Evaluation of the metabolism of PEP06,an endostatin-RGDRGD 30-amino-acid polypeptide and a promising novel drug for targeting tumor cells / 药物分析学报

PEP06 is a novel endostatin-Arg-Gly-Asp-Arg-Gly-Asp(RGDRGD)30-amino-acid polypeptide featuring a terminally fused RGDRGD hexapeptide at the N terminus.The active endostatin fragment of PEPO6 directly targets tumor cells and exerts an antitumoral effect.However,little is known about the kinetics and degradation products of PEP06 in vitro or in vivo.In this study,we investigated the in vitro metabolic stability of PEP06 after it was incubated with living cells obtained from animals of different species;we further identified the degradation characteristics of its cleavage products.PEP06 underwent rapid enzymatic degradation in multiple types of living cells,and the liver,kidney,and blood play important roles in the metabolism and clearance of the peptides resulting from the molecular degradation of PEP06.We identified metabolites of PEP06 using full-scan mass spectrometry(MS)and tandem MS(MS2),wherein 43 metabolites were characterized and identified as the degradation metabolites from the parent peptide,formed by successive losses of amino acids.The metabolites were C and N terminal truncated products of PEP06.The structures of 11 metabolites(M6,M7,M16,M17,M21,M25,M33,M34,M39,M40,and M42)were further confirmed by comparing the retention times of similar full MS spectrum and MS2 spectrum information with reference standards for the synthesized metabolites.We have demonstrated the metabolic stability of PEP06 in vitro and identified a series of potentially bioactive downstream metabolites of PEP06,which can support further drug research.

Application of laparoscopic ventral rectal fixation in rectal prolapse / 中华普通外科杂志

Objective To explore the clinical value of laparoscopic ventral rectopexy for rectal prolapse.Methods From Jan 2013 to Jan 2017,26 patients with complete rectal prolapse were divided into control group (15 patients) undergoing laparoscopic rectal fixation,and 11 patients in study group were treated with rectal ventral fixation.Results There was no significant difference in operation time,bleeding volume and exhaust time between the two groups (t =1.839,0.138,0.932,all P ＞ 0.05).In the study group,2 cases had temporarily postoperative fever.Following up for 12 to 36 months,1 case recurred in the control group and 1 case in the study group.The length of rectal prolapse was about 2 cm.Of the 7 patients with constipation in the control group,symptoms disappeared in 2 cases,symptoms improved in another 2 cases,and 5 cases had new constipation.Of the 4 patients with anal incontinence,2 cases had recovered and 1 case had symptoms improved.Among the 6 patients with constipation in the study group,symptoms disappeared in 3 cases,symptoms improved in 2 cases.Of the 3 patients with pelvic prolapse,2 cases recovered and 1 case improved.The pelvic prolapse and constipation in the study group was less severe than that in the control group (x2 =4.909,P ＜ 0.05).Conclusion Laparoscopic rectal ventral fixation for the treatment of complete rectal prolapse is less traumatic,safor and more effective.

Clinicopathological characteristics and prognosis analysis of colorectal synchronous multiple primary cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathological features and prognosis of colorectal synchronous multiple primary cancer(SMPC).</p><p><b>METHODS</b>From January 2008 to June 2011, 51 patients diagnosed with colorectal SMPC underwent surgery at Department of General Surgery of Peking University First Hospital. Their clinicopathological features, diagnosis, treatment and prognosis were summarized and analyzed. SMPC was diagnosed according to the following criteria: each tumor must have a definite pathologic picture of malignancy; metastasis or recurrence from another colorectal cancer was excluded; tumors must be distinctly separated by at least 5 cm of all intact bowel wall from each other; SMPC has abnormal cells between tumor and normal mucosa and abnormal gland of transitional zone; each cancer is infiltrating carcinoma except the carcinoma in situ; all the cancers are detected at the same time or within 6 months. Multiple primary colorectal cancer originated from familial colonic polyposis or ulcerative colitis was excluded.</p><p><b>RESULTS</b>These 51 colorectal SMPC patients accounted for 3.5% of 1 452 colorectal cancer patients in the same period at our hospital, with 32 males and 19 females, and mean age of (63±13)(29 to 82) years. Of 51 cases, 46(90.2%) had 2 original carcinoma, 3(5.9%) had 3 original carcinoma and 2(3.9%) had 4 carcinoma; 23(45.1%) complicated with colon polyps, 4(7.8%) complicated with malignancy outside the colorectum. In TNM staging, 7(13.7%), 15(29.4%), 24(47.1%) and 5(9.8%) patients were stage I(, II(, III( and IIII( respectively. Among 51 patients undergoing surgery by different procedures, 16 were subtotal colon resection, 8 were extended right colon resection, 5 were extended left hemicolon resection, 8 were right hemicolon resection plus Dixon procedure, 10 were Dixon, and 4 were right hemicolon resection plus sigmoid colon resection. Adjuvant chemotherapy and support treatment were given according to the condition after operation. A total of 105 tumors were found, including 25(23.8%) tumors in sigmoid colon, 24(22.9%) in rectum, 22(21.0%) in ascending colon and 4 in organs outside the colorectum. Tubular adenocarcinoma (86/105, 81.9%) was the main pathological type in these colorectal SMPC patients. During the follow-up of median 43.5 months, 10 cases presented local recurrence and 6 cases had liver metastasis. Multivariable analysis showed that ≤65 years old (OR=22.757, 95%CI: 1.562-331.543, P=0.002),undifferentiated carcinoma or mucous adenocarcinoma (OR=27.174, 95%CI: 2.834-260.512, P=0.004), stage III(-IIII( (OR=29.626, 95%CI: 3.216-272.884, P=0.003) were independent risk factors of postoperative 5-year recurrence and metastasis, but the number of SMPC lesions and the surgical method were not associated with postoperative 5-year recurrence and metastasis (P=0.564, P=0.513). The 3-year and 5-year survival rates of colorectal SMPC patients were 76.5% and 64.7%.</p><p><b>CONCLUSION</b>Two-original carcinoma is the most common in colorectal SMPC patients, which mainly distributes in sigmoid colon and rectum. Postoperative monitoring should be strengthened for those patients with younger age, poor pathological types and advanced staging to prevent recurrence and metastasis.</p>

Association of soluble human leukocyte antigen DQB1 with recurrent spontaneous abortion / 中华妇产科杂志

0.05). The frequency of 57 site with non Asp in the study group was significantly higher than that in the control group(P