Assessment of functional outcome following Duhamel retro-rectal pull-through surgery for Hirschsprung's disease: a follow-up study

Context: Hirschsprung's disease (HD) is one of the commonest problems requiring surgery in children. More than 95% of children present during new-born period, when they are treated with leveling colostomy and are followed with pull-through surgery a few months later, once the child has gained adequate weight to withstand a major surgery. The commonest pull through surgery done is the Duhamel retro-rectal pull-through (DRPT) repair. Settings and Design: This is a retrospective study of children who presented to one unit in our institute, a tertiary care referral hospital for children less than 12 years, with HD and underwent DRPT procedure during the period between July 2017 to June 2020. The children were evaluated after three years of follow-up for fecal incontinence and constipation. The study was conducted in children diagnosed with classical segment recto-sigmoid HD who underwent surgery. The children who were diagnosed with HD other than classical segment, who underwent primary pull through surgery and who underwent other repairs for HD were excluded from the study. Results: Thirty-two children underwent DRPT procedure during the study period. Of them, five (15.6%) children were lost on follow-up and one (3.1%) child had expired in the immediate post-operative period. Twenty-six children were included in the study. The bowel function score was calculated. The mean age of definitive surgery was 4.2 years. The follow-up period was a minimum of three years. Only two children had a "good" score of eighteen and above. Nineteen children had a "fair" score of 13-17. Five children had a "poor" score of less than thirteen, and among them, two had a "very poor" score of less than nine. The mean BFS was 13.72. Conclusions: Functional outcomes following Duhamel procedure are satisfactory, with 7.7% of children are in the fringe of requiring another surgery for constipation and pseudo-incontinence. (AU)

Postoperative analgesic efficacy of nefopam after anorectal surgery: a retrospective observational study

Objective: To examine the effectiveness of nefopam on postoperative pain control after anorectal surgeries. Methods: We retrospectively reviewed the electronic medical records of patients who underwent anorectal surgeries from January 2019 to March 2022 at two medical centers. The data were divided into nefopam and conventional groups. The primary outcome was the number of patients who requested additional opioids in the 24-h postoperative period. The secondary outcomes were numeric rating pain scores (NRPS) within a 24-h postoperative period and analgesic drugs-related side effects. Results: Eighty-seven patients in the conventional group and 60 in the nefopam group were recruited. The nefopam group reported less additional opioid consumption than the conventional group in all dimensions of analysis, including overall, adjusted to anesthetic techniques and types of surgery. However, these did not reach statistical significance (P = 0.093). Only patients in the nefopam group who underwent hemorrhoidectomy under TIVA or spinal anesthesia significantly required fewer additional opioids (P = 0.016, 60% mean difference). Similarly, the 24-h postoperative morphine consumption was lower in the nefopam group (mean difference = -3.4, 95%CI: 0.72,6.08). Furthermore, significantly lower NRPS were reported in the nefopam group during the 12-18 h postoperative period (P = 0.009). On the other hand, analgesic drugs related side effects were similar in both groups. Conclusions: The administration of nefopam after major anorectal surgery is beneficially evident in reducing postoperative opioid requirements. (AU)

Serie de casos de sangrado intraluminal postoperatorio en colectomía izquierda / Case series of postoperative intraluminal bleeding in left colectomy

Introducción: El sangrado digestivo intraluminal postoperatorio es una entidad poco frecuente y su manifestación clínica no difiere de la hemorragia digestiva baja de otra etiología. A pesar de que su presentación más habitual es la hematoquecia autolimitada en la primera deposición, en un discreto porcentaje puede requerir transfusiones, tratamiento endoscópico, hemodinámico, o incluso cirugía. Objetivo: Analizar los pacientes con sangrado digestivo intraluminal postoperatorio tratados en un centro de alta complejidad y realizar una revisión bibliográfica del tema. Diseño: Estudio retrospectivo, descriptivo. Material y métodos: Pacientes con sangrado anastomótico durante el post operatorio inmediato de una colectomía izquierda, operados en el Servicio de Cirugía General y Coloproctología desde enero del 2017 a diciembre del 2021. Las variables estudiadas fueron edad, sexo, anticoagulación y su causa, descenso de hemoglobina, cirugía realizada y su indicación, vía de abordaje, configuración de la anastomosis, electividad de la cirugía, complicaciones, días de internación y manejo terapéutico. Resultados: Se incluyeron 4 pacientes con una edad media de 72 (rango 54-87) años y una distribución por sexo de 1:1. En todos la colectomía izquierda fue programada y en 3 el abordaje fue laparoscópico. La anastomosis fue termino-terminal con sutura mecánica circular. Todos los pacientes presentaron sangrado en las primeras 24 horas postoperatorias. El tratamiento fue decidido de acuerdo a la condición hemodinámica: en los 2 pacientes con estabilidad hemodinámica fue suficiente el tratamiento conservador con reanimación y transfusiones. Los otros 2 que presentaron inestabilidad hemodinámica requirieron manejo intervencionista con endoscopía rígida, videocolonoscopía y cirugía. Conclusión: El sangrado intraluminal es una complicación poco frecuente de la anastomosis colorrectal que requiere manejo intervencionista solo en los pacientes que presentan inestabilidad hemodinámica. (AU)

Introduction: Postoperative intraluminal gastrointestinal bleeding is a rare entity and its clinical manifestation does not differ from lower gastro-intestinal bleeding of another etiology. Despite the fact that its most common presentation is self-limited hematochezia at the first stool, in a small percentage it may require transfusions, endoscopic or hemodynamic management, or even surgery. Aim: To analyze the patients with postoperative intraluminal gastrointestinal bleeding treated in a tertiary center and to carry out a bibliographic review of the subject. Design: Retrospective descriptive study. Material and methods: Patients with immediate postoperative anastomotic bleeding from a left colectomy, operated on at the General Surgery and Coloproctology Service from January 2017 to December 2021 were included. The variables recorded were age, sex, anticoagulation and its cause, decrease in hemoglobin, procedure performed and its indication, surgical approach, type of anastomosis, electiveness of surgery, complications, hospital stay and management. Results: Four patients with a mean age of 72 (range 54-87) years and a 1:1 gender distribution were included. All procedures were elective and 3 laparoscopic. All anastomoses were performed end-to-end with a circular stapler. All patients presented bleeding in the first 24 postoperative hours. The treatment was decided according to the hemodynamic condition; patients with hemodynamic stability (2) received medical treatment while those with hemodynamic instability (2) required interventional management with rigid endoscopy, colonoscopy and surgery. Conclusion: Intraluminal bleeding is a rare complication of colorectal anastomosis that requires interventional management only in patients with hemodynamic instability. (AU)

Interposición hepatodiafragmática del colon / Hepatodiaphragmatic Interposition of the Colon

Hombre de 72 años con antecedentes de diabetes mellitus tipo 2 y sustitución protésica de cadera derecha hace dos años, que ingresó por dolor localizado en región posterolateral del miembro inferior derecho y dificultad para deambular. El examen físico mostró mucosas hipocoloreadas, abdomen depresible e indoloro con borramiento de la submatidez hepática normal e impotencia funcional con calor y dolor en la articulación coxofemoral. La radiografía del tórax (figura A) reveló un hemidiafragma derecho elevado y el colon transverso estaba interpuesto entre el hígado y el diafragma. Esta anormalidad anatómica es conocida como el signo de Chilaiditi y puede conducir a un diagnóstico falso positivo de neumoperitoneo (figura B de archivo). El signo de Chilaiditi se debe casi siempre a la interposición del colon transverso, aunque puede ser intestino delgado. Cuando se asocia al dolor abdominal, la entidad recibe el nombre de síndrome de Chilaiditi(AU)

Uso de stent en estenosis colorrectal benigna / Stent utilization in benign colorectal stenosis

Introducción. La estenosis colorrectal benigna hace referencia a una condición anatómica caracterizada por una disminución del diámetro de la luz intestinal distal a la válvula ileocecal, ocasionando una serie de signos y síntomas de tipo obstructivo. Es una entidad poco frecuente, secundaria en la gran mayoría de veces a la realización de anastomosis intestinales al nivel descrito. El objetivo de esta investigación fue determinar la utilidad del stentcolónico en estenosis secundaria a patología colorrectal no neoplásica. Métodos. Estudio descriptivo de una cohorte de pacientes que desarrolló estenosis colorrectal de origen benigna confirmada por colonoscopía, en 3 hospitales de alta complejidad de la ciudad de Medellín, Colombia, entre los años 2007 y 2021. Resultados. Se incluyeron 34 pacientes con diagnóstico de estenosis colorrectal de origen benigno, manejados con stents metálicos autoexpandibles. La mediana de seguimiento fue de 19 meses y se obtuvo éxito clínico en el 73,5 % de los casos. La tasa de complicación fue del 41,2 %, dada principalmente por reobstrucción y migración del stent, y en menor medida por perforación secundaria a la colocación del dispositivo. Conclusión. Los stents metálicos autoexpandibles representan una opción terapéutica en pacientes con obstrucción colorrectal, con altas tasas de mejoría clínica en pacientes con patología estenosante no maligna. Cuando la derivación por medio de estoma no es una opción, este tipo de dispositivos están asociados a altas tasas de éxito clínico y mejoría de la calidad de vida de los pacientes

Introduction. Benign colorectal stenosis refers to an anatomical condition characterized by a decrease in the diameter of the intestinal lumen distal to the ileocecal valve, which might cause a series of obstructive signs and symptoms. It is a rare entity, caused in the vast majority of cases due to intestinal anastomosis at the described level. The purpose of this study is to determine the performance of colonic stents in the management of non-malignant colorectal strictures. Methods. Descriptive study of a cohort of patients who developed a benign colorectal stenosis confirmed by colonoscopy in three high-complexity hospitals in the city of Medellín, Colombia, between 2007 and 2021. Results. Thirty-four patients diagnosed with benign colorectal stenosis managed with self-expanding metal stents were included in the study. Median follow-up was 19 months, obtaining clinical success in 73.5% of cases, with a complication rate of 41.2%, mainly due to reobstruction and migration of the stent, and to a lesser extent due to perforation secondary to device placement.Conclusion. Self-expanding metallic stents represent a therapeutic option in patients with colorectal obstruction caused by non-malignant stenosing pathology. When diversion through a stoma is not an option, this type of device is associated with high rates of clinical success and improvement in the patients' quality of life

Proteínas oxidadas de origen animal y su impacto sobre la salud intestinal / Oxidized proteins of animal origin and their impact on intestinal health / Proteínas oxidadas de origem animal e seu impacto na saúde intestinal

Los alimentos de origen animal como la carne de pollo, res, pescado y cerdo poseen una amplia demanda en todo el mundo debido, entre otros aspectos, a su valor nutricional, asociado al alto contenido proteico. No obstante, este tipo de proteínas son susceptibles de sufrir reacciones de oxidación, las cuales pueden mediar procesos de fragmentación, agregación, pérdida de solubilidad, funcionalidad y digestibilidad proteica; eventos implicados en la pérdida de su valor nutricional. En este sentido, las proteínas agrega­das tienden a no ser digeridas en el tracto gastrointestinal y acumularse en el intestino (colon), donde la microbiota colónica las degrada a productos mutagénicos como fenol y p-cresol, lo que incrementa el riesgo de cáncer colorrectal. Por otra parte, los ami­noácidos o péptidos oxidados liberados en la digestión podrían incorporarse en las vías de señalización celular intestinal y favorecer o exacerbar procesos intestinales crónicos como colon irritable o enfermedad de Crohn. Debido al gran interés de esta temática en los últimos años, el objetivo de esta revisión es realizar una descripción general del impacto de proteínas oxidadas de origen animal sobre la salud intestinal.

Animal foods such as chicken, beef, fish and pork are in wide demand throughout the world due, among other things, to their nutritional value, associated with their high protein content. However, this type of protein is susceptible to oxidation reactions, which can mediate processes of fragmentation, aggregation, loss of solubility, functionality, and protein digestibility, which are events involved in the loss of their nutritional value. In this sense, aggregated proteins tend not to be digested in the gastrointestinal tract and accumulate in the intestine (colon), where the colonic microbiota degrades them into mutagenic products such as phenol and p-cresol, which increases the risk of colorectal cancer. On the other hand, the oxidized amino acids or peptides released in digestion could be incorporated into intestinal cell signaling pathways and favor or exacerbate chronic intestinal processes such as irritable bowel syndrome or Crohn's disease. Due to the great interest in this topic in recent years, the objective of this review is to provide a general overview of the impact of oxidized proteins of animal origin on intestinal health.

Alimentos de origem animal como frango, carne bovina, peixe e carne suína são muito procurados em todo o mundo devido, entre outros fatores, ao seu valor nutricional, associado ao seu alto teor de proteínas. No entanto, esse tipo de proteína é suscetível a reações de oxidação, que podem mediar processos de fragmentação, agregação, perda de solubilidade, funcionalidade e digestibilidade da proteína; eventos envolvidos na perda de seu valor nutritivo. Nesse sentido, as proteínas agregadas tendem a não ser digeridas no trato gastrointestinal e se acumulam no intestino (cólon), onde a microbiota colônica as degrada em produtos mutagênicos como fenol e p - cresol, aumentando o risco de câncer colorretal. Por outro lado, os aminoácidos ou peptídeos oxidados liberados na digestão poderiam ser incorporados às vias de sinalização das células intestinais e favorecer ou exacerbar processos intestinais crônicos, como a síndrome do intestino irritável ou a doença de Crohn. Devido ao grande interesse neste tema nos últimos anos, o objetivo desta revisão é fornecer uma descrição geral do impacto das proteínas oxidadas de origem animal na saúde intestinal.

Quantitative evaluation of radiotherapy plan in precise external beam radiotherapy process management for cervical cancer / 南方医科大学学报

OBJECTIVE@#To identify the problems in clinical radiotherapy planning for cervical cancer through quantitative evaluation of the radiotherapy plans to improve the quality of the plans and the radiotherapy process.@*METHODS@#We selected the clinically approved and administered radiotherapy plans for 227 cervical cancer patients undergoing external radiotherapy at Sun Yat-sen University Cancer Center from May, 2019 to January, 2022. These plans were transferred from the treatment planning system to the Plan IQTM workstation. The plan quality metrics were determined based on the guidelines of ICRU83 report, the GEC-ESTRO Working Group, and the clinical requirements of our center and were approved by a senior clinician. The problems in the radiotherapy plans were summarized and documented, and those with low scores were re-planned and the differences were analyzed.@*RESULTS@#We identified several problems in the 277 plans by quantitative evaluation. Inappropriate target volume selection (with scores < 60) in terms of GTV, PGTV (CI) and PGTV (V66 Gy) was found in 10.6%, 65.2%, and 1% of the plans, respectively; and the PGTV (CI), GTV, and PCTV (D98%, HI) had a score of 0 in 0.4%, 10.1%, 0.4%, 0.4% of the plans, respectively. The problems in the organs at risk (OARs) involved mainly the intestines (the rectum, small intestine, and colon), found in 20.7% of the plans, and in occasional cases, the rectum, small intestine, colon, kidney, and the femoral head had a score of 0. Senior planners showed significantly better performance than junior planners in PGTV (V60 Gy, D98%), PCTV (CI), and CTV (D98%) (P≤0.046) especially in terms of spinal cord and small intestine protection (P≤0.034). The bowel (the rectum, small intestine and colon) dose was significantly lower in the prone plans than supine plans (P < 0.05), and targets coverage all met clinical requirements. Twenty radiotherapy plans with low scores were selected for re-planning. The re-planned plans had significantly higher GTV (Dmin) and PTV (V45 Gy, D98%) (P < 0.05) with significantly reduced doses of the small intestines (V40 Gy vs V30 Gy), the colon (V40 Gy vs V30 Gy), and the bladder (D35%) (P < 0.05).@*CONCLUSION@#Quantitative evaluation of the radiotherapy plans can not only improve the quality of radiotherapy plan, but also facilitate risk management of the radiotherapy process.

Perioperative management and operative treatment of malignant tumor of anal canal merging severe abdominal protuberance / 中华胃肠外科杂志

Objective: To report the perioperative management and robot-assisted minimally invasive surgery results of one case with malignant tumor of anal canal combined with severe abdominal distention. Methods: A 66-year-old male suffer from adenocarcinoma of anal canal (T3N0M0) with megacolon, megabladder and scoliosis. The extreme distention of the colon and bladder result in severe abdominal distention. The left diaphragm moved up markedly and the heart was moved to the right side of the thoracic cavity. Moreover, there was also anal stenosis with incomplete intestinal obstruction. Preoperative preparation: fluid diet, intravenous nutrition and repeated enema to void feces and gas in the large intestine 1 week before operation. Foley catheter was placed three days before surgery and irrigated with saline. After relief of abdominal distention, robotic-assisted abdominoperineal resection+ subtotal colectomy+colostomy was performed. Results: Water intake within 6 hours post-operatively; ambulance on Day 1; anal passage of gas on Day 2; semi-fluid diet on Day 3; safely discharged on Day 6. Conclusion: Robotic-assisted minimally invasive surgery is safe and feasible for patients with malignant tumor of anal canal combined with severe abdominal distention after appropriate and effective preoperative preparation to relieve abdominal distention.

Advances in colonic manometry in adults with colonic motility disorders / 中华胃肠外科杂志

In recent years, colonic manometry has been gradually introduced into clinical practice. It helps clinicians to gain a better understanding of the physiology and pathophysiology of colonic contractile activity in healthy adults and patients with colonic dysfunction. More and more patterns of colonic motility are being discovered with the help of colonic manometry. However, the clinical significance of these findings still needs to be further investigated. This review enhances our understanding of colonic motility and the current state of development and application of colonic manometry, as well as the limitations, future directions and potential of the technique in assessing the impact of treatment on colonic motility patterns, by analyzing and summarizing the literature related to colonic manometry.

Mechanism of intestinal injury induced by WNT2B high-expressed fibroblasts in Crohn's disease / 中华儿科杂志

Objective: To explore the mechanism of intestinal tissue damage induced by macrophages activated by WNT2B high-expressed fibroblasts. Methods: This study involved biological information analysis, pathological tissue research and cell experimental research. The biological information of the colon tissue from the children with inflammatory bowel disease in previous study was analyzed again with single-cell sequencing. The pathological tissues were collected by colonoscopy from 10 children with Crohn's disease treated in the Department of Gastroenterology of Guangzhou Women and Children's Medical Center from July 2022 to September 2022. According to the findings of colonoscopy, tissues with obvious inflammation or ulceration were classified as the inflammatory group, while tissues with slight inflammation and no ulceration were classified as the non-inflammatory group. HE staining was performed to observe the pathological changes of the colon tissues. Macrophage infiltration and CXCL12 expression were detected by immunofluorescence. In terms of cell experiments, fibroblasts transfected with WNT2B plasmid or empty plasmid were co-cultured with salinomycin treated or non-treated macrophages, respectively; the expression of proteins through Wnt classical pathway were detected by western blotting. Macrophages treated with SKL2001 were used as the experimental group, and those with phosphate buffer as the control group. The expression and secretion of CXCL12 in macrophages were detected by quantitative Real-time PCR and enzyme-linked immunosorbent assay (ELISA). T-test or rank sum test were used for the comparison between groups. Results: Single-cell sequencing analysis suggested that macrophages were the main cells in inflammatory bowel disease colon tissue, and there was interaction between WNT2B high-expressed fibroblasts and macrophages. HE staining of the 10 patients ((9.3±3.8) years old, 7 males and 3 females) showed that the pathological score of colon tissue in the inflammatory group was higher than that in the non-inflammatory group (4 (3, 4) vs. 2 (1, 2) points, Z=3.05, P=0.002). Tissue immunofluorescence indicated that the number of infiltrating macrophages in the inflammatory group was significantly higher than that in the non-inflammatory group under high power field of view (72.8±10.4 vs.8.4±3.5, t=25.10, P<0.001), as well as the number of cells expressing CXCL12 (14.0±3.5 vs. 4.7±1.9, t=14.68, P<0.001). In cell experiments, western blotting suggested an elevated level of glycogen synthase kinase-3β phosphorylation in macrophages co-cultured with fibroblast transfected with WNT2B plasmid, and salinmycin could reverse this change. Real-time PCR suggested that the transcription level of CXCL12 in the experimental group was higher than that in the control group (6.42±0.04 vs. 1.00±0.03, t=183.00, P<0.001), as well as the expression and secretion of CXCL12 by ELISA ((465±34) vs. (77±9) ng/L, t=13.21, P=0.006). Conclusion: WNT2B high-expressed fibroblasts can secrete WNT2B protein and activate the Wnt classical signaling pathway thus enhancing the expression and secretion of CXCL12 in macrophages, inducing the development of intestinal inflammation of Crohn's disease.

Clinical characteristics of patients with colon complications after necrotizing pancreatitis: a retrospective cohort study / 中华外科杂志

Objective: To investigate the clinical characteristics of colon complications in patients with necrotizing pancreatitis(NP). Methods: The clinical data of 403 patients with NP admitted to the Department of General Surgery,Xuanwu Hospital, Capital Medical University from January 2014 to December 2021 were retrospectively analyzed. There were 273 males and 130 females,aged (49.4±15.4) years(range: 18 to 90 years). Among them,there were 199 cases of biliary pancreatitis,110 cases of hyperlipidemic pancreatitis,and 94 cases of pancreatitis caused by other causes. A multidisciplinary diagnosis and treatment model was used to diagnose and treat patients. Depending on whether the patients had colon complications,they were divided into colon complications group and noncolon complications group. Patients with colon complications were treated with anti-infection therapy,parental nutritional support,keeping the drainage tube unobstructed,and terminal ileostomy. The clinical results of the two groups were compared and analyzed using a 1∶1 propensity score match(PSM) method. The t test,χ2 test, or rank-sum test was used to analyze data between groups,respectively. Results: The incidence of colon complications was 13.2%(53/403),including 15 cases of colon obstruction,23 cases of colon fistula,and 21 cases of colon hemorrhage. After PSM,the baseline and clinical characteristics at admission of the two groups of patients were comparable (all P>0.05). In terms of clinical outcome,compared to patients with NP without colon complications,the number of patients with colon complications who received minimally invasive intervention(88.7%(47/53) vs. 69.8%(37/53),χ2=5.736,P=0.030),the number of minimally invasive interventions (M(IQR))(2(2) vs. 1(1), Z=4.638,P=0.034),the number of patients with multiple organ failure(45.3%(24/53) vs. 32.1%(17/53),χ2=4.826,P=0.041),and the number of extrapancreatic infections(79.2%(42/53) vs. 60.4%(32/53),χ2=4.476,P=0.034) increased significantly. The time required for enteral nutrition support(8(30)days vs. 2(10) days, Z=-3.048, P=0.002), parental nutritional support(32(37)days vs. 17(19)days, Z=-2.592, P=0.009),the length of stay in the ICU(24(51)days vs. 18(31)days, Z=-2.268, P=0.002),and the total length of stay (43(52)days vs. 30(40)days, Z=-2.589, P=0.013) were also significantly prolonged. However,mortality rates in the two groups were similar(37.7%(20/53) vs. 34.0%(18/53),χ2=0.164,P=0.840). Conclusions: Colonic complications in NP patients are not rare,which can lead to prolonged hospitalization and increased surgical intervention. Active surgical intervention can help improve the prognosis of these patients.

Therapeutic effect of ursodeoxycholic acid-berberine supramolecular nanoparticles on ulcerative colitis based on supramolecular system induced by weak bond / 中国中药杂志

Ulcerative colitis(UC) is a recurrent, intractable inflammatory bowel disease. Coptidis Rhizoma and Bovis Calculus, serving as heat-clearing and toxin-removing drugs, have long been used in the treatment of UC. Berberine(BBR) and ursodeoxycholic acid(UDCA), the main active components of Coptidis Rhizoma and Bovis Calculus, respectively, were employed to obtain UDCA-BBR supramolecular nanoparticles by stimulated co-decocting process for enhancing the therapeutic effect on UC. As revealed by the characterization of supramolecular nanoparticles by field emission scanning electron microscopy(FE-SEM) and dynamic light scattering(DLS), the supramolecular nanoparticles were tetrahedral nanoparticles with an average particle size of 180 nm. The molecular structure was described by ultraviolet spectroscopy, fluorescence spectroscopy, infrared spectroscopy, high-resolution mass spectrometry, and hydrogen-nuclear magnetic resonance(H-NMR) spectroscopy. The results showed that the formation of the supramolecular nano-particle was attributed to the mutual electrostatic attraction and hydrophobic interaction between BBR and UDCA. Additionally, supramolecular nanoparticles were also characterized by sustained release and pH sensitivity. The acute UC model was induced by dextran sulfate sodium(DSS) in mice. It was found that supramolecular nanoparticles could effectively improve body mass reduction and colon shortening in mice with UC(P<0.001) and decrease disease activity index(DAI)(P<0.01). There were statistically significant differences between the supramolecular nanoparticles group and the mechanical mixture group(P<0.001, P<0.05). Enzyme-linked immunosorbent assay(ELISA) was used to detect the serum levels of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6), and the results showed that supramolecular nanoparticles could reduce serum TNF-α and IL-6 levels(P<0.001) and exhibited an obvious difference with the mechanical mixture group(P<0.01, P<0.05). Flow cytometry indicated that supramolecular nanoparticles could reduce the recruitment of neutrophils in the lamina propria of the colon(P<0.05), which was significantly different from the mechanical mixture group(P<0.05). These findings suggested that as compared with the mechanical mixture, the supramolecular nanoparticles could effectively improve the symptoms of acute UC in mice. The study provides a new research idea for the poor absorption of small molecules and the unsatisfactory therapeutic effect of traditional Chinese medicine and lays a foundation for the research on the nano-drug delivery system of traditional Chinese medicine.

Mechanism of tryptanthrin in treatment of ulcerative colitis in mice based on serum metabolomics / 中国中药杂志

This study aims to explore the effect of tryptanthrin on potential metabolic biomarkers in the serum of mice with ulcerative colitis(UC) induced by dextran sulfate sodium(DSS) based on liquid chromatography-mass spectrometry(LC-MS) and predict the related metabolic pathways. C57BL/6 mice were randomly assigned into a tryptanthrin group, a sulfasalazine group, a control group, and a model group. The mouse model of UC was established by free drinking of 3% DSS solution for 11 days, and corresponding drugs were adminsitrated at the same time. The signs of mice were observed and the disease activity index(DAI) score was recorded from the first day. Colon tissue samples were collected after the experiment and observed by hematoxylin-eosin(HE) staining. The levels of interleukin-4(IL-4), interleukin-10(IL-10), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-8(IL-8) in the serum were measured by enzyme linked immunosorbent assay(ELISA). The serum samples were collected from 6 mice in each group for widely targeted metabolomics. The metabolic pathways were enriched by MetaboAnalyst 5.0. The results showed that compared with the model group, tryptanthrin treatment decreased the DAI score(P<0.05), alleviated the injury of the colon tissue and the infiltration of inflammatory cells, lowered the levels of proinflammatory cytokines, and elevated the levels of anti-inflammatory cytokines in the serum. The metabolomic analysis revealed 28 differential metabolites which were involved in 3 metabolic pathways including purine metabolism, arachidonic acid metabolism, and tryptophan metabolism. Tryptanthrin may restore the metabolism of the mice with UC induced by DSS to the normal level by regulating the purine metabolism, arachidonic acid metabolism, and tryptophan metabolism. This study employed metabolomics to analyze the mechanism of tryptanthrin in the treatment of UC, providing an experimental basis for the utilization and development of tryptanthrin.

Effect and mechanism of Bovis Calculus on ulcerative colitis by inhibiting IL-17/IL-17RA/Act1 signaling pathway / 中国中药杂志

This study aimed to elucidate the effect and underlying mechanism of Bovis Calculus in the treatment of ulcerative colitis(UC) through network pharmacological prediction and animal experimental verification. Databases such as BATMAN-TCM were used to mine the potential targets of Bovis Calculus against UC, and the pathway enrichment analysis was conducted. Seventy healthy C57BL/6J mice were randomly divided into a blank group, a model group, a solvent model(2% polysorbate 80) group, a salazosulfapyridine(SASP, 0.40 g·kg~(-1)) group, and high-, medium-, and low-dose Bovis Calculus Sativus(BCS, 0.20, 0.10, and 0.05 g·kg~(-1)) groups according to the body weight. The UC model was established in mice by drinking 3% dextran sulfate sodium(DSS) solution for 7 days. The mice in the groups with drug intervention received corresponding drugs for 3 days before modeling by gavage, and continued to take drugs for 7 days while modeling(continuous administration for 10 days). During the experiment, the body weight of mice was observed, and the disease activity index(DAI) score was recorded. After 7 days of modeling, the colon length was mea-sured, and the pathological changes in colon tissues were observed by hematoxylin-eosin(HE) staining. The levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6), and interleukin-17(IL-17) in colon tissues of mice were detected by enzyme-linked immunosorbent assay(ELISA). The mRNA expression of IL-17, IL-17RA, Act1, TRAF2, TRAF5, TNF-α, IL-6, IL-1β, CXCL1, CXCL2, and CXCL10 was evaluated by real-time polymerase chain reaction(RT-PCR). The protein expression of IL-17, IL-17RA, Act1, p-p38 MAPK, and p-ERK1/2 was investigated by Western blot. The results of network pharmacological prediction showed that Bovis Calculus might play a therapeutic role through the IL-17 signaling pathway and the TNF signaling pathway. As revealed by the results of animal experiments, on the 10th day of drug administration, compared with the solvent model group, all the BCS groups showed significantly increased body weight, decreased DAI score, increased colon length, improved pathological damage of colon mucosa, and significantly inhibited expression of TNF-α,IL-6,IL-1β, and IL-17 in colon tissues. The high-dose BCS(0.20 g·kg~(-1)) could significantly reduce the mRNA expression levels of IL-17, Act1, TRAF2, TRAF5, TNF-α, IL-6, IL-1β, CXCL1, and CXCL2 in colon tissues of UC model mice, tend to down-regulate mRNA expression levels of IL-17RA and CXCL10, significantly inhibit the protein expression of IL-17RA,Act1,and p-ERK1/2, and tend to decrease the protein expression of IL-17 and p-p38 MAPK. This study, for the first time from the whole-organ-tissue-molecular level, reveals that BCS may reduce the expression of pro-inflammatory cytokines and chemokines by inhibiting the IL-17/IL-17RA/Act1 signaling pathway, thereby improving the inflammatory injury of colon tissues in DSS-induced UC mice and exerting the effect of clearing heat and removing toxins.

Anemoside B4 regulates fatty acid metabolism reprogramming in mice with colitis-associated cancer / 中国中药杂志

The study aimed to investigate the effect of anemoside B4(B4) on fatty acid metabolism in mice with colitis-associated cancer(CAC). The CAC model was established by azoxymethane(AOM)/dextran sodium sulfate(DSS) in mice. Mice were randomly divided into a normal group, a model group, and low-, medium-, and high-dose anemoside B4 groups. After the experiment, the length of the mouse colon and the size of the tumor were measured, and the pathological alterations in the mouse colon were observed using hematoxylin-eosin(HE) staining. The slices of the colon tumor were obtained for spatial metabolome analysis to analyze the distribution of fatty acid metabolism-related substances in the tumor. The mRNA levels of SREBP-1, FAS, ACCα, SCD-1, PPARα, ACOX, UCP-2, and CPT-1 were determined by real-time quantitative PCR(RT-qPCR). The results revealed that the model group showed decreased body weight(P<0.05) and colon length(P<0.001), increased number of tumors, and increased pathological score(P<0.01). Spatial metabolome analysis revealed that the content of fatty acids and their derivatives, carnitine, and phospholipid in the colon tumor was increased. RT-qPCR results indicated that fatty acid de novo synthesis and β-oxidation-related genes, such as SREBP-1, FASN, ACCα, SCD-1, ACOX, UCP-2, and CPT-1 mRNA expression levels increased considerably(P<0.05, P<0.001). After anemoside B4 administration, the colon length increased(P<0.01), and the number of tumors decreased in the high-dose anemoside B4 group(P<0.05). Additionally, spatial metabolome analysis showed that anemoside B4 could decrease the content of fatty acids and their derivatives, carnitine, and phospholipids in colon tumors. Meanwhile, anemoside B4 could also down-regulate the expression of FASN, ACCα, SCD-1, PPARα, ACOX, UCP-2, and CPT-1 in the colon(P<0.05, P<0.01, P<0.001). The findings of this study show that anemoside B4 may inhibit CAC via regulating fatty acid metabolism reprogramming.

Platycodon grandiflorus polysaccharide regulates colonic immunity through mesenteric lymphatic circulation to attenuate ulcerative colitis / 中国天然药物

Platycodon grandiflorus polysaccharide (PGP) is one of the main components of P. grandiflorus, but the mechanism of its anti-inflammatory effect has not been fully elucidated. The aim of this study was to evaluate the therapeutic effect of PGP on mice with dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) and explore the underlying mechanisms. The results showed that PGP treatment inhibited the weight loss of DSS-induced UC mice, increased colon length, and reduced DAI, spleen index, and pathological damage within the colon. PGP also reduced the levels of pro-inflammatory cytokines and inhibited the enhancement of oxidative stress and MPO activity. Meanwhile, PGP restored the levels of Th1, Th2, Th17, and Treg cell-related cytokines and transcription factors in the colon to regulate colonic immunity. Further studies revealed that PGP regulated the balance of colonic immune cells through mesenteric lymphatic circulation. Taken together, PGP exerts anti-inflammatory and anti-oxidant effect and regulates colonic immunity to attenuate DSS-induced UC through mesenteric lymphatic circulation.

Yinlai Decoction Protects Microstructure of Colon and Regulates Serum Level of D-Lactic Acid in Pneumonia Mice Fed with High-Calorie and High-Protein Diet / 中国结合医学杂志

OBJECTIVE@#To investigate the effect of Yinlai Decoction (YD) on the microstructure of colon, and activity of D-lactic acid (DLA) and diamine oxidase (DAO) in serum of pneumonia mice model fed with high-calorie and high-protein diet (HCD).@*METHODS@#Sixty male Kunming mice were randomly divided into 6 groups by the random number table method: normal control, pneumonia, HCD, HCD with pneumonia (HCD-P), YD (229.2 mg/mL), and dexamethasone (15.63 mg/mL) groups, with 10 in each group. HCD mice were fed with 52% milk solution by gavage. Pneumonia mice was modeled with lipopolysaccharide inhalation and was fed by gavage with either the corresponding therapeutic drugs or saline water, twice daily, for 3 days. After hematoxylin-eosin staining, the changes in the colon structure were observed under light microscopy and transmission electron microscope, respectively. Enzyme-linked immunosorbent assay was used to detect the protein levels of DLA and DAO in the serum of mice.@*RESULTS@#The colonic mucosal structure and ultrastructure of mice in the normal control group were clear and intact. The colonic mucosal goblet cells in the pneumonia group tended to increase, and the size of the microvilli varied. In the HCD-P group, the mucosal goblet cells showed a marked increase in size with increased secretory activity. Loose mucosal epithelial connections were also observed, as shown by widened intercellular gaps with short sparse microvilli. These pathological changes of intestinal mucosa were significantly reduced in mouse models with YD treatment, while there was no significant improvement after dexamethasone treatment. The serum DLA level was significantly higher in the pneumonia, HCD, and HCD-P groups as compared with the normal control group (P<0.05). Serum DLA was significantly lower in the YD group than HCD-P group (P<0.05). Moreover, serum DLA level significantly increased in the dexamethasone group as compared with the YD group (P<0.01). There was no statistical significance in the serum level of DAO among groups (P>0.05).@*CONCLUSIONS@#YD can protect function of intestinal mucosa by improving the tissue morphology of intestinal mucosa and maintaining integrity of cell connections and microvilli structure, thereby reducing permeability of intestinal mucosa to regulate the serum levels of DLA in mice.

Composite Sophora Colon-Soluble Capsule Ameliorates DSS-Induced Ulcerative Colitis in Mice via Gut Microbiota-Derived Butyric Acid and NCR+ ILC3 / 中国结合医学杂志

OBJECTIVE@#To investigate the effects of composite Sophora colon-soluble Capsule (CSCC) on gut microbiota-mediated short-chain fatty acids (SCFAs) production and downstream group 3 innate lymphoid cells (ILC3s) of dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice model.@*METHODS@#The main components of CSCC were analyzed by hybrid ultra-high-performance liquid chromatography ion mobility spectromety quadrupole time-of-flight mass spectrometry (UHPLC-IM-QTOF/MS). Twenty-four male BALB/c mice were randomly divided into 4 groups (n=6) by using a computer algorithm-generated random digital, including control, DSS model, mesalazine, and CSCC groups. A DSS-induced colitis mice model was established to determine the effects of CSCC by recording colonic weight, colonic length, index of colonic weight, and histological colonic score. The variations in ILC3s were assessed by immunofluorescence and flow cytometry. The results of gut microbiota and SCFAs were acquired by 16s rDNA and gas chromatography-mass spectrometry (GC-MS) analysis. The expression levels of NCR+ ILC3-, CCR6+ Nkp46- (Lti) ILC3-, and ILCreg-specific markers were detected by enzyme-linked immunosorbent assay, and real-time quantitative polymerase chain reaction and Western blot, respectively.@*RESULTS@#The main components of CSCC were matrine, ammothamnine, Sophora flavescens neoalcohol J, and Sophora oxytol U. After 7 days of treatment, CSCC significantly alleviated colitis by promoting the reproduction of intestinal probiotics manifested as upregulation of the abundance of Bacteroidetes species and specifically the Bacteroidales_S24-7 genus (P<0.05). Among the SCFAs, the content of butyric acid increased the most after CSCC treatment. Meanwhile, compared with the model group, Lti ILC3s and its biomarkers were significantly downregulated and NCR+ ILC3s were significantly elevated in the CSCC group (P<0.01). Further experiments revealed that ILC3s were differentiated from Lti ILC3s to NCR+ ILC3s, resulting in interleukin-22 production which regulates gut epithelial barrier function.@*CONCLUSION@#CSCC may exert a therapeutic effect on UC by improving the gut microbiota, promoting metabolite butyric acid production, and managing the ratio between NCR+ ILC3s and Lti ILC3s.

TRPV1 participates in the protective effect of propolis on colonic tissue of ulcerative colitis / 中南大学学报(医学版)

OBJECTIVES@#Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) mainly characterized by inflammation, ulceration and erosion of colonic mucosa and submucosa. Transient receptor potential vanilloid 1 (TRPV1) is an important mediator of visceral pain and inflammatory bowel disease. This study aims to investigate the protective effect of water soluble propolis (WSP) on UC colon inflammatory tissue and the role of TRPV1.@*METHODS@#Male SD rats were randomly divided into 6 groups (n=8): a normal control (NC) group, an ulcerative colitis model (UC) group, a low-WSP (L-WSP) group, a medium-WSP (M-WSP) group, a high-WSP (H-WSP) group, and a salazosulfapyridine (SASP) group. The rats in the NC group drank water freely, and the other groups drank 4% dextran sulfate sodium (DSS) solution freely for 7 d to replicate the ulcerative colitis model. Based on the successful replication of the UC, the L-WSP, M-WSP, and H-WSP groups were given 50, 100, and 200 mg/kg of water-soluble propolis by gavage for 7 d, and the SASP group was given 100 mg/kg of sulfasalazine by gavage for 7 d. The body weight of rats in each group was measured at the same time every day, the fecal traits and occult blood were observed to record the disease activity index (DAI). After intragastric administration, the animals were sacrificed after fasted 24 h. Serum and colonic tissue were collected, and the changes of MDA, IL-6 and TNF-α were detected. The pathological changes of colon tissues were observed by HE staining, and the expression of TRPV1 in colon tissues was observed by Western blotting, immunohistochemistry, and immunofluorescence.@*RESULTS@#The animals in each group that drank DSS freely showed symptoms such as weight loss, decreased appetite, depressed state, and hematochezia, indicating that the model was successfully established. Compared with the NC group, DAI scores of other groups were increased (all P<0.05). MDA, IL-6, TNF-α in serum and colon tissues of the UC group were increased compared with the NC group (all P<0.01), and they were decreased after WSP and SASP treatment (all P<0.01). The results of showed that the colon tissue structure was obviously broken and inflammatory infiltration in the UC group, while the H-WSP group and the SASP group significantly improved the colon tissue and alleviated inflammatory infiltration. The expression of TRPV1 in colon tissues in the UC group was increased compared with the NC group (all P<0.01), and it was decreased after WSP and SASP treatment.@*CONCLUSIONS@#WSP can alleviate the inflammatory state of ulcerative colitis induced by DSS, which might be related to the inhibition of inflammatory factors release, and down-regulation or desensitization of TRPV1.

Mechanism of famous classical formula Huaihua Powder in treatment of ulcerative colitis based on metabonomics / 中国中药杂志

Ultra-high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry(UHPLC-Q-TOF-MS) was employed in this study to observe the effect of Huaihua Powder on the serum metabolites of mice with ulcerative colitis and reveal the mechanism of Huaihua Powder in the treatment of ulcerative colitis. The mouse model of ulcerative colitis was established by dextran sodium sulfate salt(DSS). The therapeutic effect of Huaihua Powder on ulcerative colitis was preliminarily evaluated based on the disease activity index(DAI), colon appearance, colon tissue morphology, and the content of inflammatory cytokines such as tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-1β(IL-1β). UHPLC-Q-TOF-MS was employed to profile the endogenous metabolites of serum samples in blank control group, model group, and low-, medium-, and high-dose Huaihua Powder groups. Multivariate analyses such as principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and orthogonal partial least squares discriminant analysis(OPLS-DA) were performed for pattern recognition. Potential biomarkers were screened by Mass Profiler Professional(MPP) B.14.00 with the thresholds of fold change≥2 and P<0.05. The metabolic pathways were enriched by MetaboAnalyst 5.0. The results showed that Huaihua Powder significantly improved the general state and colon tissue morphology of mice with ulcerative colitis, reduced DAI, and lowered the levels of TNF-α, IL-6, and IL-1β in serum. A total of 38 potential biomarkers were predicted to be related to the regulatory effect of Huaihua Powder, which were mainly involved in glycerophospholipid metabolism, glycine, serine, and threonine metabolism, mutual transformation of glucuronic acid, and glutathione metabolism. This study employed metabolomics to analyze the mechanism of Huaihua Powder in the treatment of ulcerative colitis, laying a foundation for the further research.