Factores asociados al desenlace en niños con mal rotación intestinal manejados en el Hospital Infantil de San Vicente Fundación, Medellín, Colombia / Factors associated with outcome in children with intestinal malrotation managed at the Hospital Infantil of San Vicente Fundación, Medellín, Colombia

Introducción. El intestino primitivo rota durante la vida embrionaria. Cuando ocurre de forma inadecuada aparece la malrotación intestinal que puede llevar a la obstrucción o al vólvulo del intestino medio. La incidencia disminuye con el aumento de la edad. La malrotación intestinal es una de las principales causas de complicaciones del tracto gastrointestinal en la edad pediátrica. Métodos. Estudio retrospectivo, observacional, transversal y analítico, de la experiencia durante 10 años en pacientes menores de 15 años con diagnóstico de malrotación intestinal, tratados en el Hospital Infantil de San Vicente Fundación, en Medellín, Colombia. Se buscó la asociación entre variables demográficas, clínicas e imagenológicas con los desenlaces. Resultados. Se obtuvieron 58 pacientes con malrotación intestinal, 65 % menores de 1 año. En 29,3 % de los pacientes se hizo el diagnóstico con la presentación clínica; los síntomas predominantes fueron distensión abdominal y emesis. En el 24,1 % se confirmó el diagnóstico con imágenes. Las variables con una diferencia estadísticamente significativa a favor de encontrar una malrotación complicada fueron choque séptico (OR=11,7), síndrome de respuesta inflamatoria sistémica (OR=8,4) y deshidratación (OR=5,18). Conclusiones. La malrotación intestinal tiene complicaciones como perforación, peritonitis, vólvulo e intestino corto. El vólvulo se acompaña de shock y sepsis, con mortalidad hasta del 50 %. Las imágenes diagnósticas son una ayuda, pero no se puede basar la conducta médica en estas porque ninguna imagen garantiza el diagnóstico definitivo. Los signos de alarma son poco específicos. En menores de un año con emesis, distensión y dolor abdominal se debe sospechar malrotación intestinal.

Introduction. The primitive intestine rotates during embryonic life. When it occurs inappropriately, intestinal malrotation appears, which can lead to obstruction or midgut volvulus. The incidence decreases when age increases. Intestinal malrotation is one of the main causes of complications of the gastrointestinal tract in pediatric age. Method. Retrospective, observational, cross-sectional and analytical study of the experience over 10 years in patients under 15 years of age with a diagnosis of intestinal malrotation, treated at Hospital Infantil of San Vicente Fundación, in Medellín, Colombia. The association between demographic, clinical and imaging variables with the outcomes was sought. Results. There were 58 patients with intestinal malrotation, 65% under one year of age. In 29.3% of patients, intestinal malrotation was diagnosed clinically. The predominant symptoms were abdominal distension and emesis. In 24.1% the diagnosis was confirmed with imaging. The variables with a statistically significant difference in favor of finding a complicated malrotation were septic shock (OR=11.7), systemic inflammatory response syndrome (OR-8.4), and dehydration (OR=5.18). Conclusions. Malrotation has complications such as perforation, peritonitis, volvulus, and short bowel. Volvulus is accompanied by shock and sepsis, with mortality of up to 50%. Diagnostic images are helpful, but medical conduct cannot be based on them because no image guarantees a definitive diagnosis. The warning signs are not very specific. In children under one year of age with emesis, distension and abdominal pain, intestinal malrotation should be suspected.

Divertículo de Meckel complicado. Experiencia de 15 años en un hospital interzonal / Complicated Meckel's diverticulum. Fifteen years of experiencein an interzonal hospital in the Province of Buenos Aires

Introducción: el divertículo de Meckel es la anomalía congénita más frecuente del tracto gastrointestinal. Puede presentarse con hemorragia, obstrucción intestinal o diverticulitis, complicaciones que disminuyen con la edad, por lo que en el adulto el diagnóstico suele ser incidental. El tratamiento de las complicaciones es quirúrgico, mediante diverticulectomía o resección segmentaria del intestino delgado, dependiendo de sus características morfológicas. Objetivo: analizar nuestra experiencia en el manejo del divertículo de Meckel complicado en un período de 15 años. Diseño: estudio descriptivo, observacional, transversal, retrospectivo. Material y métodos: se revisaron las historias clínicas de los pacientes operados por divertículo de Meckel complicado en el Servicio de Cirugía General del Hospital San Roque durante el periodo 2007-2022. Se registraron datos demográficos, presentación clínica, diagnóstico preoperatorio, tratamiento quirúrgico, complicaciones postoperatorias y hallazgos histopatológicos. Resultados: se incluyeron 25 pacientes, 21 (84%) hombres, 3 menores de 18 años. La presentación clínica fue un síndrome de fosa iliaca derecha en el 80% de los casos, obstrucción intestinal en el 16% y hemorragia en el 4%. En solo 2 casos se realizó el diagnóstico preoperatorio, confirmado mediante tomografía computada. Se realizó diverticulectomía en el 68% de los pacientes y resección segmentaria el 32%. El abordaje fue laparotómico en el 64%, principalmente en el periodo inicial y laparoscópico en el 36%. Hubo una complicación IIIb de Clavien-Dindo en un paciente pediátrico tratado con drenaje percutáneo. En un solo paciente (4%), que se presentó con hemorragia digestiva masiva, se encontró epitelio de tipo gástrico y páncreas ectópico en el divertículo. Conclusiones: En nuestra experiencia el divertículo de Meckel complicado se presentó predominantemente en hombres. La complicación más frecuente en el adulto fue la diverticulitis. El diagnóstico preoperatorio fue infrecuente y realizado por tomografía computada. La diverticulectomía es suficiente en la mayoría de los casos. Actualmente, la laparoscopia es una herramienta segura, rentable y eficiente que permite el diagnóstico y tratamiento oportunos de esta entidad. (AU)

Introduction: Meckel's diverticulum is the most common congenital malformation of the gastrointestinal tract. It can present with bleeding, intesti-nal obstruction or diverticulitis, complications that decrease with age, so in adults the diagnosis is usually incidental. Treatment of complications is surgical, through diverticulectomy or segmental resection of the small intestine, depending on its morphological characteristics. Objective: to analyze our experience in the management of complicated Meckel's diverticulum over a period of 15 years. Design: descriptive, observational, cross-sectional, retrospective study. Materials and methods: the medical records of patients operated on for complicated Meckel's diverticulum in the General Surgery Service of the San Roque Hospital during the period 2007-2022 were reviewed. Demo-graphic data, clinical presentation, preoperative diagnosis, surgical treatment, postoperative complications, and histopathological findings were recorded. Results: twenty-five patients were included, 21 (84%) men, 3 under 18 years of age. The clinical presentation was a right iliac fossa syndrome in 80% of cases, intestinal obstruction in 16% and hemorrhage in 4%. In only 2 cases was the preoperative diagnosis made, confirmed by computed tomography. Diverticulectomy was performed in 68% of patients and segmental resection in 32%. The approach was by laparotomy in 64%, mainly in the initial period, and by laparoscopy in 36%. There was a Clavien-Dindo IIIb complication in a pediatric patient treated with percutaneous drain-age. In only one patient (4%), who presented with massive gastrointestinal bleeding, gastric-type epithelium and ectopic pancreas were found in the diverticulum. Conclusions: In our experience, complicated Meckel's diverticulum occurred predominantly in men. The most frequent complication in adults was diverticulitis. Preoperative diagnosis was infrequent and was made by computed tomography. Diverticulectomy is sufficient in most cases. Currently, laparoscopy is a safe, profitable and efficient tool that allows for the timely diagnosis and treatment of this entity. (AU)

Vólvulo cecal: reporte de un caso / Cecal volvulus: a case report

El vólvulo cecal es una causa rara de abdomen oclusivo agudo. Cada año, aproximadamente 2,8-7,1 personas por millón se ven afectadas por esta patología. Se estima que el vólvulo cecal representa el 25-40% de todo el vólvulo del colon. Causa alrededor del 1-1,5% de las oclusiones intestinales en adultos. La mayoría de los pacientes presentan síntomas de hinchazón, estreñimiento, náuseas y vómitos. Hasta el 50% puede tener síntomas intermitentes antes de la torsión. Su baja prevalencia dificulta su diagnóstico preoperatorio, siendo diagnosticado frecuentemente durante la cirugía. Presentamos el caso de un hombre de 66 años que ingresa por dolor abdominal, cuyos métodos de imagen complementarios iniciales fueron diagnósticos de abdomen agudo oclusivo y finalmente durante la cirugía se observó un vólvulo cecal

The cecal volvulus is a rare cause of an acute occlusive abdomen. Each year, approximately 2.8-7.1 people per million are affected by this pathology. It is estimated that the cecal volvulus represents 25-40% of all the colon volvulus. Causing about 1-1.5% of intestinal occlusions in adults. Most patients have symptoms of bloating, constipation, nausea, and vomiting. Up to 50% may have intermittent symptoms before torsion. Its low prevalence hinders its preoperative diagnosis, being frequently diagnosed during surgery. We present a case of a 66-year-old man admitted for abdominal pain, whose initial complementary imaging methods were diagnostic of acute occlusive abdomen and finally a cecal volvulus was observed during surgery

Trimethylamine N-oxide and kidney diseases: what do we know? / N-óxido de trimetilamina e doenças renais: o que sabemos?

Abstract In the human gut, there is a metabolically active microbiome whose metabolic products reach various organs and are used in the physiological activities of the body. When dysbiosis of intestinal microbial homeostasis occurs, pathogenic metabolites may increase and one of them is trimethyl amine-N-oxide (TMAO). TMAO is thought to have a role in the pathogenesis of insulin resistance, diabetes, hyperlipidemia, atherosclerotic heart diseases, and cerebrovascular events. TMAO level is also associated with renal inflammation, fibrosis, acute kidney injury, diabetic kidney disease, and chronic kidney disease. In this review, the effect of TMAO on various kidney diseases is discussed.

Resumo No intestino humano, existe um microbioma metabolicamente ativo cujos produtos metabólicos alcançam diversos órgãos e são utilizados nas atividades fisiológicas do corpo. Quando ocorre disbiose da homeostase microbiana intestinal, os metabólitos patogênicos podem aumentar, e um deles é o N-óxido de trimetilamina (TMAO). Acredita-se que o TMAO tenha um papel na patogênese da resistência à insulina, diabetes, hiperlipidemia, doenças cardíacas ateroscleróticas e eventos cerebrovasculares. O nível de TMAO também está associado à inflamação renal, fibrose, lesão renal aguda, doença renal diabética e doença renal crônica. Nesta revisão, discute-se o efeito do TMAO em diversas doenças renais.

Fístula enterocutánea: un enfoque desde las generalidades y el estado nutricional / Enterocutaneous fistula: An approach based on generalities and nutritional status

Introducción. Una fístula es una conexión anormal entre dos superficies epitelizadas. Cerca del 80 % de las fístulas entero-cutáneas son de origen iatrogénico secundarias a cirugía, y un menor porcentaje se relacionan con traumatismos, malignidad, enfermedad inflamatoria intestinal o isquemia. La morbilidad y las complicaciones asociadas pueden ser significativas, como la desnutrición, en la que intervienen múltiples factores. Métodos. Se realizó una búsqueda de la literatura en las bases de datos de PubMed, Google Scholar y SciELO, utilizando las palabras claves descritas y se seleccionaron los artículos más relevantes de los últimos años. Resultados. La clasificación de las fístulas se basa en su anatomía, su gasto o secreción diaria y su localización. Existe una tríada clásica de las complicaciones: sepsis, desnutrición y anomalías electrolíticas. El control del gasto de la fístula, el drenaje adecuado de las colecciones y la terapia antibiótica son claves en el manejo precoz de estos pacientes. Los estudios recientes hacen hincapié en que la sepsis asociada con la desnutrición son las principales causas de mortalidad. Conclusiones. Esta condición representa una de las complicaciones de más difícil y prolongado tratamiento en cirugía abdominal y colorrectal, y se relaciona con importantes tasas de morbilidad, mortalidad y altos costos para el sistema de salud. Es necesario un tratamiento multidisciplinario basado en la reanimación con líquidos, el control de la sepsis, el soporte nutricional y el cuidado de la herida, entre otros factores.

Introduction. A fistula is an abnormal connection between two epithelialized surfaces. About 80% of enterocutaneous fistulas are of iatrogenic origin secondary to surgery, and a smaller percentage are related to trauma, malignancy, inflammatory bowel disease or ischemia. The associated morbidity and complications can be significant, such as malnutrition, in which multiple factors intervene. Methods. A literature search was carried out in the PubMed, Google Scholar and SciELO databases using the keywords described and the most relevant articles from recent years were selected. Results. The classification of fistulas is based on their anatomy, their daily secretion output, and their location. There is a classic triad of complications: sepsis, malnutrition and electrolyte abnormalities. Control of fistula output, adequate drainage of the collections and antibiotic therapy are key to the early management of these patients. Recent studies emphasize that sepsis associated with malnutrition are the main causes of mortality. Conclusions. This condition represents one of the most difficult and prolonged complications to treat in abdominal and colorectal surgery, and is related to significant rates of morbidity, mortality and high costs for the health system. Multidisciplinary treatment based on fluid resuscitation, sepsis control, nutritional support, and wound care, among other factors, is necessary.

Osificación heterotópica mesentérica como causa de obstrucción intestinal en un paciente con abdomen séptico / Mesenteric Heterotopic Ossification as a Cause of Intestinal Obstruction in a Patient with a Septic Abdomen

Presentación del caso. Se trata de un masculino de 49 años, con historia de un trauma abdominal cerrado con un objeto contuso sin alteraciones hemodinámicas. La ecografía focalizada de traumatismos resultó positiva a líquido libre en la cavidad abdominal en tres ventanas. Intervención terapéutica. Fue sometido a múltiples laparotomías exploratorias con lavados de cavidad abdominal posterior a presentar un cuadro de abdomen séptico Björk 4, quien después de 38 días de estancia intrahospitalaria presentó una fístula enteroatmosférica que causaba un déficit nutricional. En una intervención quirúrgica se realizó el cierre de la fístula enteroatmosférica, con el hallazgo de tejido óseo trabecular en cavidad abdominal, correspondiente a osificación heterotópica intraabdominal de formación reciente. Evolución clínica. Luego de la anastomosis del intestino delgado presentó signos de obstrucción intestinal, a causa de esto, se realizó una nueva laparotomía exploratoria, en la que se encontró tejido óseo adherido al mesenterio del intestino delgado que generó una obstrucción completa, se extirpó el material óseo y se logra restablecer el flujo intestinal liberando la obstrucción en el intestino delgado

Case presentation. A 49-year-old male, with a history of blunt abdominal trauma with a blunt object without hemodynamic alterations. The focused trauma ultrasound was positive for free fluid in the abdominal cavity in three windows. Treatment.The patient underwent multiple exploratory laparotomies with peritoneal lavage after presenting a septic abdomen (Björk 4), who after 38 days of intrahospital stay presented an enteroatmospheric fistula that caused a large nutritional deficit. In a surgical intervention, the enteroatmospheric fistula was closed, with the finding of trabecular bone tissue in the abdominal cavity, corresponding to intra-abdominal heterotopic ossification of recent formation. Outcome. After the small intestine anastomosis, he presented signs of intestinal obstruction, because of this, a new exploratory laparotomy was performed, in which bone tissue was found adhered to the mesentery of the small intestine that generated a complete obstruction. The bone material was removed and the intestinal flow was reestablished, freeing the obstruction in the small intestine

Perforación colónica por endoprótesis biliar impactada / Colonic perforation due to impacted biliary stent

Introducción. La colocación de endoprótesis biliares es cada día más frecuente por ser actualmente una de las mejores opciones para el tratamiento de patologías de la vía biliar. La migración de las endoprótesis es una de las complicaciones que puede ocurrir en hasta un 10,8 % de los pacientes, pero en muy raras ocasiones llegan a causar una perforación intestinal. Caso clínico. Se trata de una paciente de 61 años, a quien cinco años atrás se le realizó una colangiopancreatografía retrógrada endoscópica por coledocolitiasis. Consultó por presentar dolor abdominal, y al examen físico se encontraron abdomen agudo y plastrón en fosa ilíaca izquierda a la palpación. La tomografía computarizada informó un cuerpo extraño a nivel del colon descendente, con perforación del mismo. Se realizó laparotomía exploratoria y colostomía por perforación del colon sigmoides secundaria a prótesis biliar migrada. Resultados. La paciente evolucionó favorablemente y a los seis meses se realizó el cierre de la colostomía, sin complicaciones. Conclusión. Los pacientes a quienes se les colocan prótesis biliares requieren un seguimiento adecuado para evitar complicaciones que, aunque raras, pueden ocurrir, como la migración intestinal con perforación. El tratamiento de dichas complicaciones se hace por vía endoscópica, laparoscópica o laparotomía en caso de complicación severa.

Introduction. Endoscopic placement of biliary stents is becoming more common every day, as it is currently one of the best options for the treatment of bile duct pathologies. One of the complications that can occur is the migration of the endoprostheses in up to 10.8% of patients, which in very rare cases can cause intestinal perforation. Clinical case. This is a 61-year-old female patient, who underwent endoscopic retrograde cholangiopancreatography five years ago for choledocholithiasis. She consulted due to abdominal pain, with a physical examination that upon palpation documented an acute abdomen and a palpable plastron in the left iliac fossa. The computed tomography revealed a foreign body at the level of the descending colon, with perforation. Exploratory laparotomy and colostomy were performed due to perforation of the sigmoid colon secondary to migrated biliary prosthesis. Results. The patient progressed favorably and six months later the colostomy was closed without complications. Conclusions. Patients who receive biliary stents require adequate follow-up to avoid complications that, although rare, may occur, such as intestinal migration with intestinal perforation. The treatment of these complications can be endoscopic, laparoscopic or laparotomy in case of severe complication.

Development and application of in vitro intestinal absorption model based on microfluidic chips / 药学实践杂志

The intestine is the main site of oral drug absorption, and the epithelial cells of the intestine contain villi and microvilli, which promote secretion, cell adhesion, and absorption by increasing surface area and other factors. Traditional two-dimensional/three-dimensional (2D/3D) cell culture models and animal models have played an important role in studying drug absorption, but their application is limited due to the lack of sufficient predictability of human pharmacokinetics or ethical issues, etc. Therefore, mimicking the core structure and key functions of the human intestine based on in vitro live cells has been the focus of research on constructing a microfluidic chip-based intestinal model. The model is a microfluidic chip bionic system that simulates the complex microstructure, microenvironment, and physiological functions of the human intestine using microfabrication technology. Compared with 2D cell culture and animal experiments, the intestinal microarray model can effectively simulate the human in vivo environment and is more specific in drug screening. The research progress and applications in disease modeling, drug absorption and transport of intestinal microarray models and intestine-related multi-organ coupled microarray models at home and abroad were reviewed in this paper. The current challenges of intestinal chip simulating intestinal homeostasis and diseases were summarized，in order to provide reference for the further establishment of a more reliable in vitro intestinal chip model.

Biological Connotation of Pathogenesis of Colorectal Cancer Due to Damp-heat Accumulation Based on Immune Response-intestinal Microbial Axis / 中国实验方剂学杂志

Colorectal cancer （CRC） is a malignant tumor of the intestinal tract with changes in bowel habits， blood in the stool， and pain as the main clinical manifestations. With the change in lifestyle and diet structure in recent years， the incidence of CRC has been increasing year by year. The pathogenesis of CRC is closely related to abnormal immune response and chronic inflammation， intestinal microbial dysbiosis， and the production of oncogenic metabolites. There is a two-way communication between the intestinal microbiota and the body's immunity， which not only plays a key role in maintaining the body's health but also has a close relationship with the development of diseases. An increasing number of studies have shown that abnormal immune responses accelerate the disease process by producing inflammatory factors， causing chronic inflammation in the body， disrupting the intestinal mucosal barrier， and increasing mucosal permeability， thus resulting in dysbiosis of the intestinal microbial ecology and a large number of pathogenic microorganisms and their metabolites. In addition， dysbiosis of intestinal microbes， by suppressing the normal immune response， leads to the disruption of multiple metabolic pathways in the body， affecting the internal and external stress response of the intestine， inducing inflammation， and thus producing disease. Therefore， the complex crosstalk mechanism between the immune response and intestinal microbial axis is closely related to the development of CRC. Based on traditional Chinese medicine theory and clinical research， it was found that dietary factors are an important causative factor in the development of CRC. The deficiency of positive energy is the root cause of the disease， and damp-heat accumulation is the key pathogenesis. Through modern medical and biological research， it is believed that abnormal immune response is the microscopic manifestation of damp-heat entrapment， while intestinal microbial dysbiosis is the biological basis of toxic injection into the large intestine， and in the pathogenesis of CRC， the imbalance of immune response-intestinal microbial axis is compatible with damp-heat accumulation in traditional Chinese medicine. This study aims to explore the biological connotation of CRC due to damp-heat accumulation from the immune response-intestinal microbial axis， so as to interpret the pathogenesis of CRC due to damp-heat accumulation with objective data and provide new ideas and theoretical basis for the pathogenesis and treatment strategies of CRC due to damp-heat accumulation.

Mechanism of Yiqi Jiedu Formula Against Ischemic Stroke Based on Microbial-gut-brain Axis / 中国实验方剂学杂志

ObjectiveTo explore the possible mechanism of the Yiqi Jiedu formula （YQ） in treating ischemic stroke （IS） from the perspective of the microbial-gut-brain axis （MGBA）. MethodRats were randomly divided into five groups， with six in each group， including sham surgery group， model group， and low， medium， and high dose YQ groups （1， 5， and 25 mg·kg-1）. Except for the sham surgery group， all other groups were established with a middle cerebral artery occlusion （MCAO） model using the thread occlusion method. The success of modeling was determined through neurobehavioral scoring， and the protective effect of YQ on IS was evaluated. Then， the changes in gut microbiota before and after MCAO modeling and YQ administration were compared using 16S rDNA sequencing technology， and the possible biological pathways related to the effect of this formula were analyzed. The expression of inflammatory factors such as interleukin-6 （IL-6）， interleukin-17A （IL-17A）， and interleukin-10 （IL-10） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the expression of tight junction proteins ZO-1 and Occludin in brain and intestinal tissue， and hematoxylin-eosin staining （HE） was used to observe pathological changes in the cerebral cortex and colon， so as to validate the possible mechanism of action. ResultYQ significantly improved the neurobehavioral score of MCAO rats （P<0.01） and played a good regulatory role in intestinal microbial disorders caused by enriched pathogens and opportunistic pathogens during the acute phase. Among them， significantly changed microorganisms include Morgentia， Escherichia Shigella， Adlercreutzia， and Androbacter. Bioinformatics analysis found that these bacteria may be related to the regulation of inflammation in the brain. Compared with the blank group， the detection of inflammatory factors in the serum of IS model rats showed an increase in inflammatory factors IL-6 and IL-17A （P<0.01） and a decrease in the content of anti-inflammatory factor IL-10 （P<0.01）. Compared with the model group， the content of inflammatory factors IL-6 and IL-17A in the serum of the treatment group decreased （P<0.05）， and that of anti-inflammatory factor IL-10 increased （P<0.01）. The expression results of barrier proteins ZO-1 and Occludin in brain and intestinal tissue showed that the expression levels of both decreased in IS model rats （P<0.05）， while the expression levels of both increased in the treatment group （P<0.05）. ConclusionAcute cerebral ischemia can lead to an imbalance of intestinal microbiota and damage to the intestinal barrier， and it can increase intestinal permeability. YQ can regulate intestinal microbiota imbalance caused by ischemia， inhibit systemic inflammatory response， and improve the disruption of the gut-blood brain barrier， preventing secondary cascade damage to brain tissue caused by inflammation. The MGBA may be an important mechanism against the IS.

Effect of Atractylodis Macrocephalae Rhizoma on Short-chain Fatty Acids and Intestinal Barrier in Mice with Slow-transit Constipation / 中国实验方剂学杂志

ObjectiveTo investigate the mechanism of Atractylodis Macrocephalae Rhizoma（AMR） in the treatment of slow-transmission constipation（STC） by observing the effects of AMR on short-chain fatty acids and intestinal barries in STC mice. MethodForty-eight male KM mice were randomly divided into blank group， model group， AMR low-， medium-， high-dose groups（2.5， 5， 10 g·kg-1） and mosapride group（2.5 mg·kg-1）. Except for the blank group， all groups were gavaged with loperamide suspension（5 mg·kg-1） twice daily for 14 d to construct the STC mouse model. At the same time， each drug administration group was given the corresponding drug by gavage for consecutive 14 d， the blank and model groups were gavaged with equal volume of distilled water. The effects of the treatment of AMR on body mass， defecation frequency， fecal water content and intestinal propulsion rate of mice were observed， the pathological changes of mouse colon were observed by hematoxylin-eosin（HE） staining and periodic acid-Schiff（PAS） staining， the levels of gastrin（GAS） and motilin（MTL） in serum were detected by enzyme-linked immunosorbent assay（ELISA）， gas chromatography-mass spectrometry（GC-MS） was used to detect the contents of short-chain fatty acids（SCFAs） in mouse feces， real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） and Western blot were used to determine the mRNA and protein expression levels of zonula occludens-1（ZO-1）， Occludin， and Claudin-1 in the colon of mice. ResultCompared with the blank group， the body mass， defecation frequency， fecal water content and intestinal propulsion rate of mice in the model group were significantly decreased（P<0.05， P<0.01）， the arrangement of colonic tissues was disordered， and the number of goblet cells was reduced， the levels of GAS and MTL in serum were significantly decreased（P<0.01）， and the levels of SCFAs in the feces were on a decreasing trend， with the contents of acetic acid， propionic acid， butyric acid， isobutyric acid and valeric acid were significantly decreased（P<0.05， P<0.01）， the mRNA and protein expression levels of ZO-1， Occludin and Claudin-1 in the colonic tissues were significantly decreased（P<0.01）. The above results suggested that STC mouse model was successfully constructed. Compared with the model group， the body mass， defecation frequency， fecal water content and intestinal propulsion rate of mice in AMP administration groups all increased significantly（P<0.05， P<0.01）， the mucosal layer of the colonic tissues was structurally intact without obvious damage， and the number of goblet cells increased， serum levels of GAS and MTL were significantly increased（P<0.01）， the contents of SCFAs in the feces were all on a rising trend， with the contents of acetic， propionic， butyric and isobutyric acids rising significantly（P<0.05， P<0.01）， the mRNA and protein expression levels of ZO-1， Occludin and Claudin-1 in the colonic tissues were significantly increased（P<0.05， P<0.01）. ConclusionAMR is able to improve the constipation symptoms in STC mice， and its mechanism may be related to increasing the contents of SCFAs in the intestine as well as promoting the mRNA and protein expression levels of ZO-1， Occludin and Claudin-1 in the colon.

Da Chengqitang Protects Intestinal Barrier in Septic Mice via Endogenous Antimicrobial Peptide mCRAMP / 中国实验方剂学杂志

ObjectiveMolecular docking and animal experiments were employed to explore the protective effect and mechanism of Da Chengqitang （DCQD） on intestinal barrier in septic mice. MethodText mining method was used to screen the active ingredients in DCQD. AutoDock Tools and Discovery Studio were used to study the interactions of active components with the core target proteins ［claudin-1， tumor necrosis factor （TNF）-α， interleukin （IL）-6， endogenous antimicrobial peptide mCRAMP， Toll-like receptor 4 （TLR4）， and myeloid differentiation primary response gene 88 （MyD88）］ in sepsis. Fifty C57BL/6 mice were randomized into sham， model， low- and high-dose （4 g∙kg-1 and 8 g∙kg-1） DCQD， and ulinastatin groups （n=10）. Before， during， and after the day of modeling surgery， each group was administrated with corresponding drugs. The mice in other groups except the model group were subjected to modeling by cecal ligation and puncture. Enzyme-linked immunosorbent assay （ELISA） was used measure the serum level of D-lactic acid to assess intestinal mucosa permeability. Hematoxylin-eosin staining was employed to observe the histopathological changes in the ileum and assess the intestinal mucosal damage and inflammatory infiltration. Western blotting was employed to determine the expression levels of tight junction proteins claudin-1 and occludin in the ileal tissue， which were indicative of the bowel barrier function. The TNF-α and IL-6 levels were measured by ELISA to assess the intestinal inflammation. The expression of mCRAMP in the ileal tissue was observed by immunohistochemistry. The mRNA levels of mCRAMP， TLR4， and MyD88 in mouse ileal tissue were determined by Real-time polymerase chain reaction， on the basis of which the mechanism of DCQD in protecting the intestinal barrier of septic mice was explored. ResultMolecular docking results showed that most of the 10 active ingredients of DCQD that were screened out by text mining could bind to sepsis targets by van der Waals force， hydrogen bonding， and other conjugated systems. The results of animal experiments showed that compared with the model group， low- or high-dose DCQD lowered the D-lactic acid level in the serum （P<0.01）， alleviated damage to the ileal tissue and mucosal edema， protected the small intestine villus integrity， reduced inflammatory cell infiltration， promoted the expression of claudin-1 （P<0.01）， lowered the IL-6 level （P<0.01）， up-regulated the mRNA and protein levels of mCRAMP （P<0.01）， and down-regulated the mRNA and protein levels of TLR4 and MyD88 （P<0.01） in the ileal tissue. In addition， high-dose DCQD lowered the TNF-α level and promoted the expression of occludin in the ileum tissue （P<0.01）， and low-dose DCQD up-regulated the protein level of occludin in the ileum tissue （P<0.05）. ConclusionDCQD has a protective effect on intestinal barrier in septic mice. It can reduce intestinal inflammation， repair intestinal mucosal damage， improve the tight junction protein level， and reduce intestinal mucosal permeability by up-regulating the mRNA and protein levels of mCRAMP and the down-regulating the expression of genes in the TLR4/MyD88 pathway.

Modified Liuwei Dihuangtang Combined with Losartan Potassium Regulates ACE1/AngⅡ/AT1R Axis and Intestinal Flora in Rat Model of Diabetic Kidney Disease / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of modified Liuwei Dihuangtang in preventing and treating renal injury in diabetic kidney disease （DKD） via the angiotensin-converting enzyme 1 （ACE1）/angiotensin Ⅱ （AngⅡ）/angiotensin Ⅱ type 1 receptor （AT1R） axis. MethodFifty male SD rats were randomized into a normal group （n=8） and a modeling group （n=42）. The rats in the modeling group were fed with a high-sugar and high-fat diet for 6 weeks and intraperitoneally injected with 35 mg·kg-1 streptozotocin （STZ） to establish the model of DKD. After successful modeling， the rats were randomized into model， traditional Chinese medicine （modified Liuwei Dihuangtang granules 21 g·kg-1）， western medicine （losartan potassium， 33 mg·kg-1）， and integrated Chinese and western medicine （losartan potassium 33 mg·kg-1 combined with modified Liuwei Dihuangtang granules 21 g·kg-1） groups. The levels of fasting blood glucose （FBG）， urinary protein （Up）， blood urea nitrogen （Bun）， and serum creatinine （SCr） were measured in each group after 8 consecutive weeks of drug intervention. Enzyme-linked immunosorbent assay was employed to determine the serum levels of ACE1， AngⅡ， and AT1R. Western blot was employed to measure the protein levels of ACE1， AngⅡ， and AT1R in the renal tissue. The pathological and morphological changes of the renal tissue were observed after hematoxylin-eosin （HE） staining， Masson staining， and periodic acid Schiff 's （PAS） staining. The fecal samples of rats in each group were collected for 16S rDNA high-throughput sequencing. ResultCompared with the normal group， the model group showed elevated levels of Up， FBG， Bun， SCr， ACE1， AngⅡ， and AT1R （P<0.01）， serious lesions in the renal tissue， up-regulated protein levels of ACE1， AngⅡ， and AT1R （P<0.01）， increased Firmicutes/Bacteroidetes （F/B） ratio， decreased relative abundance of Lactobacillus， and increased relative abundance of Moralella and Bifidobacteria. Compared with the model group， drug intervention lowered the levels of Bun， SCr， ACE1， AngⅡ， and AT1R （P<0.01） and alleviated the pathological changes in the renal tissue. Chinese medicine and integrated Chinese and western medicine lowered the levels of Up and FBG （P<0.01）， and western medicine and integrated Chinese and western medicine down-regulated the protein levels of ACE1， AngⅡ， and AT1R. In addition， Chinese medicine down-regulated the protein levels of AngⅡ （P<0.01） as well as ACE1 and AT1R （P<0.05）. Chinese medicine and integrated Chinese and western medicine decreased the F/B ratio， and western medicine and Chinese medicine increased the relative abundance of Blautia. Chinese medicine and integrated Chinese and western medicine increased the relative abundance of Lactobacillus， Ruminococcus undetermined genera， and Bifidobacteria， decreased the relative abundance of Moralella， and increased the Chao 1 and Ace indexes （P<0.05）. Compared with the western medicine group， the integrated Chinese and western medicine group showed lowered levels of Up （P<0.01）， Bun （P<0.05）， and ACE1 and AT1R （P<0.01）， down-regulated protein levels of ACE1， AngⅡ， and AT1R （P<0.05）， alleviated pathological changes in the renal tissue， increased relative abundance of Bifidobacteria， and increased Chao 1 and Ace indexes （P<0.05）. ConclusionModified Liuwei Dihuangtang combined with losartan potassium can mitigate renal fibrosis by regulating the ACE1/AngⅡ/AT1R axis， increasing the relative abundance of Lactobacillus and Bifidobacterium， reducing the relative abundance of Moralella， improving the richness and evenness of intestinal flora， and alleviating pathological damage in the renal tissue.

Mechanism of Bushen Yijing Method in Treatment of Oligoasthenozoospermia Based on Intestinal Microbiota / 中国实验方剂学杂志

Oligoasthenozoospermia is the main cause of male infertility， with complex and diverse causes. Currently， there are still some unclear causes of oligoasthenozoospermia in clinical practice， known as idiopathic oligoasthenozoospermia. With the development of high-throughput sequencing technology， it has been found that intestinal microbiota disorder may be an important promoting factor for the onset of oligoasthenozoospermia. Traditional Chinese medicine believes that "deficiency of kidney essence" is the core pathogenesis of oligoasthenozoospermia. In clinical practice， the method of tonifying the kidney and strengthening the essence has a significant therapeutic effect on oligoasthenozoospermia， but its mechanism of action has not been fully elucidated. Based on the basic theories of traditional Chinese medicine and molecular biology research， it has been found that there is a similarity between "kidney essence" and intestinal microbiota. During the onset of oligoasthenozoospermia， the disorder of intestinal microbiota has similarities with the pathogenesis of "deficiency of kidney essence" in traditional Chinese medicine. Moreover， traditional Chinese medicine for tonifying the kidney and strengthening the essence can regulate the disorder of intestinal microbiota， which may be one of the effective mechanisms for the treatment of oligoasthenozoospermia with the Bushen Yijing method. Based on this， this article explored the mechanism of Bushen Yijing method of traditional Chinese medicine in treating oligoasthenozoospermia from the perspective of intestinal microbiota， so as to provide new ideas for the treatment of oligoasthenozoospermia with traditional Chinese medicine.

Pathogenesis of Diabetes from Theory of Spleen Deficiency Causing Diabetes Based on Intestinal Innate Immunity / 中国实验方剂学杂志

In western medicine， the small intestine anatomically belongs to the digestive system and is also an important immune organ of the body. The innate immune system of the small intestine consists of a tissue barrier， innate immune cells， and innate immune molecules. The dysfunction of any part can cause metabolic disorders and eventually lead to diabetes. In the pathogenesis of diabetes， traditional Chinese medicine （TCM） has the theory of ''spleen deficiency causing diabetes''， which points out that the impaired spleen function results in inadequate transformation， impaired essence spread， and turbidity by essence accumulation， which is the core pathological link of blood glucose metabolism disorder in diabetes. In terms of the relationship between the small intestine and the spleen， the theory of TCM holds that the small intestine is located in the abdomen and the abdomen is dominated by the spleen. The digestion， absorption， and endocrine functions of the small intestine are also similar to the functions of spleen in governing movement and transformation and spreading essence by virtue of spleen Qi. Therefore， the anatomical and physiological functions of the small intestine in western medicine are closely related to the spleen in TCM. At the same time， the spleen is closely related to the innate immune function of the small intestine in TCM. The spleen participates in the generation and distribution of defense Qi， and the process of defense Qi playing the external function is similar to the process of the activation of the innate immune response. The spleen is also an important organ involved in fluid metabolism， which can cooperate with the lung and kidney to timely remove turbid fluid from the body. It can also work with the stomach as the hub of Qi ascending and descending and regulate the physiological activities of "clear Yang" and "turbid Yin"， so as to ensure the homeostasis of the internal environment of the body， which is the basis for maintaining the normal function of the innate immunity of the small intestine. Therefore， taking "spleen deficiency causing diabetes" as a bridge， the theory of TCM and western medicine were combined to explain the relationship between small intestinal innate immunity imbalance and the pathogenesis of diabetes from the perspective of TCM， which is helpful to understand the pathogenesis of diabetes in a deeper level and also provide a new perspective and new way for the prevention and treatment of this disease with TCM.

Mechanism of Qingfei Huatan Zhuyu Decoction in Treatment of COPD Based on "Lung and Intestinal Co-treatment" / 中国实验方剂学杂志

ObjectiveTo observe the effect of Qingfei Huatan Zhuyu decoction on the lung and intestinal function of rats with chronic obstructive pulmonary diseases （COPD） and explore the deep-seated mechanism of its embodiment of lung and intestinal co-treatment. MethodA total of 60 Wistar rats were randomly divided into six groups， with 10 rats in each group， and the groups were control group， model group， acute syrup group （10 g·kg-1·d-1）， and low， medium， and high-dose groups （10， 15， 20 g·kg-1·d-1） of Qingfei Huatan Zhuyu decoction. The COPD rat model was established by lipopolysaccharide tracheal drip combined with the smoke inhalation method， and the acute syrup group and the Qingfei Huatan Zhuyu decoction group were administered by gavage with corresponding dose concentrations respectively， while the rest groups were controlled by saline gavage， and the lung function and blood gas indexes of rats were monitored after the last administration. The histopathological changes in the lung and intestine were observed microscopically. The expression of serum interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and secretory immunoglobulin A （IgA） in colon tissue were measured by enzyme-linked immunosorbent assay （ELISA）. The biochemical indexes such as serum diamine oxidase （DAO）， D-lactic acid， and malondialdehyde （MDA） were measured. Immunohistochemistry was used to detect the expression of tight junction protein （Occludin） in rat colon tissue. The expression of F4/80 positive alveolar macrophages in rat lung tissue， and the expression of α-actin （α-SMA） and colonic atresia small band protein-1 （ZO-1） were determined by immunofluorescence. The protein expression of p-NF-κB p65， NF-κB p65， p-p38 MAPK， and p-p38 MAPK and the expression of Occludin and ZO-1 in colon tissue were detected in rat lung tissue by Western blot. ResultCompared with the normal group， the model group had pulmonary dysfunction， reduced forced vital capacity （FVC）， arterial partial oxygen pressure （PaO2）， arterial oxygen saturation （SaO2）， and dynamic lung compliance （Cdyn） （P<0.01）， and the pathological changes in the lung and intestine were obvious. The expressions of IL-6， TNF-α， DAO， D-lactic acid， and MDA in serum were increased （P<0.05，P<0.01）， and the protein expression ratio of p-NF-κB p65/NF-κB p65 and p-p38 MAPK/p38 MAPK in lung tissue was increased. The expression of F4/80 positive macrophages in lung tissue was enhanced. The expression of IgA， Occludin， and ZO-1 in colon tissue decreased （P<0.05，P<0.01）. Compared with the model group， the pulmonary function of the rats in the acute syrup group and groups of Qingfei Huatan Zhuyu decoction was significantly improved， and the FVC， PaO2， SaO2， and Cdyn were increased （P<0.05， P<0.01）. The pathological changes in the lung and intestine were significant. The expressions of IL-6， TNF-α， DAO， D-lactic acid， and MDA in serum were decreased （P<0.05，P<0.01）， and the expressions of F4/80 positive macrophages in lung tissue were decreased （P<0.01）. The protein expression ratio of p-NF-κB p65/NF-κB p65 and p-p38 MAPK/p38 MAPK in lung tissue decreased （P<0.01）， and the expression of IgA， Occludin， and ZO-1 in colon tissue increased （P<0.01）. ConclusionQingfei Huatan Zhuyu decoction can effectively reduce the symptoms of COPD rats， and its mechanism of action is related to inhibiting the inflammatory response of lung tissue and improving the barrier function of the intestinal mucosa.

Improvement effects of limonin on intestinal injury and intestinal flora disturbance in rats with ulcerative colitis and its mechanism / 中国药房

OBJECTIVE To investigate the improvement effects of limonin on intestinal injury and intestinal flora disturbance in rats with ulcerative colitis （UC） and its mechanism. METHODS UC rat models were established， and 70 rats with successful modeling were randomly divided into model group， limonin low-， medium-， and high-dose groups （12.5， 25， 50 mg/kg）， and sulfasalazine group （positive control group，500 mg/kg）， with 14 rats in each group. Another 14 rats were selected as the control group. After modeling， each group was given the corresponding drug or equal amount of normal saline， once a day， for 2 weeks. Twenty-four hours after the last administration， the general condition of rats was observed and the body weight was measured， and colon tissue was collected for colonic mucosal damage index （CMDI） scoring； the levels of interleukin-1β （IL-1β）， IL-6 and tumor necrosis factor-α （TNF-α） in colon tissue were detected； the pathological changes of colon tissue were observed； the protein expressions of Claudin-1， Occludin， ZO-1， high mobility group protein B1 （HMGB1） and receptor for advanced glycation end products （RAGE） in colon tissue were detected； fecal 16S rRNA sequencing was used to detect the relative abundance of zhangxiaxia5287@163.com intestinal microbiota in rats. RESULTS Compared with the control group， the rats in the model group were in poor mental state， with darker fur， irritable mood， disordered arrangement of colon glands， inflammatory cell infiltration， cell necrosis and edema； CMDI score， the levels of IL-1β， IL-6 and TNF-α， protein expressions of HMGB1 and RAGE in colon tissue， the relative abundance of Proteobacteria and Bacteroidetes were significantly increased （P＜0.05）； body weight， the protein expressions of Claudin-1， Occludin and ZO-1 in colon tissue， the relative abundance of Firmicutes in the intestine were significantly decreased （P＜0.05）. Compared with the model group， general situation and pathological damage of colonic tissue in limonin groups were improved， the levels of the above indicators were significantly reversed （P＜0.05）， and in a dose-dependent manner （P＜0.05）； there was no significant difference in various indexes between sulfasalazine group and limonin high-dose group （P＞0.05）. CONCLUSIONS Limonin can improve intestinal injury and intestinal flora disturbance in UC model rats， the mechanism of which may be associated with the down-regulation of HMGB1/RAGE signaling pathway.

Effect of Intestinal Microecology on Diabetic Kidney Disease Based on Yin-Yang Theory / 中国实验方剂学杂志

Diabetic kidney disease （DKD） is the main cause of end-stage renal disease. Its high prevalence， mortality rate， and medical cost bring a heavy economic burden to society and families， and DKD has become one of the most important public health problems. Intestinal microecology is the most important and complex micro-ecosystem in the human body， which is involved in important life activities such as material and energy metabolism， immune system regulation， and signal transduction， thereby maintaining the dynamic balance of the human internal environment. The dynamic balance between the intestinal microecology and the body is essentially a Yin-Yang balance. Once this balance is broken， intestinal microbiota imbalance， intestinal mucosal barrier damage， immune dysfunction， and reduction of metabolite short-chain fatty acids （SCFAs） will occur， which play an important role in the progression of DKD. From the perspective of the Yin-Yang theory of traditional Chinese medicine （TCM）， the imbalance of intestinal microecology in DKD is equivalent to the excessive or insufficient constraint of Yin and Yang， or Yin deficiency affecting Yang， or Yang deficiency affecting Yin， or waning and waxing of Yin and Yang. For different pathogenesis changes， "Yin disease treated through Yang"， "treating Yin for Yang"， or "treating Yang for Yin" methods are adopted to regulate intestinal microbiota， inhibit immune inflammation， protect intestinal mucosal barrier， and increase SCFAs through TCM， thereby reconciling Yin and Yang to achieve the condition where "Yin is at peace and Yang is compact". Based on the Yin-Yang theory， this paper intended to interpret the scientific connotation of TCM in the treatment of DKD with intestinal microecology as the target and TCM in the treatment of DKD by regulating intestinal microecology as the breakthrough point to provide a novel insight for the occurrence and development of DKD and the mechanism of TCM.

Chinese Medicine in Treatment of Ulcerative Colitis by Regulating Intestinal Flora： A Review / 中国实验方剂学杂志

Ulcerative colitis （UC） is a chronic， non-specific inflammatory bowel disease. The pathogenesis of this disease is complex and is attributed to multiple factors. Intestinal mucosal barrier damage is the basic pathological change of UC， and intestinal flora disorder is one of the important characteristics of UC. Intestinal flora plays a key role in the pathological process of UC by regulating intestinal mucosal immunity and inflammatory response to repair the damaged intestinal mucosal barrier. At present， western medicine has the advantages of rapid action onset and significant short-term efficacy， but the curative effect of long-term use is not good， accompanied by many adverse reactions， causing great physical and mental pain to patients. Therefore， it is urgent to explore new treatment methods with definite long-term efficacy and mild adverse reactions. A large number of studies have shown that Chinese medicine can regulate intestinal flora through multiple targets in an all-around way， restore the homeostasis of the flora， and repair the damaged intestinal mucosal barrier， thereby inhibiting the progression of UC. Numerous studies have shown that the active components， monomers， and compounds of Chinese medicine can effectively antagonize UC by regulating the intestinal flora to improve the intestinal mucosal immunity， reduce the inflammatory response of the intestinal mucosa， and restore the normal physiological function of the intestinal mucosal barrier， providing a new strategy for UC prevention and treatment. Although there are some studies of the regulation of intestinal flora by Chinese medicine to prevent and treat UC， those studies have the shortcomings of systematic and comprehensive inadequacy. Therefore， based on the research status of UC， intestinal flora， and Chinese medicine treatment， this study reviewed the relationship between intestinal flora and UC and clarified the key role of intestinal flora in the occurrence and development of UC. At the same time， this paper comprehensively summarized the Chinese medicine that targeted the regulation of intestinal flora for the treatment of UC in the past five years to provide new strategies and ideas for UC treatment.