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Background: In patients with metastatic colorectal cancer (mCRC), Quxie Cap-sule (QX)—a combination of conventional therapy (including chemotherapy, targeted therapy or supportive care)—has shown a significant overall survival benefit compared with placebo and might have the property of dual effects of antitumor and immunity enhancement, both mediated by the microbiome. In preclinical models, QX has also shown activity against colorectal cancer. This study aimed to describe how the aforementioned effects of QX look after when focusing on the patients in third or above line setting. Methods: A Simon’s Minimax two-stage phase II design was used in this study, which enrolled mCRC patients who progressed after second-line treatment. Patients received conventional therapy plus QX until disease progression or unacceptable toxicity. Before and after 1-month intervention, we collected patients’ stool samples for microbiome analysis by 16s rRNA sequencing approaches. And the microbiome analysis before and after 1-month intervention was done through bioinformation analysis platform. Results: Fifteen patients were enrolled and gut microbiome were analyzed from 7 of 10 patients that with PFS over 3.7 months. Microbiome community analysis on genus level showed that the proportion of Lachnospiraceae_UCG-001 (0.04% vs 1.06%, P = .02249) significantly increased after conventional therapy plus QX while the proportion of Alistipes (2.96% vs 1.35%, P = .03461), Flavonifractor (0.04% vs 0.02%, P = .02249), Bifidobacterium (6.11% vs 1.14%, P = .02249) and Butyricimonas (0.24% vs 0.11%, P = .03603) significantly decreased after intervention . LEfSe analysis showed that after intervention, samples were highly related with unclassified-f-lachnospiraceae , Eubacterium and Lachnospiraceae_UCG-001 . Conclusions: Decrease of gut bacteria with potential roles in carcinogenesis of colorectal cancer and increase in the abundance of gut anticancer bacteria such as Lachnospiraceae may partly explain how conventional therapy combined with QX can influence carcinogenesis and tumor progression in colon cancer. Trial registration: Chinese Clinical Trial Registry (ChiCTR2100053874).

Objective: To investigate the role of Traditional Chinese Medicine (TCM) syndrome type, gut microbiome distribution, and host immunity function in predicting the early and advanced clinical stages of colorectal cancer (CRC). Methods: A cross-sectional case-control study was performed which included 48 early stage and 48 advanced patients with CRC enrolled from March 2018 to December 2020. 16S rRNA gene sequencing was performed to analyze the gut microbiomes of the patients, while T and B lymphocyte subsets in peripheral blood were assessed using flow cytometry. TCM syndrome type was measured using the spleen deficiency syndrome (SDS) scale. Results: The abundance levels of Prevotella, Escherichia-Shigella , and Faecalibacterium in the gut microbiota were significantly increased in the advanced group, while Bacteroides was significantly decreased. Phascolarctobacterium was detectable only in the early metaphase group, whereas Alistipes was detectable only in the advanced group. The lymphocyte ( P = .006), T helper cell (TH) ( P = .002), cytotoxic T cell (TC) ( P = .003), double positive T cell (DPT) ( P = .02), and total T counts ( P = .001) were significantly higher in the early metaphase group than in the advanced metaphase group. Compared with patients with early stage CRC, the advanced group had a higher SDS score. After adjusting for clinical stage, Spearman’s correlation analysis showed interactions among gut microbiome abundance, T cell level, and SDS score. Multivariate logistic analysis showed that after controlling for the SDS score, abundance of Alistipes and Faecalibacterium , and double negative T cell (DNT) level, DPT was significantly associated with a lower risk of advanced-stage disease (hazard ratio, 0.918; P = .022). Conclusion: Our study suggested associations between clinical stage, SDS, gut microbiota, and T lymphocytes, which provided insights for a potential prediction model for the disease progression of CRC.

Aim: Quxie capsule (QX), a compound of 21 kinds of Traditional Chinese Medicine (TCM) herbs, has been used to treat patients with metastatic colorectal cancer (mCRC) and could suppress the growth of colon cancer. However, the mechanisms of QX inhibiting colorectal cancer remain unclear. In current study, we attempted to determine the anti-colorectal cancer (CRC) effects of QX and the mechanisms of QX in alleviating colorectal cancer. Methods: A colitis-associated colon cancer (CAC) model was established by intraperitoneally injecting mice with AOM followed by 3 cycles of 2% DSS in water. During establishment of CAC model, we orally gavaged mice with QX. Hematoxylin and eosin (H&E) and immunohistochemistry were performed to assess lesion of the colonic tumors. The expression of pro-inflammatory cytokines in colonic tumors was measured by qPCR. The proportion of immune cells in colonic tumors was analyzed by flow cytometry. Internal transcribed spacer (ITS) sequencing and 16S rRNA gene sequencing were performed to detect intestinal microbiota. The expression of glycolytic related enzymes, lactate production, and extracellular acidification rate (ECAR) were used to assess the level of aerobic glycolysis. Results: QX markedly inhibited intestinal tumorigenesis by decreasing the expression of pro-inflammatory cytokines and the proportion of myeloid-derived suppressor cells (MDSCs), and increasing the proportion of CD8 + T cells in colon tumors. Fecal microbiota sequencing revealed that QX increased the relative abundances of intestinal symbiotic probiotics, such as, Lactobacillus , Bifidobacterium and Faecalibacterium genera. What’s more, opportunistic pathogens, Bacteroides genera and Aspergillus - Aspergillus fumigatus , exhibited remarkably reduced abundances in mice treated with QX compared with untreated CAC mice. Further experiments showed that QX significantly reduced glycolysis of colon tumor and suppressed A. fumigatus -induced glycolytic metabolism of colon cancer cells. Conclusions: QX alleviates the development of CRC at least in part through modulating intestinal microbiota and reducing A. fumigatus -induced aerobic glycolysis of colon cancer cells.

Integrative oncology has developed for about 20 years in some countries; however, integrative oncology is still a relative new term for most China’s oncologists. Thus, it is essential to summarize the experience and expertise, share details of differing existing models and discuss future perspectives to help define and guide practice in integrative oncology in China. This study presents a summary of the basic characteristics, status, and challenges of integrative oncology in China, and also reports on China’s integrative physicians’ service delivery, clinical practice and research patterns of integrative oncology by an online national survey, including 405 oncologists. It is easy for cancer patients to access to integrative therapies in China. Public funding is sufficient for integrative oncology in China, and services are often provided through general hospitals and academic hospitals. Most (95.3%) of oncologists showed a positive attitude toward the development of integrative oncology. More than half (55.6%) of the oncologists worried about the influence on integrative oncology of COVID-19, especially for routine treatment, follow-up and holding seminars. We found that integrative oncology in China has swiftly developed in recent years. However, we suggest that standard diagnosis and treatment patterns and national professional guidelines should be set up as soon as possible.

Introduction: Spleen Deficiency Syndrome (SDS) is recognized as one of the most common Traditional Chinse Medicine (TCM) syndromes in patients with colorectal cancer (CRC). However so far there is no existing patient-reported outcome (PRO) to evaluate SDS. Our study aimed to develop and validate a PRO TCM-SDS scale for CRC in China. Methods: We developed an initial 8-item TCM-SDS scale for CRC based on literature review and consultation with experts. We then pilot tested the scale ( n = 40) and performed item revision. We conducted a survey study among CRC patients from oncology clinics at a TCM Hospital to further determine the reliability and validity of the scale. Results: Among 100 patients finally enrolled and analyzed in the survey study, 46% were female with median age of 60 years old, 77% had left side tumors and 23% had stage IV disease. Factor loading indicated that there were three domains within TCM-SDS scale. The final TCM-SDS scale involves 5 items including “ I feel loss of appetite,” “I feel abdomen fullness,” “I feel my arms and legs lack strength,” “I feel short of breath when talking,” and “My stool is formless” (Cronbach’s alpha coefficient 0.76). We calculated the total score of the scale by summing the 5 individual items and normalizing them to a value maximum of 10, with higher scores indicating greater burden of spleen deficiency syndrome. The average spleen deficiency score for all patients was 3.55 ± 1.54. Among them, those who had stage IV disease had higher scores than stage I-III patients (4.30 vs 3.38, P = .015). Test-retest reliability after 2 weeks showed Pearson coefficient of 0.67 and all items were highly related ( P

Aim: Quxie capsule(QX), a TCM compound, had shown benefit on survival outcomes for metastatic colorectal cancer(mCRC) patients and could inhibit tumor growth through immune regulation. This study aimed to evaluate whether such effect is associated with gut microbiome modulation. Method: We conducted a randomized double-blinded placebo controlled clinical trial in Xiyuan Hospital, China Academy of Chinese Medical Sciences. All patients were randomly assigned into QX or placebo control group. Before and after 1-month interventions, we collected patients’ stool samples for microbiome analysis by 16s rRNA sequencing approaches, as well as blood samples to analyze T lymphocyte subsets by flow cytometry methods. Microbiome analysis among groups was done through bioinformation analysis platform. The study had been proved by the ethics committee of Xiyuan Hospital (2016XLA122-1) had been registered on Chinese Clinical Trial Registry (registration number: ChiCTR2000029599). All patients consented before enrollment. Results: We randomly assigned 40 patients and 34 were finally analyzed. Among them, 29% were female, with an average age of 63 years old, and 74% had liver or lung metastasis. Both CD4 T(TH) cell and CD8 T(TC) cell counts increased after QX treatment, while TH cells were significantly more in QX than in control group (737 vs 449, P = .024). Microbiome community analysis on Class level showed that the proportion of Actinobacteria declined in the control group, but significantly increased after QX treatments (0.83% vs 4.7%, P = .017). LEfSe analysis showed that after treatments, samples from QX group were highly related with Oscillibacter , Eubacterium , and Lachnospiraceae. RDA analysis showed that after QX interventions, stool samples and microbiome species had relevance with TC/TH cells counts but were not statistically significant. Heatmap analysis on Genus level revealed that after QX treatments, higher amounts of TH cells were significantly associated with less abundance of g_Bifidobacterium (coef. −0.76, P = .002), Collinsella (coef.−0.61, P = .02), Ruminiclostridium_ 9 (coef. −0.64, P = .01). Conclusion: QX capsule could enhance TH cells level among mCRC patients and increase the abundance of gut anticancer bacteria such as Actinobacteria as well as butyrate-producing bacteria such as Lachnospiraceae. These results indicated that QX capsule might have the property of dual effects of antitumor and immunity enhancement, both mediated by the microbiome.

Quxie capsule (QX), a herbal remedy used in traditional Chinese medicine, is routinely used in advanced colorectal cancer treatment in Xiyuan Hospital in Beijing, China. However, the mechanism(s) underlying the effect of QX in colorectal cancer remain unclear, which hampers the optimal use of QX for the treatment of the disease. The transcription factor forkhead box O1 (Foxo1) plays important roles in regulation of cell cycle, apoptosis, and immune response in various cancers. In this study, we examined the antitumor efficacy of QX in a mouse model of colorectal cancer and further investigated the mechanism by which QX regulated Foxo1 protein-mediated pathways. QX administered via gavage daily for 2 weeks in mice carrying CT26 mouse colon tumors resulted in significantly lower mean tumor weight (0.93 ± 0.32 g) compared with that in vehicle control-treated mice (1.57 ± 0.57 g, P

Background: Traditional Chinese medicine (TCM) is widely used among Chinese cancer patients. However, little is known about Chinese patients’ expectations and barriers toward using TCM for cancer. Methods: We conducted a cross-sectional survey within a patient-support group, the Beijing Anti-Cancer Association. We measured the outcome, Chinese cancer survivors’ expectations and barriers toward TCM utilization, using a modified version of ABCAM (Attitudes and Beliefs towards Complementary and Alternative Medicine), the ABTCM (Attitudes and Beliefs towards Traditional Chinese Medicine). We used multivariate models to evaluate the impact of socioeconomic status and clinical factors on their expectations and barriers (including treatment concerns and logistical challenges domain) toward TCM. Results: Among 590 participants, most patients expected TCM to boost their immune system (96%), improve their physical health (96%), and reduce symptoms (94%). Many had logistical challenges (difficulty decocting herbs (58%) and finding a good TCM physician (55%)). A few were concerned that TCM might interfere with conventional treatments (7.6%), and that many TCM treatments are not based on scientific research (9.1%). In the multivariable regression model, age ≤60 years was independently associated with higher expectation score ( P = .031). Age ≤60 years (coefficient 5.0, P = .003) and localized disease (coefficient 9.5, P = .001) were both associated with higher treatment concerns. Active employment status (coefficient 9.0, P = .008) and localized disease (coefficient 7.5, P = .030) were related to more logistical challenges. Conclusion: Age and cancer stage were related to Chinese cancer patients’ perceived expectations and barriers toward TCM use. Understanding these attitudes is important for reshaping the role that TCM plays in China’s patient-centered comprehensive cancer care model.