参一胶囊联合FOLFOX4方案治疗索拉非尼耐药的晚期原发性肝癌的临床研究

目的 建立高效液相结合一测多评（HPLC-QAMS）法同时测定金果含片中哈巴苷、哈巴俄苷、柚皮芸香苷、橙皮苷、川陈皮素、橘红素、麦冬甲基黄烷酮A和甲基麦冬二氢高异黄酮B的方法。方法 采用Agilent HC C18色谱柱（250 mm×4.6 mm，5 μm），流动相为乙腈-0.05%磷酸溶液，梯度洗脱；检测波长为210 nm（哈巴苷和哈巴俄苷）和296 nm（柚皮芸香苷、橙皮苷、川陈皮素、橘红素、麦冬甲基黄烷酮A和甲基麦冬二氢高异黄酮B）；体积流量1.0 mL/min；进样量10 μL；柱温30℃。进行专属性试验、线性关系考察、精密度试验、稳定性试验、重复性试验、加样回收率试验。以橙皮苷为内参物，建立该成分与哈巴苷、哈巴俄苷、柚皮芸香苷、川陈皮素、橘红素、麦冬甲基黄烷酮A和甲基麦冬二氢高异黄酮B的相对校正因子（RCF），并计算金果含片中8种成分的含量，同时与外标法的测定结果进行比较，验证该方法的可行性。结果 哈巴苷、哈巴俄苷、柚皮芸香苷、橙皮苷、川陈皮素、橘红素、麦冬甲基黄烷酮A和甲基麦冬二氢高异黄酮B检测质量浓度的线性范围分别为6.54～163.50、2.27～56.75、8.16～204.00、17.95～448.75、1.88～47.00、0.54～13.50、1.48～37.00和0.76～19.00 μg/mL（r值范围0.999 1～0.999 8）；平均加样回收率及RSD值分别为99.85%（0.76%）、97.62%（1.07%）、100.09%（0.64%）、99.80%（0.71%）、97.48%（1.44%）、98.25%（1.60%）、96.90%（1.03%）、96.87%（1.31%），方法学验证结果均符合要求。HPLC-QAMS法计算值与外标法实测值无显著性差异。结论 所建立的HPLC-QAMS法简便、有效、准确，可用于金果含片中多指标成分含量的同时测定，为提升金果含片的质量控制方法提供参考依据。

Clinical study on Shenyi Capsules combined with FOLFOX4 chemotherapy regimen in treatment of sorafenib resistant advanced primary liver cancer

Objective To investigate the clinical effect of Shenyi Capsules combined with FOLFOX4 chemotherapy regimen in treatment of sorafenib resistant advanced primary liver cancer. Methods Patients (80 cases) with sorafenib resistant advanced primary liver cancer in the First Affiliated Hospital of Nanyang Medical College from March 2018 to January 2020 were divided into control and treatment groups according to admission parity order, and each group had 40 cases. Patients in the control group were given FOLFOX4 chemotherapy regimen, took 2 weeks as a cycle, treated for 4 cycles:Patients in the control group were intravenous infusion administered with Oxaliplatin Injection on the first day, 85 mg/m², were intravenous infusion administered with Calcium Folinate for injection on the first to second day, 200 mg/m², and were intravenous infusion administered with Fluorouracil Injection on the first to second day, 400 mg/m², continuous intravenous drip administered with Fluorouracil Injection of 600 mg/m². Patients in the treatment group were po administered with Shenyi Capsules on the basis of the control group at 0.5 h before meals, 20 mg/time, twice daily, treated for 8 weeks. After treatment, the clinical efficacies were evaluated, and the quality of life, the immune function, and the serum levels of tumor markers in two groups were compared. Results After treatment, the clinical effective rate (47.50%) and objective remission rate (82.50%) in the treatment group were higher than those in the control group (25.00%) and objective remission rate (55.00%) (P<0.05). After treatment, the each dimension scores of SF-36 in two groups were increased, and there was a difference between the same group before and after treatment (P<0.05). After treatment, the each dimension scores of SF-36 in the treatment group were higher than those in the control group (P<0.05). After treatment, the IgG, IgA, IgM, CD3⁺, and CD4⁺ in two groups were increased, and there was a difference before and after treatment in the same group (P<0.05). After treatment, the IgG, IgA, IgM, CD3⁺, and CD4⁺ in the treatment group were higher than those in the control group (P<0.05). After treatment, the levels of AFP, CEA, and CA-125 in two groups were decreased, and there was a difference between the same group before and after treatment (P<0.05). After treatment, the levels of AFP, CEA, and CA-125 in the treatment group were lower than those in the control group (P<0.05). Conclusion Shenyi Capsules combined with FOLFOX4 chemotherapy regimen in treatment of sorafenib resistant advanced primary liver cancer can effectively delay disease progression, improve patients'' quality of life and immune function, and reduce the serum level of tumor markers.