1.Mechanism of Modified Si Junzitang and Shashen Maidong Tang in Improving Sensitivity of Cisplatin in EGFR-TKI Resistant Lung Adenocarcinoma Cells Based on Aerobic Glycolysis
Yanping WEN ; Yi JIANG ; Liping SHEN ; Haiwei XIAO ; Xiaofeng YANG ; Surui YUAN ; Lingshuang LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):39-46
ObjectiveTo investigate the mechanism of modified Si Junzitang and Shashen Maidong Tang [Yiqi Yangyin Jiedu prescription (YQYYJD)] in enhancing the sensitivity of cisplatin in epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)-resistant lung adenocarcinoma cells based on aerobic glycolysis. MethodsThe effects of different concentrations of YQYYJD (0, 2, 3, 4, 5, 6, 7, 8 g·L-1) and cisplatin (0, 3, 6, 9, 12, 15, 18, 21, 24, 27 mg·L-1) on the proliferation and activity of PC9/GR cells were detected by the cell counting kit-8 (CCK-8) assay after 24 hours of intervention. The half-maximal inhibitory concentration (IC50) for PC9/GR cells was calculated to determine the concentrations used in subsequent experiments. PC9/GR cells were divided into blank group (complete medium), YQYYJD group (5 g·L-1), cisplatin group (12 mg·L-1), and combined group (YQYYJD 5 g·L-1 + cisplatin 12 mg·L-1). After 24 hours of intervention, cell viability was measured using CCK-8 assay. Cell proliferation was assessed by colony formation assay, and cell migration was evaluated by scratch and Transwell assays. Glucose consumption, lactate production, and adenosine triphosphate (ATP) levels were measured by colorimetric assays. The expression levels of glycolysis-related proteins, including hexokinase 2 (HK2), phosphofructokinase P (PFKP), pyruvate kinase M2 (PKM2), lactate dehydrogenase A (LDHA), glucose transporter 1 (GLUT1), and monocarboxylate transporter 4 (MCT4), were determined by Western blot. ResultsBoth YQYYJD and cisplatin inhibited the viability of PC9/GR cells in a concentration-dependent manner. The IC50 of PC9/GR cells for YQYYJD and cisplatin were 5.15 g·L-1 and 12.91 mg·L-1, respectively. In terms of cell proliferation, compared with the blank group, the cell survival rate and the number of colonies formed in the YQYYJD group, cisplatin group, and combined group were significantly decreased (P<0.01). Compared with the YQYYJD and cisplatin groups, the combined group showed a further significant reduction in cell survival rate and colony formation (P<0.01). In terms of cell migration, compared with the blank group, the cell migration rate and the number of cells passing through the Transwell membrane in the YQYYJD group, cisplatin group, and combined group were significantly decreased (P<0.01). Compared with the YQYYJD and cisplatin groups, the combined group exhibited a further significant reduction in cell migration rate and the number of cells passing through the Transwell membrane (P<0.01). In terms of glycolysis, compared with the blank group, glucose consumption, lactate production, and ATP levels in the YQYYJD group, cisplatin group, and combined group were significantly decreased (P<0.01). Compared with the YQYYJD and cisplatin groups, the combined group showed a further significant reduction in glucose consumption, lactate production, and ATP levels (P<0.05). Compared with the blank group, the protein expression levels of HK2, PFKP, PKM2, and LDHA in the YQYYJD, cisplatin, and combined groups were significantly decreased (P<0.01). The combined group showed a further significant reduction in the expression levels of these proteins compared with the YQYYJD and cisplatin groups (P<0.01). No significant differences were observed in the protein expression levels of GLUT1 and MCT4 among the groups. ConclusionYQYYJD can synergistically inhibit the proliferation and migration of PC9/GR cells and enhance their sensitivity to cisplatin. The mechanism may be related to the downregulation of the expression of glycolysis-related rate-limiting enzymes, including HK2, PFKP, PKM2, and LDHA, thereby inhibiting glycolysis.
2.A randomized controlled clinical study on the prevention and treatment of adverse bleeding events caused by chemotherapy in patients with advanced lung cancer with Yiqi Yangxue Shengsui (益气养血生髓方) Formula
Yu LIAO ; Fangfang LIU ; Cheng LI ; Surui YUAN ; Lingshuang LIU
Adverse Drug Reactions Journal 2025;27(10):577-583
Objective:To observe the clinical effect of the Yiqi Yangxue Shengsui Formula in the prevention and treatment of adverse bleeding events caused by platinum-based dual drugs combined with bevacizumab chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). Methods:A prospective, single-center, randomized controlled trial design was adopted. The research subjects were patients with stage Ⅲb-Ⅳb non-squamous NSCLC who were hospitalized at Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from December 2022 to March 2024. Patients who met the inclusion criteria were randomly assigned to the experimental group and the control group in a 1∶1 ratio. The control group received a platinum-based doublet regimen [pemetrexed disodium for injection+cisplatin/carboplatin, or paclitaxel protein-bound for injection+cisplatin/carboplatin] combined with bevacizumab for 4 courses of treatment; the experimental group was treated with the same regimen plus the traditional Chinese medicine Yiqi Yangxue Shengsui Formula, nourishing blood and generating bone marrow. The primary observation index was the incidence and grade of adverse bleeding events during the 4 courses of treatment. The secondary observation indices were the occurrence time and duration of bleeding, the grade of the lowest platelet count during treatment, the platelet count grade at the time of bleeding, and coagulation function indicators. Results:A total of 77 patients were included, with 39 in the experimental group and 38 in the control group. Among them, 29 were male (37.7%) and 48 were female (62.3%); 35 were aged 65 years or older and 42 were younger than 65 years. There were no statistically significant differences between the 2 groups in terms of gender, age, lung cancer stage, pathological type, and chemotherapy drug selection ( P> 0.05). The incidence of adverse bleeding events in the experimental group was significantly lower than that in the control group [17.9%(7/39) vs. 39.5%(15/38), P=0.037]. There was no statistically significant difference in the grading of adverse bleeding events between the 2 groups ( P>0.05). The duration of bleeding in the experimental group was shorter than that in the control group [(2.57±1.13) days vs. (5.67±1.80) days, P<0.001]. The minimum platelet count classification during the treatment period, and the platelet count classification at the time of bleeding in the experimental group were both better than those in the control group ( P<0.05). The prothrombin time and international normalized ratio when bleeding occurred in the experimental group were both lower than those in the control group [(10.96±0.39) s vs. (11.49±0.50) s and 0.97±0.04 vs. 1.02±0.06, P<0.05]. There were no statistically significant differences between the 2 groups of patients in terms of activated partial thromboplastin time, fibrinogen degradation products and D-dimer ( P>0.05). Conclusion:The Yiqi Yangxue Shengsui formula can effectively prevent and treat bleeding adverse events related to platinum-based dual-drug chemotherapy combined with bevacizumab in patients with advanced NSCLC. The mechanism may be related to the increase of platelet count and the improvement of exogenous coagulation function indicators.
3.A randomized controlled clinical study on the prevention and treatment of adverse bleeding events caused by chemotherapy in patients with advanced lung cancer with Yiqi Yangxue Shengsui (益气养血生髓方) Formula
Yu LIAO ; Fangfang LIU ; Cheng LI ; Surui YUAN ; Lingshuang LIU
Adverse Drug Reactions Journal 2025;27(10):577-583
Objective:To observe the clinical effect of the Yiqi Yangxue Shengsui Formula in the prevention and treatment of adverse bleeding events caused by platinum-based dual drugs combined with bevacizumab chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). Methods:A prospective, single-center, randomized controlled trial design was adopted. The research subjects were patients with stage Ⅲb-Ⅳb non-squamous NSCLC who were hospitalized at Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from December 2022 to March 2024. Patients who met the inclusion criteria were randomly assigned to the experimental group and the control group in a 1∶1 ratio. The control group received a platinum-based doublet regimen [pemetrexed disodium for injection+cisplatin/carboplatin, or paclitaxel protein-bound for injection+cisplatin/carboplatin] combined with bevacizumab for 4 courses of treatment; the experimental group was treated with the same regimen plus the traditional Chinese medicine Yiqi Yangxue Shengsui Formula, nourishing blood and generating bone marrow. The primary observation index was the incidence and grade of adverse bleeding events during the 4 courses of treatment. The secondary observation indices were the occurrence time and duration of bleeding, the grade of the lowest platelet count during treatment, the platelet count grade at the time of bleeding, and coagulation function indicators. Results:A total of 77 patients were included, with 39 in the experimental group and 38 in the control group. Among them, 29 were male (37.7%) and 48 were female (62.3%); 35 were aged 65 years or older and 42 were younger than 65 years. There were no statistically significant differences between the 2 groups in terms of gender, age, lung cancer stage, pathological type, and chemotherapy drug selection ( P> 0.05). The incidence of adverse bleeding events in the experimental group was significantly lower than that in the control group [17.9%(7/39) vs. 39.5%(15/38), P=0.037]. There was no statistically significant difference in the grading of adverse bleeding events between the 2 groups ( P>0.05). The duration of bleeding in the experimental group was shorter than that in the control group [(2.57±1.13) days vs. (5.67±1.80) days, P<0.001]. The minimum platelet count classification during the treatment period, and the platelet count classification at the time of bleeding in the experimental group were both better than those in the control group ( P<0.05). The prothrombin time and international normalized ratio when bleeding occurred in the experimental group were both lower than those in the control group [(10.96±0.39) s vs. (11.49±0.50) s and 0.97±0.04 vs. 1.02±0.06, P<0.05]. There were no statistically significant differences between the 2 groups of patients in terms of activated partial thromboplastin time, fibrinogen degradation products and D-dimer ( P>0.05). Conclusion:The Yiqi Yangxue Shengsui formula can effectively prevent and treat bleeding adverse events related to platinum-based dual-drug chemotherapy combined with bevacizumab in patients with advanced NSCLC. The mechanism may be related to the increase of platelet count and the improvement of exogenous coagulation function indicators.
4.Study of Symptom Burden and Symptom Clusters at the End of Thoracic Radiotherapy in 220 Patients with Lung Cancer
Lijun SONG ; Jie LIU ; Simeng REN ; Xuejiao MA ; Surui YUAN ; Daorui LI
World Science and Technology-Modernization of Traditional Chinese Medicine 2023;25(6):2140-2146
Objective To investigate the characteristics of symptom burden and extract symptom clusters in lung cancer patients at the end of thoracic radiotherapy.Methods Lung cancer patients receiving Thoracic Radiotherapy were collected from 20 tertiary hospitals in China,including Guang'anmen Hospital of the Chinese Academy of Traditional Chinese Medicine,during November 2014—September 2017,and the MDASI-TCM scale assessed patient symptoms at the end of radiotherapy,and descriptive statistics and exploratory factor analysis explored symptom burden and the distribution of TCM symptom clusters.Results At the end of radiotherapy,45.1%of patients reported two or more moderate to severe symptoms,with fatigue being the most prevalent and severe symptom.Fatigue(31.4%),cough(30.9%),expectoration(24.1%),distress(23.2%)and shortness of breath(20.9%)were the top five symptoms from the highest to the lowest in the incidence of moderate to severe symptoms.The enjoyment of life(36.4%)had the highest incidence of interference with moderate to severe symptoms.Exploratory Factor analysis extracted three symptom clusters,namely the excessive heat and damaged yin-Spleen and stomach disorders related symptom cluster,the heart and spleen-deficient related symptom cluster,and the lung qi-unfriendly related symptom cluster,with a cumulative variance contribution of 70.1%.Conclusion Lung cancer patients undergoing thoracic radiotherapy have a certain symptom burden at the end of radiotherapy.The identification of symptom burden and symptom group characteristics is conducive to promoting standardization of TCM syndrome differentiation and laying a preliminary foundation for formulating reasonable and effective TCM intervention measures in the future.

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