changes were analyzed by hematoxylin–eosin staining, and inflammatory factor expressions in serum were determined by enzyme-linked immunosorbent assay. Immunohistochemistry and western blot were performed to quantify ferroptosis-related protein expressions. Thiobarbituric acid reactive substances (TBARS) kits and colorimetric assay kit were applied to detect lipid peroxidation levels and Fe²⁺ content, respectively. In vitro experiments also included quantitative real-time polymerase chain reaction, cell counting kit-8, and C11 BODIPY staining. CPT-11 induced aggravation of intestinal tissue damage, inflammatory factor release, Fe²⁺ accumulation, upregulation of lipid peroxidation and 15-Lipoxygenase (ALOX15) expression, and downregulation of glutathione peroxidase 4 (Gpx4) and SLC7A11 in vivo in rats; however, Baicalein dose-dependently reversed the effects of CPT-11. Baicalein elevated cell viability, reduced lipid peroxidation and Fe²⁺ accumulation, and elevated Gpx4 and SLC7A11 levels, whereas ALOX15 overexpression reversed the effects of Baicalein on a CPT-11-induced IEC-6 cell injury model. In conclusion, Baicalein plays a mitigating role in CPT-11-induced delayed diarrhea via ALOX15-mediated ferroptosis.     

甘草酸对伊立替康在大鼠体内的肠道毒性影响及其作用机制研究

目的：研究甘草酸（glycyrrhizin,GL）能否防治伊立替康（irinotecan,CPT-11）所致的大鼠迟发性腹泻,并探讨其可能的作用机制。方法：大鼠随机分成4组：正常对照组、GL组、CPT-11腹泻模型组、GL＋CPT-11腹泻治疗组。腹泻模型采用连续4天尾静脉（iv）给予CPT-11（80mg·kg-1·d-1）。观察大鼠在静脉给予GL（25mg·kg-1·d-1）治疗下,腹泻得分、体重等指标变化;同时检测血浆和结肠炎症因子前列腺素E2（PGE2）水平变化。结果：相比CPT-11腹泻模型组,GL＋CPT-11腹泻治疗组大鼠提早1天腹泻改善、体重回升,血浆和结肠中PGE2水平也明显低于腹泻模型组。结论：GL对CpT-11诱导的严重迟发性腹泻模型的大鼠有-定的防治作用。其作用机制可能与GL抗炎作用有关。     

伊立替康联合卡培他滨二线治疗晚期胃癌

目的探讨伊立替康（CPT-11）联合卡培他滨二线治疗晚期胃癌的近期疗效及不良反应。方法对30例晚期胃癌患者给予CPT-11 180mg·m^-2于化疗第1天静脉滴注90min;卡培他滨1250mg·m^-2,分早晚2次口服,连服14d,21d为1个周期。每2个周期后进行评价疗效。治疗期间进行不良反应评估。结果30例患者中25例可评价疗效,其中完全缓解1例,部分缓解9例,稳定10例,进展5例,总有效率为40．0％,临床反应率为80．0％。常见不良反应为中性粒细胞减少、迟发性腹泻、恶心、呕吐和手足综合征等,多为Ⅰ～Ⅱ度。结论CPT-11联合卡培他滨二线治疗进展期胃癌,疗效较好,不良反应可耐受,且用药方便,值得临床广泛推广应用。     

Irinotecan (CPT-11) in metastatic colorectal cancer patients resistant to 5-fluorouracil (5-FU): a phase II study

The efficacy and toxicity of irinotecan (CPT-11) 350 mg/m(2) i.v. once every 3 weeks was assessed in 60 patients with advanced colorectal cancer (CRC) showing failure to 5-fluorouracil (5-FU) treatment. The overall objective response rate was 13.6% (1 complete response and 4 partial responses) and 25 patients (42.4%) showed stable disease; the median time to disease progression was 4.4 months and the median survival was 10.5 months. The main non-hematological toxicities were alopecia (80.3% of patients), diarrhea (75.0%), and nausea/vomiting (71.7%); neutropenia was the main hematological toxicity. Grade 3 or 4 diarrhea appeared in 21 of 131 cycles (16.1%), whereas grade 3 or 4 neutropenia appeared in 78 cycles (25.0%). In conclusion, the present phase II study confirms that CPT-11 350 mg/m(2) every 3 weeks is active and well tolerated as second-line chemotherapy for CRC in 5-FU resistant patients.     

伊立替康联合氟尿嘧啶/亚叶酸钙治疗转移性结直肠癌

目的观察伊立替康联合亚叶酸钙及氟尿嘧啶方案治疗FOLFOX4方案失败的晚期结直肠癌的临床疗效及毒副反应。方法用CPT-11联合5-FU/CF方案治疗晚期结直肠癌患者28例,采用2周方案化疗,至少2个周期,即CPT-11180mg/m2静脉滴注,第1天;四氢叶酸200mg/m2静脉滴注,第1、2天;5-FU400mg/m2静脉推注,第1、2天;5-FU600mg/m2静脉滴注22h,第1、2天。按照WHO实体瘤近期客观疗效评定标准进行评价。结果全组28例患者均可评价疗效及不良反应。其中完全缓解0例,部分缓解10例,稳定9例,进展9例,有效率为35.7%。中位肿瘤进展时间TTP6.5个月,中位生存时间MST为12.5个月。不良反应主要是骨髓抑制,恶心、呕吐,脱发及延迟性腹泻。结论伊立替康联合5-FU/CF为二线治疗晚期结直肠癌安全有效的方案。     

Pharmacokinetic changes of irinotecan by intestinal alkalinization in an advanced colorectal cancer patient

The prevention of irinotecan (CPT-11)-induced diarrhea, a well-known adverse reaction to the drug, by treatment with intestinal alkalinization has been carried out in patients with colorectal cancer in Japan. Under acidic conditions, CPT-11 and its active metabolite, SN-38, exists preferably as the lactone form, whereas both exist as the carboxylate form under basic conditions. It has been suggested that the lactone forms of both CPT-11 and SN-38 are diffused passively across the intestinal mucosal membranes, whereas the carboxylate forms are actively transported. The intestinal uptake rate of both forms appears to be pH sensitive under physiological conditions, but it remains unclear whether intestinal alkalinization treatment affects the pharmacokinetics of CPT-11 and SN-38. This study was designed to evaluate the pharmacokinetics of CPT-11 and SN-38 in a colorectal cancer patient with or without alkalinization treatment. We found that intestinal alkalinization significantly decreased the plasma levels of CPT-11 and SN-38. In particular, the AUC of SN-38 was markedly decreased to 56 from 107 ng.h/mL. Intestinal alkalinization was effective in preventing CPT-11-induced diarrhea, but this treatment changed the pharmacokinetics of CPT-11 and SN-38 in the body.     

Excretion Into Gastrointestinal Tract of Irinotecan Lactone and Carboxylate Forms and Their Pharmacodynamics in Rodents

Purpose. To investigate the excretion of irinotecan hydrochloride (CPT-11) and its active metabolite, SN-38, into the gastrointestinal lumen via the biliary and/or intestinal membrane route after dosing with lactone and carboxylate forms of CPT-11, and to evaluate the toxic and antitumor effects of the two forms. Methods. The excretions of CPT-11 and SN-38 were investigated by the in situ perfusion technique using rats. The incidence of delayed diarrhea was evaluated after i.v. dosing (60 mg/kg) with CPT-11 lactone and carboxylate forms for 4 days. Antitumor activity and changes in body weight were investigated in mice with Meth A tumors. Results. The excretion of CPT-11 into bile was greater in dosing with CPT-11 carboxylate than that with its lactone form, whereas the exsorption across intestinal membrane was greater in dosing with CPT-11 lactone than that with its carboxylate form. Dosing with CPT-11 lactone dose-dependently inhibited the increase in tumor weights in Meth A tumor mice, whereas the dosing with its carboxylate form reduced the antitumor effect. Conclusions. The decreased antitumor effect caused by dosing with the CPT-11 carboxylate form could be due to less accumulation in the tissue including tumor cells resulting from the rapid elimination of the form in the body.     

St. John's wort attenuates irinotecan-induced diarrhea via down-regulation of intestinal pro-inflammatory cytokines and inhibition of intestinal epithelial apoptosis

Diarrhea is a common dose-limiting toxicity associated with cancer chemotherapy, in particular for drugs such as irinotecan (CPT-11), 5-fluouracil, oxaliplatin, capecitabine and raltitrexed. St. John's wort (Hypericum perforatum, SJW) has anti-inflammatory activity, and our preliminary study in the rat and a pilot study in cancer patients found that treatment of SJW alleviated irinotecan-induced diarrhea. In the present study, we investigated whether SJW modulated various pro-inflammatory cytokines including interleukins (IL-1beta, IL-2, IL-6), interferon (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) and intestinal epithelium apoptosis in rats. The rats were treated with irinotecan at 60 mg/kg for 4 days in combination with oral SJW or SJW-free control vehicle at 400 mg/kg for 8 days. Diarrhea, tissue damage, body weight loss, various cytokines including IL-1beta, IL-2, IL-6, IFN-gamma and TNF-alpha and intestinal epithelial apoptosis were monitored over 11 days. Our studies demonstrated that combined SJW markedly reduced CPT-11-induced diarrhea and intestinal lesions. The production of pro-inflammatory cytokines such as IL-1beta, IFN-gamma and TNF-alpha was significantly up-regulated in intestine. In the mean time, combined SJW significantly suppressed the intestinal epithelial apoptosis induced by CPT-11 over days 5-11. In particular, combination of SJW significantly inhibited the expression of TNF-alpha mRNA in the intestine over days 5-11. In conclusion, inhibition of pro-inflammatory cytokines and intestinal epithelium apoptosis partly explained the protective effect of SJW against the intestinal toxicities induced by irinotecan. Further studies are warranted to explore the potential for STW as an agent in combination with chemotherapeutic drugs to lower their dose-limiting toxicities.     

伊立替康联合雷替曲塞方案二线治疗晚期胃癌的临床研究

目的观察伊立替康（CPT-11）联合雷替曲塞二线治疗晚期胃癌的疗效及不良反应。方法对23例一线化疗方案治疗失败或缓解后再进展的晚期胃癌患者进行化疗,方案为伊立替康150 mg·m^-290 min静滴D1;雷替曲塞3 mg·m^-215 min静滴D1;3周为1个周期,2个周期后评价疗效。治疗期间进行不良反应评估。结果 23例均可评价毒副反应和远期疗效,其中22例患者均可评价近期疗效,有效率为54.54%,中位生存期为5个月（95%CI：3.8-6.2月）。常见毒副反应有中性粒细胞减少、贫血、恶性呕吐、血小板减少、迟发性腹泻等。结论伊立替康联合雷替曲塞在晚期胃癌二线治疗中有一定疗效,毒副作用可耐受,值得进一步临床研究。