Clinical Observation on Jiechang Qingre Pills Combined with Conventional Western Medicine Therapy in Improving Dampness-heat Syndrome of Large Intestine at Active Stage of Ulcerative Colitis / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of Jiechang Qingre pills for dampness-heat syndrome of large intestine at active stage of ulcerative colitis （UC） and investigate its effect on inflammatory factors. Method:One hundred and eight patients with active UC were divided into observation group and control group. Both groups were treated with Mesalazine enteric-coated tablets， 2 g/times， 2 times/day， for 2 weeks. If symptoms were poorly controlled， prednisone acetate tablets would be used instead， 0.75 mg·kg^-1·d^-1in 3 times by oral administration. Patients in the observation group took Jiechang Qingre pills， 10 g/time， 3 times/day before meals. Patients in the control group took Jiechang Qingre pills simulated drug， 10 g/time， 3 times/day before meals. The course of treatment was 12 weeks in both groups and the patients were followed up for 3 months. The modified Mayo score was used to evaluate disease activity. Before and after treatment， large intestine dampness-heat syndrome score， inflammatory bowel disease questionnaire （IBDQ）， mucosal histology assessment and scores of major symptoms and intestinal mucosal lesion severity were graded. The incidence of non-reactivity， hormone failure， hormone dependence， and early recurrence were recorded 2 weeks after treatment. Tumor necrosis factor-<italic>α </italic>（TNF-<italic>α</italic>）， interleukin-6（IL-6） and IL-17 levels were measured before and after treatment. Result:The clinical effective rate in the observation group was 94.00% （47/50）， higher than 77.55% （38/49） in the control group （<italic>χ</italic>²=5.514，<italic>P</italic><0.05）. The clinical remission rate was 82.00%（41/50） in the observation group， higher than 61.22% （30/49） in the control group （<italic>χ</italic>²=5.266，<italic>P</italic><0.05）. The endoscopic response rate was 96.00% （48/50） in the observation group， higher than 79.59% （39/49） in the control group （<italic>χ</italic>²=6.251，<italic>P</italic><0.05）. The rate of mucosal healing in the observation group was 90.00% （45/50）， higher than 79.59% （35/49） in the control group （<italic>χ</italic>²=5.503，<italic>P</italic><0.05）. The scores of diarrhea， purulent stool， abdominal pain， tenesmus， hyperemia， edema， erosion and ulcer in the observation group were lower than those in the control group （<italic>P</italic><0.01）. The rate of non-reactivity in the observation group was 16.00% （8/50）， lower than 34.69% （17/49） in the control group（<italic>χ</italic>²=4.581，<italic>P</italic><0.05）. The hormone failure rate in the observation group was 37.50%（3/8）， lower than 64.71%（11/17）in the control group，but the difference was not statistically significant（tested by the exact probaility method）. The hormone dependence rate in the observation group was 12.50%（1/8）， lower than 23.53% （4/17） in the control group，but the difference was not statistically significant（tested by the exact probaility method）. The early recurrence rate in the observation group was 14.00% （7/50）， lower than 32.65%（16/49） in the control group（<italic>χ</italic>²=4.827，<italic>P</italic><0.05）. The scores of Mayo， dampness and heat syndrome and Geboes index in the observation group were lower than those in the control group （<italic>P</italic><0.01）， and the IBDQ scores were significantly higher than those in the control group （<italic>P</italic><0.01）. The TNF-<italic>α， </italic>IL-6 and IL-17 levels of the patients in the observation group were lower than those in the control group （<italic>P</italic><0.01）. Conclusion:Based on the routine treatment of western medicine， Jiechang Qingre pills treatment for the patients with active UC can effectively induce clinical remission， alleviate inflammatory reaction， promote intestinal mucosal healing， improve clinical symptoms， quality of life and the response of treatment. Its clinical efficacy and enteroscopy efficacy are better than western medicine treatment alone， so it is worthy of clinical use.

Effect of Koumine on Proliferation and Apoptosis of Colorectal Cancer Cells via ROS/JNK/FoxO3a Signaling Pathway / 中国实验方剂学杂志

Objective:To explore the effect and underlying mechanism of koumine （Kou） at different concentrations （0， 100， 200， 400 μmol·L^-1） on the proliferation and apoptosis of colorectal cancer HCT-116 cells. Method:After 24 hours of<italic> in vitro</italic> intervention with HCT-116 cells by Kou， cell counting kit-8 （CCK-8） assay was used to detect its effect on cell proliferation. Flow cytometry was used to detect cell cycle， apoptosis， and reactive oxygen species （ROS） expression. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of forkhead box O3a （FoxO3a）. Cells were transfected with small interfering ribonucleic acid （siRNA）. Western blot was employed to detect the protein expression of the FoxO3a target gene. Result:Compared with the conditions in the blank group， Kou treatment reduced the proliferation rate of HCT-116 cells （<italic>P</italic><0.05， <italic>P</italic><0.01） in a dose-dependent manner， caused cell cycle arrest in the G₀/G₁ phase， and induced the apoptosis of HCT-116 cells （<italic>P</italic><0.05， <italic>P</italic><0.01）， which was positively correlated with the concentration of Kou. FoxO3a siRNA interference reduced the expression of FoxO3a and its downstream target genes cyclin-dependent kinase inhibitor 1A （p21）， cyclin-dependent kinase inhibitor 1B （p27）， and Bcl-2 interacting mediator of cell death （Bim） （<italic>P</italic><0.01）. Kou treatment induced the activation of c-Jun <italic>N</italic>-terminal kinase （JNK） in HCT116 cells. SP600125 （JNK specific inhibitor） treatment inhibited the Kou-induced FoxO3a activation and the expression of its downstream target genes. <italic>N</italic>-acetyl cysteine （NAC） treatment reduced Kou-induced ROS levels （<italic>P</italic><0.01） and JNK signal activation. The above results were significantly different from those in the blank group （<italic>P</italic><0.01）. Conclusion:Kou can effectively inhibit the proliferation of HCT-116 cells and promote apoptosis， and the mechanism may be related to the regulation of the ROS/JNK/FoxO3a pathway.

Spleen tyrosine kinase inhibits proliferation and promotes apoptosis of colorectal cancer cells in vitro via regulating Fra-1 / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of spleen tyrosine kinase (SYK) overexpression on proliferation and apoptosis of colorectal cancer cells and explore the possible mechanism.</p><p><b>METHODS</b>The mRNA expressions of SYK and Fra?1 in 10 clinical specimens of colorectal cancer and 10 adjacent tissues were measured with qRT?PCR, and their protein expressions were detected with Western blotting. The recombinant plasmid pcDNA.3.1?SYK was constructed and transfected into colorectal cancer cells to induce SYK overexpression, and the cell viability and proliferation were assessed using by MTT assay and BrdU assay, respectively; caspase?3 activity in the cells was evaluated with a commercial kit and the cell apoptosis was analyzed with Annexin?V FITC/PI assay.</p><p><b>RESULTS</b>The expressions of SYK were significantly decreased in colorectal cancer tissues and colorectal cancer cell lines. Transfection of pcDNA.3.1?SYK into the colorectal cancer cells induced obviously upregulated mRNA and protein expressions of SYK, which caused a significant suppression of the cell viability and proliferation and enhancement of the cell apoptosis along with a significant inhibition of Fra?1 expression.</p><p><b>CONCLUSION</b>s SYK overexpression inhibits the proliferation and promotes apoptosis of colorectal cancer cells, and these effects are possibly mediated by the regulation of Fra?1 expression by SYK.</p>