Hepatic tuberculosis particularly in the absence of military tuberculosis is rare.It can occur as a primary case or due to reactivation of an old tubercular focus.We report case of a 24 year old married female who die...Hepatic tuberculosis particularly in the absence of military tuberculosis is rare.It can occur as a primary case or due to reactivation of an old tubercular focus.We report case of a 24 year old married female who died of primary hepatic tuberculosis.She had no evidence of tuberculosis elsewhere.Appropriale treatment initiated early can result in marked recovery whereas failure to recognize this entity can prove to be fatal.展开更多
BACKGROUND While tuberculosis(TB)itself is a common disease,isolated TB of the liver is a rare entity.Tubercular involvement of the liver is more commonly a part of a disseminated disease of the hepatic parenchyma.In ...BACKGROUND While tuberculosis(TB)itself is a common disease,isolated TB of the liver is a rare entity.Tubercular involvement of the liver is more commonly a part of a disseminated disease of the hepatic parenchyma.In contrast,isolated hepatic TB spread through the portal vein from the gastrointestinal tract is seldom encountered in clinical practice,with only a few sporadic cases and short series available in the current literature.Vascular complications,such as portal vein thrombosis(PVT),have rarely been reported previously.CASE SUMMARY A 22-year-old man was hospitalized with complaints of a 3-mo history of fever and weight loss of approximately 10 kg.He had a 10-year hepatitis B virus(HBV)infection in his medical history.Contrast-enhanced computed tomography(CECT)confirmed hepatosplenomegaly,with hypodensity of the right lobe of the liver and 2.1 cm thrombosis of the right branch of the portal vein.A liver biopsy showed epithelioid granulomas with a background of caseating necrosis.ZiehlNelson staining showed acid-fast bacilli within the granulomas.The patient was diagnosed with isolated hepatic TB with PVT.Anti-TB therapy(ATT),including isoniazid,rifapentine,ethambutol,and pyrazinamide,was administered.Along with ATT,the patient was treated with entecavir as an antiviral medication against HBV and dabigatran as an anticoagulant.He remained asymptomatic,and follow-up sonography of the abdomen at 4 mo showed complete resolution of the PVT.CONCLUSION Upon diagnosis of hepatic TB associated with PVT and HBV coinfection,ATT and anticoagulants should be initiated to prevent subsequent portal hypertension.Antiviral therapy against HBV should also be administered to prevent severe hepatic injury.展开更多
BACKGROUND Hepatic tuberculosis(TB)is uncommon clinically.Because of a lack of specific signs,characteristic symptoms and clinical manifestations and because pathological samples are difficult to obtain,hepatic TB is ...BACKGROUND Hepatic tuberculosis(TB)is uncommon clinically.Because of a lack of specific signs,characteristic symptoms and clinical manifestations and because pathological samples are difficult to obtain,hepatic TB is easily missed or misdiagnosed.CASE SUMMARY A 62-year-old Chinese man presented with jaundice for 1 wk and no abnormal laboratory tests other than elevated bilirubin,aminotransferases and C-reactive protein.Computed tomography(CT)of the abdomen showed a mass in the left lobe of the liver and hepatic hilum with striped calcified foci.Mild enhancement was visible at the edges,along with extensive intrahepatic biliary ductal dilatation in the right lobe of the liver.In the arterial phase of both CT and magnetic resonance imaging,the main trunk and right branch of the portal artery were partially visualized.Magnetic resonance cholangiopancreatography(MRCP)indicated that the left lobe of the liver and most of the bile ducts in the hilum were not visible.Pathological examination revealed coagulative necrosis,and granulomatous nodules were seen around areas of necrosis;therefore,TB was considered.CONCLUSION Hepatic tuberculosis is easily misdiagnosed or missed on imaging.Percutaneous puncture biopsy is the most useful tool for definitive diagnosis.展开更多
To evaluate hepatic injury induced by antituberculosis drugs(ATDs) when administered orally for 2, 4, 6 and 8 weeks and the therapeutic potential of propolis(bee hive product) against ATDs induced hepatic injury. Meth...To evaluate hepatic injury induced by antituberculosis drugs(ATDs) when administered orally for 2, 4, 6 and 8 weeks and the therapeutic potential of propolis(bee hive product) against ATDs induced hepatic injury. Methods: The ATDs were administered for 8 weeks as well as propolis extract at three different doses(100, 200, 400 mg/kg) conjointly for 8 weeks in rats. Silymarin(50 mg/kg) was given as positive control. Animals were euthanized after 8 weeks; blood and liver samples were collected to perform various biochemicals, serological and histopathological and ultramorphological studies. Results: Significant increase(P < 0.05) in aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, triglyceride and cholesterol along with reduction in glucose and albumin level were noted after ATDs induced hepatic injury. Significant increase(P < 0.05) in lipid peroxidation, triglyceride, cholesterol and CYP2E1 activity; decline in reduced glutathione, catalase, superoxide dismutase, glutathione reductase, glutathione peroxidase, glucose-6-phosphatase dehydrogenase activity were observed after ATDs intoxication. Due to presence of a wide range of flavonoids and polyphenols in propolis extract, its administration reduced hepatic injury and maintained biochemical indices towards control. Histopathological and electron microscopic observations indicated hepatoprotective potential of propolis at cellular level whereas, TNF-α, IL-6 and IGF-1 confirmed therapeutic potential of propolis at molecular level. Conclusions: It can be concluded that propolis possess hepatoprotective potential against ATDs induced hepatic injury that may prove itself as a clinically useful natural product in management of drug induced liver injury.展开更多
Primary hepatic leiomyosarcoma is a very rare disease,accounting for less than 1%of all primary hepatic malignancies[1].As a malignant tumor of the smooth muscle,it originates in the hepatic blood vessels,bile ducts o...Primary hepatic leiomyosarcoma is a very rare disease,accounting for less than 1%of all primary hepatic malignancies[1].As a malignant tumor of the smooth muscle,it originates in the hepatic blood vessels,bile ducts or round ligaments of the liver[2,3].The clinical manifestations are nonspecific,and tumors are usually asymptomatic until they are relatively large in size.Primary hepatic leiomyosarcoma is characterized by a relatively poor prognosis and aggressive metastatic potential[3].The specific etiology and pathogenesis of primary hepatic leiomyosarcoma are still unclear.Several studies indicated that primary hepatic leiomyosarcoma might be related to acquired immune deficiency syndrome[4],Epstein-Barr virus[5],immunosuppression after organ transplantation[6],hepatitis virus[7,8],Hodgkin’s lymphoma[9]and other medical histories.Here,we present a case of primary hepatic leiomyosarcoma.展开更多
Background:Skeletal tuberculosis(TB)remains a persistent clinical and research chal-lenge due to its chronic course,osteolytic destruction,and the limitations of existing animal models,which often require high-level b...Background:Skeletal tuberculosis(TB)remains a persistent clinical and research chal-lenge due to its chronic course,osteolytic destruction,and the limitations of existing animal models,which often require high-level biosafety containment or fail to repli-cate human skeletal pathology.Methods:This study developed a biosafe,accessible,and versatile murine model of skeletal TB using Mycobacterium smegmatis,a fast-growing,nonpathogenic myco-bacterial species with high genomic homology to Mycobacterium tuberculosis.Three infection routes-subperiosteal calvarial injection,intratibial injection,and intra-cardiac inoculation-were systematically evaluated for their ability to induce lo-calized versus disseminated bone infection under standard biosafety level(BSL)-1 conditions.Results:Subperiosteal calvarial and intratibial injection of M.smegmatis induced local-ized bone lesions characterized by osteolysis,sequestrum formation,granulomatous inflammation,and increased osteoclast activity.Intratibial infection additionally trig-gered compartment-specific immune responses,including neutrophil and macrophage expansion,transient B-cell depletion,and activation of interferon-γ^(+)(IFN-γ^(+))T cells,reflecting active immune remodeling at the infection site.Systemic dissemination via intracardiac injection reproducibly generated progressive vertebral and tibial bone destruction with organized granuloma formation and immune cell infiltration but without prominent sequestrum formation.Compared to intratibial infection,intracar-diac delivery exhibited lower intragroup variability and more closely recapitulated the diffuse progression of extrapulmonary skeletal tuberculosis.Conclusions:This M.smegmatis-based murine model provides a straightforward,reliable,and immunopathologically relevant platform for exploring host-pathogen dynamics,immune-driven bone destruction,and early-stage therapeutic testing in skeletal TB,all within standard BSL-1 laboratories.This model fills a critical gap by enabling BSL-1 research into skeletal TB mechanisms and drug development.展开更多
BACKGROUND Tuberculous osteitis is a chronic,granulomatous bone infection that frequently results in impaired bone healing following surgery.Despite surgical intervention and prolonged anti-tuberculous therapy,complet...BACKGROUND Tuberculous osteitis is a chronic,granulomatous bone infection that frequently results in impaired bone healing following surgery.Despite surgical intervention and prolonged anti-tuberculous therapy,complete bone regeneration often remains unachieved,contributing to subsequent orthopedic complications.AIM To investigate the efficacy and safety of pamidronate in promoting bone regeneration following surgical treatment of experimental animal tuberculous osteitis.METHODS A controlled randomized basic study of rabbit femoral tuberculosis induced by Mycobacterium tuberculosis strain H37Rv included surgical removal of infected tissue and implantation of osteoinductive bone grafts with the following animal allocation to one of three groups:(1)Bisphosphonates alone;(2)Bisphosphonates combined with anti-tuberculous therapy;and(3)Anti-tuberculous therapy alone.The control group consisted of animals that received no surgical or medical treatment.Clinical evaluations,biochemical markers,micro-computed tomography imaging,and histomorphometry analyses were conducted at 3 months and 6 months postoperatively.RESULTS Pamidronate treatment significantly reduced early implant resorption,increased osteoblastic activity,improved trabecular bone regeneration,and maintained graft integrity compared to the anti-tuberculous therapy-only group.Histologically,pamidronate led to enhanced vascular remodeling and increased bone matrix formation.Crucially,bisphosphonate therapy demonstrated safety,compatibility with anti-tuberculous medications,and did not exacerbate tuberculous inflammation.Furthermore,micro-computed tomography analysis revealed a significant increase in trabecular thickness and density in pamidronate-treated groups,underscoring the anabolic effects of bisphosphonates.Morphometric evaluation confirmed a marked reduction in osteoclast number and activity at graft interfaces.These combined radiological,histological,and biochemical data collectively demonstrate the efficacy of pamidronate as an adjunctive agent in enhancing bone repair outcomes following surgical intervention for tuberculous osteitis.CONCLUSION A single intravenous dose of pamidronate significantly enhances bone regeneration and prevents implant resorption following surgical treatment of tuberculous osteitis.The following prospective studies are needed.展开更多
Advanced age impairs bone fracture healing;the underlying mechanism of this phenomenon remains unknown.We determined that apolipoprotein E(ApoE)increases with age and causes poor fracture healing.After deletion of hep...Advanced age impairs bone fracture healing;the underlying mechanism of this phenomenon remains unknown.We determined that apolipoprotein E(ApoE)increases with age and causes poor fracture healing.After deletion of hepatic ApoE expression(ΔApoE),24-month-oldΔApoE mice displayed a 95%reduction in circulating ApoE levels and significantly improved fracture healing.ApoE treatment of aged BMSCs inhibited osteoblast differentiation in tissue culture models;RNA-seq,Western blot,immunofluorescence,and RT-PCR analyses indicated that the Wnt/β-catenin pathway is the target of this inhibition.Indeed,we showed that ApoE had no effect on cultures with stabilizedβ-catenin levels.Next,we determined that Lrp4 serves as the osteoblast cell surface receptor to ApoE,as expression of Lrp4 is required in ApoE-based inhibition of Wnt/β-catenin signaling and osteoblast differentiation.Importantly,we validated this ApoE-Lrp4-Wnt/β-catenin molecular mechanism in human osteoblast differentiation.Finally,we identified an ApoE-neutralizing antibody(NAb)and used it to treat aged,wildtype mice 3 days after fracture surgery resulting in fracture calluses with 35%more bone deposition.Our work here identifies novel liver-to-bone cross-talk and a noninvasive,translatable therapeutic intervention for aged bone regeneration.展开更多
Tuberculosis(TB),one of the oldest infectious diseases caused by Mycobacterium tuberculosis,poses a considerable challenge to global public health.There are approximately 10 million new TB cases worldwide annually,and...Tuberculosis(TB),one of the oldest infectious diseases caused by Mycobacterium tuberculosis,poses a considerable challenge to global public health.There are approximately 10 million new TB cases worldwide annually,and TB claims the lives of nearly 3 million people each year,making it one of the leading causes of death from a single infectious disease[1].China ranks third globally in terms of TB burden,with approximately 733,000 TB cases reported in 2023[2].Based on the ecological model of health determinants developed by Whitehead and Dahlgren,health determinants can be classified into direct causes.展开更多
Tuberculosis(TB)continues to pose a significant threat to global public health,necessitating rapid and precise diagnostic methods and comprehensive detection of antimicrobial resistance(AMR)to facilitate timely clinic...Tuberculosis(TB)continues to pose a significant threat to global public health,necessitating rapid and precise diagnostic methods and comprehensive detection of antimicrobial resistance(AMR)to facilitate timely clinical management.Traditional diagnostic techniques suffer from extended turnaround times and limited ability to comprehensively profile AMR,often resulting in delayed therapeutic interventions.Highthroughput sequencing(HTS)technologies have revolutionized pathogen research by significantly improving diagnostic speed and accuracy.In the context of TB,diverse sequencing strategies and platforms are being employed to fulfill specific research goals,ranging from elucidating the molecular mechanisms underlying AMR to characterizing the genomic diversity among clinical isolates.This review systematically examines current progress in the application of HTS for rapid pathogen identification,comprehensive AMR profiling,epidemiological studies,advances in novel drugs,and vaccine development.Furthermore,we address existing technological limitations and bioinformatics challenges and explore the future directions necessary for effectively integrating HTS-based methodologies into global TB control efforts.展开更多
Objective To determine the proportions of drug-resistant tuberculosis(TB),its trends,and the drug resistance-conferring mutations among patients with pulmonary TB aged 10-24 years in China.Methods The data of patients...Objective To determine the proportions of drug-resistant tuberculosis(TB),its trends,and the drug resistance-conferring mutations among patients with pulmonary TB aged 10-24 years in China.Methods The data of patients with pulmonary TB were retrieved from a national drug-resistant TB survey for analysis.Joinpoint regression software was used to analyze time trends.We also used whole genome sequencing to analyze the lineages and drug resistance-conferring mutations of 621 isolates.Results Among 4,235 patients with pulmonary TB,the proportion of new cases of multidrug-resistant tuberculosis(MDR-TB)was 3.18%(95%confidence interval[CI]:2.37-4.15)for adolescents and 3.76%(95%CI:3.03-4.60)for young adults;for previously treated patients,MDR-TB accounted for 11.25%(95%CI:5.28-20.28)of adolescents and 11.05%(95%CI:6.88-16.55)of young adults.The proportion of patients with MDR-TB remained stable among both new and previously treated patients aged 10-24 years during the study period.Through whole genome sequencing,we found that the most common mutations in the MDR-TB strains were Ser315Thr in the katG gene(71.74%)and Ser450Leu in the rpoB gene(50.00%).Conclusion This study revealed a high proportion of MDR-TB among adolescents and young adults,indicating that urgent and comprehensive measures are needed to reduce the emergence and transmission of drug-resistant TB among this population in China.展开更多
Objective Post tuberculosis lung disease(PTLD)manifests in various forms,including tuberculosisassociated chronic obstructive pulmonary disease(TB-COPD),yet the clinical features of PTLD remain undercharacterized.This...Objective Post tuberculosis lung disease(PTLD)manifests in various forms,including tuberculosisassociated chronic obstructive pulmonary disease(TB-COPD),yet the clinical features of PTLD remain undercharacterized.This study aimed to assess longitudinal changes in lung function over a 5-year period and to identify predictors of airflow obstruction in a cohort of patients treated for active pulmonary TB.Methods Patients with active pulmonary TB were enrolled in this study and were followed during treatment,at treatment completion and five years post-treatment.Assessments included lung function and chest CT,analyzing longitudinal trends and airflow obstruction risk factors.Results Among 53 patients(mean age 36.9±13.9 years;64.2%male),7 patients(13.2%)exhibited airflow obstruction.At the 5-year follow-up,the mean FEV_(1)/FVC declined significantly(76.27%±12.04%vs.80.23%±11.02%,P<0.001)and 9 patients(17.0%)exhibited airflow obstruction.Seven of these patients predominantly showed air trapping consistent with small airway disease on chest CT,aligning with TB-COPD phenotype.Notably,four young-to-middle-aged patients(<60 years old)had persistent obstruction over the five years.Conclusion The initial test revealed that 13.2%of patients presented with airflow obstruction.By the 5-year follow-up,this proportion had increased to 17.0%,with most cases demonstrating imaging findings aligning with TB-COPD,even among younger,non-smoking individuals.These findings emphasize the importance of long-term follow-up and routine lung function assessments in TB survivors.展开更多
Diabetes is accompanied by oxidative damage,inflammation,and disorder of metabolic profiles.Dietary procyanidins have been reported to alleviate symptoms of diabetes,however,the underlying mechanism through which proc...Diabetes is accompanied by oxidative damage,inflammation,and disorder of metabolic profiles.Dietary procyanidins have been reported to alleviate symptoms of diabetes,however,the underlying mechanism through which procyanidins impact liver metabolic function remains unclear.Here,the effects of p eanut skin procyanidins(PSP)on oxidative stress,inflammatory injury,and dysregulated metabolism in the liver of diabetic mice were evaluated.The results showed that PSP r educed the accumulation of cholesterol and alleviated oxidative stress and inflammatory response in the liver.Moreover,PSP enhanced i nsulin signaling by increasing hepatic protein expression of insulin receptor substrate 1/phosphatidylinositol-3-kinase/protein kinase B.Untargeted metabolomics revealed that PSP altered bile acid biosynthesis,alpha linolenic acid and linoleic acid,arachidonic acid,and glycolipid metabolism in the liver.This study reveals positive effects of PSP in alleviating liver dysfunction in diabetic mice.展开更多
To assess the effectiveness of vaccination in contaminated environments,this study introduces a modeling framework that encompasses two transmission routes,namely direct human-to-human contact and indirect human-to-en...To assess the effectiveness of vaccination in contaminated environments,this study introduces a modeling framework that encompasses two transmission routes,namely direct human-to-human contact and indirect human-to-environment contact,as well as the implementation of new M72/AS01_(E)vaccine.Motivated by this,a coupled age-structured tuberculosis(TB)model is proposed.Its well-posedness requirement is verified using the integrated semigroup theory.Furthermore,this study presents a comprehensive analysis of threshold dynamics associated with the proposed model.Specifically,the global stability of the disease-free and positive steady states is demonstrated by employing Lyapunov functionals.Lastly,the effects of the vaccination with M72/AS01_(E)and contaminated environments on TB control are numerically simulated.Experimental results indicate that high concentrations of Mycobacterium tuberculosis in contaminated environments may somewhat impede TB control efforts,but that large-scale deployment of new vaccine could significantly reduce the prevalence of TB.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is a major type of liver cancer worldwide.In advanced stages,portal vein tumor thrombosis(PVTT)and jaundice are common,whereas obstructive jaundice(OJ)is relatively rare.Both co...BACKGROUND Hepatocellular carcinoma(HCC)is a major type of liver cancer worldwide.In advanced stages,portal vein tumor thrombosis(PVTT)and jaundice are common,whereas obstructive jaundice(OJ)is relatively rare.Both conditions markedly reduce survival and increase therapeutic complexity.Recently,hepatic artery infusion chemotherapy(HAIC)in combination with targeted immunotherapy has shown promise for advanced HCC.CASE SUMMARY We report a 47-year-old male with advanced HCC complicated by PVTT and OJ,who was admitted with marked jaundice of the skin and sclera.Imaging revealed a large hepatic mass(14.5 cm×11.3 cm)in the right lobe with associated portal vein tumor thrombus.The tertiary bile duct was only mildly dilated,making percutaneous transhepatic cholangiography drainage infeasible.The patient underwent reduced-dose HAIC,which resulted in significant tumor shrinkage and marked reduction in serum bilirubin.This improvement enabled sequential treatment with lenvatinib and camrelizumab.After six cycles,both liver function and alphafetoprotein levels improved.The patient achieved a progression-free survival of 20 months and an overall survival of 29 months.CONCLUSION HAIC can treat high-bilirubin HCC with PVTT and OJ,allowing for subsequent targeted immunotherapy.展开更多
Malignant vascular tumors of the liver include rare primary hepatic mesenchymal tumors developed in the background of a normal liver parenchyma. Most of them are detected incidentally by the increased use of performin...Malignant vascular tumors of the liver include rare primary hepatic mesenchymal tumors developed in the background of a normal liver parenchyma. Most of them are detected incidentally by the increased use of performing imaging techniques. Their diagnosis is challenging, involving clinical and imaging criteria, with final confirmation by histology and immunohistochemistry. Surgery represents the mainstay of treatment. Liver transplantation(LT) has improved substantially the prognosis of hepatic epithelioid hemangioendothelioma(HEHE), with 5-year patient survival rates of up to 81%, based on the European Liver Intestine Transplantation AssociationEuropean Liver Transplant Registry study. Unfortunately, the results of surgery and LT are dismal in cases of hepatic angiosarcoma(HAS). Due to the disappointing results of very short survival periods of approximately 6-7 mo after LT, because of tumor recurrence and rapid progression of the disease, HAS is considered an absolute contraindication to LT. Recurrences after surgical resection are high in cases of HEHE and invariably present in cases of HAS. The discovery of reliable prognostic markers and the elaboration of prognostic scores following LT are needed to provide the best therapeutic choice for each patient.Studies on a few patients have demonstrated the stabilization of the disease in a proportion of patients with hepatic vascular tumors using novel targeted antiangiogenic agents, cytokines or immunotherapy. These new approaches,alone or in combination with other therapeutic modalities, such as surgery and classical chemotherapy, need further investigation to assess their role in prolonging patient survival. Personalized therapeutic algorithms according to the histopathological features, behavior, molecular biology and genetics of the tumors should be elaborated in the near future for the management of patients diagnosed with primary malignant vascular tumors of the liver.展开更多
Detection and treatment of drug resistance in extrapulmonary tuberculosis(EPTB)is a major challenge worldwide.Drug resistance in EPTB has not been studied extensively.However,patients with drug-resistant EPTB have bee...Detection and treatment of drug resistance in extrapulmonary tuberculosis(EPTB)is a major challenge worldwide.Drug resistance in EPTB has not been studied extensively.However,patients with drug-resistant EPTB have been reported to have poor outcomes[1].Rifampicin and isoniazid are the cornerstone drugs in the management of EPTB.Resistance in Mycobacterium(M.)tuberculosis to these drugs commonly arises due to mutations in the‘rpoB’gene and‘katG&inhA’genes,which confer resistance to rifampicin and isoniazid,respectively.Treatment outcomes are affected by the presence of these mutations.In addition,anatomical and physiological barriers impede the effective delivery of drugs to the affected extrapulmonary site[1].An analysis of the frequency of mutations in drug resistant M.tuberculosis strains causing EPTB in our region can help identify patterns of drug resistance.This,in turn,can provide inputs that may be used for modifying standard treatment regimens to make them more effective.The present study aims to identify the frequency and pattern of mutations in the‘rpoB’gene and‘katG&inhA’genes in M.tuberculosis strains isolated from EPTB samples.展开更多
Tuberculosis(TB)remains a critical global health challenge,with 10.8 million new cases and over 1.25 million deaths reported annually,disproportionately affecting low-income regions.Despite its use,the Bacillus Calmet...Tuberculosis(TB)remains a critical global health challenge,with 10.8 million new cases and over 1.25 million deaths reported annually,disproportionately affecting low-income regions.Despite its use,the Bacillus Calmette-Guérin(BCG)vaccine provides limited protection against adult pulmonary TB,necessitating novel solutions.The messenger RNA(mRNA)vaccine technology,proven effective in combating coronavirus disease 2019,offers significant promise for TB prevention.These vaccines elicit robust immune responses by encoding antigens that stimulate humoral and cell-mediated immunity,essential for combating mycobacterium TB.Unlike traditional methods,mRNA vaccines are highly adaptable,scalable,and capable of targeting emerging strains.Preclinical studies highlight the enhanced efficacy of mRNA TB vaccines over BCG,demonstrating their ability to reduce bacterial burdens and generate memory T-cell responses critical for long-term protection.However,challenges persist,including mRNA instability,cold-chain storage needs,and mycobacterium’s complex immune evasion strategies.Innovative solutions,such as lipid nanoparticle delivery systems and selfamplifying mRNA platforms,are being developed to address these barriers.The initiation of clinical trials,notably BioNTech’s BNT164,marks a pivotal advancement in TB vaccine development.These trials focus on safety,immuno genicity,and efficacy,particularly in regions with high TB prevalence.While logistical and financial hurdles remain,mRNA vaccines hold transformative potential to bridge critical gaps in TB prevention.Their adaptability extends to tackling co-infections like human immunodeficiency virus,further amplifying their impact on global health.By integrating mRNA vaccines into existing TB control strategies,these advancements could revolutionize prevention efforts,especially in regions where current solutions fall short.Continued innovation and investment are crucial to harnessing the full potential of mRNA vaccines,positioning them as a cornerstone in the fight against TB and its global eradication.展开更多
BACKGROUND Hepatic eosinophilic pseudotumor(HEPT)is a rare condition that mimics ma-lignant hepatic tumors,posing significant diagnostic challenges.This case report highlights the importance of considering parasitic i...BACKGROUND Hepatic eosinophilic pseudotumor(HEPT)is a rare condition that mimics ma-lignant hepatic tumors,posing significant diagnostic challenges.This case report highlights the importance of considering parasitic infections like Fasciola hepatica(F.hepatica)in the differential diagnosis of hepatic masses,especially in endemic regions,to prevent unnecessary interventions.CASE SUMMARY A 40-year-old female presented with a 1-month history of epigastric pain and significant weight loss.Imaging revealed a hepatic mass,initially misdiagnosed as intrahepatic cholangiocarcinoma.Laboratory results showed marked eosinophilia,and histopathological examination confirmed significant eosinophilic infiltration without malignancy.Serological testing identified F.hepatica infection.The patient was treated with a single dose of triclabendazole,leading to complete symptom resolution and normalization of hepatic imaging findings within days.CONCLUSION HEPT due to F.hepatica can closely mimic malignancy;timely antiparasitic treat-ment is crucial for resolution.展开更多
BACKGROUND Wedged hepatic venous pressure(WHVP)is a crucial variable for accurately assessing the hepatic venous pressure gradient(HVPG)and is vital for the diagnosis and prognostic evaluation of patients with portal ...BACKGROUND Wedged hepatic venous pressure(WHVP)is a crucial variable for accurately assessing the hepatic venous pressure gradient(HVPG)and is vital for the diagnosis and prognostic evaluation of patients with portal hypertension(PH).AIM To investigate the anatomical characteristics of balloon-occluded hepatic venous angiography in patients with PH and analyze the relationship between the WHVP and portal venous pressure(PVP).METHODS This retrospective study included 877 patients with PH who met the inclusion criteria from January 2020 to June 2024.Routine and innovative hepatic venous angiography was performed during transjugular intrahepatic portosystemic shunt procedures to measure hepatic venous and PVPs.All patients'angiographic images were collected for analysis.The associations between WHVP and PVP in each group were analyzed via linear regression analysis,and a predictive model was established.RESULTS The 877 patients had a mean age of 52.6±13.0 years,with 582 males and 295 females.Patients were categorized into four groups on the basis of their anatomical structure.All groups showed strong correlations between WHVP and PVP.The regression coefficient between the WHVP and PVP in the hepatic right vein-portal venous angiography group was 0.884(P<0.05);in the hepatic right vein-accessory hepatic venous angiography group,it was 0.721(P<0.05);in the hepatic right vein-middle hepatic venous angiography group,it was 0.344(P<0.05);and in the hepatic right vein-nonangiography group,it was 0.293(P<0.05).CONCLUSION The presence and anatomical classification of hepatic venous collaterals are key factors influencing the relationship between WHVP with and PVP.Based on the different anatomical classifications of hepatic veins,WHVP can be used to estimate PVP,improving the accuracy of PVP prediction.展开更多
文摘Hepatic tuberculosis particularly in the absence of military tuberculosis is rare.It can occur as a primary case or due to reactivation of an old tubercular focus.We report case of a 24 year old married female who died of primary hepatic tuberculosis.She had no evidence of tuberculosis elsewhere.Appropriale treatment initiated early can result in marked recovery whereas failure to recognize this entity can prove to be fatal.
文摘BACKGROUND While tuberculosis(TB)itself is a common disease,isolated TB of the liver is a rare entity.Tubercular involvement of the liver is more commonly a part of a disseminated disease of the hepatic parenchyma.In contrast,isolated hepatic TB spread through the portal vein from the gastrointestinal tract is seldom encountered in clinical practice,with only a few sporadic cases and short series available in the current literature.Vascular complications,such as portal vein thrombosis(PVT),have rarely been reported previously.CASE SUMMARY A 22-year-old man was hospitalized with complaints of a 3-mo history of fever and weight loss of approximately 10 kg.He had a 10-year hepatitis B virus(HBV)infection in his medical history.Contrast-enhanced computed tomography(CECT)confirmed hepatosplenomegaly,with hypodensity of the right lobe of the liver and 2.1 cm thrombosis of the right branch of the portal vein.A liver biopsy showed epithelioid granulomas with a background of caseating necrosis.ZiehlNelson staining showed acid-fast bacilli within the granulomas.The patient was diagnosed with isolated hepatic TB with PVT.Anti-TB therapy(ATT),including isoniazid,rifapentine,ethambutol,and pyrazinamide,was administered.Along with ATT,the patient was treated with entecavir as an antiviral medication against HBV and dabigatran as an anticoagulant.He remained asymptomatic,and follow-up sonography of the abdomen at 4 mo showed complete resolution of the PVT.CONCLUSION Upon diagnosis of hepatic TB associated with PVT and HBV coinfection,ATT and anticoagulants should be initiated to prevent subsequent portal hypertension.Antiviral therapy against HBV should also be administered to prevent severe hepatic injury.
文摘BACKGROUND Hepatic tuberculosis(TB)is uncommon clinically.Because of a lack of specific signs,characteristic symptoms and clinical manifestations and because pathological samples are difficult to obtain,hepatic TB is easily missed or misdiagnosed.CASE SUMMARY A 62-year-old Chinese man presented with jaundice for 1 wk and no abnormal laboratory tests other than elevated bilirubin,aminotransferases and C-reactive protein.Computed tomography(CT)of the abdomen showed a mass in the left lobe of the liver and hepatic hilum with striped calcified foci.Mild enhancement was visible at the edges,along with extensive intrahepatic biliary ductal dilatation in the right lobe of the liver.In the arterial phase of both CT and magnetic resonance imaging,the main trunk and right branch of the portal artery were partially visualized.Magnetic resonance cholangiopancreatography(MRCP)indicated that the left lobe of the liver and most of the bile ducts in the hilum were not visible.Pathological examination revealed coagulative necrosis,and granulomatous nodules were seen around areas of necrosis;therefore,TB was considered.CONCLUSION Hepatic tuberculosis is easily misdiagnosed or missed on imaging.Percutaneous puncture biopsy is the most useful tool for definitive diagnosis.
基金financially supported by UGC Major Research Project [(F42-520/2013(SR)]
文摘To evaluate hepatic injury induced by antituberculosis drugs(ATDs) when administered orally for 2, 4, 6 and 8 weeks and the therapeutic potential of propolis(bee hive product) against ATDs induced hepatic injury. Methods: The ATDs were administered for 8 weeks as well as propolis extract at three different doses(100, 200, 400 mg/kg) conjointly for 8 weeks in rats. Silymarin(50 mg/kg) was given as positive control. Animals were euthanized after 8 weeks; blood and liver samples were collected to perform various biochemicals, serological and histopathological and ultramorphological studies. Results: Significant increase(P < 0.05) in aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, triglyceride and cholesterol along with reduction in glucose and albumin level were noted after ATDs induced hepatic injury. Significant increase(P < 0.05) in lipid peroxidation, triglyceride, cholesterol and CYP2E1 activity; decline in reduced glutathione, catalase, superoxide dismutase, glutathione reductase, glutathione peroxidase, glucose-6-phosphatase dehydrogenase activity were observed after ATDs intoxication. Due to presence of a wide range of flavonoids and polyphenols in propolis extract, its administration reduced hepatic injury and maintained biochemical indices towards control. Histopathological and electron microscopic observations indicated hepatoprotective potential of propolis at cellular level whereas, TNF-α, IL-6 and IGF-1 confirmed therapeutic potential of propolis at molecular level. Conclusions: It can be concluded that propolis possess hepatoprotective potential against ATDs induced hepatic injury that may prove itself as a clinically useful natural product in management of drug induced liver injury.
文摘Primary hepatic leiomyosarcoma is a very rare disease,accounting for less than 1%of all primary hepatic malignancies[1].As a malignant tumor of the smooth muscle,it originates in the hepatic blood vessels,bile ducts or round ligaments of the liver[2,3].The clinical manifestations are nonspecific,and tumors are usually asymptomatic until they are relatively large in size.Primary hepatic leiomyosarcoma is characterized by a relatively poor prognosis and aggressive metastatic potential[3].The specific etiology and pathogenesis of primary hepatic leiomyosarcoma are still unclear.Several studies indicated that primary hepatic leiomyosarcoma might be related to acquired immune deficiency syndrome[4],Epstein-Barr virus[5],immunosuppression after organ transplantation[6],hepatitis virus[7,8],Hodgkin’s lymphoma[9]and other medical histories.Here,we present a case of primary hepatic leiomyosarcoma.
基金Southwest Hospital Boqing Innovation Fund,Grant/Award Number:2024BQCXJJ-9Fundings for Young Investigators of PLA,Grant/Award Number:2022-JCJQ-QT-004+3 种基金NSFC Key Projects of the Regional Innovation and Development Joint Fund,Grant/Award Number:U23A20413China Postdoctoral Science Foundation,Grant/Award Number:2023M744280National Natural Science Foundation of China,Grant/Award Number:82103778,82172449 and 82172489Southwest Hospital Postdoctoral Starting Fund,Grant/Award Number:5175ZA36BP。
文摘Background:Skeletal tuberculosis(TB)remains a persistent clinical and research chal-lenge due to its chronic course,osteolytic destruction,and the limitations of existing animal models,which often require high-level biosafety containment or fail to repli-cate human skeletal pathology.Methods:This study developed a biosafe,accessible,and versatile murine model of skeletal TB using Mycobacterium smegmatis,a fast-growing,nonpathogenic myco-bacterial species with high genomic homology to Mycobacterium tuberculosis.Three infection routes-subperiosteal calvarial injection,intratibial injection,and intra-cardiac inoculation-were systematically evaluated for their ability to induce lo-calized versus disseminated bone infection under standard biosafety level(BSL)-1 conditions.Results:Subperiosteal calvarial and intratibial injection of M.smegmatis induced local-ized bone lesions characterized by osteolysis,sequestrum formation,granulomatous inflammation,and increased osteoclast activity.Intratibial infection additionally trig-gered compartment-specific immune responses,including neutrophil and macrophage expansion,transient B-cell depletion,and activation of interferon-γ^(+)(IFN-γ^(+))T cells,reflecting active immune remodeling at the infection site.Systemic dissemination via intracardiac injection reproducibly generated progressive vertebral and tibial bone destruction with organized granuloma formation and immune cell infiltration but without prominent sequestrum formation.Compared to intratibial infection,intracar-diac delivery exhibited lower intragroup variability and more closely recapitulated the diffuse progression of extrapulmonary skeletal tuberculosis.Conclusions:This M.smegmatis-based murine model provides a straightforward,reliable,and immunopathologically relevant platform for exploring host-pathogen dynamics,immune-driven bone destruction,and early-stage therapeutic testing in skeletal TB,all within standard BSL-1 laboratories.This model fills a critical gap by enabling BSL-1 research into skeletal TB mechanisms and drug development.
基金Supported by Russian Science Foundation Grant,No.24-15-00185.
文摘BACKGROUND Tuberculous osteitis is a chronic,granulomatous bone infection that frequently results in impaired bone healing following surgery.Despite surgical intervention and prolonged anti-tuberculous therapy,complete bone regeneration often remains unachieved,contributing to subsequent orthopedic complications.AIM To investigate the efficacy and safety of pamidronate in promoting bone regeneration following surgical treatment of experimental animal tuberculous osteitis.METHODS A controlled randomized basic study of rabbit femoral tuberculosis induced by Mycobacterium tuberculosis strain H37Rv included surgical removal of infected tissue and implantation of osteoinductive bone grafts with the following animal allocation to one of three groups:(1)Bisphosphonates alone;(2)Bisphosphonates combined with anti-tuberculous therapy;and(3)Anti-tuberculous therapy alone.The control group consisted of animals that received no surgical or medical treatment.Clinical evaluations,biochemical markers,micro-computed tomography imaging,and histomorphometry analyses were conducted at 3 months and 6 months postoperatively.RESULTS Pamidronate treatment significantly reduced early implant resorption,increased osteoblastic activity,improved trabecular bone regeneration,and maintained graft integrity compared to the anti-tuberculous therapy-only group.Histologically,pamidronate led to enhanced vascular remodeling and increased bone matrix formation.Crucially,bisphosphonate therapy demonstrated safety,compatibility with anti-tuberculous medications,and did not exacerbate tuberculous inflammation.Furthermore,micro-computed tomography analysis revealed a significant increase in trabecular thickness and density in pamidronate-treated groups,underscoring the anabolic effects of bisphosphonates.Morphometric evaluation confirmed a marked reduction in osteoclast number and activity at graft interfaces.These combined radiological,histological,and biochemical data collectively demonstrate the efficacy of pamidronate as an adjunctive agent in enhancing bone repair outcomes following surgical intervention for tuberculous osteitis.CONCLUSION A single intravenous dose of pamidronate significantly enhances bone regeneration and prevents implant resorption following surgical treatment of tuberculous osteitis.The following prospective studies are needed.
基金supported by a Borden Scholars awardDuke Claude D.Pepper Older Americans Independence Center Pilot Award(P30AG028716)by the NIH/NIA(R01AG081393)。
文摘Advanced age impairs bone fracture healing;the underlying mechanism of this phenomenon remains unknown.We determined that apolipoprotein E(ApoE)increases with age and causes poor fracture healing.After deletion of hepatic ApoE expression(ΔApoE),24-month-oldΔApoE mice displayed a 95%reduction in circulating ApoE levels and significantly improved fracture healing.ApoE treatment of aged BMSCs inhibited osteoblast differentiation in tissue culture models;RNA-seq,Western blot,immunofluorescence,and RT-PCR analyses indicated that the Wnt/β-catenin pathway is the target of this inhibition.Indeed,we showed that ApoE had no effect on cultures with stabilizedβ-catenin levels.Next,we determined that Lrp4 serves as the osteoblast cell surface receptor to ApoE,as expression of Lrp4 is required in ApoE-based inhibition of Wnt/β-catenin signaling and osteoblast differentiation.Importantly,we validated this ApoE-Lrp4-Wnt/β-catenin molecular mechanism in human osteoblast differentiation.Finally,we identified an ApoE-neutralizing antibody(NAb)and used it to treat aged,wildtype mice 3 days after fracture surgery resulting in fracture calluses with 35%more bone deposition.Our work here identifies novel liver-to-bone cross-talk and a noninvasive,translatable therapeutic intervention for aged bone regeneration.
基金supported by the National Natural Science Foundation of China(82574173,82003516)Jiangsu Provincial Natural Science Foundation(BK20251958)+2 种基金Jiangsu Provincial Medical Key Discipline(ZDXK202250)Top Talent Awards Project Fund(RDF-TP-0023,RDF-TP-0030)Postgraduate Research Fund(PGRS2112022)at Xi'an Jiaotong-Liverpool University.
文摘Tuberculosis(TB),one of the oldest infectious diseases caused by Mycobacterium tuberculosis,poses a considerable challenge to global public health.There are approximately 10 million new TB cases worldwide annually,and TB claims the lives of nearly 3 million people each year,making it one of the leading causes of death from a single infectious disease[1].China ranks third globally in terms of TB burden,with approximately 733,000 TB cases reported in 2023[2].Based on the ecological model of health determinants developed by Whitehead and Dahlgren,health determinants can be classified into direct causes.
基金supported by the CAMS Innovation Fund for Medical Sciences(CIFMS)(2021-I2M-1-038 and 2023-I2M-2-001)the Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences(2019PT310029 and 2023-PT310-04).
文摘Tuberculosis(TB)continues to pose a significant threat to global public health,necessitating rapid and precise diagnostic methods and comprehensive detection of antimicrobial resistance(AMR)to facilitate timely clinical management.Traditional diagnostic techniques suffer from extended turnaround times and limited ability to comprehensively profile AMR,often resulting in delayed therapeutic interventions.Highthroughput sequencing(HTS)technologies have revolutionized pathogen research by significantly improving diagnostic speed and accuracy.In the context of TB,diverse sequencing strategies and platforms are being employed to fulfill specific research goals,ranging from elucidating the molecular mechanisms underlying AMR to characterizing the genomic diversity among clinical isolates.This review systematically examines current progress in the application of HTS for rapid pathogen identification,comprehensive AMR profiling,epidemiological studies,advances in novel drugs,and vaccine development.Furthermore,we address existing technological limitations and bioinformatics challenges and explore the future directions necessary for effectively integrating HTS-based methodologies into global TB control efforts.
基金funded by the National Key Research and Development Program of China(grant number 2022YFC2305204).
文摘Objective To determine the proportions of drug-resistant tuberculosis(TB),its trends,and the drug resistance-conferring mutations among patients with pulmonary TB aged 10-24 years in China.Methods The data of patients with pulmonary TB were retrieved from a national drug-resistant TB survey for analysis.Joinpoint regression software was used to analyze time trends.We also used whole genome sequencing to analyze the lineages and drug resistance-conferring mutations of 621 isolates.Results Among 4,235 patients with pulmonary TB,the proportion of new cases of multidrug-resistant tuberculosis(MDR-TB)was 3.18%(95%confidence interval[CI]:2.37-4.15)for adolescents and 3.76%(95%CI:3.03-4.60)for young adults;for previously treated patients,MDR-TB accounted for 11.25%(95%CI:5.28-20.28)of adolescents and 11.05%(95%CI:6.88-16.55)of young adults.The proportion of patients with MDR-TB remained stable among both new and previously treated patients aged 10-24 years during the study period.Through whole genome sequencing,we found that the most common mutations in the MDR-TB strains were Ser315Thr in the katG gene(71.74%)and Ser450Leu in the rpoB gene(50.00%).Conclusion This study revealed a high proportion of MDR-TB among adolescents and young adults,indicating that urgent and comprehensive measures are needed to reduce the emergence and transmission of drug-resistant TB among this population in China.
基金supported by the National Science and Technology Major Project for the Prevention and Control of Emerging and Major Infectious Diseases[2025ZD01908702]Peking University Medicine Fund of Fostering Young Scholars’Scientific&Technological innovation[BMU2024YFJHP014]supported by Fundamental Research Funds for the Central Universities+1 种基金Key Clinical Projects of Peking University Third Hospital[BYSYZD2022014]Peking University Third Hospital[2025024].
文摘Objective Post tuberculosis lung disease(PTLD)manifests in various forms,including tuberculosisassociated chronic obstructive pulmonary disease(TB-COPD),yet the clinical features of PTLD remain undercharacterized.This study aimed to assess longitudinal changes in lung function over a 5-year period and to identify predictors of airflow obstruction in a cohort of patients treated for active pulmonary TB.Methods Patients with active pulmonary TB were enrolled in this study and were followed during treatment,at treatment completion and five years post-treatment.Assessments included lung function and chest CT,analyzing longitudinal trends and airflow obstruction risk factors.Results Among 53 patients(mean age 36.9±13.9 years;64.2%male),7 patients(13.2%)exhibited airflow obstruction.At the 5-year follow-up,the mean FEV_(1)/FVC declined significantly(76.27%±12.04%vs.80.23%±11.02%,P<0.001)and 9 patients(17.0%)exhibited airflow obstruction.Seven of these patients predominantly showed air trapping consistent with small airway disease on chest CT,aligning with TB-COPD phenotype.Notably,four young-to-middle-aged patients(<60 years old)had persistent obstruction over the five years.Conclusion The initial test revealed that 13.2%of patients presented with airflow obstruction.By the 5-year follow-up,this proportion had increased to 17.0%,with most cases demonstrating imaging findings aligning with TB-COPD,even among younger,non-smoking individuals.These findings emphasize the importance of long-term follow-up and routine lung function assessments in TB survivors.
基金supported by the project of National Natural Science Foundation of China(32272331 and 82560638)Guizhou Provincial Science and Technology Projects(Qiankehe[2024]youth 326)+1 种基金Zunyi Science and Technology Projects(Zunshikehe HZ zi 2024312 hao)Guizhou Provincial Health Commission Science and Technology Fund(gzwkj2025-512).
文摘Diabetes is accompanied by oxidative damage,inflammation,and disorder of metabolic profiles.Dietary procyanidins have been reported to alleviate symptoms of diabetes,however,the underlying mechanism through which procyanidins impact liver metabolic function remains unclear.Here,the effects of p eanut skin procyanidins(PSP)on oxidative stress,inflammatory injury,and dysregulated metabolism in the liver of diabetic mice were evaluated.The results showed that PSP r educed the accumulation of cholesterol and alleviated oxidative stress and inflammatory response in the liver.Moreover,PSP enhanced i nsulin signaling by increasing hepatic protein expression of insulin receptor substrate 1/phosphatidylinositol-3-kinase/protein kinase B.Untargeted metabolomics revealed that PSP altered bile acid biosynthesis,alpha linolenic acid and linoleic acid,arachidonic acid,and glycolipid metabolism in the liver.This study reveals positive effects of PSP in alleviating liver dysfunction in diabetic mice.
文摘To assess the effectiveness of vaccination in contaminated environments,this study introduces a modeling framework that encompasses two transmission routes,namely direct human-to-human contact and indirect human-to-environment contact,as well as the implementation of new M72/AS01_(E)vaccine.Motivated by this,a coupled age-structured tuberculosis(TB)model is proposed.Its well-posedness requirement is verified using the integrated semigroup theory.Furthermore,this study presents a comprehensive analysis of threshold dynamics associated with the proposed model.Specifically,the global stability of the disease-free and positive steady states is demonstrated by employing Lyapunov functionals.Lastly,the effects of the vaccination with M72/AS01_(E)and contaminated environments on TB control are numerically simulated.Experimental results indicate that high concentrations of Mycobacterium tuberculosis in contaminated environments may somewhat impede TB control efforts,but that large-scale deployment of new vaccine could significantly reduce the prevalence of TB.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a major type of liver cancer worldwide.In advanced stages,portal vein tumor thrombosis(PVTT)and jaundice are common,whereas obstructive jaundice(OJ)is relatively rare.Both conditions markedly reduce survival and increase therapeutic complexity.Recently,hepatic artery infusion chemotherapy(HAIC)in combination with targeted immunotherapy has shown promise for advanced HCC.CASE SUMMARY We report a 47-year-old male with advanced HCC complicated by PVTT and OJ,who was admitted with marked jaundice of the skin and sclera.Imaging revealed a large hepatic mass(14.5 cm×11.3 cm)in the right lobe with associated portal vein tumor thrombus.The tertiary bile duct was only mildly dilated,making percutaneous transhepatic cholangiography drainage infeasible.The patient underwent reduced-dose HAIC,which resulted in significant tumor shrinkage and marked reduction in serum bilirubin.This improvement enabled sequential treatment with lenvatinib and camrelizumab.After six cycles,both liver function and alphafetoprotein levels improved.The patient achieved a progression-free survival of 20 months and an overall survival of 29 months.CONCLUSION HAIC can treat high-bilirubin HCC with PVTT and OJ,allowing for subsequent targeted immunotherapy.
文摘Malignant vascular tumors of the liver include rare primary hepatic mesenchymal tumors developed in the background of a normal liver parenchyma. Most of them are detected incidentally by the increased use of performing imaging techniques. Their diagnosis is challenging, involving clinical and imaging criteria, with final confirmation by histology and immunohistochemistry. Surgery represents the mainstay of treatment. Liver transplantation(LT) has improved substantially the prognosis of hepatic epithelioid hemangioendothelioma(HEHE), with 5-year patient survival rates of up to 81%, based on the European Liver Intestine Transplantation AssociationEuropean Liver Transplant Registry study. Unfortunately, the results of surgery and LT are dismal in cases of hepatic angiosarcoma(HAS). Due to the disappointing results of very short survival periods of approximately 6-7 mo after LT, because of tumor recurrence and rapid progression of the disease, HAS is considered an absolute contraindication to LT. Recurrences after surgical resection are high in cases of HEHE and invariably present in cases of HAS. The discovery of reliable prognostic markers and the elaboration of prognostic scores following LT are needed to provide the best therapeutic choice for each patient.Studies on a few patients have demonstrated the stabilization of the disease in a proportion of patients with hepatic vascular tumors using novel targeted antiangiogenic agents, cytokines or immunotherapy. These new approaches,alone or in combination with other therapeutic modalities, such as surgery and classical chemotherapy, need further investigation to assess their role in prolonging patient survival. Personalized therapeutic algorithms according to the histopathological features, behavior, molecular biology and genetics of the tumors should be elaborated in the near future for the management of patients diagnosed with primary malignant vascular tumors of the liver.
文摘Detection and treatment of drug resistance in extrapulmonary tuberculosis(EPTB)is a major challenge worldwide.Drug resistance in EPTB has not been studied extensively.However,patients with drug-resistant EPTB have been reported to have poor outcomes[1].Rifampicin and isoniazid are the cornerstone drugs in the management of EPTB.Resistance in Mycobacterium(M.)tuberculosis to these drugs commonly arises due to mutations in the‘rpoB’gene and‘katG&inhA’genes,which confer resistance to rifampicin and isoniazid,respectively.Treatment outcomes are affected by the presence of these mutations.In addition,anatomical and physiological barriers impede the effective delivery of drugs to the affected extrapulmonary site[1].An analysis of the frequency of mutations in drug resistant M.tuberculosis strains causing EPTB in our region can help identify patterns of drug resistance.This,in turn,can provide inputs that may be used for modifying standard treatment regimens to make them more effective.The present study aims to identify the frequency and pattern of mutations in the‘rpoB’gene and‘katG&inhA’genes in M.tuberculosis strains isolated from EPTB samples.
文摘Tuberculosis(TB)remains a critical global health challenge,with 10.8 million new cases and over 1.25 million deaths reported annually,disproportionately affecting low-income regions.Despite its use,the Bacillus Calmette-Guérin(BCG)vaccine provides limited protection against adult pulmonary TB,necessitating novel solutions.The messenger RNA(mRNA)vaccine technology,proven effective in combating coronavirus disease 2019,offers significant promise for TB prevention.These vaccines elicit robust immune responses by encoding antigens that stimulate humoral and cell-mediated immunity,essential for combating mycobacterium TB.Unlike traditional methods,mRNA vaccines are highly adaptable,scalable,and capable of targeting emerging strains.Preclinical studies highlight the enhanced efficacy of mRNA TB vaccines over BCG,demonstrating their ability to reduce bacterial burdens and generate memory T-cell responses critical for long-term protection.However,challenges persist,including mRNA instability,cold-chain storage needs,and mycobacterium’s complex immune evasion strategies.Innovative solutions,such as lipid nanoparticle delivery systems and selfamplifying mRNA platforms,are being developed to address these barriers.The initiation of clinical trials,notably BioNTech’s BNT164,marks a pivotal advancement in TB vaccine development.These trials focus on safety,immuno genicity,and efficacy,particularly in regions with high TB prevalence.While logistical and financial hurdles remain,mRNA vaccines hold transformative potential to bridge critical gaps in TB prevention.Their adaptability extends to tackling co-infections like human immunodeficiency virus,further amplifying their impact on global health.By integrating mRNA vaccines into existing TB control strategies,these advancements could revolutionize prevention efforts,especially in regions where current solutions fall short.Continued innovation and investment are crucial to harnessing the full potential of mRNA vaccines,positioning them as a cornerstone in the fight against TB and its global eradication.
文摘BACKGROUND Hepatic eosinophilic pseudotumor(HEPT)is a rare condition that mimics ma-lignant hepatic tumors,posing significant diagnostic challenges.This case report highlights the importance of considering parasitic infections like Fasciola hepatica(F.hepatica)in the differential diagnosis of hepatic masses,especially in endemic regions,to prevent unnecessary interventions.CASE SUMMARY A 40-year-old female presented with a 1-month history of epigastric pain and significant weight loss.Imaging revealed a hepatic mass,initially misdiagnosed as intrahepatic cholangiocarcinoma.Laboratory results showed marked eosinophilia,and histopathological examination confirmed significant eosinophilic infiltration without malignancy.Serological testing identified F.hepatica infection.The patient was treated with a single dose of triclabendazole,leading to complete symptom resolution and normalization of hepatic imaging findings within days.CONCLUSION HEPT due to F.hepatica can closely mimic malignancy;timely antiparasitic treat-ment is crucial for resolution.
基金Supported by Capital Medical University Affiliated Beijing Shijitan Hospital Talent Development Program during the 14th Five-Year Plan,No.2023 LJRCLFQ.
文摘BACKGROUND Wedged hepatic venous pressure(WHVP)is a crucial variable for accurately assessing the hepatic venous pressure gradient(HVPG)and is vital for the diagnosis and prognostic evaluation of patients with portal hypertension(PH).AIM To investigate the anatomical characteristics of balloon-occluded hepatic venous angiography in patients with PH and analyze the relationship between the WHVP and portal venous pressure(PVP).METHODS This retrospective study included 877 patients with PH who met the inclusion criteria from January 2020 to June 2024.Routine and innovative hepatic venous angiography was performed during transjugular intrahepatic portosystemic shunt procedures to measure hepatic venous and PVPs.All patients'angiographic images were collected for analysis.The associations between WHVP and PVP in each group were analyzed via linear regression analysis,and a predictive model was established.RESULTS The 877 patients had a mean age of 52.6±13.0 years,with 582 males and 295 females.Patients were categorized into four groups on the basis of their anatomical structure.All groups showed strong correlations between WHVP and PVP.The regression coefficient between the WHVP and PVP in the hepatic right vein-portal venous angiography group was 0.884(P<0.05);in the hepatic right vein-accessory hepatic venous angiography group,it was 0.721(P<0.05);in the hepatic right vein-middle hepatic venous angiography group,it was 0.344(P<0.05);and in the hepatic right vein-nonangiography group,it was 0.293(P<0.05).CONCLUSION The presence and anatomical classification of hepatic venous collaterals are key factors influencing the relationship between WHVP with and PVP.Based on the different anatomical classifications of hepatic veins,WHVP can be used to estimate PVP,improving the accuracy of PVP prediction.
