Clinical Effect of Changyanqing Mixture Combined with Mesalazine Enteric-coated Tablets for Maintenance Treatment of Ulcerative Colitis in Remission Period / 中国实验方剂学杂志

Objective:This study aims to evaluate the clinical effect of Changyanqing mixture combined with mesalazine enteric-coated tablets in the maintenance treatment of ulcerative colitis（UC） in remission period. Method:The 140 patients with UC in remission period were randomly divided into control group （70 cases） and observation group （70 cases）. The 61 patients in control group completed the therapy （6 cases lost or lost to follow-up and 3 were eliminated）， 63 patients in observation group completed the therapy （5 cases lost or lost to follow-up and 2 were eliminated）. Both groups′ patients got treatment of lifestyle adjustment， and they also took mesalazine enteric-coated tablets orally， 0.5 g/time， 3 times/day. Patients in observation group took Changyanqing mixture orally for a month in the morning and evening every day， 150 mL/time， and then changed to 150 mL/time， 1 time/day， for 3 consecutive months， finally changed to once every other day for 8 months. Patients in control group took simulated medicine of Changyanqing mixture orally in the same way as observation group. The treatment was continued for 12 months. When UC recurred during the treatment， patients took mesalazine enteric-coated tablets orally at 1 g/time， 3 times/day until remission， when the above intervention plan was continued to be adopted. The recurrence rate， first recurrence time within 12 months （duration from remission to Mayo≥3） and the degree of disease activity at recurrence were recorded. Scores of traditional Chinese medicine（TCM）syndrome and inflammatory bowel disease questionnaire （IBDQ） were evaluated once every 2 months. Before treatment， and at the 6^th and 12^th month after treatment， colonoscopy and mucosal histology were performed once， enteroscopic mucosal scores， Geboes index of mucosal histology were evaluated， and fecal calprotectin（FC） levels were detected. Also， safety evaluation was conducted. Result:During 12 months， the recurrence rate in observation group was 20.63% （13/63）， lower than 39.34% （24/61） in control group（<italic>P</italic><0.05）， the frequency of recurrence and the first recurrence duration in observation group were all less than those in control group（<italic>P</italic><0.01）. All these meant the disease activity of patients in observation group was lighter than that in control group （<inline-formula><alternatives><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"><mml:msup><mml:mrow><mml:mi>χ</mml:mi></mml:mrow><mml:mrow><mml:mn mathvariant="normal">2</mml:mn></mml:mrow></mml:msup></mml:math><graphic specific-use="big" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="alternativeImage/444CE72A-DE9D-4013-BB0B-F487F60C8DC8-M003.jpg"><?fx-imagestate width="3.30200005" height="3.64066648"?></graphic><graphic specific-use="small" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="alternativeImage/444CE72A-DE9D-4013-BB0B-F487F60C8DC8-M003c.jpg"><?fx-imagestate width="3.30200005" height="3.64066648"?></graphic></alternatives></inline-formula>=5.947， <italic>P</italic><0.05）. After repeated measurements of variance analysis， scores of TCM syndrome， enteroscopic mucosal scores， Geboes index and FC levels in two groups gradually increased（<italic>P</italic><0.05）， and scores of IBDQ gradually decreased （<italic>P</italic><0.05） during the 12-month period. At the second， fourth， sixth， eighth， tenth and twelfth month， scores of TCM syndromes in observation group were lower than those in control group （<italic>P</italic><0.01）， and scores of IBDQ were higher than those in control group （<italic>P</italic><0.01）. At the sixth and twelfth month after treatment， intestinal endoscopic mucosal scores， Geboes index and FC levels in observation group were all lower than those in control group （<italic>P</italic><0.01）. And there were no adverse reactions related to Changyanqing mixture. Conclusion:Changyanqing mixture combined with mesalazine enteric-coated tablets in the maintenance treatment of patients with UC in remission can control the FC level， further reduce the recurrence rate， delay the recrudescence-time， reduce the frequency of UC and the disease activity， maintain the good remission state of UC， stabilize the quality of life of patients， and ensure the safety of clinical use.

Clinical Efficacy of Changyanqing Mixture on Chronic Recurrent Ulcerative Colitis with Damp-heat Ayndrome of Large Intestine / 中国实验方剂学杂志

Objective::To observe the clinical efficacy of Changyanqing mixture on chronic recurrent ulcerative colitis (UC) with damp-heat syndrome of large intestine and the effect on the recurrence of disease, in order to discuss the mechanism of action in terms of the neuro-endocrine-immune inflammation network. Method::One hundred and twelve patients were randomly divided into control group (55 cases) and observation group (57 cases) by random number table. Patients in control group got mesalazine slow release tablets, 0.1 g/time, 4 times/days, and those the score of Mayo≥7 were added with prednisone acetate tablets, 0.75 mg·kg-1·d-1, and bifidobacterium viable powder with warm water after dinner, 1 pack/day, 2 times/days. In addition to the therapy of control group, patients in observation group were also given Changyanqing mixture in the morning and evening, 1 pack/day. A course of treatment was 6 weeks, and patients got further consultation once a week. During the remission stage, patients in both groups got mesalazine slow release tablets, 0.5 g/time, 3 times/days, and patients in observation group were added with Changyanqing mixture until the score of damp-heat syndrome of large intestine reduced by more than 90%. The number of patients entering the remission stage of 6 weeks and the time of remission stage were recorded. Before and after treatment, colonoscopy was detected, and Geboes index, Baron, damp-heat syndrome of large intestine and Mayo were scored. And levels of peripheral blood interleukin-6 (IL-6), IL-8, IL-10, IL-17, vasoactive intestinal peptide (VIP), motilin (MTL) and neuropeptide (NPY) were detected, and relapse at the 24-week follow-up was recorded. Result::After the 6-week treatment, the clinical efficacy in observation group was 100%, which was higher than 89.09%in control group (P<0.05). And the healing rate of mucosa was 96.4%, which was higher than 81.82%in control group (P<0.05). And the response rate in two groups was 100%. At the 6th month after the treatment, the clinical remission rate in observation group was 91.23%, which was higher than 76.36%in control group (χ2=4.581, P<0.05). And the average remission time was shorter than that in control group (P<0.01). After treatment, scores of colonic mucosa, Geboes index, colonic mucosa and Mayo were all lower than those in control group (P<0.01). And levels of IL-6, IL-8, IL-17, VIP and MTL were lower than those in control group (P<0.01), while levels of IL-10 and NPY were higher than those in control group (P<0.01). The relapse rate in observation group was 17.54%, which was lower than 38.18%in control group (χ2=5.955, P<0.05). And the mean recurrence time was longer than that in control group (P<0.01). Conclusion::In addition to the routine western medicine therapy, Changyanqing mixture can alleviate the condition of patients by shortening the course of the disease, reducing the recurrence rate, delaying the recurrence time, and regulating the nerve-endocrine-immune inflammation network.

Screening of specific binding peptide targeting blood vessel of human esophageal cancer in vivo in mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Cancer of the esophagus and gastroesophageal junction remains a virulent malignancy with poor prognosis. Rapid progresses were made in chemotherapeutic agents and the development of molecular markers allowed better identification of candidates for targeted therapy. This study aimed to identify the candidate peptides used for anti-angiogenic therapy of esophageal cancer by in vivo screening C7C peptide library for peptides binding specifically to blood vessels of human esophageal cancer.</p><p><b>METHODS</b>The phage displayed C7C peptide library was injected intravenously into mice bearing human esophageal tumor xenografts under renal capsule. After 5 rounds of screening, 13 clones were picked up individually and sequenced. During each round of screening, titers of phage recovery were calculated from tumor xenograft and control tissues. Homing of these 9 peptides to tumor vessel was detected by calculating phage titers in the tumor xenograft and control tissues (lung and spleen) after each phage was injected into mice model, and compared with the distribution of phage M13 and VIII-related antigen in tumor xenograft by immunohistochemical staining. Comparisons among groups of data were made using one-way analysis of variance (ANOVA), followed by the Bonferroni multiple comparisons test.</p><p><b>RESULTS</b>The number of phage recovered from tumor tissue of each round increased gradually in tumor group while decreased in control groups (P < 0.01 in tumor and spleen, P < 0.05 in lung). Immunohistochemical staining showed similar staining pattern with M13 antibody or VIII-related antigen antibody, suggesting that phages displaying the selected peptides could home to blood vessel of human esophageal cancer. According to their DNA, 9 corresponding peptide sequences were deduced. And the homing ability to blood vessel of phages displaying the selected peptides was confirmed by comparing with their recovery in tumor and control tissues. Two motifs, YSXNXW and PXNXXN, were also obtained by analyzing the homology of these peptide sequences. The staining distribution of phage with the sequence of PNPNNST was similar to that of the blood vessel marker factor VIII-related antigen staining. After sequencing, each phage with the selected peptide of PNPNNST with 1.0 × 10(11) pfu/ml was injected intravenously into mice. The homing ability to tumor vessel of these 9 kinds of peptides in the xenograft was higher than control tissues (lung and spleen).</p><p><b>CONCLUSION</b>Nine peptides obtained from in vivo screening homed to the blood vessel of human esophageal cancer, and the two motifs of YSXNXW and PXNXXN are the possible biochemical recognition units binding to vascular endothelial cells of esophageal cancer.</p>