In Vivo Reversal of P-Glycoprotein-Mediated Drug Resistance in a Breast Cancer Xenograft and in Leukemia Models Using a Novel, Potent, and Nontoxic Epicatechin EC31.

The modulation of P-glycoprotein (P-gp, ABCB1) can reverse multidrug resistance (MDR) and potentiate the efficacy of anticancer drugs. Tea polyphenols, such as epigallocatechin gallate (EGCG), have low P-gp-modulating activity, with an EC50 over 10 µM. In this study, we optimized a series of tea polyphenol derivatives and demonstrated that epicatechin EC31 was a potent and nontoxic P-gp inhibitor. Its EC50 for reversing paclitaxel, doxorubicin, and vincristine resistance in three P-gp-overexpressing cell lines ranged from 37 to 249 nM. Mechanistic studies revealed that EC31 restored intracellular drug accumulation by inhibiting P-gp-mediated drug efflux. It did not downregulate the plasma membrane P-gp level nor inhibit P-gp ATPase. It was not a transport substrate of P-gp. A pharmacokinetic study revealed that the intraperitoneal administration of 30 mg/kg of EC31 could achieve a plasma concentration above its in vitro EC50 (94 nM) for more than 18 h. It did not affect the pharmacokinetic profile of coadministered paclitaxel. In the xenograft model of the P-gp-overexpressing LCC6MDR cell line, EC31 reversed P-gp-mediated paclitaxel resistance and inhibited tumor growth by 27.4 to 36.1% (p < 0.001). Moreover, it also increased the intratumor paclitaxel level in the LCC6MDR xenograft by 6 fold (p < 0.001). In both murine leukemia P388ADR and human leukemia K562/P-gp mice models, the cotreatment of EC31 and doxorubicin significantly prolonged the survival of the mice (p < 0.001 and p < 0.01) as compared to the doxorubicin alone group, respectively. Our results suggested that EC31 was a promising candidate for further investigation on combination therapy for treating P-gp-overexpressing cancers.

Role of daytime variation in pharmaceutical effects of sufentanil, dezocine, and tramadol: A matched observational study.

The role of daytime variation in the comprehensive pharmaceutical effects of commonly used opioid analgesics in clinical setting remains unclear. This study aimed to explore the differences in daytime variation among elective surgery patients who were scheduled to receive preemptive analgesia with equivalent doses of sufentanil, dezocine, and tramadol in the morning and afternoon. The analgesic effect was assessed by changes in the pressure pain threshold before and after intravenous administration of sufentanil, dezocine, and tramadol. Respiratory effects were evaluated using pulse oximetry, electrical impedance tomography, and arterial blood gas analysis. Other side effects, including nausea, sedation, and dizziness, were also recorded, and blood concentration was measured. The results showed that the analgesic effects of sufentanil, dezocine, and tramadol were significantly better in the morning than in afternoon. In the afternoon, sufentanil had a stronger sedative effect, whereas dezocine had a stronger inhibitory respiratory effect. The incidence of nausea was higher in the morning with tramadol. Additionally, significant differences in different side effects were observed among three opioids. Our results suggest that the clinical use of these three opioids necessitates the formulation of individualized treatment plans, accounting for different administration times, to achieve maximum analgesic effect with minimal side effects.

Circadian Clock-Controlled Checkpoints in the Pathogenesis of Complex Disease.

The circadian clock coordinates physiology, metabolism, and behavior with the 24-h cycles of environmental light. Fundamental mechanisms of how the circadian clock regulates organ physiology and metabolism have been elucidated at a rapid speed in the past two decades. Here we review circadian networks in more than six organ systems associated with complex disease, which cluster around metabolic disorders, and seek to propose critical regulatory molecules controlled by the circadian clock (named clock-controlled checkpoints) in the pathogenesis of complex disease. These include clock-controlled checkpoints such as circadian nuclear receptors in liver and muscle tissues, chemokines and adhesion molecules in the vasculature. Although the progress is encouraging, many gaps in the mechanisms remain unaddressed. Future studies should focus on devising time-dependent strategies for drug delivery and engagement in well-characterized organs such as the liver, and elucidating fundamental circadian biology in so far less characterized organ systems, including the heart, blood, peripheral neurons, and reproductive systems.

Disruption of SND1-MTDH Interaction by a High Affinity Peptide Results in SND1 Degradation and Cytotoxicity to Breast Cancer Cells In Vitro and In Vivo.

Staphylococcal nuclease domain-containing protein 1 (SND1) is a multifunctional oncoprotein overexpressed in breast cancer. Binding of metadherin (MTDH) to SND1 results in the stabilization of SND1 and is important in the initiation and progression of breast cancer. Disruption of such interaction is a potential therapeutic for breast cancer. SN1/2 domain of SND1 was used as bait in a phage display screening to identify a 12-amino acid peptide 4-2. The activity of peptide 4-2 was evaluated by ELISA, coimmunoprecipitation, MTS, Western blot analysis, and xenograft mouse model. Peptide 4-2 could disrupt SND1-MTDH interaction. Cell penetrating derivative of peptide 4-2 (CPP-4-2) could penetrate and kill breast cancer cells by disrupting SND1-MTDH interaction and degrading SND1. Tryptophan 10 (W10) of peptide 4-2 was essential in mediating cytotoxicity, SND1 interaction, SND1-MTDH disruption, and SND1 degradation. CPP-4-2 could inhibit the growth of breast cancer in a xenograft mouse model. The SND1-interacting peptide 4-2 could kill breast cancer cells both in vitro and in vivo by interacting with SND1, disrupting SND1-MTDH interaction, and inducing SND1 degradation. W10 was an essential amino acid in the activity of peptide 4-2.

MR Defecography in Assessing Functional Defecation Disorder: Diagnostic Value of the Defecation Phase in Detection of Dyssynergic Defecation and Pelvic Floor Prolapse in Females.

OBJECTIVE: Dyssynergic defecation (DD) and pelvic floor prolapse often coexist in female functional defecation disorder. A retrospective study was performed to evaluate the ability of dynamic MR sequences with the straining and defecation phase to detect paradoxical puborectalis contraction and occult multiple-compartments disorders. METHODS: Fifty-three females clinically diagnosed with DD underwent magnetic resonance defecography. The dynamic sequences consist of rest, squeeze, straining, and defecation. The straining phase (pre rectal filling) and defecation phase (post rectal filling) were acquired to assess for pelvic floor relaxation and pelvic organ descent. MR images were analyzed by 2 radiologists with regard to paradoxical puborectalis contraction (changes in the anorectal angle [ARA]) and the presence of pelvic organ prolapse in straining phase and defecation phase independently. Statistical analysis was performed using Wilcoxon's matched-pairs signed-ranks test and Crosstabs test for matched pairs. RESULTS: Among the 53 patients with DD, 24 individuals (45.3%) were diagnosed DD with multifocal disorders. Comparison between the straining and the defecation phase revealed that there was no significant difference in the change of the ARA (p > 0.05), while significant differences were found in cystocele, vaginal or cervical prolapse, rectocele and descending perineum syndrome between the straining and the defecation phase (p < 0.05). The defecation phase with impaired evacuation distinguished additional anterior/middle compartments findings in female DD patients. CONCLUSION: The straining phase and the defecation phase have the same ability in assessing paradoxical puborectalis contraction of the DD. Compared with the straining phase, the defecation phase provides the maximum stress to the pelvic floor resulting in complete levator ani relaxation. In addition to diagnosing the abnormal anorectal function, the defecation phase with the discharge of the rectal filling demonstrates maximum anterior/middle pelvic organ descent in DD patients.

[A multicenter randomized controlled clinical trial of Ligation of the Intersphincteric Fistula Tract Plus Bioprosthetic Anal Fistula Plug in the treatment of chronic anal fistula].

OBJECTIVE: To evaluate the effectiveness and safety of Ligation of the Intersphincteric Fistula Tract Plus Bioprosthetic Anal Fistula Plug (LIFT-plug) in the treatment of chronic anal fistula. METHODS: A total of 239 patients (199 males, 40 females) with chronic anal fistula were recruited from 5 hospitals between March 2011 and April 2013. These patients were randomly assigned to the experimental group (n=119) treated with LIFT-plug or the control group (n=120) treated with LIFT. The follow-up period was 180 days. The collected data included healing rate, the median healing time, the recurrence rate, the Visual Analogue Scale (VAS), the incontinence rate, and the safety indicators associated with the anal fistula plug. RESULTS: The healing rate of the experimental group was better than the control group (96.5% vs 83.7%, P<0.05). The median healing time of the experimental group was 22 days and the latter was 30 days (P<0.05). By the end of the follow-up period, there was no recurrence found in the two groups. The VAS and the incontinence rate had no statistically significant difference between the two groups. There were no adverse events associated with the anal fistula plug in the experimental group. CONCLUSION: LIFT-plug is simple, less invasive, and with shorter healing time and more satisfactory healing rate in treating chronic anal fistula compared with LIFT.

Essential oil of Cinnamon exerts anti-cancer activity against head and neck squamous cell carcinoma via attenuating epidermal growth factor receptor - tyrosine kinase.

PURPOSE: Impressed by the exceptional anticancer activity of cinnamon, the present study was conducted to elucidate the anticancer potential of essential oil of Cinnamon (EOC). METHODS: EOC was tested against various cell lines (FaDu, Detroit-562 and SCC-25) of head and neck squamous cell carcinoma (HNSCC) using MTT assay. The Hep-2 cell xenograft model was used to assess the positive bio-activity of EOC. EGFR-TK inhibitory assay was also carried out to explain the possible mechanism of action of EOC. Moreover, to rationalise the key contacts responsible for attenuating EGFR, the major component of EOC, i.e., trans-cinnamaldehyde, as identified by GC-MS analysis, was subjected to molecular docking experiments with the catalytic domain of EGFR protein model. RESULTS: EOC exhibited significant anticancer activity with percent inhibition 66.12, 87.32, and 99.34%, against FaDu, Detroit-562 and SCC-25, respectively. Moreover, EOC reduced the tumor burden to 43.5% in Hep-2 cell xenograft model along with 89% inhibition of EGFR-TK activity in the EGFR-TK inhibitory assay. Docking experiments showed that trans-cinnamaldehyde was proficiently fitted into the inner grove of the active site of EGFR by making close inter-atomic contacts with the key catalytic residues Val702, Ala719, Lys721, Leu764, Thr766 and Leu820 and with inhibition constant Ki = 775.93 µM. CONCLUSION: EOC exhibits significant anticancer activity against HNSCC cells in vitro. The mechanism underlying its anticancer action was attributed to the suppression of EGFR-TK. It also significantly suppressed the tumor growth in Hep-2 cell xenograft model.

[A multi-center, randomized, double-blind, placebo-controlled trial of glyceryl trinitrate ointment in the treatment of anal fissure].

OBJECTIVE: To evaluate the clinical efficacy and safety of glyceryl trinitrate (GTN) ointment in the treatment of anal fissure. METHODS: In this multi-center, randomized, double-blind and placebo-controlled trial, 240 chronic anal fissure patients from 7 clinical centers were randomized to receive eight-week treatment with GTN ointment (treatment group) or vaseline ointment (control group) respectively. Healing rate, visual analogue score (VAS), maximum anal resting pressure (MARP) and adverse reactions were recorded and compared. RESULTS: A total of 221 patients (92.1%) finished the trial, including 114 patients in treatment group (95.0%, 114/120) and 107 in control group (89.2%, 107/120). At the endpoint of treatment (56 d), 90 patients in treatment group (78.9%, 90/114) healed completely compared to 31 patients in control group (29.0%, 31/107), and decrease rates of VAS in the two groups were (94.8±15.7)% and (61.2±35.7)% respectively, both differences were statistically significant (P<0.01). MARP after first administration was (20.2±18.5) mm Hg in treatment group (n=12) and (7.1±14.7) mm Hg in control group (n=6), which was not significantly different (P=0.152). Adverse reaction incidence was higher in treatment group (42.1% vs. 9.3%, P<0.05), while these adverse reactions were mainly headache and fullness in head, which were self-limiting. CONCLUSION: GTN ointment can effectively promote healing and relieve pain in anal fissure with safety and tolerance.

[Ligation of the intersphincteric fistula tract plus bioprosthetic anal fistula plug (LIFT-plug) in the treatment of transsphincteric perianal fistula].

OBJECTIVE: To assess the treatment outcome of ligation of the intersphincteric fistula tract plus bioprosthetic anal fistula plug(LIFT-plug) for transsphincteric perianal fistulas. METHODS: Clinical data of 36 patients with transsphincteric perianal fiftula who were managed by the LIFT-plug technique between November 2010 and February 2012 were analyzed retrospectively. RESULTS: Clinical healing of the fistula, defined as the absence of drainage with no evidence of residual fistula tract, occurred in 34(94.4%) patients. The operative time ranged from 12 to 35 minutes(mean, 17 minutes). The median postoperative length of stay was 5 days. The median healing time was 18 days. No complications requiring intervention occurred. The postoperative follow up was at least 3 months and two patients had recurrence(5.6%). CONCLUSIONS: LIFT-plug procedure for the management of transsphincteric perianal fistulas is simple with high healing rate, minimal invasiveness, quick healing, and without disturbance to anal function. LIFT-plug is an ideal procedure for intrasphinteric fistula.

[Study of healing mechanism of acellular dermal matrix in the treatment of anal fistula].

OBJECTIVE: To evaluate the efficacy of acellular dermal matrix(ADM) in the closure of anal fistula in an experimental porcine model, and to explore its healing mechanism. METHODS: The fistula-in-ano model was created and treated with ADM in the porcine model (n=14). Fistula specimens were obtained at hour 12, 24 and day 3, 7, 14, 28, 60 respectively with 2 pigs in each time point. Hematoxylin and eosin staining and immunohistochemical staining for the alpha smooth muscle actin (α-SMA) were performed. RESULTS: At 12 hours after implantation, neutrophils and scattered cells with a fibroblastic appearance were present at the interface and began to infiltrate into the ADM. The cell density increased from hour 12 (218.2±58.2) to day 7(998.7±128.0) (P<0.01), and decreased from day 7 to day 28. Mature vessels and myofibroblasts stained with α-SMA were identified at the edge of ADM at day 7. The density of vessels (11.2±3.3 vs. 30.5±5.2, P<0.01) and myofibroblasts (3.8±0.8 vs. 6.8±0.4, P<0.01) increased from day 7 to day 14. Partially organized bundles of muscle were found at day 60. CONCLUSIONS: ADM is a reasonable new option for the closure of anal fistula. The ability of ADM to become vascularized and remodeled by autologous cells may be advantageous for anal fistula healing and other chronic septic wound.

[Efficacy of cellulose on functional constipation].

OBJECTIVE: To assess the clinical efficacy and safety of cellulose on functional constipation. METHODS: A prospective, self-controlled, multicenter clinical trial of cellulose was conducted for 2 weeks in 240 patients with functional constipation according to the Rome III( criteria. Symptoms and characters of feces before and after the treatment were observed and evaluated according to a score scheme. RESULTS: In the 240 patients, the frequencies of defecation increased and the characters of feces was improved significantly after 2-week treatment. There were no adverse reactions observed throughout the clinical trial. The total efficacy was 82.1% at day 7 and 90.7% at day 14. The satisfactory rate of doctors was 83.8% and of patients was 83.8%. CONCLUSION: Cellulose is effective and safe in the treatment of chronic functional constipation.

[Application of pelvic floor dynamic MRI combining defecography with homemade high conformable sacculus in the management of obstructed defecation syndrome].

OBJECTIVE: To evaluate the sensitivity and feasibility of pelvic floor dynamic MRI combining defecography with homemade high conformable sacculus in the management of obstructed defecation syndrome. METHODS: One hundred and nine female with pelvic floor disorders, such as difficult defecation, fecal incontinence or urinary incontinence, pelvic pain, were treated from July 2007 to March 2009. Pelvic floor dynamic MRI and defecography with homemade high conformable sacculus was performed in the patients to evaluate pelvic floor anatomy. RESULTS: Fifty-four cases (49.6%) of cystocele and 11 cases (10.1%) of rectouterine pouch hernia, 29 cases (26.6%) of perineum prolapse and 71 cases (65.2%) of rectocele were found by dynamic MRI. The dynamic MRI also revealed 19 cases (18.2%) of external sphincter trophy and 32 cases (29.4%) of spastic pelvic floor syndrome. Compared with defecography, dynamic MRI was more positive in diagnosing enterocele. Defecography Of the patients, sacrum-rectal separate was found in 33 cases (30.3%) and rectal mucosal prolapse or internal rectal intussusceptions in 41 cases (37.7%) by defecography, while dynamic MRI found none. CONCLUSIONS: As a new noninvasive imaging technique to evaluate the pelvic floor function, dynamic MRI is more sensitive, especially for patients with complicated multi-organs prolapse, and its deficiency could be remedied by defecography.

[A novel capsule-style manometric system and its application on non-invasive measurement of pancolonic pressure].

Pan-colonic motility was studied under normal conditions with a novel capsule-style system. A single use telemetry capsule embedded with one pressure sensor was ingested by subjects. It is capable of transmitting colonic pressure wirelessly greater than 130 h. Time of capsule entering segmental colon was determined by ultrasonic detection for tracing the batteries in capsule. The ultrasonic electrodes were mounted on the surface of subjects' ileocecum, navel as well as the junction of left colon and rectosigmoid colon in sequence. They were identified by abdominal X-rays with radiopaque markers. The confirming X-rays showed all telemetry capsules were detected successfully when passing through the key points in colon. A total of 613 h of colorectal recording was obtained from 20 healthy subjects. When compared with the parameters in the time of waking, the number of contractions and the area under contractions were significantly (P<0.05) decreased during sleep (21 +/- 5 vs 15 +/- 4 h(-1); 463 +/- 54 vs 342 +/- 45 mmHg x s x min(-1)). The colonic motility exhibited significant regional variation in the circadian behavior, as well as in its response to waking and meal. The clinical study proved the reliability and non-invasiveness of the system. It may represent a useful tool for the study on physiology and pathology of colonic motor disorders.

An anorectal fistula treatment with acellular extracellular matrix: a new technique.

AIM: To investigate a new technique of the anorectal fistula treatment with acellular extracellular matrix (AEM). METHODS: Thirty patients with anorectal fistula were treated with AEM. All fistula tracts and primary openings were identified using conventional fistula probe. All tracts were curetted with curet and irrigated with hydrogen peroxide and metronidazole. The AEM was pulled into the fistula tract from secondary to primary opening. The material was secured at the level of the primary opening. The excess AEM was trimmed at skin level at the secondary opening. RESULTS: All of the 30 patients had successful closure of their fistula after a 7-14 d follow-up. The healing rate of anal fistula in treatment group was 100%. The ache time, healing time and anal deformation of treatment group were obviously superior to traditional surgical methods. CONCLUSION: Using AEM anal fistula plug in treatment that causes the anorectal fistula is safe and successful in 100% of patients. It can reduce pain, shorten disease course and protect anal function.

Non-invasive measurement of pan-colonic pressure over a whole digestive cycle: clinical applications of a capsule-style manometric system.

AIM: To study the prolonged colonic motility under normal conditions with a novel capsule-style micro-system and to assess its clinical significance. METHODS: A single use telemetry capsule (10 mm in diameter, 20 mm in length) embedded with a pressure sensor was ingested by the subjects. The sensor is capable of transmitting colonic pressure wirelessly for more than 130 h. The time of capsule entering the segmental colon was detected by ultrasound. The ultrasonic electrodes were mounted on the surface of the ileocecum and navel and at the junction of the left and rectosigmoid colon of the subjects in sequence, which were identified by abdominal X-rays with radiopaque markers. To verify the accuracy and reliability of ultrasonic detection of telemetry capsules at key points of colon, the segmental colonic transit time was simultaneously recorded by using radiopaque markers. RESULTS: The signal lamp showed that all recorders could receive the radio signal transmitted by the telemetry capsule. The X-rays showed that all telemetry capsules were detected successfully when they were passing through the key points of colon. There was a significant correlation between the transit results obtained by ultrasonic detection or by radiopaque markers. Colorectal recording was obtained from 20 healthy subjects during 613 h (411 h during waking, 202 h during sleep). Compared to waking, the number of pressure contractions and the area under pressure contractions were significantly (P < 0.05) decreased during sleep (21 +/- 5 h(-1) vs 15 +/- 4 h(-1), 463 +/- 54 mmHg x s/min vs 342 +/- 45 mmHg x s/min). The colonic motility exhibited significant regional variations both in the circadian behavior and in response to waking and meal. CONCLUSION: The capsule-style micro-system is reliable and noninvasive, and may represent a useful tool for the study of physiology and pathology of colonic motor disorders.

[The pathological characters and its clinical significance of internal hemorrhoids].

OBJECTIVE: To investigate the pathological characters and the corresponding clinical significance of internal hemorrhoids tissues. METHODS: Normal anal cushion and internal haemorrhoids tissue samples were obtained after stapled haemorrhoidectomy procedure from 24 grade III hemorrhoidal patients. The macroscopically normal cushions served as own controls and the normal cushions from a patient without a history of haemorrhoids as quality control. Routine Hematoxylin-Eosin and orcein were performed for elastic fibers. RESULTS: Compared with the corresponding normal anal cushions, the subepithelial vessels especially the cavernous vessels of the hemorrhoidal tissues showed obvious structural impair, retrograde changes, and the internal elastic lamina were ruptured and discontinuous. In addition, thrombosis and subsequent ischemic changes were observed. The Trietz's muscle and the fibro-elastic tissues showed hypertrophy, distortion, rupture and tortility. Obvious mucosal injury was observed in the mucous of hemorrhoidal tissues. Venous dilatation was infrequent in the hemorrhoidal tissues. CONCLUSIONS: The anal cushions of hemorrhoids disease patients show significant pathological changes. The pathological changes include structural impair, retrograde changes of the cavernous vessels and the hypertrophy, distortion, rupture and tortility of the Trietz's muscle and the fibroelastic tissues, and mucosal injury of the mucous membranes. These pathological changes are the basis of pathogenesis and development of hemorrhoids.

[Efficacy of intersphincteric resection in the sphincter-preserving operation for ultra-lower rectal cancer].

OBJECTIVE: To evaluate the clinical efficacy of intersphincteric resection in the sphincter- preserving operation for ultra-lower rectum cancer. METHODS: Thirty-one rectal cancer patients with the distal edge of the tumour less than 2 cm from the dentate line were evaluated. Eighteen advanced rectal cancer patients received preoperative chemo-radiation. Total mesorectal excision (TME) was performed with the rectum immobilized down, and the puborectal ligament and partial levator cut to the level of the dentate line. In some well-exposed patients, it was possible to further immobilize the rectum between the external sphincter ring and the rectum inner sphincter wall. In anal approach,good exposure was attained and the cut-line was made vertically to the anal canal 2 cm below the lower edge of the tumor, and further intersphincteric immobilization was made upright. Colon or colon pouch were anastomosed to the distal anal wall. RESULTS: There was no peri-operative death. Thirty patients had good fecal control. Twenty-nine patients showed no evidence of recurrence or metastasis after follow-up for 12 months. Recurrence occurred in one case 1 year after operation. Another one had higher CEA 19.9 level, but without evidence of metastasis. CONCLUSION: Radical resection can be attained and anal sphincter preserved by intersphincter resection which is an alternative sphincter-preserving operation.

[Comparison of the efficacy and safety of compound carraghenates cream and compound carraghenates suppository in the treatment of mixed hemorrhoids].

OBJECTIVE: To evaluate and compare the efficacy and safety of titanoreine cream with compound carraghenates suppository in the treatment of mixed hemorrhoids. METHODS: Two hundred and fifty-two patients with mixed hemorrhoids were enrolled in this randomized,open, multicentral trial. Patients applied titanoreine cream (study group, n=133) or compound carraghenates suppository (control group, n=119). The symptomatic relief including pain,bleeding and edema was evaluated by scoring system at 30 minutes, 3 hours, 6 hours, 1 day, 2 days, 3 days, 4 days, 6 days after administration. RESULTS: Symptoms were significantly improved in both groups (87.3%, 94.8%, respectively) excepting symptom of pain relief, but there was no significant difference between two groups (P > 0.05). The pain scores were lower at every observing point in the study group than those in the control group (P< 0.05). The proportions of the patients with pain relief and all symptoms relief were both higher in the study group than that in the control group at 30 min, 3 h after drug used (both P< 0.01). No side effect was found during the triad. CONCLUSION: Titanoreine cream has predominance of relieving pain and response time compared with compound carraghenates suppository, but other effects on mixed hemorrhoid are similar between the two groups.

[Treatment and mechanism of compound carraghenates suppository to rat acute rectal mucous injury].

OBJECTIVE: To investigate the treatment and mechanism of compound carraghenates suppository to rat acute rectal mucous injury. METHODS: The model of rat acute rectal mucous injury was established by 3% acetic acid. Two hundred and forty rats were divided equally into control and experimental group. The rats of experimental group were administrated with 20 mg carraghenates suppository via rectum twice a day, but rats of control group were not administrated with carraghenates suppository. Thirty rats in both groups were executed at different time points. The pathologic changes were observed and the rectal mucous injury was scored. Immunohistochemical staining was used to evaluate the effect of carraghenates suppository on expression of VEGF, iNOS, IL-8, MMP9, HIF-1 alpha and PCNA in the two groups. RESULTS: The scores of rectal mucous injury was lower, the pathologic changes such as hyperaemia, edema, destroy of glands were less severe, and tissue repair time was shorter in experimental group compared with those in the control group at 24 h, 78 h and 120 h after administration of carraghenates suppository. No obvious cicatrisation was observed in experimental group. Expression of VEGF and MMP9 was significantly lower in experimental group compared with those in the control group at 24 h after administration. Expression of VEGF, iNOS, IL-8, MMP9, HIF-1alpha and PCNA were statistically decreased in experimental group than those in the control group at 72 h, 120 h after administration. MVD in experimental group was statistically decreased than that in the control group. CONCLUSION: The compound carraghenates suppository can reduce the rectal mucous injury from 3% acetic acid, and accelerate the wound healing without obvious cicatrisation. The compound carraghenates suppository can reduce the expression of MMP9, VEGF, IL-8, PCNA, iNOS and HIF-1 alpha, which may play a role in its protective mechanism.