Emerging role of exosomes in ulcerative colitis: Targeting NOD-like receptor family pyrin domain containing 3 inflammasome.

Ulcerative colitis (UC) is a chronic recurrent inflammatory bowel disease. Despite ongoing advances in our understanding of UC, its pathogenesis is yet unelucidated, underscoring the urgent need for novel treatment strategies for patients with UC. Exosomes are nanoscale membrane particles that mediate intercellular communication by carrying various bioactive molecules, such as proteins, RNAs, DNA, and metabolites. The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is a cytosolic tripartite protein complex whose activation induces the maturation and secretion of proinflammatory cytokines interleukin-1ß (IL-1ß) and IL-18, triggering the inflammatory response to a pathogenic agent or injury. Growing evidence suggests that exosomes are new modulators of the NLRP3 inflammasome, with vital roles in the pathological process of UC. Here, recent evidence is reviewed on the role of exosomes and NLRP3 inflammasome in UC. First, the dual role of exosomes on NLRP3 inflammasome and the effect of NLRP3 inflammasome on exosome secretion are summarized. Finally, an outlook on the directions of exosome-NLRP3 inflammasome crosstalk research in the context of UC is proposed and areas of further research on this topic are highlighted.

Macrophages in ulcerative colitis: A perspective from bibliometric and visual analysis.

Objectives: Despite the many reported studies on macrophages in ulcerative colitis (UC), the overall research trends in this field are unclear. This study evaluates the research trends and hotspots regarding macrophages in UC using bibliometric analysis. Methods: A systematic search was conducted in the Web of Science database to identify publications related to macrophages in UC from 2012 to 2021. R package 'bibliometrix', VOSviewers, CiteSpace and Microsoft Excel were utilised for the bibliometric analysis. Results: 1074 articles published between 2012 and 2021 were analysed. The number of publications on macrophages in UC showed a consistently increasing trend, with USA and China as the leading contributors to this field. Notably, Georgia State University and Nanjing University contributed significantly to this field. Among the authors, Wang Y had the highest productivity, while Wu X received the most citations. The journal Gut was identified as the most authoritative journal in this field. Co-citation analysis revealed that the exploration of the mechanisms of macrophages in UC through in vivo and in vitro experiments was the primary focus of research. Moreover, the emerging research hotspots included keywords such as 'macrophage polarization', 'gut microbiota' and 'NLRP3 inflammasome'. Conclusions: Research on macrophages in UC holds significant value and practical implications. Additionally, China demonstrated prolific output in this field, while the USA had the most influential contributions. Currently, research hotspots are centred around the modulation of gut microbiota to regulate macrophage polarization and macrophage pyroptosis as potential strategies for mitigating UC.

Curculigoside mitigates dextran sulfate sodium­induced colitis by activation of KEAP1­NRF2 interaction to inhibit oxidative damage and autophagy of intestinal epithelium barrier.

Curculigoside (CUR), a primary active ingredient of Curculigo orchioides Gaertn, serves an important role in the intervention of numerous diseases, including ulcerative colitis, rheumatoid arthritis, myocardial ischemia, etc. However its specific mechanisms of therapy have not been fully elucidated. The aim of the present study was to elucidate the mechanisms underlying the anti­oxidative stress and anti­ulcerative colitis (UC) effects of CUR. Mouse model of dextran sulfate sodium (DSS)­induced colitis, along with Caco2 and mouse intestine organoid in vitro models were used. The effect of CUR on mitigating the symptoms of chronic colitis was investigated. Through ELISA experiments, it was observed that CUR alleviated the inflammation status in mice with chronic colitis. This was evidenced by the downregulation of inflammatory cytokines such as TNF­α and IL­6 and ­1ß and decreased neutrophil infiltration along with downregulated myeloperoxidase activity. CUR helped in maintaining the barrier functions of intestinal epithelium. In vitro TNF­α stimulation of organoids and H2O2 stimulation of Caco2 cells demonstrated the capabilities of CUR to rescue cells from oxidative stress. There was activation of Nrf2 both in vivo and in vitro, accompanied by enhanced autophagy. Mechanistic studies of cells and Nrf2 knockout mice demonstrated that Nrf2 served a pivotal role in inhibition of UC by curculigoside via interaction with Kelch­like ECH­associated protein 1 (Keap1). In vitro and in vivo experiments confirmed that CUR activated Nrf2 via Keap1/Nrf2 interaction, resulting in decreased oxidative stress and promoted autophagy. These findings demonstrated that CUR could effectively mitigate colitis and may have clinical application in UC therapy.

The efficiency and safety of modified tissue-selecting therapy stapler combined with complete anal canal epithelial preservation operation in circumferential mixed hemorrhoids: a randomized controlled trial.

PURPOSE: This study aimed to explore the efficiency and safety of modified tissue-selecting therapy stapler combined with complete anal canal epithelial preservation operation (M-TST-CACP) in the treatment of circumferential mixed hemorrhoids. METHODS: This was a single-center, statistical analyst-blinded, randomized controlled trial (RCT). A total of 306 patients were finally included for analysis. The efficiency (efficacy, recurrence, anal smoothness, quality of life, and wound healing time) and safety (anal incontinence, pain level, anal stenosis, urinary retention, perianal edema, and postoperative bleeding) were evaluated. The statistical difference in continuous data between M-TST-CACP group and procedure for prolapse and hemorrhoids (PPH) group was compared using t-test or Mann-Whitney U test. The statistical difference in counting data between the two groups were compared using Pearson χ2 test. Difference within each group in different time points was evaluated using repeated-measures analysis of variance. RESULTS: M-TST-CACP group showed a higher cure rate (6 months: 74.51% vs. 64.71%, P = 0.044), lower recurrence (6 months: 0% vs. 4.58%, P = 0.015; 12 months: 0.65% vs. 5.88%, P = 0.010), lower anal incontinence score (1 month: 1.29 ± 1.17 vs. 1.93 ± 1.33; 3 months: 1.07 ± 0.87 vs. 1.59 ± 1.01; 6 months: 0.58 ± 0.61 vs. 1.00 ± 0.90; all P < 0.001), and lower rate of anal stenosis (1 month: 0% vs. 7.84%; 3 months: 0% vs. 9.80%; both P < 0.001) than the PPH group. CONCLUSIONS: M-TST-CACP had better efficiency and safety than the PPH, which could be a reasonable adoption for the surgeons to treat circumferential mixed hemorrhoids.

Tissue-selecting-technique mega-window stapler combined with anal canal epithelial preservation operation in prolapsed hemorrhoids.

OBJECTIVE: This study aimed to compare the efficiency of these two combined surgeries [prolapse and hemorrhoids (PPH) combined with the external hemorrhoidectomy and inferior internal hemorrhoid ligation; tissue selecting technique with mega-window stapler (TST-MS) combined with anal canal epithelial preservation operation]. METHODS: This is a single-center, evaluator-blinded randomized controlled trial (RCT). A total of 204 participants were randomly divided into the two groups. The anal function, reoccurrence, intraoperative variables, and operative complications were assessed. The measurement data were compared by paired t test and rank sum test. Chi-squared or Fisher's exact test was used for count data and rank sum test for ranked data. To assess differences within each group in different time points, the repeated-measures analysis of variance was conducted. RESULTS: TST-MS combined with anal canal epithelial preservation operation had lower Wexner score of anal incontinence (Z = 3.062, P = 0.002), higher patients' satisfaction degree (t = 7.32, P < 0.001), less residual skin tags (χ2 = 18.141, P < 0.001), longer operative time (Z = -2.281, P = 0.023), and bigger volume of excised rectal mucosa (t = 2.35, P = 0.020). There was no significant difference between the two groups in the anal canal circumference, recurrence, intraoperative blood loss, weight of excised rectal mucosa, anal pain, bleeding, urinary retention, anal edge edema, and anatomical anal stenosis (all P > 0.05). CONCLUSIONS: TST-MS combined with anal canal epithelial preservation operation showed better clinical efficiency in the treatment of prolapsed hemorrhoids. TRIAL REGISTRATION: This study has been registered in Chinese Clinical Trial Registry (ChiCTR2000038533).

MicroRNA-16 inhibits the TLR4/NF-κB pathway and maintains tight junction integrity in irritable bowel syndrome with diarrhea.

Irritable bowel syndrome with diarrhea (IBS-D) is a chronic and relapsing inflammatory disorder in which pathogenesis has been shown to be in part the result of miRNA-mediated signaling. Here, we investigated the alleviatory role of miR-16 in IBS-D. First, we established an IBS-D mouse model using colonic instillation of acetic acid and developed an IBS-D cell model using lipopolysaccharide exposure. The experimental data demonstrated that miR-16 was underexpressed in the serum of IBS-D patients, as well as in the colorectal tissues of IBS-D mouse models and lipopolysaccharide-exposed intestinal epithelial cells. Next, miR-16 and TLR4 were overexpressed or inhibited to characterize their roles in the viability and apoptosis of intestinal epithelial cells, inflammation, and epithelial tight junction. We found that miR-16 overexpression increased the viability of intestinal epithelial cells, maintained tight junction integrity, and inhibited cell apoptosis and inflammation. We showed that miR-16 targeted TLR4 and inhibited the TLR4/NF-κB signaling pathway. Additionally, inhibition of NF-κB suppressed the long noncoding RNA XIST, thereby promoting enterocyte viability, inhibiting apoptosis and cytokine production, and maintaining tight junction integrity. In vivo experiments further verified the alleviatory effect of miR-16 on IBS-D symptoms in mice. Taken together, we conclude that miR-16 downregulates XIST through the TLR4/NF-κB pathway, thereby relieving IBS-D. This study suggests that miR-16 may represent a potential target for therapeutic intervention against IBS-D.

Evaluation of the clinical efficacy and safety of TST33 mega hemorrhoidectomy for severe prolapsed hemorrhoids.

BACKGROUND: The pathogenesis of hemorrhoids is mainly anal cushion prolapse. Although the traditional treatment has a certain curative effect, it is not ideal. The remission rate of postoperative symptoms is low. Even if temporary remission is achieved, patients with hemorrhoids easily relapse after 1-2 years. The new technique of using staplers to treat prolapsed hemorrhoids has good therapeutic effects in clinical practice. AIM: To explore the effect of TST33 mega stapler prolapse and hemorrhoid mucosal resection in the treatment of patients with severe prolapsed hemorrhoids. METHODS: A total of 204 patients with severe prolapse hemorrhoids who were admitted to the department of anorectal in our hospital from April 2018 to June 2020 were selected, and the patients were randomly divided into group A and group B with 102 cases in each group using a randomized controlled clinical research program. Patients in Group A were treated with a TST33 mega stapler and hemorrhoid mucosal resection to treat prolapse, and patients in Group B were treated according to the Procedure for Prolapse and Hemorrhoids; the operation time, intraoperative blood loss, hospital stay, the difference in operation time, intraoperative blood loss, hospitalization time, pain degree before and after operation, degree of anal edema, anal Wexner score, and surgical complications were compared between the two groups of patients. RESULTS: The operation time, intraoperative blood loss and hospitalization time in Group A were significantly lower than those in Group B (P < 0.05). The cure rate of Group A was 98.04%, compared with 95.10% cure rate of Group B, and the difference was not statistically significant (P > 0.05). The visual analogue scale (VAS) at 12 h and 24 h postoperatively in Group A were significantly lower than those in Group B (P < 0.05). The comparison of the VAS scores between Group A and Group B at 48 h, 72 h and 96 h postoperatively revealed that the difference was not statistically significant (P > 0.05). One day postoperatively, the degree of perianal edema in Group A was compared with that in Group B, and the difference was not statistically significant (P > 0.05). Seven days postoperatively, the degree of perianal edema in Group A was significantly lower than that in Group B (P < 0.05). The comparison of anal Wexner scores between the two groups preoperatively and at 1 mo, 3 mo and 6 mo postoperatively showed that the difference was not statistically significant (P > 0.05). The Wexner scores of the two groups at 1 mo, 3 mo and 6 mo postoperatively were significantly lower than the scores preoperatively (P < 0.05). The postoperative complication rate of Group A was 2.94% lower than that of Group B (11.76%), which was statistically significant (P < 0.05). CONCLUSION: TST33 mega anastomotic hemorrhoidectomy treatment for patients with severe prolapse hemorrhoids, leads to less postoperative pain, the rapid recovery of perianal edema and has fewer complications.

Prophylactic Moxibustion in Preventing Postoperative Urinary Retention of Hemorrhoidectomy: A Study Protocol for a Randomized Controlled Trial.

Backgrounds: Postoperative urinary retention (POUR) is one of the most common complications after hemorrhoidectomy. The best treatment for POUR is prevention and should be involved in the whole perioperative period. Moxibustion has been used to treat urinary retention for thousands of years, and clinical studies have also proved its effects. We try to carry out a randomized, controlled, prospective study to observe whether prophylactic moxibustion could effectively reduce the incidence of POUR of hemorrhoidectomy in 24 h. Methods: This study is a single-center, evaluator-blinded, randomized, and controlled trial. Participants who meet the inclusion and exclusion criteria in this RCT will be randomly assigned to either the treatment group (moxibustion) or the control group (tamsulosin hydrochloride) in a 1:1 ratio according to a computer-generated randomization list. Both moxibustion and tamsulosin will be used 1, 10, and 24 h after operation, respectively. The outcomes of occurrence of POUR, time to first urination, catheterization rate, urinary tract infection, length of hospitalization, and adverse effects will be recorded. Discussion: The findings of the study will help to explore the preventive efficacy of prophylactic moxibustion against POUR of hemorrhoidectomy in 24 h. Trial Registration: CHiCTR, CHiCTR2000039350, registered 24 October, 2020, http://www.chictr.org.cn/showproj.aspx?proj = 63204.

Indications, Feasibility, and Safety of TST STARR Plus Stapler for Degree III Hemorrhoids: A Retrospective Study of 125 Hemorrhoids Patients.

Background: Stapler hemorrhoidopexy (SH) has been widely accepted for hemorrhoids patients because of its low postoperative pain, but it is also associated with a high recurrence rate. The recurrence might be due to failure to completely remove the prolapsed tissue or insufficient removal capacity of the instruments. Removing more prolapsed tissue to reduce the recurrence is believed to benefit more severe prolapsed hemorrhoids patients. Methods: We evaluated the short- and long-term safety and efficacy in 125 hemorrhoids patients who underwent SH in 2013-2015. Eighty patients had prolapsed tissue less than half of the circular anal dilator (CAD) and underwent a procedure for prolapsing hemorrhoids (PPH), while the remaining 45 patients with hemorrhoid prolapse greater than half of the CAD were treated with a tissue selection therapy stapler stapled transanal rectal resection plus (TST STARR+). Results: There were no significant differences between the two groups in terms of operative time, hospitalization time, overall satisfaction or complications. At follow-up of up to 4 years after surgery, there was no significant difference in recurrence rates between TST STARR+ group and PPH group (5.2% vs. 4.7%, p < 0.05). The mean width and volume of the resected tissues were significantly larger in the TST STARR+ group than in the PPH group (4.8 vs. 2.9 cm, 10.2 vs. 4.4 cm3, P < 0.05). Conclusion: The TST STARR+ procedure can remove more hemorrhoidal tissue than PPH and it is better suited for patients with severe annular prolapsed hemorrhoids greater than half of the CAD. It has the advantages of convenient to operate, rapid recovery, fewer complications, and long-term satisfactory results.

Efficacy and safety of Qinghua Zhixie Decoction against diarrhea-predominate irritable bowel syndrome: A protocol for a randomized controlled trial.

BACKGROUND: Diarrhea-predominant irritable bowel syndrome (D-IBS) is the main subtypes of irritable bowel syndrome (IBS). In recent years, more than half of IBS patients have received complementary and alternative medicine. Traditional Chinese herbal formula is widely used in Asia, and clinical studies have also found that Chinese herbal formula could significantly improve abdominal pain and diarrhea. We plan to carry out a randomized, controlled, double blind, clinical studies to observe the clinical efficacy of Qinghua Zhixie decoction in the treatment of D-IBS. METHODS: Four hundred sixty-four participants will be randomly assigned to the treatment group and control group. Patients in both groups would take medications and stimulations simultaneously. The outcomes of IBS symptom severity score, quality of life, psychological states, and recurrence rate will be recorded. Statistics will be analyzed with the SPSS 22.0. CONCLUSIONS: The findings of the study will identify the safety and efficacy of Qinghua Zhixie decoction in the treatment of D-IBS. TRIAL REGISTRATION OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/C8MHW.

Eriodictyol suppresses the malignant progression of colorectal cancer by downregulating tissue specific transplantation antigen P35B (TSTA3) expression to restrain fucosylation.

Eriodictyol is a natural flavonoid with many pharmacological effects, such as anti-oxidation, anti-inflammation, anti-tumor, and neuroprotection. Besides, it has been reported that flavonoids play an important role in protein glycosylation. The fucosylation structure is closely associated with processes of various tumor metastases. TSTA3 is involved in the de novo synthesis and can convert cellular GDP-D-mannose into GDP-L-fucose. It was predicted on the STITCH database that eriodictyol interacted with TSTA3. In addition, literature has confirmed that TSTA3 is upregulated in CRC and can regulate the proliferation and migration of breast cancer cells. Herein, the precise effects of eriodictyol on the clone-forming, proliferative, migratory and invasive abilities of CRC cells as well as EMT process were assessed. Moreover, the correlation among eriodictyol, TSTA3, and fucosylation in these malignant behaviors of CRC cells was evaluated, in order to elucidate the underlying mechanism. The current work discovered that eriodictyol inhibited the viability, clone-formation, proliferation, migration, invasion, and EMT of CRC cells, and that these inhibitory effects of eriodictyol on the malignant behavior of CRC cells were reversed by TSTA3 overexpression. Additionally, eriodictyol suppresses fucosylation by downregulating the TSTA3 expression. Results confirmed that fucosylation inhibitor (2-F-Fuc) inhibited clone formation, proliferation, migration, invasion, as well as EMT of CRC cells and eriodictyol treatment further reinforced the suppressing effects of 2-F-Fuc on the malignant behavior of CRC cells. We conclude that eriodictyol suppresses the clone-forming, proliferative, migrative and invasive abilities of CRC cells as well as represses the EMT process by downregulating TSTA3 expression to restrain fucosylation.

Efficacy and Safety of Sphincter-Preserving Surgery in the Treatment of Complex Anal Fistula: A Network Meta-Analysis.

BACKGROUND: There are many surgical methods of sphincter preservation in treating complex anal fistula, but the therapeutic effects of each operation are different. Therefore, this study aimed to compare the impact of other treatment methods through a network meta-analysis to evaluate the best sphincter preservation method for treating complex anal fistula. METHODS: We searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, VIP Journal Database, and the Wanfang Database to collate randomized controlled trials on sphincter-preserving surgery for complex anal fistula. RESULTS: A total of 29 articles were included in this meta-analysis. The cure rates showed no statistically significant differences between any two interventions (P > 0.05). The recurrence rate results showed that the rate of patients after Fistulectomy was higher than others (P < 0.05). The incidence rate of complications showed that the incidence rate after fistulectomy treatment was higher than that of others (P < 0.05). The surface under the cumulative ranking (SUCRA) was used to arrange their advantages and disadvantages, and a larger SUCRA value indicates that the intervention may be more effective. The results showed that TROPIS may have the highest cure rate (SUCRA = 78.6%), stem cell transplantation (SCT) may have the lowest recurrence rate (SUCRA = 85.5%), and imLIFT may have the least complications (SUCRA = 88.2%). CONCLUSION: According to the existing literature data, for patients with complex anal fistula, TROPIS may be the surgical method with the highest cure rate, SCT may be the treatment method with the lowest recurrence rate, and imLIFT may be the surgical method with the lowest incidence of postoperative complications. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, identifier: CRD42020221907.

Cayratia japonica Prevents Ulcerative Colitis by Promoting M2 Macrophage Polarization through Blocking the TLR4/MAPK/NF-κB Pathway.

Background and Aims: Several components of Cayratia japonica (CJ) such as rutin and quercetin have shown anti-inflammatory effect, yet its function in ulcerative colitis (UC) remains to be clarified. This study focuses on the modulatory effect of CJ on UC as well as molecular mechanism by which CJ regulates macrophage polarization in UC. Methods: The targets related to CJ components and UC were, respectively, obtained through in silico analysis, and their intersection targets were selected for pathway enrichment analysis. RAW264.7 cells were stimulated with lipopolysaccharide (LPS) to induce M1 macrophages. Expression of the macrophage polarization M1 marker CD11b and M2 marker CD206 was measured to determine the phenotype of macrophages. The mouse model was treated with dextran sodium sulfate (DSS) to induce UC to observe the effects of CJ on UC in vivo. Results: The in silico analysis suggested the crucial significance of TLR4 and its downstream MAPK/NF-κB pathways in the modulatory effect of CJ on UC. Furthermore, experimental data revealed that CJ could promote M2 macrophage polarization but alleviate immune inflammation and reduce colon damage in DSS-evoked UC model. Additionally, CJ can inhibit the expression of TLR4/MAPK/NF-κB signaling pathway to enhance the M2-like polarization. Conclusion: Hence, CJ may exert anti-inflammatory effects and an inhibitory role in UC by inhibiting the TLR4/MAPK/NF-κB pathway and subsequent M1-like macrophage polarization.

Efficacy and Safety of Maxing Xianchang Su in the Treatment of Functional Constipation: A Randomized Controlled Trial.

BACKGROUND: Functional constipation (FC) is one of the prevalent gastrointestinal disorders that affect people of all ages. Long-term FC has significant effects on the quality of life of patients. Although commonly used drugs have reliable short-term effects, they are easily addictive and have side effects. Therefore, pursuing a convenient drug-food homogenous program is critical for FC patients. Maxing Xianchang Su is a functional food based on traditional Chinese medicine. To investigate the efficacy and safety of Maxing Xianchang Su in FC treatment, we conducted a randomized controlled trial. METHODS: We carried out a prospective multicenter randomized parallel controlled study in three hospitals in Jiangsu Province, China, from January 2020 to March 2021, which included 206 FC patients. All patients were arbitrarily assigned into a treatment group and a control group at a ratio of 1 : 1; 103 cases in each group. The treatment group was given oral Maxing Xianchang Su, whereas the control group was treated with lactulose oral solution. The course of treatment was two weeks. The two groups of patients were evaluated after six weeks for symptom improvement before and after taking the drug. Furthermore, the safety of Maxing Xianchang Su was assessed. RESULTS: Both groups of patients successfully completed the study without shedding cases. The effective rates of the treatment group and control group after two weeks were 90.6% and 67.0%, respectively. The treatment group had a better curative effect than the control group (P < 0.05). The symptom score of the two groups improved compared with that before the treatment. The difference between the two groups was statistically significant (P < 0.05). During the treatment process, neither group experienced abnormal changes in blood lipid, blood glucose, routine hematuria, or liver and kidney functions. There were no adverse reactions in both groups. CONCLUSION: Maxing Xianchang Su has a positive effect on FC treatment with reliable mid-term effect and a high level of safety.

Mechanism of QingHuaZhiXie Prescription Regulating TLR4-IECs Pathway in the Intervention of Diarrhea Predominant Irritable Bowel Syndrome.

To investigate the effect and mechanism of QingHuaZhiXie prescription on diarrhea predominant irritable bowel syndrome (D-IBS), animal models of rats were used in this study. 48 rats were randomly divided into 6 groups, containing one control group, one animal model group (D-IBS group), and four drug intervention groups (low, medium, and high dosage of QingHuaZhiXie prescription and trimebutine maleate intervention group). Abdominal withdrawal reflex (AWR) and Bristol stool form scale were recorded; the expression levels of inflammatory factors (TNF-α and IFN-γ), pathway proteins TLR4, MyD88, NF-κB, and key proteins of tight junction between intestinal epithelial cells (IECs) were detected; the microstructure of intestinal mucosal was observed by hematoxylin and eosin (H&E) staining; MPO activity was detected with immunohistochemical analysis to reflect the inflammation of tissues. Results show that QingHuaZhiXie prescription reduced diarrhea index and intestinal hypersensitivity and intestinal tissue integrity after intervention. MPO activity in QingHuaZhiXie prescription-treated rats was significantly lower relative to their model group. The expression levels of inflammatory factors and TLR4/MyD88/NF-κB pathway proteins were repressed, and the protein levels of occludin and claudin-1 increased. Meanwhile, this study also found that the remission effect of QingHuaZhiXie prescription on D-IBS increased with its dosage increase. Hence, as a therapeutic prescription for D-IBS, QingHuaZhiXie prescription could relieve D-IBS symptoms through balancing the inflammatory factors expression by inhibiting the TLR4/MyD88/NF-κB pathway and maintaining the function and structure of IECs by improving the protein levels of JAM, occludin, claudin-1, and ZO-1.

Modified tissue-selecting therapy stapler combined with complete anal canal epithelial preservation operation for the treatment of circumferential mixed haemorrhoids: a protocol for single-blind randomised controlled study.

INTRODUCTION: This protocol designed a randomised controlled trial (RCT) to evaluate the effectiveness, safety and prognostic outcomes of modified tissue selecting technique (M-TST) combined with complete anal canal epithelial preservation (CACP) among patients with circumferential mixed haemorrhoids. METHODS AND ANALYSIS: This study will be single-blinded, and recruit 348 patients who are admitted to the Changshu Hospital Affiliated to Nanjing University of Chinese Medicine and fulfil the inclusion criteria from January 2022 to December 2022. Patients will be randomly assigned to the treatment group and the control group in a 1:1 ratio. The statistician will be blinded for the allocation. The treatment group will receive M-TST combined with CACP (M-TST-CACP), while the control group will receive the procedure for prolapse and haemorrhoids. The two groups will receive the same preoperative and postoperative care. The primary outcome will be recurrence rate. The secondary outcomes will be operation time, intraoperative bleeding, incontinence, pain, postoperative complications (severe bleeding, perianal oedema, urinary retention, faecal urgency, skin tags and anal stenosis), prolapse, recovery time, quality of life, Haemorrhoid Severity Score, and Symptom Severity Score. ETHICS AND DISSEMINATION: This protocol has been approved by the Clinical Ethics Committee of the Changshu Hospital Affiliated to Nanjing University of Chinese Medicine (approval no. 202102001). TRIAL REGISTRATION NUMBER: ChiCTR2100042750.

A NEW MIXED SURGICAL TREATMENT FOR GRADES III AND IV HEMORRHOIDS: MODIFIED SELECTIVE HEMORRHOIDECTOMY COMBINED WITH COMPLETE ANAL EPITHELIAL RETENTION.

BACKGROUND: Varicose veins appear above and below the dentate line in mixed hemorrhoids, which seriously affects anal function and quality of life. AIM: To propose an improvement in tissue-selecting therapy repair of anal pad combined with complete anal canal epithelial retention comparing with Milligan-Morgan surgery. METHODS: A prospective randomized controlled study was designed enrolling 200 patients with grade III and IV hemorrhoids. They were divided into control and observation groups. The control received Milligan-Morgan surgery, and the observation the modified tissue-selecting therapy stapler combined with complete anal canal preservation surgery. All patients were followed for six months to evaluate the treatment differences. RESULTS: In final, control group included 82 and observation 87. The average operation time of the control group was significantly lower than that of the observation, while the bleeding volume was significantly lower in control group. The control group VAS score was 3 (1, 4), and observation 4 (2, 5). There was no significant difference in the incidence of urinary retention, bleeding and wound margin edema after surgery at one month postoperatively. Digital incidence of anal stenosis in the observation group was significantly lower than in control; the same occurred with residual anal margins. The postoperative anal canal diameter was significantly larger than the control group. Wexner anal incontinence score showed that no anal incontinence occurred in both groups, and the control group scored was significantly higher than observation. In final six months follow-up, the observation group did not experience any relapse and four cases were found among controls. The treatment satisfaction of the observation group was better. CONCLUSIONS: In grades III and IV hemorrhoids, modified tissue-selecting therapy combined with complete anal canal preservation had better prognosis and treatment satisfaction than Milligan-Morgan procedure, and it is a new surgical method for patients with advanced mixed hemorrhoids.

Worenine reverses the Warburg effect and inhibits colon cancer cell growth by negatively regulating HIF-1α.

BACKGROUND: Some natural compounds inhibit cancer cell growth in various cancer cell lines with fewer side effects than traditional chemotherapy. Here, we explore the pharmacological effects and mechanisms of worenine (isolated from Coptis chinensis) against colorectal cancer. METHODS: The effects of worenine on colorectal cancer cell proliferation, colony formation and cell cycle distribution were measured. Glycolysis was investigated by examining glucose uptake and consumption, lactate production, and the activities and expressions of glycolysis enzymes (PFK-L, HK2 and PKM2). HIF-1α was knocked down and stimulated in vitro to investigate the underlying mechanisms. RESULTS: Worenine somewhat altered the glucose metabolism and glycolysis (Warburg effect) of cancer cells. Its anti-cancer effects and capability to reverse the Warburg effect were similar to those of HIF-1α siRNA and weakened by deferoxamine (an HIF-1α agonist). CONCLUSION: It is suggested that worenine targets HIF-1α to inhibit colorectal cancer cell growth, proliferation, cell cycle progression and the Warburg effect.

Efficacy and safety of an innovatively modified cutting seton technique for the treatment of high anal fistula: A protocol for a randomized controlled trial.

BACKGROUND: Anal fistula is a common anorectal disease. So far, operation is still the optimal method to cure anal fistula. High anal fistula (HAF) is an even more clinically difficult disease to treat. Evidence suggested that seton placement can be a definitive treatment for HAF. However, tightening the seton brings great pain to patients, which affects the clinical application of the therapy. Also, this may lead to difficulty in controlling anal fluids and gas because of the larger scar left and the local defect in the anal after the operation. We propose an innovative seton technique for the treatment of HAF, after long term attempts, the operation of the modified seton cutting technique. The aim of our present study is to compare the difference of anal function, healing time, pain severity, recurrence, and complications between the procedure of the modified seton cutting technique and the conventional cutting seton operation against HAF with a randomized, controlled, prospective study. METHODS: 204 participants in this trial will be randomly divided into treatment group (procedure of the modified seton cutting technique) and control group (cutting seton technique) in a 1:1 ratio. The outcomes of continence state, pain severity after tightening, complete healing of fistula, duration to healing, operation time, recurrence rates, and postoperative complications will be recorded at 1, 2, 3, 4 weeks, then every month in the outpatient clinic. Data will be analyzed by SPSS version 22. CONCLUSIONS: The findings of the study will help to explore the efficacy and safety of the procedure of the modified seton cutting technique against AF. TRIAL REGISTRATION NUMBER: DOI 10.17605/OSF.IO/V6G2S.

A new mixed surgical treatment for grades iii and iv hemorrhoids: modified selective hemorrhoidectomy combined with complete anal epithelial retention / Um novo tratamento cirúrgico para hemorroidas mistas graus iii e iv: hemorroidectomia seletiva modificada combinada com retenção epitelial anal completa

ABSTRACT Background: Varicose veins appear above and below the dentate line in mixed hemorrhoids, which seriously affects anal function and quality of life. Aim: To propose an improvement in tissue-selecting therapy repair of anal pad combined with complete anal canal epithelial retention comparing with Milligan-Morgan surgery. Methods: A prospective randomized controlled study was designed enrolling 200 patients with grade III and IV hemorrhoids. They were divided into control and observation groups. The control received Milligan-Morgan surgery, and the observation the modified tissue-selecting therapy stapler combined with complete anal canal preservation surgery. All patients were followed for six months to evaluate the treatment differences. Results: In final, control group included 82 and observation 87. The average operation time of the control group was significantly lower than that of the observation, while the bleeding volume was significantly lower in control group. The control group VAS score was 3 (1, 4), and observation 4 (2, 5). There was no significant difference in the incidence of urinary retention, bleeding and wound margin edema after surgery at one month postoperatively. Digital incidence of anal stenosis in the observation group was significantly lower than in control; the same occurred with residual anal margins. The postoperative anal canal diameter was significantly larger than the control group. Wexner anal incontinence score showed that no anal incontinence occurred in both groups, and the control group scored was significantly higher than observation. In final six months follow-up, the observation group did not experience any relapse and four cases were found among controls. The treatment satisfaction of the observation group was better. Conclusions: In grades III and IV hemorrhoids, modified tissue-selecting therapy combined with complete anal canal preservation had better prognosis and treatment satisfaction than Milligan-Morgan procedure, and it is a new surgical method for patients with advanced mixed hemorrhoids.

RESUMO Racional: Veias varicosas aparecem acima e abaixo da linha dentada nas hemorroidas mistas, afetando seriamente a função anal e a qualidade de vida. Objetivo: Propor melhoria na terapia de seleção de tecido de reparo do coxim anal combinado com retenção completa epitelial do canal anal em comparação com a operação de Milligan-Morgan. Métodos: Estudo prospectivo randomizado controlado foi desenhado envolvendo 200 pacientes com hemorroidas graus III e IV. Eles foram divididos em grupos de controle e observação. O controle recebeu operação de Milligan-Morgan, e o de observação procedimento de seleção de tecido modificado combinado com operação completa de preservação do canal anal. Todos os pacientes foram acompanhados por seis meses para avaliar as diferenças de tratamento. Resultados: No final, o grupo controle incluiu 82 e o de observação 87. O tempo médio de operação do grupo controle foi significativamente menor do que o de observação, enquanto o volume de sangramento foi significativamente menor no grupo controle. O escore VAS do grupo controle foi 3 (1, 4) e no de observação 4 (2, 5). Não houve diferença significativa na incidência de retenção urinária, sangramento e edema da margem da ferida no pós-operatório de um mês. A incidência de estenose anal digital no grupo observação foi significativamente menor do que no controle; o mesmo ocorreu com as margens anais residuais. O diâmetro do canal anal pós-operatório foi significativamente maior nele do que o grupo controle. A pontuação de incontinência anal de Wexner mostrou que nenhuma incontinência ocorreu em ambos os grupos, e a pontuação do grupo de controle foi significativamente maior do que no de observação. Nos últimos seis meses de acompanhamento, o grupo observação não teve nenhuma recaída e quatro casos foram encontrados entre os controles. A satisfação com o tratamento do grupo observação foi maior. Conclusões: Nas hemorroidas graus III e IV, o tratamento de seleção de tecido modificado combinado com a preservação completa do canal anal teve melhor prognóstico e satisfação do que com o procedimento de Milligan-Morgan, e é um novo método cirúrgico para pacientes com hemorroidas mistas avançadas.