Pileflebitis en pediatría: un desafío diagnóstico / Pylephlebitis in pediatrics: A diagnostic challenge

La pileflebitis es definida como la trombosis supurativa de la vena porta como complicación de infecciones abdominales. En pediatría, la etiología más frecuente es la apendicitis, generalmente de diagnóstico tardío, que se presenta como sepsis, con una elevada mortalidad. Para el diagnóstico son necesarios métodos de diagnóstico por imágenes; los más utilizados son la ecografía Doppler y la angiotomografía. El tratamiento se basa en la intervención quirúrgica, la antibioticoterapia y la anticoagulación. Esta última tiene indicación controvertida, pero podría mejorar el pronóstico y disminuir la morbimortalidad. Se presenta un caso clínico de pileflebitis secundaria a sepsis por Escherichia coli con punto de partida en una apendicitis aguda, en un paciente pediátrico que evoluciona a la transformación cavernomatosa de la vena porta. Es de importancia conocer el manejo de esta entidad, ya que, una vez superado el cuadro inicial, requerirá un minucioso seguimiento por la posibilidad de evolucionar a la insuficiencia hepática.

Pylephlebitis is defined as suppurative thrombosis of the portal vein as a complication of abdominal infections. In pediatrics, the most frequent etiology is appendicitis, generally of late diagnosis, presenting as sepsis, with a high mortality rate. Imaging methods are necessary for diagnosis; the most common are the Doppler ultrasound and computed tomography angiography. Treatment is based on surgery, antibiotic therapy, and anticoagulation. The indication for the latter is controversial, but it may improve prognosis and decrease morbidity and mortality. Here we describe a clinical case of pylephlebitis secondary to Escherichia coli sepsis, which started as acute appendicitis in a pediatric patient who progressed to cavernomatous transformation of the portal vein. It is important to know the management of this disease because, once the initial symptoms are overcome, it will require close follow-up due to a potential progression to liver failure.

Therapeutic potential of stem cell and melatonin on the reduction of CCl4-induced liver fibrosis in experimental mice model / Potencial terapêutico de células-tronco e melatonina na redução da fibrose hepática induzida por CCl4 no modelo de ratos experimentais

Liver fibrosis is initial stage of any chronic liver disease and its end stage is develops into cirrhosis. Chronic liver diseases are a crucial global health issue and the cause of approximately 2 million deaths per year worldwide. Cirrhosis is currently the 11th most common cause of death globally. Mesenchymal stem cell (MSCs) treatment is the best way to treat acute and chronic liver disease. The aim of this study is to improve the therapeutic potential of MSCs combined with melatonin (MLT) to overcome CCl4-induced liver fibrosis and also investigate the individual impact of melatonin and MSCs against CCl4-induced liver impairment in animal model. Female BALB/c mice were used as CCL4-induced liver fibrotic animal model. Five groups of animal model were made; negative control, Positive control, CCl4+MSCs treated group, CCl4+MLT treated group and CCl4+MSCs+MLT treated group. Cultured MSCs from mice bone marrow were transplanted to CCl4-induced liver injured mice model, individually as well as together with melatonin. Two weeks after MSCs and MLT administration, all groups of mice were sacrificed for examination. Morphological and Histopathological results showed that combined therapy of MSCs+MLT showed substantial beneficial impact on CCl4-induced liver injured model, compared with MSCs and MLT individually. Biochemically, considerable reduction was observed in serum bilirubin and ALT levels of MLT+MSC treated mice, compared to other groups. PCR results shown down-regulation of Bax and up-regulation of Bcl-xl and Albumin, confirm a significant therapeutic effect of MSCs+MLT on CCI4-induced liver fibrosis. From the results, it is concluded that combined therapy of MSCs and MLT show strong therapeutic effect on CCL4-induced liver fibrosis, compared with MSCs and MLT individually.

A fibrose hepática é a fase inicial de qualquer doença hepática crônica, e em sua fase final desenvolve-se para cirrose. As doenças hepáticas crônicas são uma questão de saúde global crucial e a causa de aproximadamente 2 milhões de mortes por ano em todo o mundo. A cirrose, hoje em dia, é a 11ª causa mais comum de morte globalmente. O tratamento da célula-tronco mesenquimal (MSCs) é uma maneira eletiva de tratar a doença hepática aguda e crônica. O objetivo deste estudo é melhorar o potencial terapêutico dos MSCs combinados com a melatonina (MLT) para superar a fibrose hepática induzida por CCl4 e também investigar o impacto individual da melatonina e MSCs contra o comprometimento do fígado induzido por CCl4 no modelo animal. Os ratos BALB / C fêmeas foram usados ​​como modelo de animal fibrótico de fígado induzido por CCl4. Cinco grupos de modelo animal foram feitos: Controle Negativo, Controle Positivo, CCl4 + MSCs Tratados Grupo, Grupo Tratado CCl4 + MLT e Grupo Tratado CCl4 + MSCs + MLT. MSCs cultivados da medula óssea dos ratos foram transplantados para o modelo de camundongos de fígado induzido por CCl4, individualmente, bem como em conjunto com a melatonina. Duas semanas após a administração MSCs e MLT, todos os grupos de camundongos foram sacrificados para o exame. Os resultados morfológicos e histopatológicos mostraram que a terapia combinada do MSCs + MLT mostrou impacto benéfico substancial no modelo ferido no fígado induzido pelo CCl4, em comparação com o MSCs e o MLT individualmente. A redução bioquimicamente considerável foi observada em bilirrubina sérica e níveis ALT de ratinhos tratados com MLT + MSCs, em comparação com outros grupos. Os resultados de PCR mostraram regulação negativa do BAX e regulação positiva do BCL-XL e da albumina, confirmando um efeito terapêutico significativo do MSCs + MLT na fibrose hepática induzida por CCl4. Dos resultados, conclui-se que a terapia combinada de MSCs e MLT mostram um forte efeito terapêutico na fibrose hepática induzida por CCl4, em comparação com MSCs e MLT individualmente.

Non-linear association between long-term air pollution exposure and risk of metabolic dysfunction-associated steatotic liver disease

BACKGROUND@#Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD) has become a global epidemic, and air pollution has been identified as a potential risk factor. This study aims to investigate the non-linear relationship between ambient air pollution and MASLD prevalence.@*METHOD@#In this cross-sectional study, participants undergoing health checkups were assessed for three-year average air pollution exposure. MASLD diagnosis required hepatic steatosis with at least 1 out of 5 cardiometabolic criteria. A stepwise approach combining data visualization and regression modeling was used to determine the most appropriate link function between each of the six air pollutants and MASLD. A covariate-adjusted six-pollutant model was constructed accordingly.@*RESULTS@#A total of 131,592 participants were included, with 40.6% met the criteria of MASLD. "Threshold link function," "interaction link function," and "restricted cubic spline (RCS) link functions" best-fitted associations between MASLD and PM2.5, PM10/CO, and O3 /SO2/NO2, respectively. In the six-pollutant model, significant positive associations were observed when pollutant concentrations were over: 34.64 µg/m3 for PM2.5, 57.93 µg/m3 for PM10, 56 µg/m3 for O3, below 643.6 µg/m3 for CO, and within 33 and 48 µg/m3 for NO2. The six-pollutant model using these best-fitted link functions demonstrated superior model fitting compared to exposure-categorized model or linear link function model assuming proportionality of odds.@*CONCLUSION@#Non-linear associations were found between air pollutants and MASLD prevalence. PM2.5, PM10, O3, CO, and NO2 exhibited positive associations with MASLD in specific concentration ranges, highlighting the need to consider non-linear relationships in assessing the impact of air pollution on MASLD.

Polysaccharides from Chinese herbal medicine: a review on the hepatoprotective and molecular mechanism / 中国天然药物

Polysaccharides, predominantly extracted from traditional Chinese medicinal herbs such as Lycium barbarum, Angelica sinensis, Astragalus membranaceus, Dendrobium officinale, Ganoderma lucidum, and Poria cocos, represent principal bioactive constituents extensively utilized in Chinese medicine. These compounds have demonstrated significant anti-inflammatory capabilities, especially anti-liver injury activities, while exhibiting minimal adverse effects. This review summarized recent studies to elucidate the hepatoprotective efficacy and underlying molecular mechanisms of these herbal polysaccharides. It underscored the role of these polysaccharides in regulating hepatic function, enhancing immunological responses, and improving antioxidant capacities, thus contributing to the attenuation of hepatocyte apoptosis and liver protection. Analyses of molecular pathways in these studies revealed the intricate and indispensable functions of traditional Chinese herbal polysaccharides in liver injury management. Therefore, this review provides a thorough examination of the hepatoprotective attributes and molecular mechanisms of these medicinal polysaccharides, thereby offering valuable insights for the advancement of polysaccharide-based therapeutic research and their potential clinical applications in liver disease treatment.

Hígado graso agudo del embarazo en una adulta joven / Acute fatty liver of pregnancy in a young adult woman i: en

Se presenta el caso clínico de una gestante de 20 años de edad, quien acudió al Cuerpo de Guardia del bloque materno del Hospital General Docente Dr. Juan Bruno Zayas Alfonso de Santiago de Cuba por presentar decaimiento, náuseas y malestar general. Durante la exploración física se encontró piel sudorosa y fría, taquicardia e ictericia. Se realizaron diversos exámenes complementarios y se constató alteración hepática, así como cifras bajas de glucemia. Se diagnosticó hígado graso agudo del embarazo. Luego de varios días de hospitalizada con una evolución desfavorable, hasta llegar al estado crítico, la paciente falleció por síndrome de disfunción multiorgánica.

The case report of a 20 years pregnant woman is presented, who went to the maternal block emergency room of Dr. Juan Bruno Zayas Alfonso Teaching General Hospital in Santiago de Cuba due to run-down, nausea and diffuse discomfort. During the physical exploration sweaty and cold skin, tachycardia and jaundice were found. Diverse complementary exams were carried out and a hepatic disorder was verified, as well as low figures of glycemia. Acute fatty liver of pregnancy was diagnosed. After several days hospitalized with an unfavorable clinical course until getting to the critical state, the patient died due to multiple organ dysfunction syndrome.

Metodologías de Medición de Volumetría Hepática / Methodologies For Measuring Hepatic Volumetry

Lograr determinar el volumen total de un hígado (VHT), o volumetría hepática, pasa a ser de relevancia en diversas situaciones, tales como, vigilancia del progreso de una enfermedad de carácter crónico, planificación de resecciones y trasplantes hepáticos; y observación del clearance hepático de algunos fármacos hepatotropos. La VHT se puede realizar utilizando métodos de segmentación en el curso de una tomografía computarizada (TC), ya sean estos manual, automáticos, y semiautomáticos; mediante resonancia nuclear (RN), utilizando softwares de distintas generaciones (1ª a 4ª). La medición de VHT está indicada en pacientes sometidos a resecciones hepáticas mayores, en el contexto del tratamiento de neoplasias (carcinoma hepatocelular, colangiocarcinoma, metástasis hepáticas o tumores benignos de gran tamaño), abscesos (piogénicos, amebianos), y después de un traumatismo hepático complejo; así como también en la etapa preoperatoria de un trasplante hepático. El objetivo de este manuscrito fue generar un documento de estudio sobre métodos para determinar volumetría hepática.

SUMMARY: Being able to determine the total hepatic volume (THV), or THV, becomes relevant in various situations, such as monitoring the progress of a chronic disease, planning resections and liver transplants; and observation of the hepatic clearance of some hepatotropic drugs. THV can be performed using segmentation methods in the course of a computed tomography (CT), whether manual, automatic, or semi-automated; by nuclear resonance (NR), using software from different generations (1st to 4st). THV measurement is indicated in patients undergoing major liver resections, in the context of treatment of neoplasms (hepatocellular carcinoma, cholangiocarcinoma, liver metastases or large benign tumors), abscesses (pyogenic, amoebic), and after liver trauma complex, as well as in the preoperative stage of a liver transplant. The aim of this manuscript was to generate a study document regarding methods for determine hepatic volumetry.

Enfermedad hepática en la fibrosis quística pediátrica. Una revisión de los conocimientos actuales / Cystic fibrosis liver disease in children ­ A review of our current understanding

La fibrosis quística, la segunda enfermedad genética más frecuente, es el resultado de una proteína de canal mutada, la CFTR, que secreta iones de cloro que fluidifican las secreciones. La esperanza de vida en los pacientes ha aumentado en años recientes gracias a mejoras en el tratamiento. No obstante, las complicaciones hepáticas son la tercera causa de muerte y la comprensión de su fisiopatología es aún deficiente. Se considera que la obstrucción biliar secundaria a la presencia de secreciones espesas conduce a la cirrosis. Sin embargo, el ácido ursodesoxicólico no ha modificado la historia natural. Además, la presencia de hipertensión portal en ausencia de cirrosis no puede ser explicada. Se ha propuesto el rol de la CFTR como modulador de tolerancia inmune, que explica la presencia de una inflamación portal persistente que culmina en fibrosis. El eje intestino-hígado tendría un rol importante en la presentación y la progresión de esta enfermedad

Cystic fibrosis is the second most common genetic disease in infancy. It is the result of a mutated channel protein, the CFTR, which secretes chloride ions, fluidifying secretions. Recent improvements in the treatment have increased life expectancy in these patients. Nevertheless, liver involvement remains the third cause of death. Unfortunately, our understating of the physiopathology is still deficient. Biliary obstruction secondary to the presence of thick secretions is considered to lead to cirrhosis. However, treatment with ursodeoxycolic acid has not changed the natural history. Furthermore, the presence of portal hypertension in the absence of cirrhosis cannot be explained. Recently, the role of CFTR as modulator of immune tolerance has been proposed, which could explain the presence of a persistent portal inflammation leading to fibrosis, and the gut-liver axis would also have a role in disease presentation and progression.

Saffron reduces the liver fibrosis in mice by inhibiting the JAK/STAT3 pathway

Purpose: Chronic inflammation in the liver is a key trigger for liver injury and fibrosis in various liver diseases. Given the anti-inflammatory and antioxidant effects of Saffron, this study aimed to investigate the pharmacological effects of Saffron on hepatic inflammation and fibrosis. Methods: The mice model of hepatic fibrosis was constructed using CCl4, and Saffron was administered at low (10 mg/kg) and high (20 mg/kg) doses by gavage. Then, the changes in liver function, liver inflammation and fibrosis markers were evaluated. The effects and mechanisms of Saffron on hepatic stellate cells were further investigated in in-vitro experiments. Results: Saffron improved liver function, reduced liver inflammation and attenuated liver fibrosis in a dose-dependent manner in hepatic fibrosis mice. Furthermore, Western blotting showed that Saffron significantly inhibited JAK/STAT3 phosphorylation in fibrotic livers. Conclusions: Saffron can attenuate liver fibrosis by inhibiting the JAK/STAT3 pathway and the activation of hepatic stellate cell, providing a theoretical basis for the development of new anti-fibrotic drugs.

Biopsia hepática: experiencia en un hospital regional del sur de Chile / Liver biopsy: experience in a regional hospital in southern Chile

Introduction: Liver biopsy is an invasive procedure with a minimal rate of associated complications, which represents a highly useful strategy for the diagnosis of pathologies in the liver, when the etiology cannot be clarified by non-invasive techniques. It provides information that allows determining the progression and prognosis of liver diseases. Objectives: To evaluate the main etiology causes of liver disease in patients undergoing liver biopsy. Material and Methods: Review of the clinical record of 61 patients who underwent this procedure between 2018 and 2020 at the Hernán Henríquez Aravena hospital, demographic variables, diagnosis that motivates its performance, and associated complications. Results: Average age 58 years, of this 66% were female and 34% were male. The diagnoses that motivated this procedure were: autoimmune hepatitis, liver Tumors, and chronic liver damage of unknown etiology. 100% of the case had a satisfactory sample for the analysis and clarification of the cause of liver disease. 91% did not present complications and of the 8% associated with complications, pain was the most common. Conclusion: Liver biopsy is an effective method that allowed establishing etiology, confirming diagnosis suspicions, and evaluating the progression of liver disease with a low rate of complications.

Introducción: La biopsia hepática es un procedimiento invasivo con una tasa mínima de complicaciones asociadas, que representa una estrategia de gran utilidad para el diagnóstico de patologías a nivel del hígado, cuando a través de técnicas no invasivas no se logra esclarecer la etiología. Además, entrega información que permite determinar la progresión y pronóstico de enfermedades hepáticas. Objetivos: Evaluar las principales causas etiológicas de hepatopatías en los pacientes sometidos a biopsia hepática. Material y Método: Revisión de fichas clínicas de 61 pacientes sometidos a este procedimiento entre el año 2018 y 2020 en el hospital Hernán Henríquez Aravena, se analizaron variables demográficas, diagnóstico que motiva su realización, y complicaciones asociadas. Resultados: Edad promedio: 58 años de estos: 66% eran del sexo femenino y 34% al sexo masculino. De los diagnósticos que motivaron a la realización de la biopsia fuero: hepatitis autoinmune, tumores hepáticos y daño hepático crónico de etiología no precisada. El 100% de los casos tuvo una muestra satisfactoria para el análisis y esclarecer la causa de la hepatopatía. El 91% no presentó complicaciones y del 8% de las complicaciones presentadas, el dolor fue la principalmente descrita. Conclusiones: La biopsia hepática es un método eficaz que permitió establecer etiología, confirmar sospechas diagnósticas y evaluar progresión de enfermedades hepáticas con una baja tasa de complicación.

Molecular pathological mechanism of liver metabolic disorder in mice with severe spinal muscular atrophy / 南方医科大学学报

OBJECTIVE@#To explore the molecular pathological mechanism of liver metabolic disorder in severe spinal muscular atrophy (SMA).@*METHODS@#The transgenic mice with type Ⅰ SMA (Smn-/- SMN20tg/2tg) and littermate control mice (Smn+/- SMN20tg/2tg) were observed for milk suckling behavior and body weight changes after birth. The mice with type Ⅰ SMA mice were given an intraperitoneal injection of 20% glucose solution or saline (15 μL/12 h), and their survival time was recorded. GO enrichment analysis was performed using the RNA-Seq data of the liver of type Ⅰ SMA and littermate control mice, and the results were verified using quantitative real-time PCR. Bisulfite sequencing was performed to examine CpG island methylation level in Fasn gene promoter region in the liver of the neonatal mice.@*RESULTS@#The neonatal mice with type Ⅰ SMA showed normal milk suckling behavior but had lower body weight than the littermate control mice on the second day after birth. Intraperitoneal injection of glucose solution every 12 h significantly improved the median survival time of type Ⅰ SMA mice from 9±1.3 to 11± 1.5 days (P < 0.05). Analysis of the RNA-Seq data of the liver showed that the expression of the target genes of PPARα related to lipid metabolism and mitochondrial β oxidation were down-regulated in the liver of type Ⅰ SMA mice. Type Ⅰ SMA mice had higher methylation level of the Fasn promoter region in the liver than the littermate control mice (76.44% vs 58.67%). In primary cultures of hepatocytes from type Ⅰ SMA mice, treatment with 5-AzaC significantly up-regulated the expressions of the genes related to lipid metabolism by over 1 fold (P < 0.01).@*CONCLUSION@#Type Ⅰ SMA mice have liver metabolic disorder, and the down-regulation of the target genes of PPARα related to lipid and glucose metabolism due to persistent DNA methylation contributes to the progression of SMA.

Clinical and immunological features of primary Sjögren's syndrome patients with positive anti-centromere protein B antibody / 北京大学学报(医学版)

OBJECTIVE@#To investigate the clinical and immunological features of primary Sjögren's syndrome (pSS) patients with positive anti-centromere protein B (CENP-B) antibody.@*METHODS@#In this cross-sectional study, the general clinical data, radiographic examination and labial salivary gland biopsy data, and serum immunological and biochemical data of patients diagnosed with pSS from January 2016 to August 2022 were evaluated. The included patients were divided into the anti-CENP-B antibody positive and negative groups. Intergroup differences were analyzed with SPSS 23.0 software. Subgroup analysis was further performed by dividing the anti-CENP-B antibody positive group into the single anti-CENP-B antibody positive and with other auto-antibodies positive groups to determine the characters related to anti-CENP-B antibody.@*RESULTS@#In this study, 288 patients with pSS were evaluated, including 75 patients with anti-CENP-B antibody positive and 213 with anti-CENP-B antibody negative. Univariate analysis showed that compared with the anti-CENP-B antibody negative group, the patients of the anti-CENP-B antibody positive group were older, had lower proportion of the patients with salivary gland enlargement and higher proportion of autoimmune liver disease. As for immunological indicators, the positive proportions of anti-SSA/Ro60, anti-Ro52, and anti-SSB antibodies were significantly lower. Moreover, the immunoglobulin (Ig) G and rheumatoid factor levels were significantly lower, while the IgM level was significantly higher in the patients of the anti-CENP-B antibody positive group. As for serum biochemical indicators, for the patients of the anti-CENP-B antibody positive group, the level of total protein (TP) was lower, the albumin/globulin ratio was higher, and the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH) were higher. Subgroup analysis showed that the levels of TP and IgA in the patients of the single anti-CENP-B antibody positive group were significantly lower than those of the patients with other autoantibodies positive group.@*CONCLUSION@#The pSS patients with anti-CENP-B antibody positive have unique clinical and immunological features of lower disease activity, less likely to involve salivary gland, higher risk for autoimmune liver disease, and higher levels of liver function indicators. Anti-CENP-B antibody may be a marker for a distinct subset of polyautoimmunity in Sjögren's syndrome.

Clinical analysis of liver dysfunction induced by SHR-1210 alone or combined with apatinib and chemotherapy in patients with advanced esophageal squamous cell carcinoma / 中华肿瘤杂志

Objective: To investigate the clinical characteristics of abnormal liver function in patients with advanced esophageal squamous carcinoma treated with programmed death-1 (PD-1) antibody SHR-1210 alone or in combination with apatinib and chemotherapy. Methods: Clinical data of 73 patients with esophageal squamous carcinoma from 2 prospective clinical studies conducted at the Cancer Hospital Chinese Academy of Medical Sciences from May 11, 2016, to November 19, 2019, were analyzed, and logistic regression analysis was used for the analysis of influencing factors. Results: Of the 73 patients, 35 had abnormal liver function. 13 of the 43 patients treated with PD-1 antibody monotherapy (PD-1 monotherapy group) had abnormal liver function, and the median time to first abnormal liver function was 55 days. Of the 30 patients treated with PD-1 antibody in combination with apatinib and chemotherapy (PD-1 combination group), 22 had abnormal liver function, and the median time to first abnormal liver function was 41 days. Of the 35 patients with abnormal liver function, 2 had clinical symptoms, including malaise and loss of appetite, and 1 had jaundice. 28 of the 35 patients with abnormal liver function returned to normal and 7 improved to grade 1, and none of the patients had serious life-threatening or fatal liver function abnormalities. Combination therapy was a risk factor for patients to develop abnormal liver function (P=0.007). Conclusions: Most of the liver function abnormalities that occur during treatment with PD-1 antibody SHR-1210 alone or in combination with apatinib and chemotherapy are mild, and liver function can return to normal or improve with symptomatic treatment. For patients who receive PD-1 antibody in combination with targeted therapy and chemotherapy and have a history of long-term previous smoking, alcohol consumption and hepatitis B virus infection, liver function should be monitored and actively managed in a timely manner.

Research progress of the regulation of orphan nuclear receptors on chronic liver diseases / 生理学报

The development of chronic liver disease can be promoted by excessive fat accumulation, dysbiosis, viral infections and persistent inflammatory responses, which can lead to liver inflammation, fibrosis and carcinogenesis. An in-depth understanding of the etiology leading to chronic liver disease and the underlying mechanisms influencing its development can help identify potential therapeutic targets for targeted treatment. Orphan nuclear receptors (ONRs) are receptors that have no corresponding endogenous ligands to bind to them. The study of these ONRs and their biological properties has facilitated the development of synthetic ligands, which are important for investigating the effective targets for the treatment of a wide range of diseases. In recent years, it has been found that ONRs are essential for maintaining normal liver function and their dysfunction can affect a variety of liver diseases. ONRs can influence pathophysiological activities such as liver lipid metabolism, inflammatory response and cancer cell proliferation by regulating hormones/transcription factors and affecting the biological clock, oxidative stress, etc. This review focuses on the regulation of ONRs, mainly including retinoid related orphan nuclear receptors (RORs), pregnane X receptor (PXR), leukocyte cell derived chemotaxin 2 (LECT2), Nur77, and hepatocyte nuclear factor 4α (HNF4α), on the development of different types of chronic liver diseases in different ways, in order to provide useful references for the therapeutic strategies of chronic liver diseases based on the regulation of ONRs.

Therapeutic potential and mechanism of Chinese herbal medicines in treating fibrotic liver disease / 中国天然药物

Liver fibrosis is a pathological condition characterized by replacement of normal liver tissue with scar tissue, and also the leading cause of liver-related death worldwide. During the treatment of liver fibrosis, in addition to antiviral therapy or removal of inducers, there remains a lack of specific and effective treatment strategies. For thousands of years, Chinese herbal medicines (CHMs) have been widely used to treat liver fibrosis in clinical setting. CHMs are effective for liver fibrosis, though its mechanisms of action are unclear. In recent years, many studies have attempted to determine the possible mechanisms of action of CHMs in treating liver fibrosis. There have been substantial improvements in the experimental investigation of CHMs which have greatly promoted the understanding of anti-liver fibrosis mechanisms. In this review, the role of CHMs in the treatment of liver fibrosis is described, based on studies over the past decade, which has addressed the various mechanisms and signaling pathways that mediate therapeutic efficacy. Among them, inhibition of stellate cell activation is identified as the most common mechanism. This article provides insights into the research direction of CHMs, in order to expand its clinical application range and improve its effectiveness.

Blueberry attenuates liver injury in metabolic dysfunction-associated liver disease by promoting the expression of mitofilin/Mic60 in human hepatocytes and inhibiting the production of superoxide / 细胞与分子免疫学杂志

Objective To study the effect and mechanism of blueberry on regulating the mitochondrial inner membrane protein mitofilin/Mic60 in an in vitro model of metabolic dysfunction-associated liver disease (MAFLD). Methods L02 human hepatocytes were induced by free fatty acids (FFA) to establish MAFLD cell model. A normal group, a model group, an 80 μg/mL blueberry treatment group, a Mic60 short hairpin RNA (Mic60 shRNA) transfection group, and Mic60 knockdown combined with an 80 μg/mL blueberry treatment group were established. The intracellular lipid deposition was observed by oil red O staining, and the effect of different concentrations of blueberry pulp on the survival rate of L02 cells treated with FFA was measured by MTT assay. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (TC), superoxide dismutase (SOD) activity, glutathione (GSH) and malondialdehyde (MDA) contents were measured by visible spectrophotometry. The expression of reactive oxygen species (ROS) in hepatocytes was observed by fluorescence microscopy, and the mRNA and protein expression of Mic60 were detected by real-time quantitative PCR and Western blot analysis, respectively. Results After 24 hours of FFA stimulation, a large number of red lipid droplets in the cytoplasm of L02 cells was observed, and the survival rate of L02 cells treated with 80 μg/mL blueberry was higher. The results of ALT, AST, TG, TC, MDA and the fluorescence intensity of ROS in blueberry treated group were lower than those in model group, while the levels of SOD, GSH, Mic60 mRNA and protein in blueberry treated group were higher than those in model group. Conclusion Blueberry promotes the expression of Mic60, increases the levels of SOD and GSH in hepatocytes, and reduces the production of ROS, thus alleviating the injury of MAFLD hepatocytes and regulating the disorder of lipid metabolism.

Copper homeostasis dysregulation promoting cell damage and the association with liver diseases / 中华医学杂志(英文版)

Copper plays an important role in many metabolic activities in the human body. Copper level in the human body is in a state of dynamic equilibrium. Recent research on copper metabolism has revealed that copper dyshomeostasis can cause cell damage and induce or aggravate some diseases by affecting oxidative stress, proteasome, cuprotosis, and angiogenesis. The liver plays a central role in copper metabolism in the human body. Research conducted in recent years has unraveled the relationship between copper homeostasis and liver diseases. In this paper, we review the available evidence of the mechanism by which copper dyshomeostasis promotes cell damage and the development of liver diseases, and identify the future research priorities.

Fontan-associated liver disease current status and transplantation consideration / 中华肝脏病杂志

Fontan-associated liver disease (FALD) is one of the main complications after the Fontan procedure, manifesting mostly as liver fibrosis and even cirrhosis, with a high incidence rate and a lack of typical clinical symptoms that seriously affect patient prognosis. The specific cause is unknown, although it is considered to be associated with long-term elevated central venous pressure, impaired hepatic artery blood flow, and other relevant factors. The absence of association between laboratory tests, imaging data, and the severity of liver fibrosis makes clinical diagnosis and monitoring difficult. A liver biopsy is the gold standard for diagnosing and staging liver fibrosis. The most important risk factor for FALD is time following the Fontan procedure; therefore, it is recommended to do a liver biopsy 10 years after the Fontan procedure and to be cautious for the presence of hepatocellular carcinoma. Combined heart-liver transplantation is a recommended choice with favorable outcomes for patients with Fontan circulatory failure and severe hepatic fibrosis.

Research progress of the regulatory role of autophagy in metabolic liver diseases / 中华肝脏病杂志

Autophagy is one of several hepatic metabolic processes in which starved cells are supplied with glucose, free fatty acids, and amino acids to produce energy and synthesize new macromolecules. Moreover, it regulates the quantity and quality of mitochondria and other organelles. As the liver is a vital metabolic organ, specific forms of autophagy are necessary for maintaining liver homeostasis. Protein, fat, and sugar are the three primary nutrients that can be altered by different metabolic liver diseases. Drugs that have an effect on autophagy can either promote or inhibit autophagy, and as a result, it can either increase or inhibit the three major nutritional metabolisms that are affected by liver disease. Thus, this opens up a novel therapeutic option for liver disease.

Analysis of the characteristics of retracted scientific papers in the field of global liver diseases published by Chinese scholars / 中华肝脏病杂志

Objective: To analyze the characteristics of scientific papers in the field of global liver diseases published by Chinese scholars that were retracted for diverse reasons from the Retraction Watch database, so as to provide a reference to publishing-related papers. Methods: The Retraction Watch database was retrieved for retracted papers in the field of global liver disease published by Chinese scholars from March 1, 2008 to January 28, 2021. The regional distribution, source journals, reasons for retraction, publication and retraction times, and others were analyzed. Results: A total of 101 retracted papers that were distributed across 21 provinces/cities were retrieved. Zhejiang area (n = 17) had the most retracted papers, followed by Shanghai (n = 14), and Beijing (n = 11). The vast majority were research papers (n = 95). The journal PLoS One had the highest number of retracted papers. In terms of time distribution, 2019 (n = 36) had the most retracted papers. 23 papers, accounting for 8.3% of all retractions, were retracted owing to journal or publisher concerns. Liver cancer (34%), liver transplantation (16%), hepatitis (14%), and others were the main areas of retracted papers. Conclusion: Chinese scholars have a large number of retracted articles in the field of global liver diseases. A journal or publisher chooses to retract a manuscript after investigating and discovering more flawed problems, which, however, require further support, revision, and supervision from the editorial and academic circles.

Excerpt from the 2022 American Association for the Study of Liver Diseases clinical practice guideline: management of primary sclerosing cholangitis and cholangiocarcinoma / 中华肝脏病杂志

What are the new contents of the guideline since 2010?A.Patients with primary and non-primary sclerosing cholangitis (PSC) are included in these guidelines for the diagnosis and management of cholangiocarcinoma.B.Define "related stricture" as any biliary or hepatic duct stricture accompanied by the signs or symptoms of obstructive cholestasis and/or bacterial cholangitis.C.Patients who have had an inconclusive report from MRI and cholangiopancreatography should be reexamined by high-quality MRI/cholangiopancreatography for diagnostic purposes. Endoscopic retrograde cholangiopancreatography should be avoided for the diagnosis of PSC.D. Patients with PSC and unknown inflammatory bowel disease (IBD) should undergo diagnostic colonoscopic histological sampling, with follow-up examination every five years until IBD is detected.E. PSC patients with IBD should begin colon cancer monitoring at 15 years of age.F. Individual incidence rates should be interpreted with caution when using the new clinical risk tool for PSC for risk stratification.G. All patients with PSC should be considered for clinical trials; however, if ursodeoxycholic acid (13-23 mg/kg/day) is well tolerated and after 12 months of treatment, alkaline phosphatase (γ- Glutamyltransferase in children) and/or symptoms are significantly improved, it can be considered to continue to be used.H. Endoscopic retrograde cholangiopancreatography with cholangiocytology brushing and fluorescence in situ hybridization analysis should be performed on all patients suspected of having hilar or distal cholangiocarcinoma.I.Patients with PSC and recurrent cholangitis are now included in the new unified network organ sharing policy for the end-stage liver disease model standard.J. Liver transplantation is recommended after neoadjuvant therapy for patients with unresectable hilar cholangiocarcinoma with diameter < 3 cm or combined with PSC and no intrahepatic (extrahepatic) metastases.