ABSTRACT
Objective@# To compare the efficacy and safety of combining diosmin with Jiuhua hemorrhoid suppository versus diosmin alone for the treatment of hemorrhoid hemorrhage.@*Methods@#The Jiuhua hemorrhoid suppository study was conducted in 10 medical centers across China from April 1, 2019 to June 30, 2020. Patients with hemorrhoid bleeding were randomized in a ratio of 1 : 1 to either receive Jiuhua hemorrhoid suppository and diosmin tablets (the study group) or diosmin tablets alone (the control group). The suppository was used once a day after defecation or at bedtime after rinsing the anus with warm water. Diosmin tablets were administered only once a day (0.9 g). The primary endpoint of the study was the assessment of hemorrhoid bleeding relief 7 ± 2 days after treatment, classified as “very effective” “effective” and “ineffective”. The secondary endpoint included the evaluation of pain alleviation using the visual analogue scale (VAS, with scores ranging from 0 to 10) and edema (with scores ranging from 0 to 3). The safety of the two treatment regimens was evaluated 14 ± 2 days after drug administration.@*Results@#The full analysis set (FAS) comprised 107 participants in the study group and 111 in the control group, while the per-protocol set (PPS) included 106 participants in the study group and 111 in the control group. In terms of hemorrhoid bleeding, the proportion of very effective and effective cases in the study group were significantly higher than that in the control group [106 (99.06%) vs. 91 (81.98%), P < 0.0001] in the FAS, and the PPS results [105 (99.06%) vs. 91 (81.98%), P < 0.0001] were comparable to the FAS results. The pain VAS scores at day 7 after treatment were comparable between the two groups (0.80 ± 1.17 vs. 0.80 ± 1.20, P = 0.2177). The majority of the participants in both groups had an edema score of 0 at day 7 after treatment [96 (89.72%) vs. 99 (91.67%), P = 0.370 5]. Adverse events (AEs) occurred in 9 patients (8.4%) in the study group and 3 patients (2.7%) in the control group. In addition, 5 AEs in the study group and 1 AE in the control group were possibly in association with the study drug.@*Conclusion@#Compared with the administration of diosmin oral tablets alone, the addition of Jiuhua hemorrhoid suppository to the tablets demonstrates enhanced efficacy in addressing hemorrhoid bleeding, with satisfactory patient adherence and acceptable safety.
ABSTRACT
Human bone morphogenetic protein 2 (BMP2) is a bone-growth regulatory factor involved in the formation of bone andcartilage, and has been recognized as an attractive therapeutic target for a variety of bone diseases and defects. Here, wereport successful design of a head-to-tail cyclic peptide based on crystal structure to target BMP2. Computational alaninescanning identifies two hotspot regions at the crystal complex interface of BMP2 with its type-IA receptor; promising one isstripped from the interface to derive a linear self-inhibitory peptide RPS2[r78-94] that covers residues 78–94 of the receptorprotein. Dynamics simulation and energetics analysis reveal that the peptide is highly flexible in isolated state and cannotspontaneously bind to BMP2. The RPS2[r78-94] peptide is further extended from its N- and C-termini until reaching twospatially vicinal residues 74 and 98 in the crystal structure of intact BMP2–receptor complex system, consequently resultingin a longer peptide RPS2[r74-98], which is then cyclized in a head-to-tail manner to obtain its cyclic counterpartcycRPS2[r74-98]. Computational analysis suggests that the cyclic peptide can well maintain in a conformation similar withits active conformation in complex crystal structure, exhibiting a smaller disorder and a larger potency than its linearcounterpart. Further assays confirm that the two linear peptides RPS2[r78-94] and RPS2[r74-98] are nonbinders of BMP2,whereas, as designed, the cyclic peptide cycRPS2[r74-98] can bind to BMP2 with a moderate affinity. The cyclic peptide isexpected as a lead molecular entity to develop new and potent peptide-based drugs for BMP2-targeted therapy.