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.

Right- and left-sided colorectal cancers respond differently to traditional Chinese medicine.

AIM: To explore the differences in the responses of left-sided colorectal cancer (LSCRC) and right-sided colon cancer (RSCC) to traditional Chinese medicine (TCM). METHODS: Patients with postoperative stage I-III colorectal cancer (CRC) were enrolled and divided into the LSCRC with or without TCM and RSCC with or without TCM groups depending on the primary tumor side and TCM administration. Patients in the TCM group were given TCM for at least 6 mo. Our research adopted disease-free survival (DFS) as the primary endpoint. We applied a Cox proportional hazards regression model for the multivariate factor analysis using Stata 12.0 and SPSS 22.0 software for data analysis. RESULTS: Of the 817 patients included in our study, 617 had LSCRC (TCM group, n = 404; Non-TCM group, n = 213), and 200 had RSCC (TCM group, n = 132; Non-TCM group, n = 68). The 6-year DFS for patients with LSCRC was 56.95% in the TCM group and 41.50% in the Non-TCM group (P = 0.000). For patients with RSCC, the 6-year DFS was 52.92% in the TCM group and 37.19% in the Non-TCM group (P = 0.003). Differences between LSCRC and RSCC were not statistically significant regardless of TCM ingestion. CONCLUSION: Patients with either LSCRC or RSCC and who took TCM experienced longer DFS; furthermore, patients with RSCC benefited more from TCM in DFS.

Dietary attitudes and behaviours of women in China after the 2008 Wenchuan earthquake in three seismically different zones.

BACKGROUND AND OBJECTIVES: The sudden occurrence of the 2008 Wenchuan Earthquake not only devastated people's health, but also may have impacted on the psychological and dietary attitudes and behaviours of the survivors. Although the influence of natural disaster on people's health has been extensively investigated, there is a lack of information about the effects on people's dietary attitudes and behaviours. Our aim was to evaluate the influence of the Wenchuan earthquake on the dietary attitudes and behaviours of adult women from different zones of China in July 2008. METHODS AND STUDY DESIGN: 736 women, aged 18-55 years old, were randomly selected and interviewed after the earthquake. Women were selected from three zones: the earthquake zone (n=206), the shaking zone (n=326), and the non-seismic zone (n=204). RESULTS: Although nutrition knowledge mean scores of women in the three zones were relatively low, the women in the earthquake zone became more vigilant about the nutritional value and acceptability of food than women in the other two zones. Nevertheless, women in the earthquake zone also developed some arguably untoward, if understandable, behaviour after the disaster. They increased their consumption and tendency to stock instant food and snack items. That said, these findings were modulated by other factors such as age, residence, Body Mass Index (BMI), and nutrition knowledge itself, as were post-earthquake eating behaviours, as judged by the ordinal logistic regression analyses performed. CONCLUSIONS: The major Wenchuan earthquake was associated with differentials in dietary attitudes and behaviours among women by seismic zone.

Attenuated effects of Jianpi Qushi herbs on patients receiving FOLFOX4 after colorectal cancer surgery: A meta-analysis.

OBJECTIVE: To systematically review the attenuating effects of invigorating Pi (Spleen) and eliminating dampness (Jianpi Qushi, JPQS) herbs on post-operational colorectal cancer patients receiving FOLFOX4 [5-fluorouracil (5-FU) + folinic acid + oxaliplatin] treatment. METHODS: China National Knowledge Infrastructure, Wanfang Data, China Science and Technology Journal Database, PubMed/MEDLINE, EMBASE, and the Cochrane Library databases (up to May 2014) were searched in English or Chinese, and clinical trials with specifific inclusion criteria were collected. Data were analyzed by using Stata 12. RESULTS: The meta-analysis comprised 8 randomized clinical studies of 449 patients (238 in the treatment group and 211 in the control group). The results showed that JPQS herbs could improve the quality of life for post-operational colorectal cancer patients receiving FOLFOX4 [weighted mean difference (WMD) = 8.883, 95% confifidence interval (CI): 5.548 to 12.217]; alleviate the symptoms defifined by Chinese medicine [odds ratio (OR) = 5.741, 95% CI: 3.683 to 8.947]; and reduce the incidence rate of neutropenia [relative risk (RR) = 0.669, 95% CI: 0.503 to 0.888], decreased hemoglobin (RR = 0.654, 95% CI: 0.464 to 0.922), diarrhea (RR = 0.427, 95% CI: 0.275 to 0.662), nausea and vomiting (RR = 0.502, 95% CI: 0.390 to 0.648), and neurotoxic reactions (RR = 0.752, 95% CI: 0.595 to 0.951); however, the results showed no signifificant difference in the incidence rate of thrombocytopenia or liver and kidney dysfunction. CONCLUSION: JPQS herbs can improve the quality of life for patients undergoing FOLFOX4 treatment after colorectal cancer surgery, relieve symptoms, and somewhat reduce the adverse effects of FOLFOX4 regimen.

Zuo Jin Wan reverses P-gp-mediated drug-resistance by inhibiting activation of the PI3K/Akt/NF-κB pathway.

BACKGROUND: Zuo-Jin-Wan (ZJW), a traditional Chinese medicine formula, has been identified to be effective against drug resistance in cancer. In the present study, we investigated the effect of ZJW on acquired oxaliplatin-resistant and the PI3K/Akt/NF-κB pathway in vitro. METHODS: We tested the dose-response relationship of ZJW on reversing drug-resistance by CCK-8 assay and flow cytometry analysis in vitro. The protein expression of P-gp, MRP-2, LRP, and ABCB1 mRNA expression level were evaluated by Western blot and quantitative RT-PCR. The activities of PI3K/Akt/NF-κB pathway were also examined with or without ZJW, including Akt, IκB, p65 and their phosphorylation expression. RESULTS: We found that ZJW significantly enhanced the sensitivity of chemotherapeutic drugs and increased oxaliplatin (L-OHP)-induced cell apoptosis in a time- and dose-dependent manner. Moreover, both ZJW and a PI3K specific inhibitor (LY294002) suppressed phosphorylation of Akt (Ser473) and NF-κB, which is necessary in the activation of the PI3K/Akt/NF-κB pathway. The effect of ZJW in reversing drug-resistance and suppressing phosphorylation of Akt (Ser473) and NF-κB were weakened after treatment with a PI3K/Akt activator in HCT116/L-OHP cells. CONCLUSIONS: Our study has provided the first direct evidence that ZJW reverses drug-resistance in human colorectal cancer by blocking the PI3K/Akt/NF-κB signaling pathway, and could be considered as a useful drug for cancer therapy.

[Quantified diagnositic standard for large intestinal cancer of spleen qi deficiency syndrome.].

OBJECTIVE: To set a quantified diagnostic standard for large intestinal cancer of spleen qi deficiency syndrome. METHODS: The spleen qi deficiency syndrome was identified by experts on the basis of clinical epidemiological investigation of 311 patients suffering from large intestinal cancer. Corresponding points were assigned to the correlative factors (traditional Chinese medicine symptoms) on the basis of symptom differences between spleen qi deficiency syndrome and non-spleen-qi-deficiency syndrome. The best threshold was determined by receiver operating characteristic curve (ROC) according to syndrome differentiation from expert team, and the quantified diagnostic standard was established. The syndrome identification from the expert team which was regarded as golden standard was tested retrospectively. RESULTS: All the traditional Chinese medicine symptoms possibly related to spleen qi deficiency syndrome were analyzed based on the opinions of experts, and 28 symptoms were confirmed as candidate correlative factors. The occurrence of 11 symptoms between spleen qi deficiency syndrome and non-spleen-qi-deficiency syndrome showed statistical differences by means of crosstabs analysis (P<0.05). The 11 symptoms were filtered by logistic regression analysis, and tiredness, fatigue, loose stool, and poor appetite were finally determined as the symptoms relative to large intestinal cancer. These four symptoms were analyzed with conditional probability conversion and endowed with 16, 11, 4 and 8 points respectively. The diagnostic standard of spleen qi deficiency syndrome of large intestinal cancer was over 13 points. The sensitivity, specificity and accuracy of retrospective examination were all above 80%, and its positive likelihood ratio was 9.89. CONCLUSION: The quantified diagnostic standard for spleen qi deficiency syndrome of large intestinal cancer is in accordance with clinical characteristics of large intestine cancer and the characteristics of TCM syndrome diagnosis.

[Study of a qualitative diagnostic criterion for basic syndromes of traditional Chinese medicine in patients with primary liver cancer].

OBJECTIVE: To work out a qualitative diagnostic criterion for basic syndromes of traditional Chinese medicine in patients with primary liver cancer. METHODS: Based on the collection and analysis of related medical literature, clinical investigation, and experts' discussion, a preliminary qualitative diagnostic criterion for basic syndromes of traditional Chinese medicine in patients with primary liver cancer was formulated. Then it was used in clinic to be verified and revised repeatedly till it was improved to be a satisfied formal criterion. RESULTS: The basic syndromes listed in the qualitative diagnostic criterion for basic syndromes in patients with primary liver cancer consisted of two parts: excessive syndromes, including the syndromes of stagnation of qi, blood stasis, excess-heat and dampness, and deficient syndromes, including the syndromes of deficiency of qi, deficiency of blood, deficiency of yin and deficiency of yang. Each of the above syndromes could be diagnosed according to specific combination of its corresponding symptoms or signs. The clinical verification results showed that the total matching ratio was 73.92% between the diagnoses made according to the criterion and the diagnoses acquired from the experts' experience. CONCLUSIONS: The qualitative diagnostic criterion for basic syndromes of traditional Chinese medicine in patients with primary liver cancer is coincident with the experts' clinical practice. However, it needs to be further studied.