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Additional file 1. Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 checklist.

Additional file 2: Supplementary Table 1. Study procedure and Flow Chart (treatment phase prior to end of study).

Introduction Defining Traditional Chinese medicine (TCM) syndrome is considered the key therapeutical principle of TCM. The present study was to explore the correlation between TCM syndrome differentiation and histopathology in colorectal cancer (CRC). Methods A total of 180 patients were differentiated into 5 TCM syndrome types, including accumulated damp-heat type (ADH), deficiency of both qi and blood type (DBQB), deficiency of liver and kidney yin type (DLKY), deficiency of spleen and kidney yang type (DSKY) and qi stagnation due to spleen deficiency type (QSSD). They were also differentiated into pathologic types, including adenocarcinoma, mucous carcinoma, signet ring cell carcinoma and anaplastic carcinoma. Moreover, the expression of protein 53 (P53), cluster of differentiation 44 (CD44), non-metastasis 23 (nm23), proliferating cell nuclear antigen (PCNA) and B-cell lymphoma-2 (Bcl-2) was detected by immunohistochemistry in 61 patients. Finally, the correspondence analysis between TCM syndrome differentiation and histopathology or pathological molecular markers was conducted. Results Chi-square test of independence showed that TCM syndrome types correlated with pathological types ( χ 2 = 33.456, P = 0.001), while not with molecular markers ( χ 2 = 7.344, P = 0.834). Correspondence analysis showed that the distances between adenocarcinoma and QSSD or DLKY were the shortest among the distances of adenocarcinoma with other TCM syndrome types. Moreover, distances between mucinous carcinoma and ADH, signet ring cell carcinoma and ADH, anaplastic carcinoma and DBQB were the shortest among all the types. Conclusion TCM syndrome differentiation is strongly correlated with histopathology of colorectal cancer. TCM syndrome differentiation may be used as a supplement in the diagnosis of CRC.

MicroRNA-9-1(miR-9-1) plays an important role in the mechanism that regulates the lineage fate of differentiating hematopoietic cells. Recent studies have shown that miR-9-1 is downregulated in t (8; 21) AML. However, the pathogenic mechanisms underlying miR-9-1 downregulation and the RUNX1-RUNX1T1 fusion protein, generated from the translocation of t (8; 21) in AML, remain unclear. RUNX1-RUNX1T1 can induce leukemogenesis through resides in and functions as a stable RUNX1-RUNX1T1-containing transcription factor complex. In this study, we demonstrate that miR-9-1 expression increases significantly after the treatment of RUNX1-RUNX1T1 (+) AML cell lines with decitabine (a DNMT inhibitor) and trichostatin A (an HDAC inhibitor). In addition, we show that RUNX1-RUNX1T1 triggers the heterochromatic silencing of miR-9-1 by binding to RUNX1-binding sites in the promoter region of miR-9-1 and recruiting chromatin-remodeling enzymes, DNMTs, and HDACs, contributing to hypermethylation of miR-9-1 in t (8; 21) AML. Furthermore, because RUNX1, RUNX1T1, and RUNX1-RUNX1T1 are all regulated by miR-9-1, the silencing of miR-9-1 enhances the oncogenic activity of these genes. Besides, overexpression of miR-9-1 induces differentiation and inhibits proliferation in t (8; 21) AML cell lines. In conclusion, our results indicate a feedback circuitry involving miR-9-1 and RUNX1-RUNX1T1, contributing to leukemogenesis in RUNX1-RUNX1T1 (+) AML cell lines.