Transición en enfermedades inflamatorias intestinales: de la pediatría a la adultez / Transition in inflammatory bowel diseases: from childhood to adulthood

El 25% de los pacientes con Enfermedades Inflamatorias Intestinales (EII) se diagnostican antes de los 20 años. En la mayor parte de los centros del país se lleva a cabo la "transferencia" del paciente desde un centro de atención pediátrico a uno de adultos. La "transición" es un criterio de calidad con beneficios en el control de la EII reduciendo el número de recaídas, de hospitalizaciones y de cirugías. Por tal motivo hemos desarrollado un Programa Interdisciplinario de Transición entre dos hospitales de referencia nacional e internacional en EII. Materiales y métodos: Entre 1/2021 y 12/ 2022 se incorporaron 24 pacientes que ingresaron en 3 fases: Fase 1 Pacientes entre 14 y 16 años asistidos en el Hospital Garrahan (HG) con un abordaje interdisciplinario. Fase 2. A partir de los 17 años se realizaron 2 (dos) encuentros en el HG en conjunto con gastroenterólogos de adultos evaluando adherencia y autonomía y la Fase 3 llevada a cabo en el Hospital B. Udaondo (HBU) sólo con el equipo de adultos luego de 6 meses de realizada la transferencia evaluando adherencia al tratamiento, consultas a emergencias, internación y/o cirugías Resultados: Al inicio del Programa el 66% de los pacientes presentaban una actividad moderada a severa vs el 8% al finalizar la fase 3. Luego de la transferencia el 12,5% necesito ingreso a guardia e internación y un 8% tratamiento quirúrgico. El 83% de los pacientes continúan en seguimiento luego de 6 meses de haber sido transferidos (AU)

Twenty-five percent of patients with inflammatory bowel diseases (IBD) are diagnosed before the age of 20 years. In most centers in the country, the "transfer" of the patient from a pediatric to an adult care center is done. However, "transition" is a quality criterion with benefits in the control of IBD by reducing the number of relapses, hospitalizations, and surgeries. For this reason, we developed an Interdisciplinary Transition Program between two national and international reference hospitals in IBD. Materials and Methods: Between January 2021 and December 2022, we incorporated 24 patients into a three-phase program. Phase 1 involved patients between 14 and 16 years of age seen at Garrahan Hospital (HG) with an interdisciplinary approach. Phase 2 began from 17 years of age, with two meetings held at HG involving adult gastroenterologists to evaluate adherence and autonomy. Phase 3 was conducted at Hospital B. Udaondo (HBU) only with the adult team, six months after the transfer, evaluating adherence to treatment, emergency consultations, hospitalizations, and/or surgeries. Results: At the beginning of the program, 66% of the patients presented with moderate to severe disease activity, compared to 8% at the end of Phase 3. After the transfer, 12.5% of the patients required emergency department visits and hospitalization, and 8% required surgical treatment. Eighty-three percent of the patients continue in the program and are still being followed up six months after the transfer (AU)

Apendicectomía electiva en el manejo de la Colitis ulcerosa refractaria: Reporte de caso

Introducción: La colitis ulcerosa (CU) es una enfermedad inflamatoria intestinal que afecta el colon y el recto de etiología desconocida. Se ha planteado la apendicectomía electiva en pacientes con colitis ulcerosa refractaria como una alternativa de tratamiento. Objetivo: Comunicar el caso clínico de una paciente con CU refractaria a quien la apendicectomía electiva permitió una mejoría de su sintomatología y calidad de vida. Resultados: Se presenta el caso de una paciente de 46 años con antecedentes de hipotiroidismo y colitis ulcerosa de 2 años de evolución, con rectorragia, dolor abdominal y diarrea importante pese a la terapia biológica. Se decide apendicectomía laparoscópica electiva, logrando una mejoría sintomática de la paciente objetivada mediante la aplicación de la encuesta "Inflammatory Bowel Disease Questionnaire". El puntaje preoperatorio de la paciente fue de 60 puntos, y el postoperatorio de 176. Discusión: Se hace evidente que la colitis ulcerosa y el apéndice cecal están íntimamente relacionados. Los desafíos futuros deberían apuntarse a identificar las características clínicas que precisen qué pacientes se benefician de esta intervención.

Introduction: Ulcerative colitis (UC) is an inflammatory bowel disease that affects the colon and rectum of unknown etiology. Elective appendectomy has been proposed as a possible treatment for patients with refractory ulcerative colitis. Objective: To report the clinical case of a patient with refractory UC who showed improvement in symptomatology and quality of life after undergoing elective appendectomy. Results: We present the case of a 46-year-old patient with a 2-year history of hypothyroidism and ulcerative colitis, with rectal bleeding, abdominal pain, and significant diarrhea despite biological therapy. Elective laparoscopic appendectomy was performed, resulting in symptomatic improvement of the patient as measured by the Inflammatory Bowel Disease Questionnaire. The patient's preoperative score was 60 points, and the postoperative score was 176. Discussion: It seems evident that ulcerative colitis and the cecal appendix are intimately related. Future challenges should aim to identify clinical characteristics that determine which patients benefit from this intervention.

Silencing ANGPT2 alleviates ulcerative colitis by regulating autophagy-mediated NLRP3 inflammasome inactivation via the mTOR signaling pathway

Ulcerative colitis (UC) is a difficult intestinal disease characterized by inflammation, and its mechanism is complex and diverse. Angiopoietin-like protein 2 (ANGPT2) plays an important regulatory role in inflammatory diseases. However, the role of ANGPT2 in UC has not been reported so far. After exploring the expression level of ANGPT2 in serum of UC patients, the reaction mechanism of ANGPT2 was investigated in dextran sodium sulfate (DSS)-induced UC mice. After ANGPT2 expression was suppressed, the clinical symptoms and pathological changes of UC mice were detected. Colonic infiltration, oxidative stress, and colonic mucosal barrier in UC mice were evaluated utilizing immunohistochemistry, immunofluorescence, and related kits. Finally, western blot was applied for the estimation of mTOR signaling pathway and NLRP3 inflammasome-related proteins. ANGPT2 silencing improved clinical symptoms and pathological changes, alleviated colonic inflammatory infiltration and oxidative stress, and maintained the colonic mucosal barrier in DSS-induced UC mice. The regulatory effect of ANGPT2 on UC disease might occur by regulating the mTOR signaling pathway and thus affecting autophagy-mediated NLRP3 inflammasome inactivation. ANGPT2 silencing alleviated UC by regulating autophagy-mediated NLRP3 inflammasome inactivation via the mTOR signaling pathway.

Megacolon tóxico: A propósito de un caso / Toxic Megacolon. Case Report

RESUMEN El megacolon tóxico es una enfermedad mortal, que se presenta, con mayor frecuencia, como una complicación de la inflamación intestinal, infecciones e isquemia intestinal. Se caracteriza por la presencia de diarrea sanguinolenta, distensión abdominal, signos de toxicidad sistémica y, en estudios de imagen, se observa dilatación colónica segmentaria. Para el diagnóstico, según los criterios de Jalan, se tiene en cuenta la dilatación colónica más de 6 cm, tres de los siguientes: fiebre, taquicardia, leucocitosis o anemia, y cualquiera de los siguientes criterios: hipotensión, hipovolemia, trastorno electrolítico y estado mental alterado. En este artículo, se presenta el caso de una paciente mujer que ingresa por cuadro de dolor abdominal y diarrea crónica con estudio de imagen, en la que se visualiza dilatación de todo el marco colónico. Se realizan los estudios correspondientes y se diagnostica megacolon tóxico por colitis ulcerativa, por lo que recibe tratamiento médico con evolución favorable. Es dado de alta y reingresa por shock séptico, se realizan estudios y se identifica infección por Clostridium difficile. Se inicia tratamiento antibiótico, pero presenta evolución desfavorable, lo que ocasionó el fallecimiento de la paciente. El presente caso representa la alta mortalidad de esta enfermedad.

ABSTRACT Toxic megacolon is a fatal disease, most commonly occurring as a complication of inflammatory bowel disease, infections, and intestinal ischemia. It is characterized by the presence of bloody diarrhea, abdominal distension, signs of systemic toxicity, and segmental colonic dilation is observed in imaging studies. For the diagnosis, according to the Jalan criteria, colonic dilation of more than 6 cm is taken into account, three of the following: fever, tachycardia, leukocytosis or anemia, and any of the following criteria: hypotension, hypovolemia, electrolyte disorder and altered mental status. This article presents the case of a female patient who was admitted with abdominal pain and chronic diarrhea with an imaging study showing dilation of the entire colonic framework. The corresponding studies were carried out which indicated that she had a toxic megacolon due to colitis. ulcerative, receives medical treatment with favorable evolution, is discharged and readmitted for septic shock, studies are performed and Clostridium difficile infection is identified, antibiotic treatment is started but the evolution is unfavorable, which caused the death of the patient. The present case represents the high mortality of this disease.

Fenotipificación y genotipificación en pacientes con enfermedad inflamatoria intestinal en un centro de referencia de Colombia / Phenotyping and genotyping in patients with inflammatory bowel disease in a reference center in Colombia

RESUMEN Introducción: Se ha tratado de identificar los factores genéticos relacionados con susceptibilidad para enfermedad inflamatoria intestinal (EII), y los hallazgos actuales se inclinan por un modelo de patología complejo, sin un patrón hereditario claro. Objetivo: Realizar caracterización fenotípica y genotípica de pacientes con EII en población colombiana y describir su posible asociación con predisposición. Materiales y métodos: Serie de casos, 16 pacientes con EII por criterios clínicos y anatomopatológicos, inicio de síntomas gastrointestinales después de los 18 años. Todos tuvieron asesoramiento genético pre-test y se realizaron árboles genealógicos de mínimo tres generaciones. También, genotipificación, por medio de un panel de genes múltiples que incluía genes relacionados con EII y algunos trastornos autoinmunitarios. Finalmente, se realizó análisis genómico de variantes. Resultados: 9 mujeres y 7 hombres, con edad media de diagnóstico de EII 35 años, y 32 años para aparición de síntomas gastrointestinales. 11/16(68,75%) requirieron terapia biológica. 10/16 (62,5%) presentaron refractariedad a terapia estándar. 3/16 (18,75%) tenían antecedentes familiares positivos de EII. 100% casos presentaron al menos un single nucleotide polymorphism relacionado con riesgo de EII en más de un gen. Los genes más relacionados con colitis ulcerosa (CU), fueron CD48, CD6, y TYK2 para CU, y CD6 e ITGAM para la enfermedad de Crohn. El gen más frecuente fue CD6. Se observó en 3/16 (18,75%) presencia de hasta 5 genes, 4 en 3/16 (18,75%), y tres en 5/16 (31,25%). Conclusión: En EII hay presencia de variantes genéticas con predisposición asociada, pero sin patogenicidad confirmada, y cuya sumatoria parece contribuir en su fisiopatología.

ABSTRACT Introduction: Attempts have been made to identify the genetic factors related to susceptibility to inflammatory bowel disease (IBD), and the current conclusions are in favor of a complex pathology model, without a clear hereditary pattern. Objective: To perform phenotypic and genotypic characterization of patients with IBD in Colombian population and to describe its possible association with predisposition. Materials and methods: case series, 16 patients with IBD according to clinical and pathological criteria, onset of gastrointestinal symptoms after 18 years of age. All had pre-test genetic counseling and family trees of at least three generations were made. Also, genotyping, using a multigene panel that included genes related to IBD and some autoimmune disorders. Finally, a genomic analysis of variants was performed. Results: 9 women and 7 men, with mean age of diagnosis of IBD of 35 years, and gastrointestinal symptoms appearance of 32 years. 11/16 (68.75%) required biological therapy. 10/16 (62.5%) were refractory to standard therapy. 3/16 (18.75%) had positive family history of IBD. 100% cases presented at least one single nucleotide polymorphism related to IBD risk in more than one gene. The genes most related to ulcerative colitis (UC) were CD48, CD6, and TYK2 for UC, and CD6 and ITGAM for Crohn's disease. The most frequent gene was CD6. It was found presence of up to 5 genes in 3/16 (18.75%), 4 in 3/16 (18.75%), and three in 5/16 (31.25%). Conclusion: In IBD there is the presence of genetic variants with associated predisposition, but without confirmed pathogenicity, and whose sum seems to contribute to its pathophysiology.

Childhood lichenoid granulomatous stomatitis: a case report and literature review / 口腔疾病防治

Objective@#To investigate the classification, clinical manifestations, diagnosis, differential diagnosis and treatment of oral lichenoid lesions and provide a reference for clinical practice.@*Methods@#Hospital ethical approval and patient informed consent were obtained. We report a case of oral lichenoid lesion in children and review the diagnosis and treatment of oral lichenoid damage in the literature.@*Results@#The patient experienced repeated rupture of the dorsal surface of the tongue with pain for more than 3 years. There was a large area of tongue back surface erosion with an irregular shape, surrounded by pearly-white lines. The left erosive area was accompanied by tissue hyperplasia, which was approximately 1.5 cm × 2.0 cm, with tough texture and broad masses. The pathological diagnosis of the patient was oral lichenoid lesion. After biopsy of the dorsal surface of the tongue, the pathological diagnosis of the patient was granulomatous inflammation. The final diagnosis of lichenoid granulomatous stomatitis was made on the basis of the patient's intraoral damage features, systemic history, medication history and histopathological findings. A review of the literature suggests that oral lichenoid lesions have an unknown etiology and need to be clinically differentiated from oral lichen planus, oral lichenoid drug reactions, oral lichenoid contact damage and chronic ulcerative stomatitis. The clinical treatment of oral lichen planus is based on the topical and/or systemic use of glucocorticoids.@*Conclusion@#There are still no uniform criteria for the classification and diagnosis of oral lichenoid lesions. They rely mainly on history taking, clinical manifestations and histopathological findings, and the treatment is mainly based on the topical and/or systemic use of glucocorticoids.

Mechanism of Xiezhuo Jiedu Recipe Regulating Ferroptosis in Treatment of Ulcerative Colitis Based on Bioinformatics and Animal Experiments / 中国实验方剂学杂志

ObjectiveThe bioinformatics method was used to screen ferroptosis differential genes （FRGs） closely related to ulcerative colitis （UC）， and animal experiments were conducted to verify whether the mechanism of Xiezhuo Jiedu recipe in treating UC is related to the regulation of ferroptosis. MethodThe differentially expressed genes （DEGs） of colonic mucosa tissue of UC patients were obtained from the GEO database， and the intersection of the genes with ferroptosis genes was used to obtain FRGs. The core FRGs were obtained by cluster analysis， minimum absolute contraction and selection operator （LASSO） regression， and receiver operating characteristic curve （ROC） curve analysis. In animal experiments， the UC mouse model was prepared by making the mouse freely drink 2.5% dextran sodium sulfate （DSS）. Xiezhuo Jiedu recipe and mesalazine were given by gavage for seven days， and the inflammatory infiltration of colonic mucosa was observed by hematoxylin-eosin （HE） staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression levels of E3 ubiquitin ligase （FBXW7）， zinc finger protein （ZFP36）， solute carrier family 7 member 11 （SLC7A11）， and Toll-like receptor 4 （TLR4） in colon tissue. The protein expression levels of FBXW7， ZFP36， SLC7A11， and TLR4 in colon tissue were detected by Western blot. ResultDataset GSE87466 was screened from the GEO database， and its intersections with the ferroptosis gene were analyzed to obtain 21 FRGs. After cluster analysis， LASSO regression， and ROC analysis， core FRGs （FBXW7， ZFP36， SLC7A11， and TLR4） were obtained. Immunoinfiltration analysis showed significant differences in the expression of initial B cells， M1 macrophages， plasma cells， and M2 macrophages in the colonic mucosa tissue of UC mice， and there was a significant correlation between core FRGs and these immune cells. Further animal experiments showed that the colonic mucosa tissue of mice in the model group was disorganized and infiltrated by a large number of inflammatory cells. The inflammation of the colonic mucosa tissue of mice in each group was relieved to varying degrees after treatment with Xiezhuo Jiedu recipe and mesalazine， while the colonic mucosa tissue of mice in the high-dose group of Xiezhuo Jiedu recipe showed almost no inflammatory changes. Compared with the normal group， the protein and mRNA expressions of FBXW7， ZFP36， SLC7A11， and TLR4 in the model group were significantly increased， and the expression of core FRGs in colonic mucosa tissue of mice in all groups was significantly down-regulated after treatment with Xiezhuo Jiedu recipe and mesalazine. ConclusionFBXW7， ZFP36， SLC7A11， and TLR4 are ferroptosis genes closely related to the pathogenesis of UC， and Xiezhuo Jiedu recipe can significantly alleviate colonic mucosa inflammation in mice by down-regulating core ferroptosis genes.

Improvement of Colonic Mucosa Inflammatory Response in Mice with Ulcerative Colitis by Xiezhuo Jiedu Recipe Through miRNA-155-5p/JAK2/STAT3 Pathway / 中国实验方剂学杂志

ObjectiveThe differential expression of microRNAs （miRNAs） between the active stage and the remission stage of ulcerative colitis （UC） was analyzed by bioinformatics method， and the regulatory relationship was constructed by screening the differentially expressed genes （DEGs）. The mechanism of Xizhuo Jiedu recipe in the treatment of UC was speculated and verified by animal experiments. MethodThe miRNAs data set of colonic mucosa tissue of UC patients was obtained from the gene expression database （GEO）， and the most differentially expressed miRNAs were screened by GEO2R， Excel， and other tools as research objects. TargetScan， miRTarbase， miRDB， STRING， TRRUST， and Matescape databases were used to screen key DEGs， predict downstream transcription factors （TFs）， gene ontology （GO）， and conduct Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis. The key signaling pathways were selected for animal experiments. In animal experiments， the UC mouse model was prepared by making the mouse freely drink 2.5% dextran sodium sulfate （DSS）. Xiezhu Jiedu recipe and mesalazine were given by gavage for seven days， and the inflammatory infiltration of colonic mucosa was observed by hematoxylin-eosin （HE） staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of miR-155-5p in colon tissue. Immunohistochemistry and Western blot were used to detect the protein expression levels of cytokine signal transduction inhibitor （SOCS1）， phosphorylated transcriptional signal transductor and activator 3 （p-STAT3）， phosphorylated Janus kinase 2 （p-JAK2）， and retinoic acid-associated orphan receptor-γt （ROR-γt）. The expression levels of transforming growth factor-β （TGF-β）， interleukin-17 （IL-17）， interleukin-6 （IL-6）， and interleukin-10 （IL-10） in serum were detected by enzyme linked immunosorbent assay （ELISA）. ResultThe GSE48957 dataset was screened from the GEO database， and miR-155-5p was selected as the research object from the samples in the active and remission stages. 131 DEGs were screened. The GO/KEGG enrichment analysis was closely related to biological processes such as positive regulation of miRNA transcription and protein phosphorylation， as well as signaling pathways such as stem cell signaling pathway， IL-17 signaling pathway， and helper T cell 17 （Th17） cell differentiation. The Matescape database was used to screen out 10 key DEGs， among which SOCS1 was one of the key DEGs of miR-155-5p. Further screening of the TFS of key DEGs revealed that STAT3 was one of the main TFs of SOCS1. The results of animal experiments showed that Xiezhu Jiedu Recipe could effectively down-regulate the mRNA expression of miR-155-5p and protein expression of p-STAT3， p-JAK2， and ROR-γt in colon tissue of UC mice and the expression of IL-17 and IL-6 in serum of UC mice， up-regulate the protein expression of SOCS1 and the expression of TGF-β and IL-10， increase the level of anti-inflammatory factors， and reduce inflammatory cell infiltration. ConclusionIt is speculated that Xizhuo Jiedu recipe may interfere with SOCS1 by regulating the expression of miR-155-5p in UC mice， inhibit the phosphorylation of STAT3， inhibit the differentiation of CD4+ T cells into Th17 cells， reduce the levels of pro-inflammatory factors （IL-17 and IL-6）， and increase the levels of anti-inflammatory factors （TGF-β and IL-10）. As a result， the inflammation of colon mucosa in UC mice was alleviated.

Traditional Chinese Medicine Intervention for Ferroptosis in Treatment of Inflammatory Bowel Disease： A Review / 中国实验方剂学杂志

Inflammatory bowel disease （IBD）， mainly including ulcerative colitis （UC） and Crohn's disease （CD）， is a common chronic inflammatory disease of the gastrointestinal tract， with its incidence increasing year by year. Due to its long treatment duration， difficulty in treatment， prolonged remission， and high costs， it has attracted global attention. Exploring safe， effective， and sustainable treatment regimens has become an urgent global issue. The pathogenesis of IBD is complex， involving intestinal mucosal injury，disturbances in the internal environment， and inflammatory responses. In recent years， research has found that ferroptosis is also one of the important pathogenic factors of IBD. Ferroptosis， as a new form of non-apoptotic cell death， is characterized by iron dependence， lipid peroxidation， and imbalance in the redox system. Studies have shown that inhibiting ferroptosis in intestinal epithelial cells can protect the intestinal mucosa. Targeted intervention in ferroptosis may be a new direction for the treatment of IBD. IBD is mainly treated with drugs， including corticosteroids， aminosalicylates， biologics， and immunomodulators， but drug resistance and adverse reactions are common. Traditional Chinese medicine （TCM） has unique advantages such as low cost， low drug resistance， and fewer side effects， and has accumulated rich experience in the treatment of IBD. Scholars have confirmed that TCM can inhibit ferroptosis， and recent studies have shown that TCM can not only inhibit iron-dependent lipid peroxidation in intestinal cells but also enhance the antioxidant and anti-inflammatory abilities of intestinal mucosa， thus playing a role in the treatment of IBD. Increasing evidence suggests that TCM may treat IBD by interfering with ferroptosis. This article explores the relevance of TCM intervention in ferroptosis and the treatment of IBD， discusses the possible mechanisms of ferroptosis in IBD， and aims to provide a basis for the diagnosis and treatment of IBD.

Improvement effect of curcumin combined with fecal bacteria transplantation on mice with ulcerative colities induced by DSS / 吉林大学学报(医学版)

Objective:To discuss the improvement effect of curcumin combined with fecal bacteria transplantation on the mice with dextran sulfate sodium(DSS)-induced ulcerative colitis(UC),and to clarify the related mechanism.Methods:Fifty mice were randomly divided into control,model,curcumin,fecal bacteria transplantation,and combination groups.Except for the mice in control group(given distilled water),the mice in the other groups were given distilled water containing 2%DSS to establish the UC models.The mice in curcumin group were gavaged with 0.4 mL of 60 mg·kg-1 curcumin solution once per day for 10 d;the mice in fecal bacteria transplantation group underwent enema with 0.2 mL of fecal bacteria suspension once per day for 10 d;the mice in combination group received the enema of 0.2 mL fecal bacteria suspension and gavaged with 0.4 mL of 60 mg·kg-1 curcumin solution.At the end of the experiment,the disease activity index(DAI)and colon macroscopic damage index(CDMI)of the mice in various groups were calculated;the morphology of colon tissue of the mice in various groups was detected by HE staining;the levels of interleukin(IL)-1β,tumor necrosis factor-α(TNF-α),IL-4,and IL-10 in colon tissue of the mice in various groups were detected by enzyme-linked immunosorbent assay(ELISA)method;the expression levels of occludin and zonula occludens-1(ZO-1)mRNA and proteins in colon tissue of the mice in various groups were detected by real-time fluorescence quantitative(RT-qPCR)and Western blotting methods.Results:The intestinal mucosal epithelial structure of the mice in control group was intact and continuous with regular glandular arrangement and without inflammatory cell infiltration or ulceration;the intestinal mucosal epithelial structure of the mice in model group exhibited loss of colonic mucosal epithelium,disordered glandular arrangement,reduced goblet cells,congestion and edema in mucosal and submucosal layers,and extensive infiltration of inflammatory cells with widespread small ulcers;the intestinal mucosal epithelial structure of the mice in curcumin,fecal bacteria transplantation,and combination groups exhibited relatively intact colonic mucosal epithelial structures with reduced inflammatory cell infiltration and ameliorated mucosal and submucosal congestion and edema.Compared with control group,the DAI and CDMI of the mice in model group were increased(P<0.05),the levels of IL-1β and TNF-α were increased(P<0.05),the levels of IL-4 and IL-10 were decreased(P<0.05),and the expression levels of occludin and ZO-1 mRNA and proteins were decreased(P<0.05);compared with model group,the DAI and CDMI of the mice in curcumin,fecal bacteria transplantation,and combination groups were decreased(P<0.05),the levels of IL-1β and TNF-α were decreased(P<0.05),the levels of IL-4 and IL-10 were increased(P<0.05),and the expression levels of occludin and ZO-1 mRNA and proteins were increased(P<0.05).Compared with curcumin group and fecal bacteria transplantation group,the DAI and CDMI of the mice in combination group were decreased(P<0.05),the levels of IL-1β and TNF-α were decreased(P<0.05),the levels of IL-4 and IL-10 were increased(P<0.05),and the expression levels of occludin and ZO-1 mRNA and proteins were increased(P<0.05).Conclusion:Curcumin combined with fecal bacteria transplantation can ameliorate the pathological damage in colonic tissue of the UC mice,inhibit the secretion of inflammatory factors,and promote the repaiment of intestin mucosa.

Relationship between serum TSG-6 and col-16 levels and severity of the illness and clinical outcome in patients with active ulcerative colitis / 国际检验医学杂志

Objective To investigate the relationship between serum tumor necrosis factor α stimulated gene 6(TSG-6)and collagen ⅩⅥ(col-16)levels and severity of the illness and clinical outcome in patients with active ulcerative colitis(UC).Methods A total of 79 patients with active UC admitted to the department of gastroenterology in the hospital from January 2020 to January 2023 were selected as the active UC group,56 patients with UC in remission who were similar in gender and age to the active UC group were selected as the remission UC group,and 60 healthy subjects who underwent physical examination in the hospital during the same period were selected as the control group.Patients with active UC were divided into mild group(n=25),moderate group(n=34)and severe group(n=20)according to the modified Mayo score.Patients with active UC were divided into good prognosis group(n=58)and poor prognosis group(n=21)according to colonoscopy results after 2 months of treatment.Serum TSG-6 and col-16 levels in each group were detected by enzyme-linked immunosorbent assay,Spearman rank correlation analysis was used to analyze the relation-ship between serum TSG-6 and col-16 levels and severity of the illness,and the influence of serum TSG-6 and col-16 levels on clinical outcome was analyzed by multivariate Logistic regression.Receiver operating charac-teristic(ROC)curve was used to evaluate the predictive value of serum TSG-6 and col-16 for poor prognosis in patients with active UC.Results The serum TSG-6 and col-16 levels in active UC group and remission UC group were higher than those in control group,and the serum TSG-6 and col-16 levels in active UC group were higher than those in remission UC group,the difference was statistically significant(P＜0.05).Serum TSG-6 and col-16 levels in severe group and moderate group were higher than those in mild group,and serum TSG-6 and col-16 levels in severe group were higher than those in moderate group,with statistical significance(P＜0.05).By Spearman rank correlation analysis,serum TSG-6 and col-16 in active UC patients were positively correlated with modified Mayo scores(rs=0.695、0.627,P＜0.05).Multivariate Logistic regression analysis showed that compared with＜159.32 ng/mL,patients with serum TSG-6 interquartile interval of 289.15-413.55 ng/mL and＞413.55 ng/mL had a higher risk of poor prognosis.ROC curve analysis results showed that the area under the curve of TG-6 and col-16 in predicting poor prognosis was 0.776 and 0.764,respective-ly.The predictive value of serum TG-6 and col-16 combined detection was better than that of single index(Z=3.392,4.218,P＜0.05).Conclusion The serum TSG-6 and col-16 levels in active UC patients are ab-normally elevated,which is closely related to severity of the illness and clinical outcome.The levels of serum TSG-6 and col-16 can be used as potential biochemical indicators to judge the disease and predict the clinical outcome.

Clinical and mechanistic research progress of TCM on ulcerative colitis of liver depression and spleen deficiency / 国际中医中药杂志

Liver depression and spleen deficiency syndrome is a common syndrome type of ulcerative colitis (UC). Based on the theory of 'collaborative treatment of liver and spleen', TCM shows its effect and less adverse reactions in the treatment of UC with liver depression and spleen deficiency. The internal treatment of TCM based on syndrome differentiation and treatment by stages, as well as the external treatment of TCM based on TCM enema therapy, acupuncture therapy and acupoint application therapy, can relieve symptoms, improve relevant clinical indicators and improve the quality of life of patients. The mechanism studies show that the TCM with the effect of soothing the liver and activating the spleen plays a therapeutic role by regulating signal pathway conduction, regulating intestinal flora, and improving the level of inflammatory factors.

Clinical study on the treatment of distal ulcerative colitis with Ganyu-Pixu by the therapeutic method of Rougan Jianpi and mesalazine enema / 国际中医中药杂志

Objective:To evaluate the clinical efficacy of Rougan Jianpi therapy combined with Mesalazine enema in the treatment of distal ulcerative colitis (DUC) with Ganyu-Pixu syndrome.Methods:This study is a prospective parallel randomized controlled study. From November 2021 to May 2022, 115 patients with DUC in Changshu Hospital Affiliated to Nanjing University of Chinese Medicine were selected and randomly divided into a control group of 58 patients and a study group of 57 patients. The control group was treated with Mesalazine enema, and the study group was treated with Rougan Jianpi Decoction on the basis of the control group. Both groups were treated for 8 weeks. The severity of the disease was evaluated by using the Modified Mayo Scale, and the clinical and endoscopic efficacy was evaluated based on the changes in the score before and after treatment. TCM syndromes were scored from four aspects: abdominal pain, diarrhea, mucopurulent bloody stool, Rectal tenesmus, and anal burning. The quality of life was evaluated by using the IBD Quality of Life Scale (IBDQ). The serum TNF-αand IL-10 level were detected by using ELISA method. The adverse reactions during treatment were observed and recorded.Results:The total effective rate of the study group was 91.23% (52/57), while that of the control group was 79.31% (46/58). The difference between the two groups was no statistically significant ( Z=1.47, P=0.143). The proportion of patients in the study group who achieved clinical response[40.35% (23/57) vs. 51.72% (30/58)] and clinical relief [59.65% (34/57) vs. 43.11% (25/58)] the total proportion were significantly higher than those in the control group [100.00% (57/57) vs. 94.83% (55/58); Z=1.97, P=0.049]. The proportion of patients with endoscopic response [52.63% (30/57) vs. 56.90% (33/58)] and mucosal healing [33.33% (19/57) vs. 17.24% (10/58)] the total proportion in the study group were significantly higher than those in the control group [85.96% (49/57) vs. 74.14% (43/58); Z=2.23, P=0.026]. after treatment, the IBDQ score [(194.3±15.1) vs. (172.6±18.4), t=6.90] in the study group was significantly higher than that of the control group. After treatment, the patient's TCM symptom score: mucopurulent bloody stool [(1.7±0.8) vs. (2.0±0.6), t=2.03], rectal tenesmus [(1.5±0.6) vs. (1.8±0.6), t=2.32] and anal burning [(1.3±0.6) vs. (1.6±0.7), t=2.38] in the control group were significantly lower than those in the control group ( P<0.05). The level of IL-10 [(53.3±8.0) ng/L vs. (49.0±6.7) ng/L, t=3.10] in the study group after treatment was higher than that of the control group ( P<0.01), and TNF-α [(28.3±7.9)ng/L vs. (36.8±8.1)ng/L, t=3.58] was lower than that of the control group ( P<0.01). There were no significant adverse reactions observed during the treatment in both groups. Conclusion:Method of Rougan Jianpi combined with mesalazine enema can improve the clinical symptoms of DUC patients, improve clinical efficacy, and have good safety.

Clinical Observation of Treating Ulcerative Colitis with Acupuncture at Front Mu Points Combined with Oral Mesalazine / 昆明医科大学学报

Objective To observe the clinical efficacy of acupuncture at Front Mu point in the treatment of ulcerative colitis.Methods Sixty patients with ulcerative colitis treated at the Traditional Chinese Medicine Hospital in Kunming from August 2022 to June 2023 were collected.Using a random number table method,30 cases were assigned to each of the control group and the combined group.The treatment method involved administering oral mesalazine to the control group for a continuous period of 8 weeks,while the combined group received both oral mesalazine and acupuncture at front Mu points.The clinical efficacy,colonoscopy results score(Baron score),and colonic mucosal healing score(Geboes)before and after treatment were compared.Follow-up was conducted at 3 months to calculate the recurrence rate in the combination and control groups.Results The total effective rate in the combination group was higher than that in the control group(P<0.05),with rates of 93.33%and 67.67%,respectively.After treatment,the disease activity index,Baron score,and Geboes score decreased compared to before treatment(P<0.05),and the combination group had a lower disease activity index,Baron score,and Geboes score than the control group after treatment(P<0.05).Comparing the recurrence rates at 3 months post-treatment,the combination group was lower than the control group.Conclusion Acupuncture at Front Mu Point can significantly improve the clinical symptoms of ulcerative colitis,reduce the recurrence rate compared to patients in the control group,and is safe and reliable without serious adverse reactions.

Effect of ceria nanoparticles on activity of DSS-induced colitis in mice by eliminating active oxygen species / 上海交通大学学报（医学版）

Objective·To investigate the effect of ceria nanoparticles-polyethylene glycol(CeNP-PEG)on scavenging reactive oxygen species(ROS)and alleviating disease activity in dextran sulphate sodium(DSS)-induced colitis mice.Methods·CeNP was synthesized with the hydrates of cerium acetate,oleamine,and xylene,which was modified with polyethylene glycol-stearyl phosphatidylethanolamine(mPEG-DPSE)to obtain CeNP-PEG.Then CeNP-PEG was purified.The particle size and zeta potential of CeNP-PEG were measured by using transmission electron microscopy(TEM)and dynamic light scattering(DLS).Mouse macrophages(Raw264.7)were cultured in vitro and induced to a pro-inflammatory phenotype(M1 phenotype).M1 macrophages were treated with 0.5 μg/mL and 1.0 μg/mL CeNP-PEG,respectively,and then Western blotting was used to detect the expression changes of the proteins related with nuclear factor-κB(NF-κB)signaling pathway.DSS-induced colitis mice models were constructed,and CeNP-PEG(1.0 mg/mL)was intravenously administrated for 3 times via tail vein during the modeling period.Meanwhile,the body weight,fecal characteristics,and frequency of rectal bleeding in mice were monitored in the normal control group(Normal group),the model group(DSS group),and the CeNP-PEG treatment group.The disease activity index(DAI)was calculated to evaluate the intestinal inflammation.The level of ROS in mouse intestinal tissues was detected by dihydroethidine(DHE)staining and the mRNA expression levels of inflammatory cytokines interferon-γ(Ifn-γ),interleukin-6(Il-6),Il-1β and tumor necrosis factor-α(Tnf-α)were detected by real-time quantitative PCR(RT-qPCR).Results·The hydrated particle size of synthesized CeNP-PEG was(6.96±0.27)nm,and the average zeta potential was(-6.02±1.31)mV.Western blotting results showed that the expression of p-P65 increased in the pro-inflammatory macrophages compared with the control group.The expression of NF-κB inhibitor-α(IκB-α)decreased,and their expressions tended to recover after the intervention of different concentrations of CeNP-PEG.In the DSS-induced colitis models,mice in the CeNP-PEG treatment group lost less weight than those in the DSS group(P= 0.000)and had lower DAI scores(P=0.000).The RT-qPCR results of intestinal tissues showed that the mRNA levels of Ifn-γ,Il-1β,Il-6 and Tnf-α in the DSS group were significantly up-regulated compared with those in the Normal group(P=0.000),and all of them significantly decreased in the CeNP-PEG treatment group.The results of DHE staining showed that the fluorescence intensity of intestinal tissues in the DSS group was significantly enhanced than that in the Normal group,and the fluorescence intensity decreased in the CeNP-PEG treatment group.Conclusion·CeNP-PEG can inhibit the expression of intestinal inflammatory factors and the activation of NF-κB-related inflammatory pathway of pro-inflammatory macrophages,eliminate intestinal ROS,improve the intestinal inflammatory microenvironment,and alleviate the disease activity of DSS-induced colitis in mice.

Discussion on the Difference of Acupuncture Points Efficacy in Improving Ulcerative Colitis by"Zusanli"or"Neiguan"Based on Transcriptomics Data / 世界科学技术-中医药现代化

Objective To observe the intervention effect of acupuncture at"Zusanli"(ST36)or"Neiguan"(PC6)on the ulcerative colitis(UC)model mice.And to analyze the similarities and differences of gene transcription expression between the diseased colon and the non-diseased heart after acupuncture intervention by using transcriptomics,to explore whether there are efficacy differences between the two acupoints.Methods The UC mouse model was established by inducing dextran sulfate sodium salt(DSS).After successful modeling,the mice were randomly divided into model group,Zusanli group,and Neiguan group,with 9 mice in each group.Zusanli group and Neiguan group intervened with acupuncture at"Zusanli"and"Neiguan",respectively,30 min each time,once a day,for 5 consecutive days.The control and model groups were only bound without acupuncture.Observe the general situation of mice in each group,calculate the disease activity index(DAI),observe the morphological changes of colon tissue by HE staining.Use transcriptome sequencing technology to sequence and biologically analyze the colon tissue of mice in each group,and compare and study whether the two acupoints have differences in acupoint efficacy from the perspective of diseased tissue.At the same time,take the heart tissues of each group for comparative analysis,and discuss whether the effects of the two acupoints are different from the perspective of non-diseased tissue.Results Compared with control group,the DAI score of the model group increased significantly(P<0.001),and HE staining results showed significant pathological damage;after acupuncture at Zusanli or Neiguan,the DAI scores of UC mice were reduced considerably(P<0.05),and the pathological damage was significantly improved.The results of transcriptome sequencing and bioinformatics analysis showed that the effects of acupuncture at Zusanli or Neiguan on the colon of diseased tissue involved multiple genes,and 825 differential genes with similar changes(co-DEGs)were mainly enriched in white blood cells and chemokine pathways;there were 168 differentially expressed genes(ST36 only-DEGs)affected only by Zusanli,which were enriched to gastric acid secretion and other pathways;there were 325 differentially expressed genes(PC6 only-DEGs)only affected by Neiguan,which were enriched in cytokine-cytokine receptor interaction and other pathways.There were 95 co-DEGs in the heart of non-diseased tissue,which were mainly enriched in positive regulation of defense response and response to interleukin-1;there were 28 ST36 only-DEGs;there were114 PC6 only-DEGs,which were enriched in cardiovascular diseases and other pathways.Conclusion Acupuncture of"Zusanli"and"Neiguan"could improve UC mice's symptoms and pathological colon changes.However,through transcriptomic analysis,it was found that the two acupoints had differences in gene transcription effects on the colon of diseased tissue and the heart of non-diseased tissue,suggesting that acupoints with different distribution positions had some similarities in macro efficacy.Still,there were some differences at a micro level.

Mechanism of Atractylodes macrocephala in Treatment of Ulcerative Colitis Based on Network Pharmacology and Experimental Validation / 世界科学技术-中医药现代化

Objective To explore the molecular mechanism of Atractylodes macrocephala in the treatment of Ulcerative colitis(UC)based on network pharmacology,and verify it with animal experiments.Methods The active components of Atractylodes macrocephala was screened from the TCMSP database,the TCM-ID database,and in combination with relevant references,and the corresponding targets were obtained through Swiss database.The relevant targets of UC were obtained from GeneCards database,construct the"drug-component-target-disease"network diagram and"pathway-active ingredient-target"network diagram and draw PPI network diagram;GO function enrichment analysis and KEGG signal pathway annotation analysis were carried out.Autodock software is used for molecular docking of active components and targets.Then,the experimental validation of the network pharmacology prediction was carried out.The mouse UC model was induced by dextran sodium sulfate(DSS).The pathological changes of the colon tissue,the number of goblet cells,and the positive expression of inflammatory factorswere detected by HE staining,AB-PAS staining and immunohistochemistry in colon tissue of UC mice.Results The results have shown 30 active ingredients including atractylolactone I,II and III were screened,and 591 corresponding targets were obtained,of which the key target was IL-1β、TNF-α and so on.Molecular docking show that the core components had good binding affinity with the key targets.And the results of animal experiments showed that the alcohol extract of Atractylodes macrocephala could significantly increase the colon length,reduce the DAI score,improve the pathological changes of colon tissue of UC mice,increase the number of goblet cells,and inhibit the expression of IL-1β,TNF-α in colon tissue.Conclusion This study indicated that Atractylodes macrocephala could regulate the release of inflammatory factors through multiple components,multi-target and multi-channel,which could inhibit inflammatory reaction and play a role in improving UC.

Correlation between the Expression of Serum Elabela,LRG1 Levels and Disease Activity Index in Patients with Ulcerative Colitis / 现代检验医学杂志

Objective To investigate the expression of serum Elabela and leucine-rich-alpha-2-glycoprotein-1(LRG1)in ulcerative colitis(UC)patients and their correlation with disease activity index(DAI).Methods A total of 98 patients with UC admitted to Yuncheng Central Hospital from January to December 2022 were selected as the UC group,including 62 patients in active stage and 36 patients in remission stage.According to the severity of the disease,these patients were divided into mild group(n=26),moderate group(n=43)and severe group(n=29).In addition,these patients were grouped into gradeⅠ group(n=25),grade Ⅱ group(n=40)and grade Ⅲ group(n=33)based on the endoscopic activity index(EAI).According to the mucosal healing condition under endoscopy,these patients were divided into the healed group(n=65)and the unhealed group(n=33).Another 51 patients with colonic polyps were selected as control group 1,and 50 healthy individuals were selected as control group 2.Serum Elabela and LRG1 levels were detected by enzyme-linked immunosorbent assay(ELISA).Pearson method was used to analyze the correlation between serum Elabela,LRG1 levels and DAI in UC patients.Receiver operating characteristic(ROC)curve was applied to analyze the predictive value of serum Elabela and LRG1 for endoscopic mucosal healing.Results The levels of Elabela(4.77±1.36 ng/ml)and LRG1(352.12±39.45 ng/ml)in UC group were higher than those in control group 1(2.51±0.53 ng/ml,121.02±21.06 ng/ml)and control group 2(2.35±0.42 ng/ml,120.35±23.49 ng/ml),and the differences were statistically significant(t= 11.410～39.000,all P＜0.05).The levels of Elabela(5.26±0.54 ng/ml)and LRG1(370.42±12.49 ng/ml)in the active group were higher than those in the remission group(3.93±0.42 ng/ml,320.60±8.47 ng/ml),and the differences were statistically significant(t=12.705,21.242,all P＜0.05).The levels of Elabela(5.89±0.20 ng/ml)and LRG1(369.92±16.59 ng/ml)in the severe group were higher than those in the moderate groups(4.51±0.67 ng/ml,356.12±18.75 ng/ml)and mild groups(3.95±0.21 ng/ml,325.65±10.14 ng/ml),and the differences were statistically significant(t=3.205～35.077,all P＜0.05).The levels of Elabela(5.80±0.18 ng/ml)and LRG1(369.16±13.47 ng/ml)in grade Ⅲ group were higher than those in grade Ⅱ group(4.49±0.35 ng/ml,355.46±16.34 ng/ml)and grade Ⅰgroup(3.86±0.16 ng/ml,324.15±8.71 ng/ml),and the differences were statistically significant(t= 3.854～48.725,all P＜0.05).The levels of Elabela(5.12±0.42 ng/ml)and LRG1(367.12±14.27 ng/ml)in unhealed group were higher than those in healed group(4.08±0.37 ng/ml,322.57±10.35 ng/ml),and the differences were statistically significant(t=12.043,15.917,all P＜0.05).The serum levels of Elabela and LRG1 in UC patients were positively correlated with EAI and ESR(r=0.602,0.298;0.576,0.302,all P＜0.05),but negatively correlated with hemoglobin level(r=-0.351,-0.334,all P＜0.05).The area under the curve predicted by the combination of serum Elabela and LRG1 for endoscopic mucosal healing was 0.926(95%CI:0.880～0.958),was higher than the 0.803(95%CI:0.741～0.856)and 0.783(95%CI:0.720～0.838)predicted by Elabela and LRG1 alone,and the difference was statistically significant(Z=4.101,4.228,all P＜0.05).Conclusion The serum levels of Elabela and LRG1 in UC patients increased,and they were related to the increase of DAI and worsening of the condition.Testing serum Elabela and LRG1 can provide a reference for evaluating mucosal healing under UC endoscopy.

The role of PTTG1 in colonic inflammation by regulating intestinal epithelial cells pyroptosis / 实用医学杂志

Objective To investigate whether the pituitary tumor transformation gene 1(PTTG 1)plays a role in colitis by regulating intestinal epithelial cells pyroptosis.Methods Ten PTTG 1 wild-type(WT)mice and Ten PTTG 1 knockout(KO)mice were randomly divided into 4 groups of 5 each,respectively PTTG1 WT control and experimental group,PTTG1 KO control and experimental group.The mice in the experimental group were given 3%dextran sodium sulfate(DSS)for 6 days to induce acute colitis,and the control group was given sterile double distilled water(ddH2O).The disease activity index of the respective group of mice was observed and recorded.Mouse colonic tissue were collected,and the expression levels of NLRP3,ASC,and GSDMD were determined by immuno-histochemistry and western blot.In HCoEpiC,PTTG1 expression was knocked down using shRNA,and the cells were subsequently treated with TNF-α to induce inflammation.Then,the expression of GSDMD was detected.Results The expression of PTTG1 was decreased in colonic mucosal tissue in mice with acute colitis(P<0.01).Compared with WT mice,the colitis was significantly aggravated in PTTG1 KO mice after 3%DSS treatment.The expression of pyroptosis-related proteins was significantly up-regulated in the colon mucosal tissues of PTTG1 KO experimental mice(P<0.05).After knocking down the expression of PTTG1 in HCoEpiC and TNF-α treatment,the expression levels of GSDMD were significantly up-regulated(P<0.05).Conclusion PTTG1 reduced pyroptosis in intestinal epithelial cells(IECs),while PTTG1 loss can enhance IEC pyroptosis,aggravating colonic inflammation.

The relationship between ulcerative colitis and the risk of hypothyroidism:A two-mendelian randomization study / 实用医学杂志

Objective To investigate assess the bidirectional causal relationship between ulcerative colitis(UC)and hypothyroidism using a two-sample Mendelian randomization(TSMR).Methods Single nucleotide polymorphism(SNP)data relevant to UC and hypothyroidism were retrieved from the Finnish Biobank and the IEU database,respectively.Independent SNPs strongly associated with UC were selected as instrumental variables.Causal associations between UC and hypothyroidism were evaluated using the inverse variance weighted(IVW)method,MR-Egger regression,and weighted median estimator.Additionally,MR-PRESSO was employed to assess the hori-zontal pleiotropy and outlier SNPs.Cochran's Q test and funnel plots were performed to evaluate the heterogeneity among the SNPs.A leave-one-out analysis was conducted to examine the influence of individual SNPs on causal assessments.Results Four instrumental variables strongly associated with UC were identified.The IVW method indicated a causal relationship between UC and hypothyroidism(OR = 0.975,95%CI:0.924～0.990,P = 0.011).Cochran's Q test yielded a Q statistic of 2.566 with a p-value of 0.463,suggesting no heterogeneity among the SNPs.Both MR-Egger(P = 0.523)and MR-PRESSO(P = 0.548)tests suggested the absence of horizontal pleiotropy.However,the results of the reverse TSMR did not support a reverse causal relationship.Conclusion The findings from the TSMR analysis reveal a negative causal relationship between UC and hypothyroidism.