Lesiones de la vía biliar

La finalidad de esta revisión es mostrar el estado actual de las lesiones de vía biliar (LVB), producidas especialmente durante la colecistectomía laparoscópica. Revisaremos la etiopatogenia, los grados de compromiso biliar, las lesiones vasculares asociadas, las clasificaciones utilizadas y los factores de riesgo. Además la forma como evaluar oportunamente la magnitud de la lesión, tanto en la misma cirugía como en el postoperatorio. Igualmente se muestran las diversas alternativas terapéuticas empleadas. Todo con la finalidad de evitar graves complicaciones.

The purpose of this review is to show the current status of bile duct injury, specially produced during laparoscopic cholecystectomy. We will review etiopathogenesis, degrees of bile commitment, associated vascular lesions, classifications used and risk factors. In addition, how to assess the extent of the injury in a timely manner, both in the same surgery and in the postoperative surgery. The various therapeutic alternatives used are also shown. All in order to avoid serious complications.

Mejoría de la calidad de vida después de la reparación definitiva de la lesión de la vía biliar, evaluada con el cuestionario SF-36 / Improvement on quality of life after bile duct injury repair using the SF-36 Health Survey

RESUMEN Antecedentes: diferentes publicaciones han estudiado la fisiopatología de la lesión de la vía biliar (LVB), pero pocas han investigado los efectos psicosociales y de calidad de vida relacionados con su reparación. Objetivo: comparar la calidad de vida de pacientes antes y después de la reparación definitiva de una LVB. Material y métodos: se usó como instrumento para evaluar la calidad de vida relacionada con la salud (CVRS) el cuestionario de salud SF-36 en una serie de pacientes operados entre diciembre de 2015 y junio de 2019 para la reparación de LVB. Resultados: sobre 48 casos de reparaciones de LVB, contestaron la encuesta 22 (46%). Se compararon los ítems del formulario SF 36: diferencia en la función física, el rol físico, el dolor corporal, la salud general, la vitalidad, la función social, el rol emocional, la salud mental y el ítem de transición de salud, y todos mostraron una mejoría estadísticamente significativa (p < 0,001) después de la reparación. En el análisis univariado se observó que la salud mental se vio afectada por la presencia de una lesión compleja (p = 0,019), el rol físico y el rol emocional antes de la reparación, y mostró relación con el tipo de lesión según Strasberg (p = 0,001 y p = 0,032). Aquellos que asociaron lesión vascular presentaron una asociación negativa con la función física (p = 0,019), la vitalidad (p = 0,033), la salud mental (p = 0,005) y el dolor (p = 0,026) antes de la reparación. Conclusión: la resolución definitiva de la LVB en un centro especializado en patología hepatobiliopancreática mostró producir una significativa mejoría en la calidad de vida.

ABSTRACT Background: Different publications have examined the pathophysiology of bile duct injury (BDI), bur few studies have investigated the effects of BDIs and their subsequent repair on psychosocial and health-related quality of life Objective: The aim of this study was to compare the quality of life of patients before and after definitive BDI repair. Material and methods: The SF-36 Health Survey was used as an instrument to assess health-related quality of life (HRQL) in a series of patients operated on between December 2015 and June 2019 for BDI repair. Results: Of 48 patients who underwent BDI repair, 22 (46%) responded to the survey. The SF-36 items, which includes different domains (physical functioning, physical role functioning, bodily pain, general health, vitality, social functioning, emotional role functioning, mental health, and health transition) were compared. All domains demonstrated statistically significant improvement (p < 0.001) following repair. On univariate analysis, mental health was affected by the presence of a complex injury (p = 0.019), and physical and emotional role functioning before BDI repair were associated with the type of injury of the Strasberg classification (p = 0.001 and p = 0.032, respectively). An associated vascular injury had a negative correlation with physical functioning (p = 0.019), vitality (p = 0.033), mental health (p = 0.005), and pain (p = 0.026) prior to repair. Conclusion: The definitive resolution of BDIs at a center specialized in hepatobiliary and pancreatic surgery resulted in a significant improvement of patients' quality of life.

Duplicación del colédoco asociado a unión biliopancreática anómala: Reporte de caso / Common bile duct duplication associated with anomalous biliopancreatic junction: A case report

Introducción. La duplicación del colédoco es una anomalía congénita poco frecuente. En la mayoría de los casos este defecto se asocia a cálculos en la vía biliar, unión pancreatobiliar anómala, pancreatitis, cáncer gástrico o colangiocarcinoma. Por esta razón, el diagnóstico y el tratamiento temprano son importantes para evitar las complicaciones descritas a futuro. Métodos. Se presenta el caso de una paciente de 30 años, con antecedente de pancreatitis aguda, con cuadro de dolor abdominal crónico, a quien se le realizaron varios estudios imagenológicos sin claro diagnóstico. Fue llevada a manejo quirúrgico en donde se documentó duplicación del colédoco tipo II con unión pancreatobiliar anómala. Resultados. Se hizo reconstrucción de las vías biliares y hepatico-yeyunostomía, con adecuada evolución postoperatoria y reporte final de patología sin evidencia de tumor. Conclusión. El diagnóstico se hace mediante ecografía endoscópica biliopancreática, colangiorresonancia o colangiopancreatografía retrógrada endoscópica. El tratamiento depende de si está asociado o no a la presencia de unión biliopancreática anómala o cáncer. Si el paciente no presenta patología neoplásica, el tratamiento quirúrgico recomendado es la resección del conducto con reconstrucción de las vías biliares.

Introduction. Double common bile duct is an extremely rare congenital anomaly. This anomaly may be associated with bile duct stones, anomalous biliopancreatic junction, pancreatitis, bile duct cancer, or gastric cancers. Thus, early diagnosis and treatment is important to avoid complications. Clinical case. We report a rare case of double common bile duct associated with an anomalous biliopancreatic junction in a 30-year-old female, with prior history of acute pancreatitis, who presented with chronic abdominal pain. She underwent several imaging studies, without clear diagnosis. She was taken to surgical management where duplication of the type II common bile duct was documented with anomalous pancreatobiliary junction. Results. Reconstruction of the bile ducts and hepatico-jejunostomy were performed, with adequate postoperative evolution and final pathology report without evidence of tumor. Conclusion. Diagnosis is usually performed by an endoscopic ultrasound, magnetic resonance cholangiopancrea-tography, or endoscopic retrograde cholangiopancreatography. Treatment depends on the presence of anomalus biliopancreatic junction or concomitant cancer. In cases without associated malignancy, resection of bile duct and biliary reconstruction is the recommended surgical treatment.

Colangiocarcinoma tubulopapilar, una entidad emergente poco frecuente, a propósito de un caso

Objetivo: realizar una revisión bibliográfica y presentación de caso de colangiocarcinoma tubulopapilar. Material y Método: Se revisó la ficha médica y las características clínicas, radiológicas y patológicas del tumor, y la literatura científica respecto al carcinoma tubulopapilar. Caso Clínico: Paciente con ictericia progresiva asociado a baja de peso. El estudio imagenológico muestra amputación del tercio distal del colédoco por tejido de partes blandas, sugerente de colangiocarcinoma. Se realiza endosonografía, arrojando "fragmentos superficiales de adenocarcinoma tubulopapilar". Se realiza duodenopancreatectomía cefálica y, posteriormente, se inicia quimioterapia. Discusión: El colangiocarcinoma es una neoplasia de la vía biliar. Existen diferentes variantes histológicas, entre ellas el colangiocarcinoma tubulopapilar. Su diagnóstico se basa en estudios imagenológicos y anatomopatológicos. El principal hallazgo imagenológico va a depender del patrón de crecimiento tumoral; masiforme, periductal o intraductal. Dentro de los intraductales, se describe un carcinoma biliar con crecimiento tubulopapilar, con fenotipo pancreatobiliar epitelial. En los últimos años han sido de interés por tener mejor pronóstico. Conclusión: El colangiocarcinoma tubulopapilar es una variante histológica poco frecuente del colangiocarcinoma, que se asocia a un mejor pronóstico que otras variantes.

Objective: To conduct a literature review and present a case study of tubulopapillary cholangiocarcinoma. Material and Method: The clinical record and the clinical, radiological, and pathological characteristics of the tumor were reviewed, along with the scientific literature regarding tubulopapillary carcinoma. Case Report: Patient with progressive jaundice associated with weight loss. Imaging studies show amputation of the distal third of the common bile duct by soft tissue, suggestive of cholangiocarcinoma. Endosonography was performed, yielding "superficial fragments of tubulopapillary adenocarcinoma." Subsequently, a cephalic duodenopancreatectomy is performed, followed by chemotherapy. Discussion: Cholangiocarcinoma is a neoplasm of the biliary tract. There are different histological variants, including tubulopapillary cholangiocarcinoma. Its diagnosis is based on imaging and pathological studies. The main imaging finding will depend on the pattern of tumor growth: mass-forming, periductal, or intraductal. Among the intraductal types, a biliary carcinoma with tubulopapillary growth and an epithelial pancreatobiliary phenotype has been described. In recent years, they have been of interest due to their better prognosis. Conclusion: Tubulopapillary cholangiocarcinoma is a rare histological variant of cholangiocarcinoma that is associated with a better prognosis than other variants.

Panlitiasis biliar en un paciente masculino de 60 años con anastomosis bilioentérica colecistectomizado hace 13 años. Reporte de caso / Biliary panlitiasis in a 60-year-old male patient who un-derwent a bilioenteric anastomosis and cholecystectomy 13 years ago. Case report

Introducción: La panlitiasis se define como la presencia de múltiples cálculos en el trayecto de la vía biliar. El manejo consiste en realizar una colangiopancreatografía retrógrada endoscópica (CPRE), la exploración de la vía biliar o la anastomosis biliodigestiva (ABD), ya sea coledocoduodenoanastomosis o hepaticoyeyunoanastomosis.Objetivo: Describir el caso clínico de un paciente con panlitiasis biliar, abordando la presentación clínica, los métodos diagnósticos, el tratamiento y la evolución, con el propósito de ofrecer un recurso sólido a la comunidad médica.Presentación del caso: Se presenta un paciente de 60 años colecistectomizado hace 13 años portador de anastomosis bilioentérica con panlitiasis recidivante, se realizó un lavado de la vía biliar con salida de cálculos y pus del interior, finalmente se colocó una sonda Kehr junto con tratamiento clínico. Presentó una evolución favorable. Discusión: Este caso reveló una panlitiasis a la exploración de las vías biliares bajo visión endoscópica, a pesar de que no se encontró obstrucción, el paciente tenía antecedente de colecistectomía y contaba con una derivación hepático-yeyunal por lesión iatrogénica. La decisión del tratamiento debe ser multidisciplinaria ya que cada caso es único y dependerá de las características del paciente y las condiciones clínicas individuales.Conclusiones: La panlitiasis coledociana recidivante requirió un control farmacológico estricto para evitar recurrencia y la subsecuente exploración de la vía biliar que incrementa la morbimortalidad del paciente. Es importante el seguimiento médico continuo del paciente y la predisposición con la que cuenta para la formación de litos, pudiendo ser prevenidos, identificados y tratados de manera oportuna

Introduction: Panlithiasis is define as the presence of multiple stones in the biliary tract that is classified as primary, secondary, or mixed according to the origin of the stones. Management consists of endoscopic retrograde cholangiopancreatography (ERCP), exploration of the biliary tract, or biliodigestive anastomosis (BDA), either choledochoduodenostomy or hepaticojejunostomy. Objective: Describe the clinical case of a patient with biliary panlithiasis, addressing the cli-nical presentation, diagnostic methods, treatment and evolution, with the purpose of offering a solid resource to the medical community.Case Presentation: We present a 60-year-old male patient who underwent cholecystectomy 13 years ago and has a bilioenteric anastomosis with recurrent panlithiasis. Biliary lavage was performed with the output of stones and pus from the inside. Finally, a Kehr tube was placed along with clinical treatment. The patient showed a favorable outcome.Discussion: This case revealed a panlithiasis upon exploration of the biliary tract under endoscopic vision. Despite finding no obstruction, the patient had a history of cholecystectomy and a hepatic-jejunal diversion due to iatrogenic injury. The treatment decision should be multidisciplinary, as each case is unique and depends on the patient's characteristics and individual clinical conditions.Conclusions: Recurrent choledocholithiasis required strict pharmacological control to prevent recurrence and subsequent exploration of the biliary tract, which increases patient morbidity and mortality. Continuous medical follow-up of the patient and the predisposition with which they have for the formation of stones is important. These can be prevented, identified, and treated in a timely manner.

Íleo biliar como causa de obstrucción intestinal en una paciente de 38 años con antecedentes de tres embarazos y cesárea: reporte de caso / Gallstone ileus-induced intestinal obstruction in a 38-year-old patient with a history of three pregnancies and cesarean section: a case report

RESUMEN La obstrucción intestinal inducida por íleo biliar es una condición rara pero significativa que se produce cuando una piedra en la vesícula se aloja en el tracto gastrointestinal. Entre los principales factores de riesgo para la obstrucción intestinal inducida por íleo biliar se encuentran la edad avanzada, el sexo femenino, la diabetes, los antecedentes de enfermedad biliar como cálculos biliares, así como procedimientos quirúrgicos previos relacionados con la vesícula biliar, como la colecistectomía. También el embarazo es un factor de riesgo conocido para la enfermedad de los cálculos biliares. En este artículo, se presenta el caso de una paciente de 38 años con antecedentes de tres cesáreas previas y sin comorbilidades aparentes. Antes de acudir al departamento de emergencias, la paciente experimentó dolor abdominal con cólico moderado en la parte inferior del abdomen durante dos días. El examen físico reveló sensibilidad abdominal difusa, predominantemente en la fosa ilíaca derecha, junto con signos de irritación peritoneal. Los análisis de laboratorio mostraron un recuento de leucocitos de 11 490 células/μl y una neutrofilia del 85,6 %. Después de una laparotomía exploratoria, se confirmó el diagnóstico sospechado de íleo biliar por cálculo. Se realizó una enterolitotomía y la paciente mostró un progreso posoperatorio favorable. En conclusión, es importante considerar la obstrucción intestinal inducida por íleo biliar en pacientes con síntomas relevantes y antecedentes médicos. Este reporte de caso subraya la importancia de considerar la obstrucción intestinal inducida por íleo biliar en pacientes con síntomas gastrointestinales y antecedentes de embarazo. El diagnóstico temprano y la intervención son cruciales para prevenir complicaciones graves.

ABSTRACT Gallstone ileus-induced intestinal obstruction is a rare but significant condition that occurs when a gallstone becomes lodged in the gastrointestinal tract. Major risk factors for gallstone ileus-induced intestinal obstruction include older age, female sex, diabetes, history of gallbladder disease such as gallstones, as well as previous gallbladder-related surgical procedures such as cholecystectomy. Pregnancy is also a known risk factor for gallstone disease. We present the case of a 38-year-old patient with a history of three cesarean sections and no apparent comorbidities. Prior to her visit to the emergency department, the patient experienced moderate colicky abdominal pain in the lower abdomen for two days. The physical examination revealed diffuse abdominal tenderness, predominantly in the right iliac fossa, along with signs of irritation of the peritoneum. Laboratory tests showed a leukocyte count of 11,490 cells/µl and neutrophilia of 85.6 %. Following an exploratory laparotomy, the suspected diagnosis of gallstone ileus was confirmed. An enterolithotomy was performed, and the patient experienced good post-surgical progress. In conclusion, it is important to consider gallstone ileus-induced intestinal obstruction among patients with relevant symptoms and medical history. This case report highlights the importance of considering gallstone ileus-induced intestinal obstruction among patients with gastrointestinal symptoms and a history of pregnancy. Early diagnosis and intervention are crucial to prevent serious complications.

Role of apical sodium-dependent bile acid transporter in hepatobiliary diseases / 临床肝胆病杂志

Apical sodium-dependent bile acid transporter （ASBT） is a key transporter responsible for intestinal reabsorption of bile acid and plays an important role in maintaining bile acid and cholesterol homeostasis， and its expression is regulated by various factors including transcription factors， nuclear receptors， and intestinal microflora. The abnormal expression and function of ASBT can lead to disorders in the metabolism of bile acid and cholesterol， causing a variety of hepatobiliary diseases. At present， ASBT has attracted wide attention as a therapeutic target. This article elaborates on the biological characteristics and expression regulation mechanism of ASBT and reviews the role of ASBT in hepatobiliary diseases， in order to provide a new direction for the treatment of related diseases.

Jiedu Tongluo Tiaogan Prescription Protects Pancreatic β Cell by Targeting NLRP3 Inflammasome via TGR5/cAMP Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the intervention effect of Jiedu Tongluo Tiaogan prescription （JTTP） in protecting pancreatic β cells by targeting the bile acid Takeda G protein-coupled receptor 5 （TGR5）/cyclic adenosine monophosphate （cAMP） signaling pathway against NOD-like receptor protein 3 （NLRP3） inflammasome. MethodThirty-two male SPF-grade db/db mice were randomly divided into the model group， low-dose JTTP group （3.6 g·kg-1）， high-dose JTTP group （7.2 g·kg-1）， and metformin group （0.2 g·kg-1）. Eight db/m mice were assigned to the blank control group. The mice were treated with drugs for 8 weeks， and fasting blood glucose （FBG） was measured every 2 weeks. Oral glucose tolerance tests （OGTT） were conducted after the last administration. Enzyme-linked immunosorbent assay （ELISA） was performed to detect fasting insulin （FINS）， and the homeostasis model assessment of β-cell function （HOMA-β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and IL-1β levels were calculated. Hematoxylin-eosin （HE） staining was used to observe pathological changes in mouse pancreatic tissue. Immunofluorescence was performed to detect insulin expression in mouse pancreatic tissue. Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were used to detect the expression of proteins and mRNAs of key targets in the TGR5/cAMP signaling pathway and NLRP3 inflammasome. ResultCompared with blank group， FBG， OGTT， FINS， IL-6， TNF-α and IL-1β in model group were significantly increased （P<0.01）. Compared with model group， after 6 weeks of drug treatment， FBG level in JTTP group and metformin group decreased significantly （P<0.01）. The results of OGTT experiment showed that compared with model group， the blood glucose levels of mice in each administration group were decreased at all time points （P<0.05， P<0.01）， and the levels of FINS， TNF-α and IL-6 in JTTP dose groups and metformin group were significantly decreased. The level of IL-1β in JTTP high-dose group and metformin group was significantly decreased （P<0.01）. Pancreatic pathology showed that the islets in the model group were irregular in shape， uneven in distribution， and showed signs of atrophy. The prognosis of JTTP was that the cell count increased and the boundary was clearer. Immunofluorescence results showed that the islet cells in the blank group were arranged in an orderly and full shape with appropriate insulin secretion， while the islet cells in model group were distorted in shape， atrophy in structure and less insulin secretion. The insulin content of mice in JTTP and metformin group was significantly increased. Compared with blank group， mRNA expressions of NLRP3， apoptosis-related spot-like protein （ASC） and Caspase-1 in pancreatic tissues of model group were significantly increased （P<0.01）. Compared with model group， JTTP high-dose group and metformin group promoted the up-regulation of TGR5 and cAMP mRNA， and down-regulated the mRNA expressions of NLRP3， ASC and Caspase-1 （P<0.05， P<0.01）. Compared with blank group， the expression of TGR5 protein in model group was significantly decreased （P<0.01）. Compared with model group， TGR5 protein in JTTP high-dose group and metformin group was significantly increased （P<0.01）.

Analysis on Metabolites and Metabolic Pathways of Harmine in Rats by UPLC-Q-TOF-MS / 中国实验方剂学杂志

ObjectiveUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was used to identify the metabolites of harmine in rats， in order to explore the differences in distribution of metabolites in rats after single dose（40 mg·kg-1） intragastric administration of harmine， as well to speculate the metabolic pathways. MethodSD rats were given a single dose of harmine by intragastric administration. Plasma， bile， urine and feces samples were collected after administration， and the samples were processed for determination by UPLC-Q-TOF-MS. The separation was performed on an ACQUITY UPLC™ HSS T3 columu（2.1 mm×100 mm， 1.8 μm） with acetonitrile（A）-0.1% formic acid aqueous solution（B） as mobile phase for gradient elution（0-2 min， 5%A； 2-9 min， 5%-35%A； 9-9.5 min， 35%-100%A； 9.5-12 min， 100%A； 12-12.5 min， 100%-5%A； 12.5-14 min， 5%A）， the mass spectra were obtained in positive ion mode with electrospray ionization（ESI）， the scanning range was m/z 50-1 200. The metabolites of harmine were identified based on the information of the obtained compounds and the literature data， and the metabolic pathways were hypothesized. ResultA total of 42 compounds（harmine and its metabolites） were identified in rats， including 27 in plasma， 17 in bile， 26 in urine and 13 in feces. The metabolic pathways involved in these 42 metabolites included monohydroxylation， dihydroxylation， demethylation， glucuronidation and sulfation. ConclusionHarmine can undergo phase Ⅰ and phase Ⅱ metabolic reactions in rats， and the prototype drug is metabolized rapidly in vivo， and the metabolites are mainly excreted by the kidneys， which can provide a reference basis for the pharmacodynamics and material basis of harmine.

Research progress on anatomic vascular reconstruction in rat models of orthotopic liver transplantation / 器官移植

Establishment of rat models of liver transplantation provides an ideal animal model for resolving the problems of postoperative complications and perioperative treatment of liver transplantation. With in-depth study of the establishment of rat models of liver transplantation, classic "two-cuff" technique has been gradually employed. However, poor surgical field, vascular torsion, biliary tract injury and long anhepatic phase remain unresolved in the process of liver transplantation using traditional techniques. At present, the rat models of liver transplantation at home and abroad are modified mainly from the reconstruction of four vital anatomic structures including the suprahepatic inferior vena cava, portal vein, infrahepatic inferior vena cava and bile duct. Therefore, the latest progress in the reconstruction of the suprahepatic inferior vena cava, portal vein, infrahepatic inferior vena cava and bile duct was reviewed, aiming to provide reference for the establishment of rat models of liver transplantation and promote further development of liver transplantation techniques.

Progress on the relationship between fecal bile acid levels and different defecation frequency in children / 国际儿科学杂志

Bile acids can be categorized into primary bile acids，which are synthesized directly in liver cells，and secondary bile acids，which are formed after decomposition by intestinal bacteria. The intestinal flora is diverse and widely used，which is closely related to various functions and diseases in the human body. As one of the main metabolites of intestinal flora，bile acids have a close bidirectional regulation between them.Current research has shown a clear correlation between fecal bile acid levels and changes in gastrointestinal function.This paper will review the relationship between fecal bile acid levels and different defecation frequency in children from the perspective of changes in intestinal bile acids under diarrhea and constipation symptoms，and will provide a research direction for further exploration of the effects of different metabolites based on the composition of bile acids on defecation frequency.

Association of Serum Levels of Trace Elements in Early Pregnancy with Bile Acid Metabolism and Gestational Diabetes Mellitus:A Nested Case-Control Study / 华中科技大学学报(医学版)

Objective To explore the association between serum trace element levels in early pregnancy and gestational dia-betes mellitus(GDM),and the mediating effect of bile acid metabolism changes in this association.Methods A nested case-con-trol study was designed based on the Guangxi Zhuang Birth Cohort.A total of 248 pregnant women(case group=124,control group=124)were included from June 2015 to July 2019 in Nanning city.The concentrations of 8 trace elements and 31 bile acids in serum were measured in early pregnancy.Conditional logistic regression and BKMR models were used to analyze the associa-tion and combined effect between trace elements and GDM risk,respectively.Orthogonal partial least squares-discriminant anal-ysis(OPLS-DA)was used to screen potential bile acid biomarkers associated with GDM,and then conditional logistic regression was used to determine the association between specific bile acid levels and GDM risk.Multiple linear regression was used to e-valuate the association of serum trace element concentrations with differential bile acid metabolites.Mediation analysis was used to evaluate the mediating role of bile acids in the relationship between trace element exposure and GDM.Results After adjus-ting for confounding factors,serum vanadium(V)was found to be positively associated with the risk of GDM,while chromium(Cr),manganese(Mn),zinc(Zn),selenium(Se)and molybdenum(Mo)were negatively correlated with the risk of GDM(all P＜0.05).The OPLS-DA model and conditional Logistic regression analysis showed that taurocholic acid(TCA),glycochenodeoxy-cholic acid 3-sulfate(GCDCA-3S),glycochenodeoxycholic acid-3-O-β-glucuronide(GCDCA-3Gln),glycoursodeoxycholic acid-3-sulfate(GUDCA-3S),taurodeoxycholic acid-3-sulfate(TDCA-3S),and chenodeoxycholic acid(CDCA)might be potential bile acid metabolic markers of GDM(all P＜0.05).The concentrations of multiple trace elements were also significantly correlated with the levels of specific bile acids(all P＜0.05).Mediation analysis showed that GCDCA-3Gln and TCA mediated the associa-tion between serum Zn and Se and GDM risk,respectively(all P＜0.05).Conclusion Serum trace elements such as V and Cr are significantly associated with the risk of GDM in early pregnancy,and changes in bile acid metabolism may precede the occur-rence of GDM.It is suggested that the effect of trace elements on the metabolism of bile acids,especially conjugated bile acids,may be one of the mechanisms affecting the risk of GDM.

Role and mechanism of intestinal flora metabolites in obesity regulation / 中国组织工程研究

BACKGROUND:Gut microbiota is closely related to host energy balance and metabolism.The metabolites of intestinal flora can regulate the occurrence and development of obesity and can be a new target for the prevention and treatment of obesity. OBJECTIVE:To summarize the interaction between the intestinal flora and obesity,as well as the specific mechanism underlying regulation of obesity by metabolites of intestinal flora,thereby providing a new reference and basis for the prevention and treatment of obesity. METHODS:"Intestinal microbiota,intestinal bacteria,intestinal microbiota metabolites,short-chain fatty acids,bile acids,ipopolysaccharide,trimethylamine N-oxide,medium-chain fatty acids,tryptophan derivatives,obesity"were used as search terms in Chinese and English.Literature related to obesity from 1990 to 2022 was retrieved in PubMed and CNKI databases.According to inclusion and exclusion criteria,88 articles were finally selected. RESULTS AND CONCLUSION:Intestinal flora is closely related to the occurrence and development of obesity.For example,changes in the Firmicutes to Bacteroidetes ratio can be used as a biomarker for the diagnosis of obesity,and the occurrence of obesity can be delayed by the colonization of probiotics such as Bifidobacterium breve,Lactobacillus and Akkermansia.Intestinal flora is mainly mediated by the metabolites of intestinal flora to participate in the regulation of obesity.For example,short-chain fatty acid can regulate adipogenesis by regulating signaling pathways such as G protein-coupled receptors 41,43 and peroxisome proliferator-activated receptor γ,thus delaying the occurrence and development of obesity.Bile acids can increase insulin sensitivity and body energy expenditure by promoting the activation of G protein-coupled receptor 5 and farnesol X receptor.In addition,lipopolysaccharide,trimethylamine oxide,medium-chain fatty acids and tryptophan derivatives are also widely involved in the occurrence and development of obesity through various signaling pathways.Further studies have found that metabolites of the same bacterial community exert heterogeneous effects in the specific process of regulating obesity via different signaling pathways.For example,under the influence of high-fat diet,acetic acids can activate the parasympathetic nervous system,leading to hyperphagia and liver insulin resistance and thus accelerating the physiological course of obesity.

Anatomic classification and reconstruction of right intrahepatic bile duct in the donor liver of split liver trans-plantation / 中华消化外科杂志

Objective:To investigate the anatomic classification and reconstruction of right intrahepatic bile duct in the donor liver of split liver transplantation (SLT).Methods:The retrospective and descriptive study was constructed. The clinical data of 85 patients who underwent SLT in the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to January 2022 were collected. There were 65 males and 20 females, aged 45(range, 1-82)years. Observation indicators: (1) surgical conditions; (2) anatomy of right intrahepatic bile duct; (3) bile duct reconstruction; (4) postoperative biliary complications; (5) follow-up. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range) or M( Q1, Q3).Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Results:(1) Surgical conditions. Of the 85 donor livers, 11 donor livers were split between the left and right hemilivers, and 74 donor livers were split between the classic right trilobe and left lateral lobe. The cold ischemia time of 85 donor livers was 291(273, 354)minutes, and the operation time, anhepatic phase time and volume of intraoperative blood transfusion of 85 recipients were (497±97)minutes, 51(40, 80)minutes and 8(7, 12)U. (2) Anatomy of right intrahepatic bile duct. Of the 85 donor livers, there were 47 donor livers with classic bile duct anatomical model (type 1), of the ratio as 55.3%(47/85), and 38 donor livers with anatomical variants, of the ratio as 44.7%(38/85). Of the 38 donor livers with anatomical variants, 7 donor livers were type 2, 16 donor livers were type 3a, 2 donor livers were type 3b, 2 donor livers were type 3c, 1 donor liver was type 4, 3 donor livers were type 5a, 4 donor livers were type 5b, 3 donor livers were type 6. For bile duct splitting patterns of the 85 donor livers, 84 donor livers were split with the main trunk of common hepatic duct preserving in the right hemiliver or right trilobe, and 1 donor liver were treated with complete left and right hemiliver splitting to preserve the main trunk of the common hepatic duct in the left hemiliver and the right hemiliver in the right hepatic duct (type 1 bile duct anatomical model). There were 84 donor livers with only one bile duct opening, and 1 donor liver with two bile duct openings (type 3c bile duct anatomical model). (3) Bile duct reconstruction. Of the 85 recipients, there were 69 recipients with common bile duct end-to-end anastomosis to common bile duct of donor liver (38 donor livers with type 1 bile duct anatomical model, 5 donor livers with type 2 bile duct anatomical model, 14 donor livers with type 3a bile duct anatomical model, 2 donor livers with type 3b bile duct anatomical model, 1 donor liver with type 4 bile duct anatomical model, 3 donor livers with type 5a bile duct anatomical model, 4 donor livers with type 5b bile duct anatomical model, 2 donor livers with type 6 bile duct anatomical model), 11 recipients with jejunum anastomosis to common bile duct of donor liver (7 donor livers with type 1 bile duct anatomical model, 2 donor livers with type 2 bile duct anatomical model, 1 donor liver with type 3c bile duct anatomical model, 1 donor liver with type 6 bile duct anatomical model), 3 recipients with jejunum anastomosis to common hepatic duct of donor liver (1 donor liver with type 1 bile duct anatomical model, 2 donor livers with type 3a bile duct anatomical model), 1 recipient with jejunum anastomosis to right hepatic duct of donor liver (type 1 bile duct anatomical model), 1 recipient with common hepatic duct end-to-end anastomosis to right posterior branch of donor liver combined with jejunum of the recipient Roux-en-y anastomosis to common hepatic duct of donor liver (type 3c bile duct anatomical model). (4) Postoperative biliary complications. Of the 85 recipients, 6 cases had postoperative biliary complications, with an incidence of 7.1% (6/85). Of the 6 recipients with postoperative biliary complications, there were 5 recipients with donor liver with type 1 bile duct anatomical model, including 3 cases undergoing postoperative biliary stricture with biliary leakage and 2 cases undergoing postoperative biliary anastomotic stricture, 1 recipient with donor liver with type 3b bile duct anatomical model and undergoing postoperative biliary anastomotic stricture and bile leakage in the liver section. Cases with biliary complications were 5 in the 47 recipients with donor liver with classic bile duct anatomical model and 1 in the 38 recipients with donor liver with anato-mical variants, showing no significant difference between them ( P>0.05). (5) Follow-up. There were 83 recipients receiving followed up for 52(12,96)months. During the follow-up period, 2 recipients died due to non-biliary complication factors (1 donor liver with type 1 bile duct anatomical model and 1 donor liver with 3a bile duct anatomical model). Conclusion:The anatomical classification of right intrahepatic bile duct of donor liver in SLT is mainly classical bile duct anatomical model, and the bile duct reconstruction scheme is mainly common bile duct of donor liver end-to-end anasto-mosis to common bile duct of recipient.

Prognosis of congenital bile duct cysts after cyst resection and risk factors analysis of postoperative biliary calculus / 中华肝胆外科杂志

Objective:To study the prognosis of congenital bile duct cysts following cyst resection, and to analyze the risk factors associated with the development of postoperative biliary calculus.Methods:Clinical data of 149 patients with congenital bile duct cysts undergoing surgery in the First Affiliated Hospital of Nanjing Medical University from May 2004 to January 2022 were retrospectively analyzed, including 59 males and 90 females, with a median age of 32 (21, 47) years old. Patients were divided into two groups: the stone group ( n=51, biliary calculus occurred during the follow-ups after surgery) and non-stone group ( n=98). Clinical data such as gender, age, medical history, cyst type, biliary calculus, anastomotic stenosis and occurrence of cancer were compared. All patients were followed up via telephone consultations. A logistic regression analysis was used to identify the risk factors associated with the occurrence of biliary calculus after surgery. Results:The duration of the follow-ups was 120 (24, 211) months. The observed incidence of postoperative biliary calculus, anastomotic stricture, and cancer in the patients were 34.2% (51/149), 8.7% (13/149), and 4.7% (7/149), respectively. The logistic regression analysis indicated that incomplete cyst resection ( OR=3.332, 95% CI: 1.221-9.094) and postoperative anastomotic stenosis ( OR=13.300, 95% CI: 2.586-68.401) were associated with a higher risk of biliary calculus formation after cystectomy (all P<0.05). Conclusion:Patients with congenital bile duct cysts suffer a high risk of biliary calculus formation after cystectomy. The residual cyst and postoperative anastomotic stenosis are independent risk factors for biliary calculus after surgery.

The application of indocyanine green fluorescence imaging in laparoscopic cholecystectomy for Mirizzi syndrome types Ⅱ and Ⅲ / 中华肝胆外科杂志

Objective:To analyze the clinical value of indocyanine green (ICC) fluorescence imaging in Mirizzi syndrome type Ⅱ-Ⅲ laparoscopic cholecystectomy (LC).Methods:A retrospective analysis was performed on 80 patients diagnosed with Mirizzi syndrome types Ⅱ-Ⅲ who underdoing LC in Affiliated Hospital of Liaoning University of Traditional Chinese Medicine from October 2018 to February 2022, including 32 males and 48 females, aged (63.5±6.9) years. Patients were divided into two groups based on whether ICG fluorescence imaging technology was used, the control group ( n=38) that patients were treated with conventional LC and the experimental group ( n=42) patients were treated with LC guided by ICG fluorescence imaging. In the experimental group, the extrahepatic bile duct was identified by ICG fluorescence imaging during LC, and ICG was injected intraoperally to determine the reserved blood flow of gallbladder flap for fluorescence imaging and determine the resection line. Operation time, intraoperative blood loss, conversion rate of laparotomy and postoperative complications (bile leakage, incision infection, etc.) were compared between the two groups. Intraoperative fluorescence imaging and determination of the modified resection line of reserved gallbladder were analyzed in the observation group. Results:There was no significant difference in age, male proportion, type of Mirizzi syndrome and conversion rate of laparotomy between the two groups (all P>0.05). In the observation group, the operative time was (208.7±32.0) min, the intraoperative blood loss was (50.5±23.8) ml, and the biliary leakage was 7.1% (3/42), which was lower than that in the control group (228.2±33.9) min, (73.8±31.0) ml, 26.3% (10/38). The differences were statistically significant (all P<0.05). Of 37 cases (88%) showed common hepatic duct and common bile duct successfully in the observation group. In the observation group, ICG fluorescence imaging was used to determine the gallbladder resection line in 8 cases (19.0%). The gallbladder flap without fluorescence imaging was removed. Conclusion:ICG fluorescence imaging in LC for Mirizzi syndrome patients can identify the common bile duct and hepatic duct to guide surgical resection, determine the gallbladder flap resection line, reduce postoperative bile leakage and bleeding, and accelerate the surgical progress.

Effects of coenzyme Q10 on bile acid metabolism, obesity, and related lipid metabolism disorders in high-fat diet mice / 中华内分泌代谢杂志

Objective:To explore the effects of coenzyme Q10(CoQ10) on high-fat diet-induced obesity, lipid disorders, and bile acid metabolism in mice.Methods:Eight-week-old C57BL/6J mice were randomly divided into control group(regular chow), high-fat diet group(45% high-fat chow), and CoQ10 intervention group(45% high-fat chow+ 100 mg·kg -1·d -1CoQ10) based on their body weights according to the randomized block design. The body weight and food intake of mice in each group were collected. The levels of serum total cholesterol, triglyceride, low density lipoprotein-cholesterol, high density lipoprotein-cholesterol, alanine aminotransferase, and aspartate aminotransferase were detected. The contents of 17 bile acids in serum, liver, and colon contents of mice were detected by ultra-performance liquid chromatography-tandem mass(UPLC-MS/MS). The protein expressions of cholesterol 12α-hydroxylase(CYP8B1) and oxysterol 7α-hydroxylase(CYP7B1) in liver were detected by Western blotting. Results:CoQ10 significantly reduced body weight and ameliorated lipid metabolism disorders in mice fed a high-fat diet. Compared with the control group, serum total bile acid levels were reduced in the high-fat diet group( P<0.05); CoQ10 intervention elevated serum and colonic total bile acid levels( P=0.021, P=0.014) and increased liver, colon, and serum deoxycholic acid and ursodeoxycholic acid levels( P<0.05) in the mice compared with the high-fat diet group. Both colonic and serum deoxycholic acid levels in the CoQ10 intervention group were negatively correlated with body weights( P=0.024, P=0.019), and colonic deoxycholic acid and total cholesterol levels were also negatively correlated( P=0.006). CoQ10 increased the expression of CYP8B1 and CYP7B1 proteins in the liver of mice. Conclusion:CoQ10 can modulate bile acid metabolism in high-fat diet-fed mice and alleviate their obesity and lipid metabolism disorders.

Synchronous laparoscopic cholecystectomy combined with laparoscopic common bile duct exploration or combined with endoscopic sphincterotomy for gallstones with common bile duct stones / 中华普通外科杂志

Objective:To compare the recurrence of common bile duct stones (CBDS) in patients with gallstones and concurrent CBDS treated by two surgical approaches: synchronous laparoscopic cholecystectomy (LC) combined with laparoscopic common bile duct exploration (LCBDE) (LC+LCBDE) and synchronous LC combined with intraoperative endoscopic sphincterotomy (IO-EST) (LC+IO-EST).Methods:From Apr 2013 to Apr 2020, the clinical data of 903 patients with gallstones with CBDS who were admitted to the Clinical Medical College, Yangzhou University were retrospectively analyzed.Results:Based on the chosen surgical method, we categorized 389 cases into group A (LC+LCBDE) and 514 cases into group B (LC+IO-EST). Our findings revealed that group A had a significantly lower rate of CBDS recurrence and re-recurrent CBDS compared to group B (4.4% vs. 8.4%, P=0.024; 0.8% vs. 3.1%, P=0.010). Moreover, Logistic regression analysis after inverse probability of treatment weighting, revealed that the surgical approach implemented in group A was an independent protective factor of recurrent CBDS and second recurrence of CBDS ( OR=0.482, 95% CI: 0.365-0.637, P<0.001; OR=0.118, 95% CI:0.080-0.173, P<0.001). Conclusion:LC+LCBDE is an optimal treatment option to LC+IO-EST for patients with gallstones combined with CBDS and common bile duct ≥8 mm.

Mechanism of bis（2-ethylhexyl） phthalate in inducing cholestasis and liver injury in mice / 临床肝胆病杂志

ObjectiveTo investigate the mechanism of bis（2-ethylhexyl） phthalate （DEHP） in inducing cholestasis and liver injury in mice. MethodsIn the in vivo experiment， adult female ICR mice were randomly divided into control group （corn oil） and DEHP group （200 mg/kg/d）， and a model of cholestasis was established by intragastric administration for 4 weeks. After blood and liver tissue samples were collected from all mice， a biochemical analyzer was used to measure the level of total bile acid （TBA） in serum and the liver， and a microplate reader was used to measure alkaline phosphatase （ALP） and gamma-glutamyl transpeptidase （GGT）； HE staining was used to observe the pathological changes of the liver； RT-PCR was used to measure the mRNA expression levels of the inflammatory factors interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the liver； liquid chromatography/triple quadrupole mass spectrometry was used to measure the bile acid profile in the liver of mice. In the in vitro experiment， AML-12 mouse hepatocytes were cultured and treated with DEHP （250 µmol/L）， DCA （125 µmol/L）， and CDCA （125 µmol/L） for 24 hours， and RT-PCR was used to measure the mRNA expression levels of the inflammatory cytokines IL-1β， IL-6， and TNF-α. The independent-samples t test was used for comparison of continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the LSD-t test was used for further comparison between two groups. ResultsThe in vivo experiment showed that compared with the control group， the DEHP group had significant increases in the serum levels of TBA， ALP， and GGT and the level of TBA in the liver （the t values are respectively -4.396， -5.109， -8.504， -3.792 and -7.974， all P<0.05，）. Compared with the control group， the DEHP group had significant increases in cholic acid， chenodeoxycholic acid， taurocholic acid， deoxycholic acid， and ursodeoxycholic acid （the t values are respectively -2.802， -3.177， -2.633， -2.874 and -2.311， all P<0.05）. HE staining of the liver showed that the mice in the DEHP group had enlargement of the portal area， bile duct deformation， inflammatory cell infiltration around the bile duct， and significant increases in the mRNA expression levels of the inflammatory factors IL-1β， IL-6， and TNF-α in the liver （the t values are respectively -2.539， -2.823 and -4.636， all P<0.05）. The in vitro experiment showed that the actual difference in hepatocyte viability after 0-1 000 µmol/L DEHP treatment does not exceed 15%， but there were significant increases in the mRNA expression levels of the inflammatory cytokines IL-1β， IL-6， and TNF-α after treatment with DEHP at different concentrations of 125 µmol/L， 250 µmol/L， and 500 µmol/L （all P<0.05）. Compared with DEHP stimulation alone， the combined stimulation of CDCA and DEHP upregulates the cytokine in hepatocyte IL-1β mRNA levels （P<0.01）； the combined stimulation of DCA and DEHP can significantly increase the cytokine in hepatocyte IL-1β and IL-6 mRNA levels （all P<0.01）. ConclusionDEHP exposure can cause cholestasis and induce liver inflammation in mice， possibly by promoting the production of toxic bile acids and the secretion of inflammatory factors.

Exploring Synergistic Mechanism of Processing with Vinegar on Olibanum in Treatment of Ulcerative Colitis Based on Intestinal Flora / 中国实验方剂学杂志

ObjectiveTo explore the improving effects and its synergistic mechanism of Olibanum before and after processing with vinegar on glycodesoxycholic acid（GDCA） intervention in mice with ulcerative colitis（UC） based on the perspective of intestinal flora. MethodC57BL/6J male mice were randomly divided into the normal group， model group， GDCA group， Olibanum group（1.5 g·kg-1） and vinegar-processed Olibanum（1.5 g·kg-1） group， with 6 mice in each group. Mice in the normal group drank water freely， and mice in the other groups were given 2% dextran sulfate sodium（DSS） periodically to establish a UC mouse model. During the modeling， GDCA group， Olibanum group and vinegar-processed Olibanum group were intervened by intraperitoneally injection of GDCA（0.05 g·kg-1）. From the 13th day after modeling， Olibanum group and vinegar-processed Olibanum group were given the corresponding doses of drugs by gavage， once a day， for 36 d. During this period， the body mass of mice was recorded and the disease activity index（DAI） was assessed. On day 48， faeces were collected for 16S rRNA and metagenomic sequencing to analyse changes in intestinal flora. On the 49th day， hematoxylin-eosion（HE） staining was used to observe the colon histological lesions， enzyme-linked immunosorbent assay（ELISA） was used to determine serum levels of tumour necrosis factor-α（TNF-α）， interleukin（IL）-1β and IL-6， and Spearman correlation analysis was used to explore the correlation between differential bacterial species and inflammatory factor levels. ResultCompared with the normal group， the model group showed a significant decrease in body weight（P<0.01）， a significant increase in DAI（P<0.05）， and a significant increase in TNF-α， IL-1β and IL-6 levels（P<0.01）， and there was partial infiltration of inflammatory cells in the colon. Compared with the model group， mice in the GDCA group showed a significant decrease in body weight， a significant increase in DAI and levels of TNF-α， IL-1β and IL-6（P<0.01）， and severe disruption of colonic crypt structure， extensive infiltration of inflammatory cells， and a significant decrease in goblet cells. Compared with the GDCA group， both the Olibanum and vinegar-processed Olibanum groups showed a significant recovery in body weight， a significant decrease in DAI and levels of TNF-α， IL-6 and IL-1β（P<0.05， P<0.01）， and the modulating effect of vinegar-processed Olibanum was significantly better than that of Olibanum. Alpha diversity showed that Chao1 index of UC mice significantly increased（P<0.01） and Shannon index decreased significantly（P<0.05） in UC mice after GDCA intervention. Beta diversity showed that the microbial community structure of the 5 groups had significant changes， Olibanum and vinegar-processed Olibanum could modulate the changes in the structure of the intestinal flora in UC mice after GDCA intervention. Microbial sequencing results indicated that， compared with the normal group， the Firmicutes/Bacteroidetes ratio in the model group was significantly higher（P<0.05）， and the relative abundance of 3 genera and 5 species of flora changed significantly（P<0.05， P<0.01）. Compared with the model group， the Firmicutes/Bacteroidetes ratio in the GDCA group was significantly higher（P<0.05）， the relative abundance of 7 pathogenic bacterial genera and four species was significantly increased（P<0.05， P<0.01）， and the relative abundance of three beneficial bacterial genera and Bacteroides_intestinalis was significantly decreased（P<0.05， P<0.01）. Olibanum group and vinegar-processed Olibanum group could modulate the Firmicutes/Bacteroidetes ratio， the relative abundance of pathogenic bacteria and beneficial bacteria， and the vinegar-processed Olibanum group was significantly superior to Olibanum group in terms of modulating the Firmicutes/Bacteroidetes ratio， the relative abundance of the three genera and five species of bacteria（P<0.01， P<0.05）. Correlation analysis showed that the relative abundance of Bacteroides_intestinalis was negatively correlated with the levels of TNF-α， IL-6 and IL-1β， the relative abundance of Prevotella_sp_CAG873， Bacteroides_sp_CAG927， Bacteroidales_bacterium_52_46 and Bacteroidales_bacterium was positively correlated with TNF-α， IL-6 and IL-1β levels. ConclusionGDCA can exacerbate UC colonic inflammation， and Olibanum and vinegar-processed Olibanum have an ameliorative effect on GDCA-mediated UC， with the vinegar-processed Olibanum showing a stronger ameliorative effect， the mechanism may be related to the regulation the abundance and structure of intestinal beneficial and pathogenic bacteria， and the reduction of inflammatory factor levels.