Evaluation of efficacy and safety for compound kushen injection combined with intraperitoneal chemotherapy for patients with malignant ascites: A systematic review and meta-analysis.

Objectives: Compound Kushen injection (CKI) combined with intraperitoneal chemotherapy (IPC) is widely used in the treatment of malignant ascites (MA). However, evidence about its efficacy and safety remains limited. This review aimed to evaluate the efficacy and safety of CKI combined with IPC for the treatment of MA. Methods: Protocol of this review was registered in PROSPERO (CRD42022304259). Randomized controlled trials (RCTs) on the efficacy and safety of IPC with CKI for the treatment of patients with MA were searched through 12 electronic databases and 2 clinical trials registration platforms from inception until 20 January 2023. The Cochrane risk-of-bias tool was used to assess the quality of the included trials through the risk of bias assessment. We included RCTs that compared IPC single used or CKI combined with IPC for patients with MA schedule to start IPC. The primary outcome was identified as an objective response rate (ORR), while the secondary outcomes were identified as the quality of life (QoL), survival time, immune functions, and adverse drug reactions (ADRs). The Revman5.4 and Stata17 software were used to calculate the risk ratio (RR) at 95% confidence intervals (CI) for binary outcomes and the mean difference (MD) at 95% CI for continuous outcomes. The certainty of the evidence was assessed according to the GRADE criteria. Results: A total of 17 RCTs were assessed, which included 1200 patients. The risk of bias assessment of the Cochrane risk-of-bias tool revealed that one study was rated high risk and the remaining as unclear or low risk. Meta-analysis revealed that CKI combined with IPC had an advantage in increasing ORR (RR = 1.31, 95% CI 1.20 to 1.43, p < 0.00001) and QoL (RR = 1.50, 95% CI 1.23 to 1.83, p < 0.0001) when compared with IPC alone. Moreover, the combined treatment group showed a lower incidence of myelosuppression (RR = 0.51, 95%CI 0.40-0.64, p < 0.00001), liver dysfunction (RR = 0.33, 95%CI 0.16 to 0.70, p = 0.004), renal dysfunction (RR = 0.39, 95%CI 0.17 to 0.89, p = 0.02), and fever (RR = 0.51, 95%CI 0.35 to 0.75, p = 0.0007) compared to those of the control group. The quality of evidence assessment through GRADE criteria showed that ORR, myelosuppression, and fever were rated moderate, renal dysfunction and liver dysfunction were rated low, and QoL and abdominal pain were rated very low. Conclusion: The efficacy and safety of CKI combined with IPC were superior to that with IPC alone for the treatment of MA, which indicates the potentiality of the treatment. However, more high-quality RCTs are required to validate this conclusion. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022304259], identifier [PROSPERO 2022 CRD42022304259].

Ultra-Performance Liquid Chromatography/Mass Spectrometry-Based Metabolomics for Discovering Potential Biomarkers and Metabolic Pathways of Colorectal Cancer in Mouse Model (ApcMin/+) and Revealing the Effect of Honokiol.

Endogenous metabolites are a class of molecules playing diverse and significant roles in many metabolic pathways for disease. Honokiol (HNK), an active poly-phenolic compound, has shown potent anticancer activities. However, the detailed crucial mechanism regulated by HNK in colorectal cancer remains unclear. In the present study, we investigated the therapeutic effects and the underlying molecular mechanisms of HNK on colorectal cancer in a mouse model (ApcMin/+) by analyzing the urine metabolic profile based on metabolomics, which is a powerful tool for characterizing metabolic disturbances. We found that potential urine biomarkers were involved in the metabolism of compounds such as purines, tyrosines, tryptophans, etc. Moreover, we showed that a total of 27 metabolites were the most contribution biomarkers for intestinal tumors, and we found that the citrate cycle (TCA cycle) was regulated by HNK. In addition, it was suggested that the efficacy of HNK was achieved by affecting the multi-pathway system via influencing relevant metabolic pathways and regulating metabolic function. Our work also showed that high-throughput metabolomics can characterize the regulation of metabolic disorders as a therapeutic strategy to prevent colorectal cancer.

[Research of Feiliuping Gao and its combination with different types of drugs intervention on expression of PI3K/AKT/NF-κB in lung metastatic microenvironment].

The aim of this paper was to observe the effect of Feiliuping Gao and its combination with different types of drugs intervention on the expression of PI3K/AKT/NF-κB in lung metastatic microenvironment, and to reveal the advantage of Chinese medicine intervention time on the key molecule in lung metastatic microenvironment. The mouse model of Lewis lung carcinoma was established, and lung tissues were collected at 14 days, 21 days and 28 days after the intervention of Feiliuping Gao, and the expressions of PI3K, AKT and NF-κB were detected by immunohistochemistry and Western blot. At 14 days, there was no significant difference in PI3K expression between each group and the control group. The expression of AKT protein was significantly inhibited in the celecoxib (CLB) group, the Feiliuping Gao (FLP) combination with cyclophosphamide (FLP+CTX) group, and the Feiliuping Gao combination with celecoxib (FLP+CLB) group (P<0.05). The inhibition of AKT protein expression in FLP+CLB group was superior. The FLP+CLB group can inhibit the expression of NF-κB protein (P<0.05). At 21 days, compared with the control group, the expression of PI3K was inhibited in FLP group and the FLP+CTX group (P<0.05), while the expression of PI3K was best inhibited in the FLP+CLB group (P<0.001). Only the FLP+CLB group could significantly inhibit the expression of AKT protein (P<0.01). The FLP+CTX group had the best effect in inhibiting the expression of NF-κB protein (P<0.001). At 28 days, compared with the control group, the expression of PI3K and AKT was inhibited in the FLP+CLB group (P<0.001). Feiliuping ointment combination with celecoxib has an advantage in regulating the expression of PI3K/AKT/NF-κB molecules in lung metastatic microenvironment.

Chinese herbal decoction based on syndrome differentiation as maintenance therapy in patients with extensive-stage small-cell lung cancer: an exploratory and small prospective cohort study.

Objective. To investigate the treatment effect and treatment length of Chinese herbal decoction (CHD) as maintenance therapy on patients with extensive-stage small-cell lung cancer (ES-SCLC) and to reflect the real syndrome differentiation (Bian Zheng) practices of traditional Chinese medicine (TCM). Patients and Methods. Different CHDs were prescribed for each patient based on syndrome differentiation. The length of CHD treatment was divided into two phases for analyzing progression-free survival (PFS) and postprogression survival (PPS). Results. Three hundred and fifty-seven CHDs were prescribed based on syndrome differentiation during the study period. Median PFS was significantly longer in patients who received CHD >3 months than patients who received CHD ≤3 months in the first phase (8.7 months versus 4.5 months; hazard ratio (HR), 0.52; 95% confidence interval (CI), 0.41-0.99; P = 0.0009). Median PPS was significantly longer in patients who received CHD >7 months than patients who received CHD ≤7 months in the second phase (11.7 months versus 5.1 months; HR, 2.32; 95% CI, 1.90-2.74; P = 0.002). Conclusion. CHD could improve PFS and PPS, which are closely related to treatment time and deepness of response of first-line therapy. In addition, CHD could improve body function and keep patients in a relatively stable state.

[Effect of feiliuping ointment and its disassembled prescriptions on dendritic cell of mice with transplanted Lewis lung cancer].

OBJECTIVE: To explore the possible immuno-regulating mechanism of action of Chinese drugs in different combinations (assembled depending different therapeutic principles) through observing the effects of Feiliuping ointment (FLP) and its disassembled prescriptions on dendritic cells (DC) in blood, spleen and tumor in mice with transplanted Lewis lung cancer (LLC). METHODS: Percentages of DC in blood, spleen and tumor of mice with transplanted LLC treated by FLP and its disassembled prescriptions were estimated, and the S-100 protein expression in tumor tissue was detected by immunohistochemical method. RESULTS: The percentage of DC (per thousand) in tumor bearing mice was 0.43 +/- 0.26 in peripheral blood, and 0.32 +/- 0.16 in spleen, significantly lower than those in normal mice 4.68 +/- 0.90 and 3.68 +/- 1.58, P<0.01); and S-100 protein expression in tumor was weakened. After FLP treatment, the percentages of DC (per thousand) in tumor bearing mice were increased to 2.55 +/- 0.29 in peripheral blood and 2.70 +/- 0.63 in spleen (P<0.01), with the S-100 protein expression in tumor tissue up-regulated significantly (P<0.01). Study on different assembled prescriptions of FLP showed that the qi supplementing components of FLP displayed the optimal actions. CONCLUSION: FLP, a Chinese herbal prescription made depending on Chinese medicine therapeutic principle of strengthening body resistance and consolidating constitution, has an obvious anti-tumor effect, to improve the immunological anti-tumor function of organism by promoting the amount and expression of DC might be the possible intrinsic mechanism.