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Metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease and metabolic dysfunction and alcohol-related liver disease represent the principal subtypes of steatotic liver disease (SLD), together constituting a rapidly growing global health challenge. Latin America bears a disproportionately high burden of SLD, driven by the convergence of increasing prevalence of obesity and type 2 diabetes, high levels of harmful alcohol consumption, and a high frequency of genetic risk variants, particularly in the gene encoding patatin-like phospholipase domain-containing protein 3 (PNPLA3). These factors interact synergistically to accelerate disease progression, increasing the risk of steatohepatitis, advanced fibrosis, cirrhosis and hepatocellular carcinoma. Despite this substantial burden, the region faces major structural and health-system constraints, including fragmented health-care delivery, limited hepatology capacity, restricted access to diagnostic and therapeutic technologies, and low participation in clinical trials, all of which hinder early detection and the generation of region-specific evidence. This Review summarizes current data on the epidemiology and clinical burden of SLD in Latin America, identifies critical gaps in research and surveillance, and highlights priorities for prevention, harm reduction and health-system strengthening, including the implementation of effective public policies to reduce morbidity and mortality and improve health outcomes in the region.
As a classical prescription, Wuwei Xiaodu Decoction (WWXDD) () is composed of five medicinal components: Lonicerae Japonicae Flos, Taraxaci Herba, Chrysanthemi Indici Flos, Violae Herba, and Semiaquilegiae Radix. Originating from the Qing Dynasty, WWXDD has been widely employed in Traditional Chinese Medicine (TCM) for treating inflammatory diseases. Although numerous studies have explored various aspects of WWXDD, few comprehensive reviews have systematically synthesized its ethnopharmacological basis, phytochemistry, pharmacology, and clinical applications, which hinders the further application and commercialization of WWXDD. This review aims to provide a comprehensive summary of the traditional theory, chemical composition, pharmacological activity, and clinical evidence related to WWXDD, with a focus on current challenges and future perspectives. The literature was systematically searched in databases including Web of Science, PubMed, Scopus, and China National Knowledge Infrastructure (CNKI). The search period covered publications from 2013 to 2025. Keywords included "Wuwei Xiaodu Decoction", "WWXDD", "traditional Chinese medicine", "phytochemistry", "pharmacology", and "clinical application". Original research articles, reviews, and clinical studies relevant to the composition, pharmacological activities, quality control, and clinical applications of WWXDD were included. Duplicates, unrelated studies, and articles lacking sufficient methodological information were excluded. Chemical structures were drawn using ChemDraw 23, and the graphical abstract and schematic illustrations were created using BioRender and PowerPoint. This review firstly summarized the progress of the chemical constituents of WWXDD and discussed the advanced methods in monitoring quality of WWXDD and its herbal ingredients. Meanwhile, the attribution of each herb in WWXDD provides some theoretical basis for its efficacy. Pharmacological investigations reveal that WWXDD exhibits anti-inflammatory, anticancer, and antibacterial properties, attributable to its constituent herbs. Clinically, it has demonstrated efficacy in managing facial acne and preventing postoperative infections. Finally, it is important to note in WWXDD use that even though there is no toxicity, most drugs are cold in nature, so it is important to pay attention to the people for whom the use is contraindicated. Through systematic investigation of WWXDD's herbal components, this study enhances the mechanistic understanding of its therapeutic actions. Both preclinical and clinical evidence underscores its potential in managing complex diseases. On this basis, we summarize an actionable compound-level quality-control framework (chemical fingerprinting/multi-component quantification-spectrum-effect and bioactivity consistency-mutual confirmation with mechanistic and clinical evidence), and highlight that standardization and formula-level indicators remain key bottlenecks. In this review, current issues are discussed to inform and inspire subsequent research of WWXDD and other classical prescriptions.
Artificial intelligence (AI) is rapidly transforming the management landscape of inflammatory bowel disease (IBD). While early applications in endoscopy, digital pathology and cross-sectional imaging drew substantial attention, next-generation AI systems that enable deeper disease understanding, personalized treatment and streamlined clinical workflows are now emerging. These advances encompass the multimodal integration of endoscopic, histological and molecular data ('endo-histo-omics'); AI-assisted assessment of the intestinal barrier; remote monitoring via wearables; and the incorporation of large language models for decision-making support and patient interactions. This Perspective traces the evolution of AI in IBD from domain-specific tools to foundational platforms supporting data-driven precision medicine. We highlight validated AI applications across diagnosis, monitoring, outcome prediction and neoplasia surveillance. We also explore the expectations of key stakeholders, including clinicians, patients, regulatory bodies and industry, and discuss unresolved challenges such as explainability, integration into workflows, reimbursement and environmental sustainability. By aligning innovation with ethical and clinical priorities, AI holds the potential to redefine IBD care. Its future will be shaped by collaboration, transparency and responsible implementation, ushering in a new era of personalized, efficient and equitable care for individuals with IBD.
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Liver diseases account for 1 in 25 deaths worldwide. Owing to the asymptomatic nature across the dynamic spectrum of steatotic liver disease (SLD) and the absence of targeted screening programmes, individuals at risk of progression to cirrhosis or hepatocellular carcinoma (HCC) are unlikely to pursue liver disease testing. Historically, hepatitis B and C were the leading causes of liver injury that can progress to cirrhosis or HCC. Global efforts to implement screening and vaccination programmes, expand testing and treatment, and encourage active viral hepatitis case finding followed the widespread availability of curative treatment for hepatitis C and effective suppressive therapy and vaccines for hepatitis B, further supported by changes in law, regulation and public policy. With encouraging declines in new viral hepatitis infections in many countries, greater attention should turn to SLD, now the leading global indicator for cirrhosis and HCC. Screening and active case finding for SLD lag far behind its increasing prevalence, leaving most people undiagnosed. This Expert Recommendation draws on lessons learned from legal, regulatory and policy changes required to combat the viral hepatitis public health threat. Our recommendations can contribute to a concerted shift in legal frameworks and policies to enhance screening programmes, increase testing and improve health outcomes.
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Epithelial-derived malignancies account for the majority of human tumours and present considerable treatment challenges owing to their heterogeneity, metastatic potential and resistance to therapy. The claudin family of tetra-transmembrane proteins was identified approximately 28 years ago as containing key regulators of epithelial function. These proteins are integral components of tight junctions, which control barrier integrity, selective channel permeability and cellular organization in epithelial tissues. Subsequent murine studies revealed that claudins also have tissue-specific physiological roles, whereas clinical studies demonstrated that their expression is frequently dysregulated in various cancers, highlighting their potential as therapeutic targets. In the past few decades, increasing efforts to exploit claudins in cancer therapy have led to the development of targeted molecules, including zolbetuximab, a first-in-class CLDN-18.2-targeted antibody for the treatment of gastric cancer, which has been recently approved by the United States Food and Drug Administration. This milestone emphasizes the therapeutic potential of targeting this protein family and its possible role in expanding treatment options for cancer. In this review, we discuss the evolving landscape of claudin-targeting therapeutics, examining key advances, emerging challenges and future prospects.
The rising disease burden of inflammatory bowel disease (IBD) parallels the changing dietary landscape accompanying industrialization, underscoring the growing relevance of nutritional science in disease prevention and management. Precision nutrition has emerged as a promising approach to prevent and manage IBD through tailored dietary recommendations based on multidimensional individual characteristics, including demographics, disease natural history and multiomics traits. In this Review, we investigate the sources of heterogeneity in dietary responses and propose a stepwise framework for precision nutrition: phenotype-based precision nutrition, informed by general phenotypes in clinical and community settings; omics-based precision nutrition, targeting subgroups with shared biological features identified via omics and complementary approaches; and integrated precision nutrition, providing personalized dietary strategies informed by comprehensive, multidimensional phenotypes. Advances in large-scale longitudinal multiomics cohorts, biomarker detection and artificial intelligence are transforming data acquisition and interpretation, thereby facilitating both interventional research and real-world application of precision nutrition. Key considerations for implementing precision nutrition in IBD are discussed. This Review outlines a holistic and translational framework, aiming to advance both research and clinical practice in the prevention and management of IBD.
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Biliary tract cancers, encompassing intrahepatic, perihilar and distal cholangiocarcinoma and gallbladder cancer, are a heterogeneous group of highly aggressive malignancies. Most patients have unresectable disease at first presentation, and even those who undergo surgery are likely to have disease recurrence. Newer approaches have included liver transplantation for selected patients, and the integration of locoregional and systemic therapies has expanded the number of patients who can benefit from surgery. The advent of immune-checkpoint inhibitors and targeted therapies for patients with advanced-stage disease has prompted the exploration of these agents in earlier-stage disease settings. Despite this progress, treatment algorithms remain complex, necessitating a multidisciplinary and individualized approach to patient management. Future research should focus on optimizing patient selection through biomarker-driven strategies, including the integration of molecular profiles to guide the selection of systemic therapy, as well as refining the criteria for surgery and transplantation. These improvements will require global collaboration and novel clinical trial designs. In this Review, we describe evolving perioperative strategies for the management of patients with biliary tract cancers and highlight emerging directions in the field.
Solid-organ transplantation (for example, kidney or liver) and haematopoietic-stem-cell transplantation have revolutionized treatment of end-stage organ failure and haematological malignancies. However, long-term outcomes are often undermined by complications such as allograft rejection, graft-versus-host disease in haematopoietic-stem-cell recipients, opportunistic infections, adverse effects of drugs and decreased quality of life. Emerging evidence now highlights the gut microbiome and its metabolites (such as short-chain fatty acids) as a potentially modifiable factor influencing transplantation outcomes. Transplantation recipients frequently exhibit gut dysbiosis, which has been linked to graft function, risk of infection (for example, vulnerability to multidrug-resistant bacteria), immune-mediated complications and patient survival. Furthermore, pharmacomicrobiomics studies indicate that microorganisms can metabolize immunosuppressive drugs into less active forms (such as the conversion of the immunosuppressive drug tacrolimus into less active or toxic forms through keto-reduction, glucuronidation or deconjugation) or can activate prodrugs (such as the conversion of mycophenolate mofetil into mycophenolic acid), thereby modulating drug efficacy and safety. Here, we discuss how the intestinal ecosystem is altered and persistently shaped by transplantation-related factors and immunosuppression and how these changes correlate with clinical outcomes. We provide a perspective on leveraging microbiome insights, through biomarkers or microbiome-targeted interventions, to improve outcomes in solid-organ and stem-cell transplantation.
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Steatotic liver diseases (SLDs), including metabolic dysfunction-associated steatotic liver disease (MASLD; formerly known as non-alcoholic fatty liver disease) and alcoholic liver disease, are the leading causes of chronic hepatitis, liver dysfunction, cirrhosis and liver cancer development. Severe manifestations of MASLD and alcoholic liver disease include metabolic dysfunction-associated steatohepatitis (MASH; formerly known as non-alcoholic steatohepatitis) and alcoholic steatohepatitis (ASH) or a combination thereof, termed metabolic dysfunction and alcohol-associated liver disease. While MASH-associated and ASH-associated liver cancers display common histopathological features, the underlying cellular and molecular pathophysiological mechanisms of each are distinct. Recent studies indicate that SLDs encompass previously unrecognized spectra of heterogeneous, metabolic, immunological and genetic diseases that, in combination with lifestyle measures and individual patient comorbidities, affect disease pathogenesis and therapy response. Here, we review the current knowledge of the molecular, genetic and cellular mechanisms underlying the transition of MASH or ASH to liver cancer as well as novel developments in liver cancer risk assessment in SLDs. We further discuss possible obstacles of differential diagnosis and outline current developments in the therapeutic management of both MASH-related and ASH-related liver cancer.
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The microbiome is increasingly recognized as a key player in cancer pathogenesis and treatment response, acting through both local and systemic mechanisms. Microbial communities and their metabolites can directly influence drug metabolism, shape the immune landscape, and alter transcriptional and epigenetic programmes in the gut, systemically and in the tumour microenvironment. Emerging data support the potential of microbiome-targeted interventions (such as faecal microbiota transplantation, diet, prebiotics and probiotics) as adjuncts to conventional cancer therapies, with the goal of enhancing efficacy and reducing toxicity. This Review highlights the promise of the microbiome as a prognostic and predictive biomarker, a modifiable factor in cancer care and prevention, and a therapeutic target. We also discuss major knowledge gaps, limitations in current study designs, and the need for mechanism-guided, personalized strategies to advance clinical translation.
The management of hepatocellular carcinoma (HCC) has undergone radical change over the past decade. Immunotherapies now dominate the treatment of advanced-stage disease and are increasingly being evaluated in perioperative and intermediate-stage settings. However, in some instances, positive phase III trials have not translated into adoption by guidelines or regulatory agencies, highlighting the need to harmonize and update the current standards for trial design and end points. In response to these challenges, four scientific societies - the European Association for the Study of the Liver (EASL), the American Association for the Study of Liver Diseases (AASLD), the International Liver Cancer Association (ILCA) and the American Society of Clinical Oncology (ASCO) - appointed representatives to develop a consensus recommendations document addressing current unmet needs and future challenges in HCC trial design and end points. Through a modified Delphi process, 102 consensus statements were developed across several distinct domains: surveillance; early-stage, intermediate-stage and advanced-stage disease; transplant-related contexts; regulatory considerations; and emerging topics. The document rigorously defines target populations, stratification factors, control arms and benchmarks for expected clinical benefit. Collectively, this consensus is intended to provide a dynamic, evidence-based, multisociety roadmap for optimizing trial design, accelerating therapeutic development and improving clinically meaningful outcomes in patients with HCC.
Axial spondyloarthritis (axSpA) is a chronic inflammatory disease characterized by complex pain mechanisms that extend beyond inflammation. Although inflammatory nociceptive pain - primarily mediated by pro-inflammatory cytokines - represents the classic pathway and therapeutic target, many patients continue to experience pain despite suppression of inflammation. This residual pain often reflects non-inflammatory processes, including nociplastic and neuropathic pain. Central sensitization, a key mechanism of nociplastic pain, contributes to pain amplification and poor response to treatment. Fibromyalgia, considered the typical phenotype of nociplastic pain, can co-occur with axSpA and is associated with increased symptom burden and reduced efficacy of anti-inflammatory therapies. Neuropathic pain, albeit less common, can result from structural complications and requires targeted therapeutic approaches. In addition, biological sex differences further influence pain perception and treatment outcomes: female patients report more widespread pain, show higher rates of central sensitization and have a worse response to biologic therapies than male patients. Current treatment paradigms are effective for inflammation-driven symptoms but often fail to address the broader spectrum of pain phenotypes in axSpA. Future work should include the development of biomarkers to differentiate pain mechanisms, the refinement of assessment tools and the evaluation of multimodal therapies that target both inflammation and pain processes. This evolving understanding necessitates a shift from an inflammation-centric to a mechanism-informed approach to pain management in axSpA.