Mechanism of Preventing Recurrence of Stage II-III Colorectal Cancer Metastasis with Immuno-inflammatory and Hypoxic Microenvironment by a Four Ingredients Chinese Herbal Formula: A Bioinformatics and Network Pharmacology Analysis.

BACKGROUND: Colorectal Cancer (CRC) is one of the top three malignancies with the highest incidence and mortality. OBJECTIVE: The study aimed to identify the effect of Traditional Chinese Medicine (TCM) on postoperative patients with stage II-III CRC and explore the core herb combination and its mechanism. METHODS: An observational cohort study was conducted on patients diagnosed with stage II-III CRC from January 2016 to January 2021. The primary outcome was disease-free survival, which was compared between the patients who received TCM or not, and the secondary outcome was the hazard ratio. The relevance principle was used to obtain the candidate herb combinations, and the core combination was evaluated through an assessment of efficacy and representativeness. Then, biological processes and signaling pathways associated with CRC were obtained by Gene Ontology function, Kyoto Encyclopedia of Gene and Genomes pathway, and Wikipathway. Furthermore, hub genes were screened by the Kaplan-Meier estimator, and molecular docking was employed to predict the binding sites of key ingredients to hub genes. The correlation analysis was employed for the correlations between the hub genes and tumor-infiltrating immune cells and hypoxiarelated genes. Ultimately, a quantitative polymerase chain reaction was performed to verify the regulation of hub genes by their major ingredients. RESULTS: A total of 707 patients were included. TCM could decrease the metastatic recurrence associated with stage II-III CRC (HR: 0.61, log-rank P < 0.05). Among those patients in the TCM group, the core combination was Baizhu → Yinchen, Chenpi, and Fuling (C combination), and its antitumor mechanism was most likely related to the regulation of BCL2L1, XIAP, and TOP1 by its key ingredients, quercetin and tangeretin. The expression of these genes was significantly correlated with both tumor-infiltrating immune cells and hypoxia- related genes. In addition, quercetin and tangeretin down-regulated the mRNA levels of BCL2L1, XIAP, and TOP1, thereby inhibiting the growth of HCT116 cells. CONCLUSION: Overall, a combination of four herbs, Baizhu → Yinchen, Chenpi, and Fuling, could reduce metastatic recurrence in postoperative patients with stage II-III CRC. The mechanism may be related to the regulation of BCL2L1, XIAP, and TOP1 by its key ingredients quercetin and tangeretin.

[Clinical trial of treatment of frozen shoulder by intensive moxibustion plus acupuncture].

OBJECTIVE: To compare the clinical therapeutic effect of intensive moxibustion plus acupuncture and simple acupuncture therapy in the treatment of frozen shoulder so as to provide a reference for clinical practice. METHODS: A total of 60 patients with frozen shoulder were randomly divided into intensive moxibustion plus acupuncture group and simple acupuncture group (n＝30 per group). Acupoints Jianyu (LI15), Jianzhen (SI9), Jianliao (TE14), Tiaokou (ST38), Chengshan (BL57) and Ashi points (Extra) were punctured with filiform needles which were manipulated till the patients experienced feelings of soreness and distension in the local region, followed by retaining the needles for 40 min. For patients of the moxibustion plus acupuncture group, after acupuncture, an ignited moxa-stick segment was applied to the affected shoulder for 40－50 min. After the treatment, all patients were ordered to make a shoulder exercise (anteflexion, rear protraction, abduction and upthrow movements, etc.). The visual analogue scale (VAS) was used to assess the pain severity, and the Constant-Murley shoulder assessment scale (the total score is 100 points, including 15 points in pain severity and 20 points in daily living activities, 40 points in joint motion range, and 25 points in myodynamia) used to assess the functional state of the shoulder, and the "Standards for Diagnosis and Therapeutic Effect Evaluation of Diseases of Traditional Chinese Medicine"(1994) were employed to evaluate the therapeutic effect. RESULTS: Following the treatment, intra-group comparison showed that the VAS score was significantly reduced in both groups in comparison with their own pre-treatment (P<0.05), and the total scores of Constant-Murley scale, the scores of activities of daily living and active motion range, as well as the scores of pain integration and myodynamia, were all considerably increased in the two groups in comparison with their own pre-treatment (all P<0.05). The therapeutic effect of the moxibustion plus acupuncture was significantly superior to that of the simple acupuncture in reducing VAS score and increasing total score of Constant-Murley scale, and scores of activities of daily living and active motion range, as well as the scores of pain integration (P<0.05). Of the two 29 cases in the moxibustion plus acupuncture and simple acupuncture groups, 19 (65.52%) and 10 (34.48%) were cured, 8 (27.58%) and 12 (41.38%) experienced improvement, 2 (6.90%) and 7 (24.14%) were failed, with the effective rate being 93.10% and 75.86%, respectively. The therapeutic effective rate of the moxibustion plus acupuncture was evidently higher than that of the simple acupuncture (P<0.05)．. CONCLUSION: The therapeutic effect of intensive moxibustion plus acupuncture is superior to that of simple acupuncture in improving symptoms of frozen shoulder in patients.