The History of Controlling and Treating Infectious Diseases in Ancient China

Infectious diseases are the common enemies of mankind.In the course of historical development,they persistently threaten human health and safety.Even today,despite the developments in medical science,we cannot escape the fear and suffering caused by infectious diseases.Whether in ancient or modern times,the source of infection,route of transmission,and a susceptible population are the three key conditions for the prevalence and spread of infectious diseases.All factors closely related to these three conditions can affect the prevalence of infectious diseases.China is one of the cradles of world civilization.The ancient people accumulated a great deal of experience and lessons in the long struggle against infectious diseases.In the face of the current threat posed by widespread infectious disease,it is imperative to review and summarize ancient Chinese ideas and health policies on epidemic prevention and control to inspire contemporary efforts in the prevention and control of infectious disease.The combination of prevention-oriented epidemic prevention ideology and traditional medicine provides valuable insights,especially for impoverished and medically underserved regions.

Application of DDG-3300K Liver Reserve Function Analyzer and Relevant Nursing Procedures at the Department of Infectious Diseases

Objective: To discuss some key points about nursing in the use of DDG-3300K liver reserve function analyzer in patients at the department of infectious diseases. Method: DDG-3300K liver reserve function analyzer was applied to 5464 patients at the department of infectious diseases. The reasons for failed detection and complications related to the detection were analyzed, and the measures for improving the nursing procedures were proposed. Result: Among the 5464 patients, the detections were successful at the first attempt in 5458 patients;2 patients had leakage of liquid;2 patients were poorly prepared, and 1 case failed because of mistaken selection of CO mode, which led to adverse drug reactions;1 case did not finish the detection due to anaphylactic shock;8 patients had nausea and 6 patients had skin rash on the four limbs and torso during the detection. Conclusion: It is necessary to formulate the nursing procedures for the use of DDG-3300K liver reserve function analyzer. Moreover, preparatory work, health education, refined nursing procedures and skillful operations are closely related to the success rate and accuracy of the detection.

Autoimmune hepatitis-primary biliary cholangitis overlap syndrome complicated by various autoimmune diseases:A case report

BACKGROUND Autoimmune hepatitis(AIH)and primary biliary cholangitis(PBC)are two common clinical autoimmune liver diseases,and some patients have both diseases;this feature is called AIH-PBC overlap syndrome.Autoimmune thyroid disease(AITD)is the most frequently overlapping extrahepatic autoimmune disease.Immunoglobulin(IgG)4-related disease is an autoimmune disease recognized in recent years,characterized by elevated serum IgG4 levels and infiltration of IgG4-positive plasma cells in tissues.CASE SUMMARY A 68-year-old female patient was admitted with a history of right upper quadrant pain,anorexia,and jaundice on physical examination.Laboratory examination revealed elevated liver enzymes,multiple positive autoantibodies associated with liver and thyroid disease,and imaging and biopsy suggestive of pancreatitis,hepatitis,and PBC.A diagnosis was made of a rare and complex overlap syndrome of AIH,PBC,AITD,and IgG4-related disease.Laboratory features improved on treatment with ursodeoxycholic acid,methylprednisolone,and azathioprine.CONCLUSION This case highlights the importance of screening patients with autoimmune diseases for related conditions.

Ferritinophagy: A new idea for liver diseases regulated by ferroptosis

Background:The discovery of regulatory cell death has led to a breakthrough in the therapeutic field.Various forms of cell death,such as necrosis,apoptosis,pyroptosis,autophagy,and ferroptosis,play an important role in the development of liver diseases.In general,more than one form of cell death pathways is responsible for the disease state.Therefore,it is particularly important to study the regulation and interaction of various cell death forms in liver diseases.Data sources:We performed a PubMed search up to November 2022 with the following keywords:ferritinophagy,ferroptosis,and liver disease.We also used terms such as signal path,inducer,and inhibitor to supplement the query results.Results:This review summarized the basic characteristics of ferritinophagy and ferroptosis and the regulation of ferroptosis by ferritinophagy and reviewed the key targets and treatment strategies of ferroptosis in different liver diseases.Conclusions:Ferritinophagy is a potential therapeutic target in ferroptosis-related liver diseases.

Characterization of acute-on-chronic liver diseases: A multicenter prospective cohort study

BACKGROUND Acute-on-chronic liver disease(AoCLD)accounts for the majority of patients hospitalized in the Department of Hepatology or Infectious Diseases.AIM To explore the characterization of AoCLD to provide theoretical guidance for the accurate diagnosis and prognosis of AoCLD.METHODS Patients with AoCLD from the Chinese Acute-on-Chronic Liver Failure(ACLF)study cohort were included in this study.The clinical characteristics and outcomes,and the 90-d survival rate associated with each clinical type of AoCLD were analyzed,using the Kaplan-Meier method and the log-rank test.RESULTS A total of 3375 patients with AoCLD were enrolled,including 1679(49.7%)patients with liver cirrhosis acute decompensation(LC-AD),850(25.2%)patients with ACLF,577(17.1%)patients with chronic hepatitis acute exacer-bation(CHAE),and 269(8.0%)patients with liver cirrhosis active phase(LC-A).The most common cause of chronic liver disease(CLD)was HBV infection(71.4%).The most common precipitants of AoCLD was bacterial infection(22.8%).The 90-d mortality rates of each clinical subtype of AoCLD were 43.4%(232/535)for type-C ACLF,36.0%(36/100)for type-B ACLF,27.0%(58/215)for type-A ACLF,9.0%(151/1679)for LC-AD,3.0%(8/269)for LC-A,and 1.2%(7/577)for CHAE.CONCLUSION HBV infection is the main cause of CLD,and bacterial infection is the main precipitant of AoCLD.The most common clinical type of AoCLD is LC-AD.Early diagnosis and timely intervention are needed to reduce the mortality of patients with LC-AD or ACLF.

Parasitosis Diagnosed in the Infectious Diseases Department of the Yalgado Ouédraogo University Hospital from 2010 to 2022: Epidemiological, Clinical and Evolutionary Aspects

Introduction: Parasitic diseases remain a public health problem in Burkina Faso, as they are in other developing countries. Objective: To describe the epidemiological, clinical and evolutionary characteristics of parasitosis diagnosed in the infectious diseases department of the Yalgado Ouédraogo University Hospital. Patients and Method: This is a descriptive cross-sectional study with retrospective data collection during the period from January 1, 2010 to August 31, 2022. Results: From January 1, 2010 to August 31, 2022, a total of 2829 patients were admitted to the infectious diseases department of the Yalgado Ouédraogo University Hospital in Ouagadougou. Among them, 624 patients suffered from parasitic pathologies, representing a hospital prevalence of 22%. The patients were predominantly male with a sex ratio of 1.1. The average age was 34 years ± 11. Most patients (74.7%) lived in the capital city of Ouagadougou. Ten percent (10%) of the patients with parasitosis were infected with HIV (PLHIV). Out of a total of 624 cases of parasitosis, protozoosis represented 97%, of which 80% were malaria cases. Clinical signs were dominated by neurological signs, digestive signs and dehydration. Comorbidities were dominated by HIV infection, tuberculosis and digestive candidiasis. Under treatment, the evolution was marked by a lethality of 10%. Conclusion: Protozoosis were the most frequently diagnosed. They were dominated by malaria and opportunistic parasitosis during AIDS. These results argue for a revitalization of voluntary HIV testing and careful management of PLHIV.

Probabilistic Antibiotic Therapy in the Infectious Diseases Department of the Yalgado Ouédraogo University Hospital (CHU-YO) in Ouagadougou, Burkina Faso

Introduction: In Burkina Faso, as in most developing countries, limited access to biological tests forces practitioners to resort very often to probabilistic antibiotic therapy. The objective of this study is to determine the extent of this prescription. Patients and Methods: This was a cross-sectional study with retrospective data collection of patients hospitalized in the infectious diseases department in the period from January 1, 2005 to December 31, 2020. The records of patients who received probabilistic antibiotic therapy were included. Results: During the study period, 330 patients had received probabilistic antibiotic therapy. The majority of patients were male (53%), with a sex ratio of 1.12. The mean age of the patients was 33 years ± 14. The age range of 20 to 40 years was the most represented (42%). Fifteen percent (15%) of patients were living with HIV. The majority of patients were from urban areas (56.4%). Forty-nine percent (49%) of the patients worked in the informal sector. Clinically, the reasons for consultation were dominated by fever, alteration of general condition, neurological disorders, digestive disorders, respiratory signs, urinary signs and diffuse pain. The physical examination showed that 48.1% of the patients had meningeal irritation syndrome, 10% had convulsions and 10% had focal signs, trismus was present in 4% of the patients and facial paralysis in 3%. In the digestive system, hepatomegaly was present in 29% of patients and digestive candidiasis in 31%. Respiratory examination showed crepitus and fluid effusion syndrome in 26.83% and 20.62% of patients respectively. The presumptive diagnosis was dominated by bacterial meningitis, salmonellosis and bronchopneumonia with banal germs. In terms of treatment, the beta-lactam family of drugs was the most prescribed. They were followed by aminoglycosides and fluoroquinolones. The evolution was marked by the death of 50 patients (15%). Conclusion: The most prescribed molecules belong to the family of Beta-lactam. And this prescription improved the outcome of patients. Bacterial susceptibility studies will allow better orientation of probabilistic antibiotic therapy in order to limit the emergence of multi-resistant bacteria.

Establishment of a Predictive Model Related to Pathogen Invasion for Infectious Diseases and Its Diagnostic Value in Fever of Unknown Origin

The present study aimed to establish a list of parameters indicative of pathogen invasion and develop a predictive model to distinguish the etiologies of fever of unknown origin (FUO) into infectious and non-infectious causes.From January 2014 to September 2017,431 patients with FUO were prospectively enrolled in the study population.This study established a list of 26 variables from the following 4aspects:host factors,epidemiological factors,behavioral factors,and iatrogenic factors.Predefined predicted variables were included in a multivariate logistic regression analysis to develop a predictive model.The predictive model and the corresponding scoring system were developed using data from the confirmed diagnoses and 9 variables were eventually identified.These factors were incorporated into the predictive model.This model discriminated between infectious and non-infectious causes of FUO with an AUC of 0.72,sensitivity of 0.71, and specificity of 0.63.The predictive model and corresponding scoring system based on factors concerning pathogen invasion appear to be reliable screening tools to discriminate between infectious and non-infectious causes of FUO.

An overview of travel-associated central nervous system infectious diseases:risk assessment,general considerations and future directions

Nervous system infections are among the most important diseases in travellers.Healthy travellers might be exposed to infectious agents of central nervous system,which may require in-patient care.Progressive course is not uncommon in this family of disorders and requires swift diagnosis.An overview of the available evidence in the field is.therefore,Urgent to pave the way to increase the awareness of travel-medicine practitioners and highlights dark areas for future research.In November 2013,data were collected from PubMed,Scopus,and Web of knowledge(1980 to2013) including books,reviews,and peer-reviewed literature,Works pertained to pre-travel care,interventions,vaccinations related neurological infections were retrieved.Here we provide information on pre-travel care,vaccination,chronic nervous system disorders,and post-travel complications.Recommendations with regard to knowledge gaps,and state-of-the-art research are made.Given an increasing number of international travellers,novel dynamic ways are available for physicians to monitor spread of central nervous system infections.Newer research has made great progresses in developing newer medications,detecting the spread of infections and the public awareness.Despite an ongoing scientific discussion in the field of travel medicine,further research is required for vaccine development,state-of-the-art laboratory tests,and genetic engineering of vectors.

Conceptual Comparison of Infectious Diseases of TIBBE-AKBARI and Modern Medicine: Akhlat and Mezaj Theory

Background: Treating infectious diseases (ID) is the priority of health systems. Traditional Persian medicine (TPM) has diagnostic and preventive comments in most diseases. Readout TPM gives opportunity to know the viewpoints of ancient Iranian scholars for using these opinions in treating ID. In this regard returning to TPM options and modalities can be useful at least as complementary method in treating ID. For understanding the concepts of ID in TPM first of all it is needed to trace ID in TPM and translate them into western medicine language which is the goal of this report. Methodology: This research includes 80 ID mentioned in TIBBE-AKBARI (one of Persian Medicine textbook) for rewriting and comparing with conventional medicine findings. Findings: The majority of clinical signs, symptoms and physical examinations of ID are comparable with modern medicine except the viewpoint of TPM about aetiology which is based on Akhlat and Mezaj theory. By considering no option for antibiotic therapy in ancients time so there is a completely different opinion in treating ID with modern medicine. Conclusion: IDs have different names in TPM and conventional medicine. In contrast to modern medicine in which micro-organism are as etiologic agents, Akhlat and Mezaj theory of TPM has main role for description of ID, the subject which must to be decoded. Although they have completely different opinions in treatment, but with regard to the increasing of antibiotic resistance issue, TPM treatment comments may be useful in future in ID as complementary method beside antibiotics.

A Clinical Analysis of 293 FUO Patients, A Diagnostic Model Discriminating infectious Diseases from Non-infectious Diseases

Objective A diagnostic model was established to discriminate infectious diseases from non-infectious diseases. Methods The clinical data of patients with fever of unknown origin(FUO) hospitalized in Xiangya Hospital Central South University, from January, 2006 to April, 2011 were retrospectively analyzed. Patients enrolled were divided into two groups. The first group was used to develop a diagnostic model: independent variables were recorded and considered in a logistic regression analysis to identify infectious and non-infectious diseases(αin = 0.05, αout = 0.10). The second group was used to evaluate the diagnostic model and make ROC analysis.Results The diagnostic rate of 143 patients in the first group was 87.4%, the diagnosis included infectious disease(52.4%), connective tissue diseases(16.8%), neoplastic disease(16.1%) and miscellaneous(2.1%). The diagnostic rate of 168 patients in the second group was 88.4%, and the diagnosis was similar to the first group. Logistic regression analysis showed that decreased white blood cell count(WBC < 4.0×109/L), higher lactate dehydrogenase level(LDH > 320 U/L) and lymphadenectasis were independent risk factors associated with non-infectious diseases. The odds ratios were 14.74, 5.84 and 5.11(P ≤ 0.01), respectively. In ROC analysis, the sensitivity and specificity of the positive predictive values was 62.1% and 89.1%, respectively, while that of negative predicting values were 75% and 81.7%, respectively(AUC = 0.76, P = 0.00).Conclusions The combination of WBC < 4.0×109/L, LDH > 320 U/L and lymphadenectasis may be useful in discriminating infectious diseases from non-infectious diseases in patients hospitalized as FUO.

Invasive aspergillosis in liver transplant recipients, an infectious complication with low incidence but significant mortality

BACKGROUND Infections,including invasive fungal infections(IFIs),are among the leading causes of mortality in liver transplant recipients during the first year posttransplantation.AIM To investigate the epidemiology,clinical manifestations,risk factors,treatment outcomes,and mortality rate of post-liver transplantation invasive aspergillosis(IA).METHODS In this case-control study,22 patients with IA were identified by reviewing the archived and electronic medical records of 850 patients who received liver transplants at the Imam Khomeini Hospital complex in Tehran,Iran,between 2014 and 2019.The control group comprised 38 patients without IA infection matched for age and sex.The information obtained included the baseline characteristics of liver transplant patients,operative reports,post-transplantation characteristics of both groups and information about the fungal infection of the patient group.RESULTS The prevalence rate of IA among liver transplant recipients at Imam Khomeini Hospital was 2.7%.The risk factors of IA among studied patients included high serum creatinine levels before and post-transplant,renal replacement therapy,antithymocyte globulin induction therapy,post-transplant bile leakage,posttransplant hepatic artery thrombosis,repeated surgery within 30 d after the transplant,bacterial pneumonia before the aspergillosis diagnosis,receiving systemic antibiotics before the aspergillus infection,cytomegalovirus infection,and duration of post-transplant hospitalization in the intensive care unit.The most prevalent form of infection was invasive pulmonary aspergillosis,and the most common chest computed tomography scan findings were nodules,pleural effusion,and the halo sign.In the case group,prophylactic antifungal therapy was administered more frequently than in the control group.The antifungal therapy response rate at 12 wk was 63.7%.The 3-and 12-mo mortality rates of the patients with IA were 36.4%and 45.4%,respectively(compared with the mortality rate of the control group in 12 mo,which was zero).CONCLUSION In this study,the prevalence of IA among liver transplant recipients was relatively low.However,it was one of the leading causes of mortality following liver transplantation.Targeted antifungal therapy may be a factor in the low incidence of infections at our facility.Identifying the risk factors of IFIs,maintaining an elevated level of clinical suspicion,and initiating early antifungal treatment may significantly improve the prognosis and reduce the mortality rate of liver transplant recipients.

Progressive Characteristics of HIV Infection in the Elderly in the Cohort of the Internal Medicine Department of the Points G University Hospital, Bamako. Mali

Few data are available on HIV infection in the elderly and they are an important population in our different cohorts in view of the improvement in the quality of care over the last ten years. Objective: to determine the clinical and immunovirological characteristics as well as the acceptance of antiretroviral drugs in this patient population. This is a cohort study of the files of PLHIV (People living with HIV) aged 50 years or more, followed in the Internal Medicine Department of the Point G University Hospital between January 2007 and December 2012. Results: Out of 161 HIV-infected patients in the cohort, 38 were aged 50 years or older, of whom 11 met the criteria and were included. The median age was 55 years, 90.9% of whom were in the [50 - 59 years] age group, with 63.6% being women (sex ratio = 0.57). At admission, 3 patients (27.3%) had prurigo and 2 (18.2%) had oral-pharyngeal candidiasis. At inclusion, 45.5% of patients were classified as WHO stage 2 and one as WHO stage 4. All were on ARVs, including 10 on 1st line HIV-1 and 1 on HIV-2. On triple therapy, the average weight gain was 5.1 kg at D15 and 6.84 kg at M6. However, at M12 there was a weight loss of 1.04 kg. The mean CD4 T cell gain was +102/mm3 at M6 and +188/mm3 at 12 months. At D0, mean viral load = 565024.75 copies/mm3 [99 - 1100000] in 4/11. At M12, two patients had undetectable viral loads. Conclusion: The prevalence of HIV in elderly subjects is certainly underestimated. Thanks to triple antiretroviral therapy, PLHIV are aging with HIV but screening is not systematically proposed during consultations in elderly subjects. It is necessary to reinforce communication about HIV at all ages.

Otorhinolaryngology Diseases in HIV-Positive Patients: 208 Cases at the Donka National Hospital

Introduction: Otorhinolaryngology (ENT) diseases in patients living with Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/ AIDS) are relatively common and of concern to ENT specialists and other health professionals. Aim: It was to describe the epidemiological and diagnostic aspects of ENT and cervicofacial diseases in patients living with HIV/ AIDS. Material and Methods: This was a descriptive study with prospective data collection, conducted over a period of six months (September 16, 2019 to March 16, 2020), carried out at the ENT and Infectious Diseases Departments of the Donka National Hospital. Results: Of 522 HIV-positive patients, 208 (39.8%) presented with ENT diseases. Women represented 62.5% with a sex ratio of 0.6. The mean age was 42.21 years with extremes of 16 and 64 years. Housewives were the most represented (29.8%). Married people were the most affected (76.4%). Cervical involvement was present in 7.7% of patients. Otologic involvement accounted for 43.7%. Oral cavity and pharyngolaryngeal involvement accounted for 50.9%. Nasosinus involvement accounted for 55.7%. HIV type I was the most common (99.5%). Conclusion: Otorhinolaryngology diseases were frequent in HIV positive patients. They may constitute the first reason for consultation. However, these ENT diseases remain in appendix of the opportunistic diseases of HIV/AIDS taking the front stage.

AGK2 pre-treatment protects against thioacetamide-induced acute liver failure via regulating the MFN2-PERK axis and ferroptosis signaling pathway

Background:Acute liver failure(ALF)is an unpredictable and life-threatening critical illness.The pathological characteristic of ALF is massive necrosis of hepatocytes and lots of inflammatory cells infiltration which may lead to multiple organ failure.Methods:Animals were divided into 3 groups,normal,thioacetamide(TAA,ALF model)and TAA+AGK2.Cultured L02 cells were divided into 5 groups,normal,TAA,TAA+mitofusin 2(MFN2)-siRNA,TAA+AGK2,and TAA+AGK2+MFN2-siRNA groups.The liver histology was evaluated with hematoxylin and eosin staining,inositol-requiring enzyme 1(IRE1),activating transcription factor 6β(ATF6β),protein kinase R(PKR)-like endoplasmic reticulum kinase(PERK)and phosphorylated-PERK(p-PERK).C/EBP homologous protein(CHOP),reactive oxygen species(ROS),MFN2 and glutathione peroxidase 4(GPX4)were measured with Western blotting,and cell viability and liver chemistry were also measured.Mitochondriaassociated endoplasmic reticulum membranes(MAMs)were measured by immunofluorescence.Results:The liver tissue in the ALF group had massive inflammatory cell infiltration and hepatocytes necrosis,which were reduced by AGK2 pre-treatment.In comparison to the normal group,apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+in the TAA-induced ALF model group were significantly increased,which were decreased by AGK2 pre-treatment.The levels of MFN2 and GPX4 were decreased in TAA-induced mice compared with the normal group,which were enhanced by AGK2 pretreatment.Compared with the TAA-induced L02 cell,apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+were further increased and levels of MFN2 and GPX4 were decreased in the MFN2-siRNA group.AGK2 pre-treatment decreased the apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+and enhanced the protein expression of MFN2 and GPX4 in MFN2-siRNA treated L02 cell.Immunofluorescence observation showed that level of MAMs was promoted in the AGK2 pre-treatment group when compared with the TAA-induced group in both mice and L02 cells.Conclusions:The data suggested that AGK2 pre-treatment had hepatoprotective role in TAA-induced ALF via upregulating the expression of MFN2 and then inhibiting PERK and ferroptosis pathway in ALF.

Antiviral treatment standards for hepatitis B:An urgent need for expansion

The present letter to the editor is related to the review with the title“Past,present,and future of long-term treatment for hepatitis B virus.”Chronic hepatitis B(CHB)represents an important and pressing public health concern.Timely identification and effective antiviral therapy hold the potential to reduce liver-related mortality attributable to chronic infection with hepatitis B virus(HBV)substantially.However,the current global treatment rates for CHB remain conspicuously low,with the excessively stringent treatment criteria advocated by national CHB guidelines being a contributing factor to these low rates.Nevertheless,recent strides in comprehending this malady and the emergence of novel antiviral agents prompt the imperative re-evaluation of treatment standards to extend the sphere of potential beneficiaries.An impending need arises for a novel paradigm for the classification of patients with CHB,the expansion of antiviral treatment eligibility for HBV-infected individuals,and even the streamlining of the diagnostic process for CHB to amplify cost-effectiveness and augment survival prospects.

国际糖尿病足工作组:指南的制定和方法学(2023)——《国际糖尿病足工作组:糖尿病相关的足病预防与管理指南(2023)》的一部分

糖尿病相关的足病是造成糖尿病患者经济负担和增加社会成本的主要原因之一。本指南以主要目标为导向,以循证医学为依据,且在全球得到合理实施。践行国际糖尿病相关的足病指南对于减轻患者经济负担和社会成本有着重要影响。国际糖尿病足工作组(IWGDF)从1999年起开始发布并随后更新国际指南。2023年更新版指南相关推荐均基于推荐、评估、发展和评价分级(GRADE)系统,包括制定相关临床问题和重要结局,完成系统的文献系统综述和荟萃分析,完成评判表汇总,并且给予具体、明确、操作性强的推荐以及理论依据。本文阐述了《国际糖尿病足工作组:糖尿病相关的足病预防和管理指南(2023版)》(以下简称为指南)的制定过程。指南由7个部分组成,包括预防、糖尿病相关的足溃疡分类、减压、周围动脉病变、感染、创面愈合干预以及活动性夏科神经骨关节病,分别由7个独立的国际专家工作组编写。IWGDF编辑委员会对7个章节进行了整合和简化,形成IWGDF实践指南。指南中的每条推荐均经过IWGDF编辑委员会成员和相关领域的独立的国际专家审阅通过。本文是IWGDF指南的制定和方法学。我们相信,医务人员、公共卫生机构和政策制定者采用和实施2023年IWGDF指南,将会改善糖尿病相关的足病的预防和管理水平,从而减少全球该疾病患者和减轻该疾病引起的全球社会负担。

Silent information regulator sirtuin 1 ameliorates acute liver failure via the p53/glutathione peroxidase 4/gasdermin D axis

BACKGROUND Acute liver failure(ALF)has a high mortality with widespread hepatocyte death involving ferroptosis and pyroptosis.The silent information regulator sirtuin 1(SIRT1)-mediated deacetylation affects multiple biological processes,including cellular senescence,apoptosis,sugar and lipid metabolism,oxidative stress,and inflammation.AIM To investigate the association between ferroptosis and pyroptosis and the upstream regulatory mechanisms.METHODS This study included 30 patients with ALF and 30 healthy individuals who underwent serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)testing.C57BL/6 mice were also intraperitoneally pretreated with SIRT1,p53,or glutathione peroxidase 4(GPX4)inducers and inhibitors and injected with lipopolysaccharide(LPS)/D-galactosamine(D-GalN)to induce ALF.Gasdermin D(GSDMD)^(-/-)mice were used as an experimental group.Histological changes in liver tissue were monitored by hematoxylin and eosin staining.ALT,AST,glutathione,reactive oxygen species,and iron levels were measured using commercial kits.Ferroptosis-and pyroptosis-related protein and mRNA expression was detected by western blot and quantitative real-time polymerase chain reaction.SIRT1,p53,and GSDMD were assessed by immunofluorescence analysis.RESULTS Serum AST and ALT levels were elevated in patients with ALF.SIRT1,solute carrier family 7a member 11(SLC7A11),and GPX4 protein expression was decreased and acetylated p5,p53,GSDMD,and acyl-CoA synthetase long-chain family member 4(ACSL4)protein levels were elevated in human ALF liver tissue.In the p53 and ferroptosis inhibitor-treated and GSDMD^(-/-)groups,serum interleukin(IL)-1β,tumour necrosis factor alpha,IL-6,IL-2 and C-C motif ligand 2 levels were decreased and hepatic impairment was mitigated.In mice with GSDMD knockout,p53 was reduced,GPX4 was increased,and ferroptotic events(depletion of SLC7A11,elevation of ACSL4,and iron accumulation)were detected.In vitro,knockdown of p53 and overexpression of GPX4 reduced AST and ALT levels,the cytostatic rate,and GSDMD expression,restoring SLC7A11 depletion.Moreover,SIRT1 agonist and overexpression of SIRT1 alleviated acute liver injury and decreased iron deposition compared with results in the model group,accompanied by reduced p53,GSDMD,and ACSL4,and increased SLC7A11 and GPX4.Inactivation of SIRT1 exacerbated ferroptotic and pyroptotic cell death and aggravated liver injury in LPS/D-GalNinduced in vitro and in vivo models.CONCLUSION SIRT1 activation attenuates LPS/D-GalN-induced ferroptosis and pyroptosis by inhibiting the p53/GPX4/GSDMD signaling pathway in ALF.

Bayesian network-based survival prediction model for patients having undergone post-transjugular intrahepatic portosystemic shunt for portal hypertension

BACKGROUND Portal hypertension(PHT),primarily induced by cirrhosis,manifests severe symptoms impacting patient survival.Although transjugular intrahepatic portosystemic shunt(TIPS)is a critical intervention for managing PHT,it carries risks like hepatic encephalopathy,thus affecting patient survival prognosis.To our knowledge,existing prognostic models for post-TIPS survival in patients with PHT fail to account for the interplay among and collective impact of various prognostic factors on outcomes.Consequently,the development of an innovative modeling approach is essential to address this limitation.AIM To develop and validate a Bayesian network(BN)-based survival prediction model for patients with cirrhosis-induced PHT having undergone TIPS.METHODS The clinical data of 393 patients with cirrhosis-induced PHT who underwent TIPS surgery at the Second Affiliated Hospital of Chongqing Medical University between January 2015 and May 2022 were retrospectively analyzed.Variables were selected using Cox and least absolute shrinkage and selection operator regression methods,and a BN-based model was established and evaluated to predict survival in patients having undergone TIPS surgery for PHT.RESULTS Variable selection revealed the following as key factors impacting survival:age,ascites,hypertension,indications for TIPS,postoperative portal vein pressure(post-PVP),aspartate aminotransferase,alkaline phosphatase,total bilirubin,prealbumin,the Child-Pugh grade,and the model for end-stage liver disease(MELD)score.Based on the above-mentioned variables,a BN-based 2-year survival prognostic prediction model was constructed,which identified the following factors to be directly linked to the survival time:age,ascites,indications for TIPS,concurrent hypertension,post-PVP,the Child-Pugh grade,and the MELD score.The Bayesian information criterion was 3589.04,and 10-fold cross-validation indicated an average log-likelihood loss of 5.55 with a standard deviation of 0.16.The model’s accuracy,precision,recall,and F1 score were 0.90,0.92,0.97,and 0.95 respectively,with the area under the receiver operating characteristic curve being 0.72.CONCLUSION This study successfully developed a BN-based survival prediction model with good predictive capabilities.It offers valuable insights for treatment strategies and prognostic evaluations in patients having undergone TIPS surgery for PHT.

Dengue hemorrhagic fever with rectus sheath hematoma:A case report

Rationale:Acute pain is a medical emergency that requires prompt abdominal evaluation and management.Dengue,a mosquito-borne arboviral infection,can lead to complications such as acute abdominal pain.Patient concerns:A 72-year-old hypertensive female presented with high-grade intermittent fever with chills and rigors for four days.She was diagnosed with dengue fever(NS1Ag-reactive)the day before admission.A contrast-enhanced computed tomography of the abdomen showed a hematoma along the rectus sheath which was managed conservatively as per surgical opinion.Diagnosis:Dengue hemorrhagic fever with rectus sheath hematoma.Interventions:Blood transfusion and fluid therapy.Outcomes:Ten days after discharge,the patient reproted no pain in the right iliac fossa and the size of the hematoma was significantly reduced.Lessons:Although it is rarely seen as a cause of acute abdomen,complaints of adnominal pain should never be ignored in critical or convalescent phase of dengue fever.Radiological investigations should be promptly conducted as hematoma is often difficult to be diagnosed clinically.Delay in diagnosis of rectus sheath hematoma can be fatal.