Objective: To evaluate the effect and safety of low-dose of apatinib and S-1 combined with Jianpi Bushen Jiedu Decoction(JBJD) in patients with metastatic colorectal cancer(mCRC) who have failed second or above lines ...Objective: To evaluate the effect and safety of low-dose of apatinib and S-1 combined with Jianpi Bushen Jiedu Decoction(JBJD) in patients with metastatic colorectal cancer(mCRC) who have failed second or above lines treatment, in order to provide more treatment option for mCRC patients by integrated medicine. Methods: Thirteen patients were selected from a single-arm, open-label clinical study from April 2019 to September 2020. The patients were treated with low-dose apatinib(250 mg, once a day) and S-1(20 mg, twice a day) combined with JBJD for at least one cycle and were followed up to August 2021. The primary endpoint was disease progression-free survival(PFS). Disease control rate(DCR), objective response rate(ORR), and overall survival(OS) of patients were observed as the secondary endpoints. Adverse events were recorded as well. Results: The average age of the 13 patients was 56.5±13.0 years and 76.9% were male. The median PFS and median OS were 4.6 and 8.3 months, respectively. The ORR was 7.7%(1/13) while the DCR was 61.5%(8/13). The common adverse events were hypertension, proteinuria, elevated transaminase, and thrombocytopenia. One patient experienced thrombocytopenia of grade 3. Conclusions: Patients with mCRC after failure of the second or above lines of treatment may potentially benefit from the treatment of low-dose apatinib and S-1 combined with JBJD because of its similar effect as the standard dose of target therapy and relatively better safety.(Registration No. ChiCTR1900022673)展开更多
AIM： To investigate the antitumor and synergistic effect of Chinese medicine “Bushen huayu jiedu recipe” （recipe for invigorating the kidney, removing blood stasis and toxic substances） and chemotherapy on mice h...AIM： To investigate the antitumor and synergistic effect of Chinese medicine “Bushen huayu jiedu recipe” （recipe for invigorating the kidney, removing blood stasis and toxic substances） and chemotherapy on mice hepatocarcinoma. METHODS： Bushen huayu jiedu recipe （BSHYJDR） consisting of Chinese Cassia Bark, Psoralea, Zedoary, Rhubarb, etc. is equal to 1.5 g/mL liquid of originated herbs after being decoded, filtered, and concentrated. Kunming mice, weighing 18-22 g, were injected with 0.2 mL ascitic hepatocarcinoma H22 containing 1 × 10^7 cells/mL into armpit of the right forelimb of mice. After 24 h, the mice were weighed and randomly divided into tumor-bearing model control group, cisplatin （DDP） group, BSHYJDR high dosage group, low dosage BSHYJDR group, DDP combined with high and low dosage BSHYJDR group, 10 mice in each group. DDP group received injection intraperitoneally （ip） at the dosage of 1 mg/kg （equal to 1/10 LD50）, once a day for 4 d. High and low dosage BSHYJDR groups received intragastric BSHYJDR at the dosages of 26.6 and 13.3 g/kg （20 and 10 times each of clinical adult dosage） respectively, while tumor-bearing model group received the equal volume of distilled water once a day for 10 d. On the 11^th d, the mice were weighed and killed, then the tumor was dissected and weighed, the repression rate （RR） was calculated according to the mean weight of tumor （MWT）. RESULTS： Compared to the model group （MWT： 1.30±0.73）, DDP group （MWT： 0.41±0.09, RR： 68.46%） had a significant difference in the inhibition of hepatocarcinoma H22 （P〈0.01）. High dosage BSHYJDR group （MWT： 0.69±0.29, RR： 46.92%） also had a significant difference in inhibition （P〈0.05）, while no difference was found in low dosage BSHYJDR group （MVVT： 0.85±0.34, RR： 34.62%） （P〉0.05）. When DDP was combined with high dosage BSHYJDR （MWT： 0.29±0.17, RR： 77.69%） and low dosage BSHYJDR （MWT： 0.38±0.21, RR： 70.77%） respectively, we could see improvement of the inhibition effect of DDP on transplanted hepatocarcinoma H22. DDP combined with high dosage BSHYJDR had a significant difference （P〈0.001） compared to DDP, while DDP combined with low dosage BSHYJDR only had a little improvement that is not remarkable. CONCLUSION： Chinese medicine BSHYJDR in combination with chemotherapy can inhibit transplanted hepatocarcinorna in mice.展开更多
目的探讨筋骨疗伤膏联合补肾接骨汤对老年下肢骨折患者术后肿胀及典型Wnt/β-链蛋白(Canonical Wnt/β-catenin pathway,Wnt/β-catenin)信号通路的影响。方法收集2021年1月—2022年7月在医院骨外科进行诊治的下肢骨折患者92例,随机数...目的探讨筋骨疗伤膏联合补肾接骨汤对老年下肢骨折患者术后肿胀及典型Wnt/β-链蛋白(Canonical Wnt/β-catenin pathway,Wnt/β-catenin)信号通路的影响。方法收集2021年1月—2022年7月在医院骨外科进行诊治的下肢骨折患者92例,随机数字法分为试验组(46例)及对照组(46例)。所有受试者予以切开复位内固定术,对照组术后接受常规康复手段和热水泡脚,试验组在对照组的基础上予以筋骨疗伤膏联合补肾接骨汤。对比两组临床恢复情况、肿胀程度、疼痛评分、血液流变学指标、Wnt/β-catenin信号通路血清蛋白水平、骨痂生长情况及不良反应。数据结果应用统计学软件SPSS 19.0加以处理。结果与对照组相比,试验组完全负重锻炼、骨折愈合时间缩短,骨折延迟愈合率较低(P<0.05)。与治疗前相比,两组治疗后肿胀程度、疼痛评分均明显降低(P<0.05),与对照组相比,试验组患者肿胀程度、疼痛评分较低(P<0.05)。与治疗前相比,两组治疗后β-catenin升高,β-Ⅰ型胶原羧基端肽(βisomer of C-terminal telopeptide of type Ⅰ collagen,β-CTX)及总Ⅰ型胶原氨基端延长肽(total type Ⅰ collagen amino terminal extender peptide,T-PINP)水平均明显降低(P<0.05),与对照组相比,试验组β-catenin水平较高,β-CTX及T-PINP水平较低(P<0.05)。与治疗前相比,两组骨痂量评分、骨痂密度评分均明显升高(P<0.05),与对照组相比,试验组治疗后骨痂量评分、骨痂密度评分较高(P<0.05)。与对照组相比,试验组并发症发生率较低(P<0.05)。结论通过筋骨疗伤膏联合补肾接骨汤可减轻老年下肢骨折患者的肿胀及疼痛程度,改善血液微循环,其治疗机制可能与调节Wnt/β-catenin信号通路具有密切相关性。展开更多
目的分析基于细胞程序性死亡受体1(Programmed death receptor-1,PD-1)/细胞程序性死亡受体-配体1(Programmed death receptor ligand-1,PD-L1)通路探讨补肾解毒散结方对晚期结直肠癌患者免疫微环境的影响。方法选择2020年1月-2021年12...目的分析基于细胞程序性死亡受体1(Programmed death receptor-1,PD-1)/细胞程序性死亡受体-配体1(Programmed death receptor ligand-1,PD-L1)通路探讨补肾解毒散结方对晚期结直肠癌患者免疫微环境的影响。方法选择2020年1月-2021年12月上海中医药大学附属曙光医院胃肠外科收治的50例晚期结直肠癌患者,按照随机数字表法分为研究组和对照组。对照组(n=25)采用mFOLFOX6化疗+PD-1抑制剂,研究组(n=25)在此基础上给予补肾解毒散结方,服用2周。分别于治疗前、治疗后(化疗4个周期),采用流式细胞仪检测T淋巴细胞亚群,酶联免疫吸附法检测血清PD-1、PD-L1水平,分析其表达与临床疗效及免疫微环境的关系。结果研究组的疾病控制率(Disease control rate,DCR)为64.0%,明显高于对照组36.0%(P<0.05);治疗后,研究组CD3^(+)、CD4^(+)水平明显升高(P<0.05),CD8^(+)、CD4^(+)/CD8^(+)较治疗前差异无统计学意义(P>0.05),研究组T细胞亚群各指标均较对照组显著改善(P<0.05);治疗后,两组体液免疫指标均明显升高(P<0.05),研究组IgA、IgM水平均高于对照组(P<0.05)。研究组治疗后外周血PD-1、PD-L1水平明显降低,且低于对照组(P<0.05);研究组患者中,有效组外周血CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+)及IgA、IgG、IgM水平明显升高,PD-1、PD-L1水平明显降低(P<0.05)。结论补肾解毒散结方可调节晚期结直肠癌患者的免疫微环境,改善临床疗效,其作用机制可能与抑制PD-1/PD-L1信号通路相关。展开更多
基金Supported by National Administration of Traditional Chinese Medicine:Qihuang Scholar (No.02045004)Collaborative Pilot Project of Clinical Traditional Chinese and Western Medicine for Major and Difficult Diseases in 2019 (No.070030003)。
文摘Objective: To evaluate the effect and safety of low-dose of apatinib and S-1 combined with Jianpi Bushen Jiedu Decoction(JBJD) in patients with metastatic colorectal cancer(mCRC) who have failed second or above lines treatment, in order to provide more treatment option for mCRC patients by integrated medicine. Methods: Thirteen patients were selected from a single-arm, open-label clinical study from April 2019 to September 2020. The patients were treated with low-dose apatinib(250 mg, once a day) and S-1(20 mg, twice a day) combined with JBJD for at least one cycle and were followed up to August 2021. The primary endpoint was disease progression-free survival(PFS). Disease control rate(DCR), objective response rate(ORR), and overall survival(OS) of patients were observed as the secondary endpoints. Adverse events were recorded as well. Results: The average age of the 13 patients was 56.5±13.0 years and 76.9% were male. The median PFS and median OS were 4.6 and 8.3 months, respectively. The ORR was 7.7%(1/13) while the DCR was 61.5%(8/13). The common adverse events were hypertension, proteinuria, elevated transaminase, and thrombocytopenia. One patient experienced thrombocytopenia of grade 3. Conclusions: Patients with mCRC after failure of the second or above lines of treatment may potentially benefit from the treatment of low-dose apatinib and S-1 combined with JBJD because of its similar effect as the standard dose of target therapy and relatively better safety.(Registration No. ChiCTR1900022673)
基金Supported by the Postdoctoral Science Foundation of China, No. [2001] 5
文摘AIM： To investigate the antitumor and synergistic effect of Chinese medicine “Bushen huayu jiedu recipe” （recipe for invigorating the kidney, removing blood stasis and toxic substances） and chemotherapy on mice hepatocarcinoma. METHODS： Bushen huayu jiedu recipe （BSHYJDR） consisting of Chinese Cassia Bark, Psoralea, Zedoary, Rhubarb, etc. is equal to 1.5 g/mL liquid of originated herbs after being decoded, filtered, and concentrated. Kunming mice, weighing 18-22 g, were injected with 0.2 mL ascitic hepatocarcinoma H22 containing 1 × 10^7 cells/mL into armpit of the right forelimb of mice. After 24 h, the mice were weighed and randomly divided into tumor-bearing model control group, cisplatin （DDP） group, BSHYJDR high dosage group, low dosage BSHYJDR group, DDP combined with high and low dosage BSHYJDR group, 10 mice in each group. DDP group received injection intraperitoneally （ip） at the dosage of 1 mg/kg （equal to 1/10 LD50）, once a day for 4 d. High and low dosage BSHYJDR groups received intragastric BSHYJDR at the dosages of 26.6 and 13.3 g/kg （20 and 10 times each of clinical adult dosage） respectively, while tumor-bearing model group received the equal volume of distilled water once a day for 10 d. On the 11^th d, the mice were weighed and killed, then the tumor was dissected and weighed, the repression rate （RR） was calculated according to the mean weight of tumor （MWT）. RESULTS： Compared to the model group （MWT： 1.30±0.73）, DDP group （MWT： 0.41±0.09, RR： 68.46%） had a significant difference in the inhibition of hepatocarcinoma H22 （P〈0.01）. High dosage BSHYJDR group （MWT： 0.69±0.29, RR： 46.92%） also had a significant difference in inhibition （P〈0.05）, while no difference was found in low dosage BSHYJDR group （MVVT： 0.85±0.34, RR： 34.62%） （P〉0.05）. When DDP was combined with high dosage BSHYJDR （MWT： 0.29±0.17, RR： 77.69%） and low dosage BSHYJDR （MWT： 0.38±0.21, RR： 70.77%） respectively, we could see improvement of the inhibition effect of DDP on transplanted hepatocarcinoma H22. DDP combined with high dosage BSHYJDR had a significant difference （P〈0.001） compared to DDP, while DDP combined with low dosage BSHYJDR only had a little improvement that is not remarkable. CONCLUSION： Chinese medicine BSHYJDR in combination with chemotherapy can inhibit transplanted hepatocarcinorna in mice.
文摘目的探讨筋骨疗伤膏联合补肾接骨汤对老年下肢骨折患者术后肿胀及典型Wnt/β-链蛋白(Canonical Wnt/β-catenin pathway,Wnt/β-catenin)信号通路的影响。方法收集2021年1月—2022年7月在医院骨外科进行诊治的下肢骨折患者92例,随机数字法分为试验组(46例)及对照组(46例)。所有受试者予以切开复位内固定术,对照组术后接受常规康复手段和热水泡脚,试验组在对照组的基础上予以筋骨疗伤膏联合补肾接骨汤。对比两组临床恢复情况、肿胀程度、疼痛评分、血液流变学指标、Wnt/β-catenin信号通路血清蛋白水平、骨痂生长情况及不良反应。数据结果应用统计学软件SPSS 19.0加以处理。结果与对照组相比,试验组完全负重锻炼、骨折愈合时间缩短,骨折延迟愈合率较低(P<0.05)。与治疗前相比,两组治疗后肿胀程度、疼痛评分均明显降低(P<0.05),与对照组相比,试验组患者肿胀程度、疼痛评分较低(P<0.05)。与治疗前相比,两组治疗后β-catenin升高,β-Ⅰ型胶原羧基端肽(βisomer of C-terminal telopeptide of type Ⅰ collagen,β-CTX)及总Ⅰ型胶原氨基端延长肽(total type Ⅰ collagen amino terminal extender peptide,T-PINP)水平均明显降低(P<0.05),与对照组相比,试验组β-catenin水平较高,β-CTX及T-PINP水平较低(P<0.05)。与治疗前相比,两组骨痂量评分、骨痂密度评分均明显升高(P<0.05),与对照组相比,试验组治疗后骨痂量评分、骨痂密度评分较高(P<0.05)。与对照组相比,试验组并发症发生率较低(P<0.05)。结论通过筋骨疗伤膏联合补肾接骨汤可减轻老年下肢骨折患者的肿胀及疼痛程度,改善血液微循环,其治疗机制可能与调节Wnt/β-catenin信号通路具有密切相关性。
文摘目的分析基于细胞程序性死亡受体1(Programmed death receptor-1,PD-1)/细胞程序性死亡受体-配体1(Programmed death receptor ligand-1,PD-L1)通路探讨补肾解毒散结方对晚期结直肠癌患者免疫微环境的影响。方法选择2020年1月-2021年12月上海中医药大学附属曙光医院胃肠外科收治的50例晚期结直肠癌患者,按照随机数字表法分为研究组和对照组。对照组(n=25)采用mFOLFOX6化疗+PD-1抑制剂,研究组(n=25)在此基础上给予补肾解毒散结方,服用2周。分别于治疗前、治疗后(化疗4个周期),采用流式细胞仪检测T淋巴细胞亚群,酶联免疫吸附法检测血清PD-1、PD-L1水平,分析其表达与临床疗效及免疫微环境的关系。结果研究组的疾病控制率(Disease control rate,DCR)为64.0%,明显高于对照组36.0%(P<0.05);治疗后,研究组CD3^(+)、CD4^(+)水平明显升高(P<0.05),CD8^(+)、CD4^(+)/CD8^(+)较治疗前差异无统计学意义(P>0.05),研究组T细胞亚群各指标均较对照组显著改善(P<0.05);治疗后,两组体液免疫指标均明显升高(P<0.05),研究组IgA、IgM水平均高于对照组(P<0.05)。研究组治疗后外周血PD-1、PD-L1水平明显降低,且低于对照组(P<0.05);研究组患者中,有效组外周血CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+)及IgA、IgG、IgM水平明显升高,PD-1、PD-L1水平明显降低(P<0.05)。结论补肾解毒散结方可调节晚期结直肠癌患者的免疫微环境,改善临床疗效,其作用机制可能与抑制PD-1/PD-L1信号通路相关。
