Association of intestinal microecology with the development and progression of autoimmune hepatitis / 临床肝胆病杂志

Autoimmune hepatitis （AIH） is an autoimmune disease characterized by chronic liver inflammation， with a gradually increasing incidence rate， and its social and medical burdens cannot be neglected. Intestinal microecology is becoming a research hotspot in the field of autoimmune disease. In recent years， it has been believed that changes in intestinal microecology can cause changes in autoimmune state， microbial metabolites， and intestinal barrier， which is one of the driving factors for the onset of AIH. Early diagnosis and correct treatment can help to improve the prognosis of AIH patients. This article introduces the characteristics of gut microbiota in AIH patients， elaborates on the impact of intestinal microflora imbalance on the pathogenesis of AIH， and briefly describes related treatment regimens from the perspective of intestinal microecology， so as to comprehensively understand and explain the role of intestinal microecology in AIH and the impact of intestinal microecology balance on the pathogenesis， diagnosis， and treatment of AIH.

Protective mechanism of rhubarb decoction against inflammatory damage of brain tissue in rats with mild hepatic encephalopathy： A study based on the PI3K/AKT/mTOR signaling pathway / 临床肝胆病杂志

ObjectiveTo investigate the role and possible mechanism of action of rhubarb decoction （RD） retention enema in improving inflammatory damage of brain tissue in a rat model of mild hepatic encephalopathy （MHE）. MethodsA total of 60 male Sprague-Dawley rats were divided into blank group （CON group with 6 rats） and chronic liver cirrhosis modeling group with 54 rats using the complete randomization method. After 12 weeks， 40 rats with successful modeling which were confirmed to meet the requirements for MHE model by the Morris water maze test were randomly divided into model group （MOD group）， lactulose group （LT group）， low-dose RD group （RD1 group）， middle-dose RD group （RD2 group）， and high-dose RD group （RD3 group）， with 8 rats in each group. The rats in the CON group and the MOD group were given retention enema with 2 mL of normal saline once a day； the rats in the LT group were given retention enema with 2 mL of lactulose at a dose of 22.5% once a day； the rats in the RD1， RD2， and RD3 groups were given retention enema with 2 mL RD at a dose of 2.5， 5.0， and 7.5 g/kg， respectively， once a day. After 10 days of treatment， the Morris water maze test was performed to analyze the spatial learning and memory abilities of rats. The rats were analyzed from the following aspects： behavioral status； the serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） and the level of blood ammonia； pathological changes of liver tissue and brain tissue； the mRNA and protein expression levels of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （AKT）， and mammalian target of rapamycin （mTOR） in brain tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the MOD group， the RD1， RD2， and RD3 groups had a significantly shorter escape latency （all P<0.01）， significant reductions in the levels of ALT， AST， IL-1β， IL-6， TNF-α， and blood ammonia （all P<0.05）， significant alleviation of the degeneration， necrosis， and inflammation of hepatocytes and brain cells， and significant reductions in the mRNA and protein expression levels of PI3K， AKT， and mTOR in brain tissue （all P<0.05）， and the RD3 group had a better treatment outcome than the RD1 and RD2 groups. ConclusionRetention enema with RD can improve cognitive function and inflammatory damage of brain tissue in MHE rats， possibly by regulating the PI3K/AKT/mTOR signaling pathway.

Optimization of non-bioartificial liver technology and research advances in biological artificial liver / 临床肝胆病杂志

Liver failure is a common clinical syndrome with rapid progression and poor prognosis. Currently， there are still limited internal medical treatment methods for liver failure， and artificial liver support therapy is an effective treatment method. Non-bioartificial liver technology is widely used in clinical practice， and clinicians should determine the starting time， mode， and specific parameters of treatment according to the pathophysiological mechanism and dynamic evolution process of the disease， as well as the specific conditions of patients. Compared with non-bioartificial liver， biological artificial liver can better simulate the biological function of liver cells. At present， substantial progress has been made in its core technology， and related clinical studies are being conducted actively， suggesting a vast potential for future development. This article summarizes and discusses the optimization of non-bioartificial liver technology and the advances in biological artificial liver， in order to provide a reference for the clinical application and research of artificial liver technology.

Research advances in combined artificial liver / 临床肝胆病杂志

At present， in vitro artificial liver support system has achieved a good therapeutic effect in the diseases such as liver failure due to various causes， non-function state before and after liver transplantation， and severe cholestasis. Non-bioartificial liver （NBAL） is widely used in clinical practice through various combinations of modes， mainly the plasma exchange mode for improving coagulation factors and albumin combined with other modes for enhancing the elimination of toxic substances in the body. Bioartificial liver （BAL）， based on the design concept of the synthesis and transformation of hepatocytes， has achieved rapid development in recent years. Patients with liver failure can almost obtain the normal physiological function of human liver after NBAL detoxification and BAL synthesis and transformation of active substances in the body. NBAL mode combined with BAL with a stable therapeutic effect according to the conditions of the patient is the direction of in vitro support treatment for patients with severe liver disease in the future.

Clinical practice and research advances in artificial liver support therapy / 临床肝胆病杂志

Artificial liver support system is one of the important therapies for liver failure， and in recent years， the role of non-bioartificial liver support system in the treatment of liver failure has been gradually recognized， with wide application in non-liver failure diseases. In clinical practice， various factors should be considered to reasonably select the timing and mode of non-bioartificial liver support therapy， and standardized， individualized， and precise treatment and optimal combination of different modes are the trend of the clinical application of artificial liver support therapy. There have been constant improvements in the key techniques of bioartificial liver support system such as seed cell source and bioreactor， and some of them have entered the stage of clinical trial. Although remarkable progress has been made in the clinical practice and research of artificial liver support therapy， there are still many challenges， and it is urgently needed to solve the problems of how to further improve its efficacy and safety through technological innovation and combination optimization and how to obtain higher-level evidence-based medical evidence through high-quality clinical trials.

Role of exosomes in intrahepatic cholangiocarcinoma / 临床肝胆病杂志

Intrahepatic cholangiocarcinoma （ICC） is a special type of liver cancer with atypical clinical symptoms in the early stage， and most patients are already in the advanced stage at the time of initial diagnosis. Due to a lack of effective molecular markers and treatment options， ICC patients tend to have an extremely low five-year survival rate. Exosomes are vesicles secreted by cells that contain proteins， RNA， and lipids， and they are important carriers of intercellular communication. Recent studies have shown that exosomes play a crucial role in the development and progression of ICC， and this article reviews the role and mechanism of exosomes in the diagnosis and treatment of ICC and looks into the future treatment prospect and potential clinical application of exosomes.

An excerpt of Asia-Pacific Association for the Study of the Liver guidelines on management of ascites in liver disease （2023） / 临床肝胆病杂志

Asia-Pacific Association for the Study of the Liver published the guidelines on management of ascites in liver disease in May 2023， which introduces the diagnosis， differential diagnosis， and treatment of ascites， hyponatremia， hepatic hydrothorax， and hepatorenal syndrome in patients with liver cirrhosis and acute-on-chronic liver failure. This article summarizes the main recommendations in the guidelines， so as to provide a reference for the treatment of ascites in patients with liver diseases in China.

Research advances in porto-sinusoidal vascular disease / 临床肝胆病杂志

Porto-sinusoidal vascular disease （PSVD） is a new disease nomenclature proposed in recent years， which is an important supplement to idiopathic non-cirrhotic portal hypertension. PSVD includes the patients with specific pathological conditions， but without portal hypertension symptoms， and the patients with portal vein thrombosis or viral hepatitis. This article elaborates on the naming， epidemiology， etiology， clinical manifestations， prognosis， and treatment of PSVD， in order to improve the understanding of this disease among clinicians.

Research advances in the diagnosis and treatment of hepatic vein occlusion-type Budd-Chiari syndrome / 临床肝胆病杂志

Budd-Chiari syndrome is a rare liver vascular disease and can be classified into hepatic vein occlusion type， inferior vena cava occlusion type， and mixed type according to the location of hepatic outflow tract obstruction. This article reviews the hepatic vein occlusion type from the aspects of epidemiology， subtypes， clinical diagnosis， and treatment strategies.

Advances in the treatment of acute hepatic porphyria / 临床肝胆病杂志

Acute hepatic porphyria （AHP） is a rare disease with abnormal heme metabolism， and breakthroughs have been made in the treatment of this disease in recent years. In addition to conventional treatment methods， this article reviews new therapies for AHP that are in the stage of initial clinical application or are still in the research stage， including RNAi therapy， enzyme replacement therapy， genetic supplementation of DNA or mRNA， drug molecular chaperones， and glycine transporter inhibitors for reducing heme synthesis. Moreover， this article also reviews the treatment of AHP-related comorbidities and complications， such as hyponatremia and posterior reversible encephalopathy syndrome. High glucose infusion is the main treatment method for AHP in China， and the improvement in diagnosis and increased attention to rare diseases in China has promoted the development of the diagnosis and treatment of AHP， and it is expected to explore more suitable treatment methods for AHP in the Chinese population in the future.

Clinical diagnosis， treatment， and prognosis of gallbladder sarcomatoid carcinoma： An analysis of 16 cases / 临床肝胆病杂志

ObjectiveTo investigate the clinicopathological features， diagnosis and treatment methods， and prognosis of gallbladder sarcomatoid carcinoma （GBSC）. MethodsA retrospective analysis was performed for the clinical data of 16 patients with GBSC who were admitted to The First Affiliated Hospital of Zhengzhou University from January 2015 to April 2023， including general information， clinical manifestations， imaging features， pathological features， and treatment modality， and follow-up was performed for all patients. The Kaplan-Meier method was used to perform the survival analysis and plot the survival curve， and the Log-rank test was used for comparison between groups. ResultsAmong the 16 patients， there were 6 male patients and 10 female patients， with a mean age of 62.9±8.4 years. The main clinical manifestations were right upper abdominal pain in 13 patients （81.3%）， nausea in 5 patients （31.3%）， abdominal distension in 4 patients （25.0%）， poor appetite in 3 patients （18.8%）， weakness in 2 patients （12.5%）， fever in 2 patients （12.5%）， and jaundice in 1 patient （6.3%）， and 3 patients were asymptomatic and were found to have this disease by physical examination. Of all patients， 81.3% （13/16） were in the advanced stage （stage Ⅲ/Ⅳ） at the time of initial diagnosis. Histopathological examination showed that some cancer cells were spindle-shaped under the microscope， with marked nuclear division and noticeable heteromorphism. Immunohistochemistry showed a positive expression rate of 100% （16/16） for Vimentin， AE1/AE3， and CK8/18， and Ki-67 proliferation index was highly expressed in 81.3% （13/16） of the patients （≥50%）， with a median of 70% （range 20%‍ ‍—‍ ‍90%）. All 16 patients underwent surgical treatment， with radical surgery in 11 patients and palliative surgery in 5 patients， among whom 9 received R0 resection， 2 received R1 resection， and 5 received R2 resection， and 7 patients received adjuvant therapy after surgery. Effective follow-up was achieved for all 16 patients， with a follow-up time of 0.5‍ ‍—‍ ‍26.0 months and a median follow-up time of 11.0 months. By the end of follow-up， 2 patients survived and 14 patients died due to tumor recurrence or metastasis， with a median survival time of 10.0 months， and the 1- and 2-year cumulative survival rates after surgery were 31.3% and 8.3%， respectively. The prognostic analysis showed that TNM stage （χ2=6.727， P=0.009）， surgical approach （χ2=7.508， P=0.006）， margin condition （χ2=7.934， P=0.005）， and adjuvant therapy （χ2=4.608， P=0.032） were associated with the prognosis of patients. ConclusionThe clinical manifestations of GBSC lack specificity， and a confirmed diagnosis relies on immunohistochemical analysis. Most patients are in the advanced disease at the time of initial diagnosis and tend to have a poor prognosis. There are currently no targeted therapies for this disease， and radical surgery with negative margins and adjuvant therapy can improve the survival rate of patients.

An excerpt of American Association for the Study of Liver Diseases practice guidance on acute-on-chronic liver failure and the management of critically ill patients with cirrhosis in 2023 / 临床肝胆病杂志

The expert panel of American Association for the Study of Liver Diseases published Practice guidance on acute-on-chronic liver failure and the management of critically ill patients with cirrhosis on November 9， 2023 in Hepatology. This practice guidance elaborates on the definition of acute-on-chronic liver failure， prediction models， and the management of liver cirrhosis comorbid with acute-on-chronic liver failure and organ failure in critically ill patients， and this article gives an excerpt of the key points in the practice guidance.

Progress in the potential therapeutic mechanism of mesenchymal stem cell-derived exosomes for liver fibrosis / 中国临床药理学与治疗学

Liver fibrosis is pathological in most chronic liver diseases. Exosomes secreted by mesenchymal stem cells (MSCs) can regulate liver fibrosis through mechanisms such as inhibition of inflammatory response and proliferation of activated hepatic stellate cells, regulation of immune cells and metabolism. Therefore, MSC-derived exosomes can be used as a cell-free therapy for chronic liver disease, expanding new ideas for the treatment of chronic liver disease. Recent researches on MSC-derived exosomes in the treatment of liver fibrosis are reviewed in this article.

Role of Akkermansia muciniphila in nonalcoholic fatty liver disease / 临床肝胆病杂志

Nonalcoholic fatty liver disease （NAFLD） has become the most common chronic liver disease in the world， and it is also one of the main causes of liver cirrhosis and hepatocellular carcinoma， so it is particularly important to curb the development and progression of NAFLD in a timely manner. However， due to its complex pathogeneses， there are currently no effective methods for radical treatment. As a new generation of probiotics， Akkermansia muciniphila （Akk bacteria） can improve metabolic disorders of the body， and more and more studies have shown that Akk bacteria have a potential therapeutic effect on metabolic diseases， especially NAFLD. Therefore， this article briefly reviews the mechanism of action of Akk bacteria in NAFLD， in order to provide new ideas for improving the treatment of NAFLD and creating new therapies.

Erythropoietic protoporphyria with liver cirrhosis as the main manifestation： A case report / 临床肝胆病杂志

Erythropoietic protoporphyria （EPP） is a rare inherited metabolic disease that often involves skin， blood， and nervous systems， and EPP with the main manifestations of severe liver damage and acute abdominal pain is extremely rare. By reviewing the clinical data and genetic testing results of a patient with EPP， this article discusses the clinical features and pathogenic genes of this disease， in order to improve the understanding of the disease among hepatologists and achieve early diagnosis and treatment.

Clinical management of chronic hepatitis B virus infection comorbid with metabolic dysfunction / 临床肝胆病杂志

With the rapid growth of metabolic dysfunction （MD） worldwide， there is also a gradual increase in the number of patients with chronic hepatitis B virus （HBV） infection and MD. Comorbidity with metabolic disorders such as hyperglycemia， hypertension， and dyslipidemia may increase the risk of adverse liver outcomes and cardiovascular events in patients with chronic HBV infection and affect the response to anti-HBV therapy. The standardized management of patients with chronic HBV infection and MD has become a challenge at present， and further in-depth research on the interaction between MD and HBV and targeted management strategies will help to optimize the clinical management of patients with chronic HBV infection.

Lipid nanovehicles overcome barriers to systemic RNA delivery: Lipid components, fabrication methods, and rational design

Lipid nanovehicles are currently the most advanced vehicles used for RNA delivery, as demonstrated by the approval of patisiran for amyloidosis therapy in 2018. To illuminate the unique superiority of lipid nanovehicles in RNA delivery, in this review, we first introduce various RNA therapeutics, describe systemic delivery barriers, and explain the lipid components and methods used for lipid nanovehicle preparation. Then, we emphasize crucial advances in lipid nanovehicle design for overcoming barriers to systemic RNA delivery. Finally, the current status and challenges of lipid nanovehicle-based RNA therapeutics in clinical applications are also discussed. Our objective is to provide a comprehensive overview showing how to utilize lipid nanovehicles to overcome multiple barriers to systemic RNA delivery, inspiring the development of more high-performance RNA lipid nanovesicles in the future.

Quantitative relationship between physical activity and antihypertensives in elderly women / Relación cuantitativa entre actividad física y antihipertensivos en ancianas / Relação quantitativa entre atividade física e anti-hipertensivos em idosas

ABSTRACT Introduction: Physical activity is an important tool to manage systemic arterial hypertension. However, less is known about the relationship of physical activity with the number of antihypertensive drugs used by older adults. Objective: The aim of this study was to compare the number of antihypertensive drugs used by older female adults (aged ≥ 60 years) with a low level of physical activity with the number used by those with a high level of physical activity, and to verify how many participants used more than two antihypertensive drugs. Methods: Twenty-eight physically active older women with systemic arterial hypertension who participated in a physical activity program for community-dwelling older female adults were divided into two groups: participants who presented lower habitual physical activity levels were placed in group 1 and participants that presented higher habitual physical activity levels were placed in group 2, according to the Baecke questionnaire. In addition, the number of antihypertensive drugs used by participants was collected. Results: The number of prescribed antihypertensive drugs was 2.0 (median) for both groups investigated. There was no significant difference between groups regarding the number of antihypertensive tablets prescribed (p>0.05). Although there was no statistical difference, a higher proportion of participants from the lower physical activity group used more than two antihypertensive drugs. Conclusion: The level of habitual physical activity did not affect the number of antihypertensive tablets used by hypertensive elderly women. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMEN Introducción: La actividad física es una herramienta importante para el manejo de la hipertensión arterial sistémica. Sin embargo, se sabe poco sobre la relación de la actividad física con la cantidad de medicamentos antihipertensivos utilizados por las ancianas. Objetivo: El objetivo de este estudio fue hacer una comparación entre el número de medicamentos antihipertensivos utilizados por mujeres adultas mayores (≥ 60 años) y bajo nivel de actividad física con el número utilizado por aquellas con alto nivel de actividad física, y verificar cuántas de las participantes usaron más de dos medicamentos antihipertensivos. Métodos: Veintiocho ancianas físicamente activas con hipertensión arterial sistémica que participaron en un programa de actividad física para mujeres adultas mayores residentes en la comunidad fueran divididas en dos grupos: las participantes que presentaron niveles más bajos de actividad física habitual se ubicaron en el grupo 1 y las participantes que presentaron los mayores niveles de actividad física se ubicaron en el grupo 2, según el cuestionario de Baecke. Además, se recogió el número de medicamentos antihipertensivos utilizados por las participantes. Resultados: El número de comprimidos antihipertensivos prescritos fue de 2,0 (mediana) para ambos grupos investigados. No hubo diferencia significativa entre los grupos en cuanto al número de medicamentos antihipertensivos prescritos (p>0,05). Aunque no hubo diferencia estadística, una mayor proporción de participantes del grupo de menor actividad física usó más de dos medicamentos antihipertensivos. Conclusión: El nivel de actividad física habitual no afectó el número de comprimidos antihipertensivos utilizados por las ancianas hipertensas. Nivel de evidencia II; Estudios terapéuticos: investigación de los resultados del tratamiento.

RESUMO Introdução: A atividade física é uma importante ferramenta no manejo da hipertensão arterial sistêmica. No entanto, pouco se sabe sobre a relação entre a atividade física e a quantidade de anti-hipertensivos usados por idosos. Objetivo: O objetivo deste estudo foi realizar uma comparação entre o número de anti-hipertensivos usados por idosas (≥ 60 anos) com baixo nível de atividade física com o número usado por aquelas com alto nível de atividade física, verificando quantas participantes usaram mais de dois anti-hipertensivos. Métodos: Vinte e oito idosas fisicamente ativas com hipertensão arterial sistêmica que participavam de um programa de atividade física para idosas da comunidade foram divididas em dois grupos: as participantes que apresentaram níveis mais baixos de atividade física habitual foram colocadas no grupo 1 e as participantes que apresentaram maiores níveis de atividade física foram colocados no grupo 2, de acordo com o questionário de Baecke. Ademais, coletou-se o número de medicamentos anti-hipertensivos utilizados pelas participantes. Resultados: O número de fármacos anti-hipertensivos prescritos foi de 2,0 (mediana) para ambos os grupos investigados. Não houve diferença significativa entre os grupos quanto ao número de comprimidos anti-hipertensivos prescritos (p>0,05). Embora não tenha havido diferença estatística, uma maior proporção de participantes entre o grupo de menor atividade física utilizava mais de dois anti-hipertensivos. Conclusão: O nível de atividade física habitual não afetou a quantidade de comprimidos anti-hipertensivos utilizados pelas idosas hipertensas. Nível de evidência II; Estudos terapêuticos - Investigação dos resultados do tratamento.

Situaciones transoperatorias en pacientes pediátricos con fractura supracondílea del húmero

Introducción: Las fracturas supracondíleas del húmero en el niño, por lo general, son tratadas de manera quirúrgica, durante esa intervención se pueden presentar situaciones específicas en este tipo de enfermos. Objetivo: Actualizar y brindar información sobre algunas de las situaciones transoperatorias en pacientes con fractura supracondílea del húmero. Métodos: La búsqueda y análisis de la información se realizó en un periodo de 61 días (primero de septiembre al 31 de octubre de 2022) y se emplearon palabras de búsqueda relacionadas con la investigación. A partir de la información obtenida, se realizó una revisión bibliográfica de un total de 245 artículos publicados en las bases de datos: PubMed, Hinari, SciELO y Medline, mediante el gestor de búsqueda y administrador de referencias EndNote, de ellos, se utilizaron 29 citas seleccionadas para realizar la revisión, 28 de los últimos cinco años. Resultados: Se hace referencia a cuatro de las situaciones transoperatorias más frecuentes en este tipo de fractura. Se mencionan la conminución de la pared medial, como identificar esta situación y su conducta. En relación a las lesiones asociadas, se recomienda primero estabilizar el antebrazo y luego la fractura supracondílea. Para las fracturas inestables en flexión se recomienda la técnica a emplear. Por su parte, la conversión de la reducción cerrada a abierta está justificada en ciertas circunstancias que de forma detallada se describen en el trabajo. Conclusiones: Las fracturas supracondíleas del húmero en el niño son tratadas en su mayoría mediante tratamiento quirúrgico. Durante el transoperatorio se pueden presentar situaciones para las cuales el médico tratante debe estar preparado.

Introduction: Supracondylar fractures of the humerus in children are generally treated surgically, during surgery intervention may occur specific situations in this type of patient. Objective: To update and provide information on some of the intraoperative situations in patients with supracondylar fracture of the humerus. Methods: The search and analysis of the information was carried out in a period of 61 days (September 1st to October 31st, 2022) and search words related to the investigation were used. Based on the information obtained, a bibliographic review of a total of 245 articles published in the PubMed, Hinari, SciELO and Medline databases was carried out using the EndNote search manager and reference administrator, of which 29 selected citations were used to carry out the review, 28 of the last five years. Results: Reference is made to four of the most frequent intraoperative situations in this type of fracture. Comminution of the medial wall, how to identify this situation and its behavior are mentioned. In relation to associated injuries, it is recommended to first stabilize the forearm and then the supracondylar fracture. For unstable fractures in flexion, the technique to be used is recommended. For its part, the conversion from closed to open reduction is justified in certain circumstances that are described in the article. Conclusions: Supracondylar fractures of the humerus in children are mostly treated by surgical treatment. During the trans-operative period situations may arise for which the treating physician must be prepared.

Bothrops Moojeni Snake Venom: A Source of Potential Therapeutic Agents Against Hemostatic Disorders

Abstract Hemostasis is a complex set of biological processes responsible for blood fluidity within normal vessels and for the physiological interruption of bleeding in cases of vascular injury. Bothrops moojeni snake venom is rich in bioactive compounds of pharmacological and clinical interest since its protein components are capable of interfering with many points of the hemostatic process. Here, we present the B. moojeni venom proteins that affect hemostasis and discuss their pharmacological and clinical potential. This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. Data were obtained from the CAPES Journal Portal database, using the terms "Bothrops" AND "hemostasis", in a search for scientific articles made available in the last 20 years. Many components isolated from B. moojeni snake venom are characterized for their effect on hemostasis and possible application in the diagnosis and treatment of hemostatic disorders.