This review explores the complex interplay between the microbiome and human aging, highlighting how dysbiosis impacts host physiology and health, particularly in relation to genomic stability and telomere attrition. Recent advances in cellular and molecular biology have underscored the role of both intrinsic and extrinsic factors in human aging, with the microbiome emerging as a key determinant of host physiology and health. Dysbiosis—disruptions in microbiome composition—is linked to various age-related diseases and impacts genomic stability and telomere attrition, the progressive shortening of telomeres that limits cell division and contributes to aging. This review examines how microbiome dynamics influence aging by triggering inflammation, oxidative stress, immune dysregulation, and metabolic dysfunction, all of which affect two primary hallmarks of aging: genomic instability and telomere attrition. Understanding these interactions is essential for developing targeted interventions to restore microbiome balance and promote healthy aging, offering potential treatments to extend healthspan and alleviate aging-related diseases. The convergence of microbiome and aging research promises transformative insights and new avenues for improving global population well-being.

Castleman disease (CD) is a lymphoproliferative condition with a broad range of morphological and clinical presentations. It is categorized into distinct pathological and clinical subtypes, including localized unicentric CD, idiopathic multicentric CD, and human herpesvirus 8-associated or human herpesvirus 8-negative variants. Diagnosing CD requires adherence to internationally recognized guidelines that integrate clinical, laboratory, and histological findings. However, distinguishing CD from other diseases can be complex, as numerous benign and malignant conditions can mimic its features. Additionally, individuals diagnosed with CD are at an elevated risk of developing various malignancies. In this article, we reviewed benign and malignant conditions that can mimic CD.

Literature search is conducted and reviewed.

Mimickers of CD include follicular hyperplasia, indolent B-cell lymphoproliferative disorders, peripheral T-cell malignancies, classic Hodgkin lymphoma, follicular dendritic cell tumors, plasma cell disorders, immunoglobulin G4 -related lymphadenopathy, autoimmune-associated lymphadenopathy, infectious causes of lymphadenopathy, and systemic syndromes like POEMS and TAFRO. Various malignancies are associated with CD, including plasma cell proliferations, lymphomas, follicular dendritic cell neoplasms, and Kaposi sarcoma.

This review explores the differential diagnoses and neoplasms linked to CD, emphasizing their role in accurate classification, treatment decisions, and patient management. A comprehensive understanding of CD and its mimickers is crucial for ensuring accurate diagnosis and appropriate patient management in clinical practice.

Various vaccines have been reported as triggers of Autoimmune hepatitis (AIH). Recently, with the ongoing COVID-19 pandemic and widespread vaccination worldwide, COVID-19 vaccination-associated AIH (CA-AIH) occurring without COVID-19 infection have been reported. However, only a handful of CA-AIH cases have been reported in patients with COVID-19 infection. Therefore, we report such a case and summarize the CA-AIH with or without COVID-19 infection.

In this report, we describe a 66-year-old female who developed biopsy-proven acute-onset autoimmune hepatitis after receiving four doses of the COVID-19 vaccine and experiencing one COVID-19 infection in 2022. The patient was immediately treated with prednisone. Her liver enzymes gradually decreased to the normal range after treatment. In addition, we reviewed 20 cases of CA-AIH reported from multiple countries. The summarized data of these cases showed that CA-AIH and classic AIH share some clinical, serological, and histopathological features, such as female predominance and a middle-aged distribution. All patients had some positive circulating autoantibodies, including anti-nuclear antibody and/or positive anti-smooth muscle antibody. Histologically, CA-AIH showed a more acute onset compared to classic AIH, which typically presents with more chronic hepatitis. However, only 5 (23.8%) of the 21 cases had COVID-19 infection.

This case report provides additional evidence supporting an association of COVID-19 vaccination and/or infection with AIH, suggesting a more causal than coincident relationship. The majority of the patients of COVID-19 vaccination associated AIH show acute disease onset and may not have COVID-19 infection.

Macromolecular-based gene delivery systems have emerged as viable alternatives to non-viral vectors for gene therapy due to their versatility, biocompatibility, and capacity to efficiently deliver therapeutic cargo. These systems, primarily based on synthetic and natural polymers, offer significant advantages in terms of safety, controlled gene release, and targeted delivery. This review explores the design and synthesis of macromolecular carriers, focusing on their chemical and physical architectures, which play a key role in improving gene delivery. Catanionic polymers and their derivatives (comb, brush, and star polymers) have been extensively researched for their capacity to condense and protect genetic material. Furthermore, natural polymers like chitosan and hyaluronic acid have been modified to enhance gene delivery capabilities. These macromolecular carriers are engineered to boost circulation time, increase cellular uptake, and facilitate the controlled release of genetic material at the target site. Strategies such as incorporating targeting ligands, stimuli-responsive elements, and reducing cytotoxicity are being pursued to improve the overall efficiency and specificity of these systems. This review highlights the current state of macromolecular gene delivery systems, their applications, and the ongoing research aimed at overcoming existing challenges, paving the way for more effective non-viral gene therapies.

Persistent liver injury halts the regenerative capacity of hepatocytes and activates mechanisms that result in the replacement of normal hepatic parenchyma with extracellular matrix deposits. As liver fibrosis develops, the liver undergoes architectural changes and alterations in microcirculation that lead to increased intrahepatic vascular resistance and portal hypertension. Thrombocytopenia is a prevalent condition in patients with chronic liver disease and portal hypertension. Multiple mechanisms related to increased platelet destruction or decreased platelet production contribute to thrombocytopenia. Increased platelet destruction occurs due to splenic sequestration caused by hypersplenism or immune-mediated conditions. Decreased platelet production results from a decline in thrombopoietin production, bone marrow suppression by medications, or toxic insults. Therapies aimed at improving thrombocytopenia are controversial, and individual factors must be considered. Although hepatic venous pressure gradient measurement is the gold standard for diagnosing portal hypertension, non-invasive tests show adequate correlation with hepatic venous pressure gradients. Various clinical risk scores consider platelet counts as independent predictors of adverse liver outcomes, such as the development of esophageal varices and the presence of advanced fibrosis. Nonselective beta-blockers are the cornerstone of long-term management for clinically significant portal hypertension. Indications for transjugular intrahepatic portosystemic shunt placement include failure to control portal hypertension-related bleeding, early rebleeding, and refractory or recurrent ascites. Ultimately, liver transplantation is the only definitive cure for portal hypertension and its major complications, including thrombocytopenia. Understanding the mechanisms underlying thrombocytopenia in patients with portal hypertension and chronic liver disease is essential for accurate diagnosis and effective patient management. This review aimed to evidence on the pathophysiological mechanisms linking chronic liver disease, portal hypertension, and thrombocytopenia, and to discuss their diagnostic and therapeutic implications.

Tumors are complex systems characterized by variations across genetic, transcriptomic, phenotypic, and microenvironmental levels. This study introduced a novel framework for quantifying cancer cell heterogeneity using single-cell RNA sequencing data. The framework comprised several scores aimed at uncovering the complexities of key cancer traits, such as metastasis, tumor progression, and recurrence.

This study leveraged publicly available single-cell transcriptomic data from three human breast cancer subtypes: estrogen receptor-positive, human epidermal growth factor receptor 2-positive, and triple-negative. We employed a quantitative approach, analyzing copy number alterations (CNAs), entropy, transcriptomic heterogeneity, and diverse protein-protein interaction networks (PPINs) to explore critical concepts in cancer biology.

We found that entropy and PPIN activity related to the cell cycle could distinguish cell clusters with elevated mitotic activity, particularly in aggressive breast cancer subtypes. Additionally, CNA distributions varied across cancer subtypes. We also identified positive correlations between the CNA score, entropy, and the activities of PPINs associated with the cell cycle, as well as those linked to basal and mesenchymal cell lines.

This study addresses a gap in the current understanding of breast cancer heterogeneity by presenting a novel quantitative approach that offers deeper insights into tumor biology, surpassing traditional marker-based methods.

With the widespread application of systemic treatments for hepatocellular carcinoma, liver injury caused by molecular targeted drugs and immune checkpoint inhibitors has become a common clinical problem. The Chinese Society of Hepatology, Chinese Medical Association, organized domestic experts to summarize and analyze adverse liver reactions, as well as advances in the diagnosis and treatment related to systemic therapy for liver cancer, both domestically and internationally. Based on this work, we formulated the “Consensus on the Management of Liver Injury Associated with Targeted Drugs and Immune Checkpoint Inhibitors for Hepatocellular Carcinoma”, aiming to provide practical recommendations and decision-making guidance for clinicians in hepatology and related specialties. This guidance focuses on the monitoring, diagnosis, prevention, and treatment of liver injury during targeted and immune checkpoint inhibitor therapy, ultimately helping more liver cancer patients benefit from targeted immunotherapy.

Reprogramming of lipid metabolism has emerged as a significant characteristic of malignancy during tumor development. Research indicates a critical link between lipid metabolism and the tumor immune microenvironment. This relationship not only facilitates cancer progression by remodeling the tumor microenvironment but also influences the functionality of immune cells. Alterations in lipid metabolism regulate the function and status of immune cells within the microenvironment, impacting immune evasion and the therapeutic efficacy of tumors. Consequently, targeting lipid metabolism is a viable strategy for intervening in tumorigenesis and tumor development. This review examines the roles of key lipid molecules, such as fatty acids and cholesterol, within the tumor microenvironment, highlighting how aberrant lipid metabolism can alter immune cell function. By investigating the interactions between lipid metabolism and immune cells in this setting, the review offers novel insights into early diagnosis, screening, and immunotherapy of malignant tumors. Furthermore, lipid metabolic reprogramming may act as a biomarker for monitoring early immune escape from tumors and predicting therapeutic outcomes, thereby enhancing early diagnosis and personalized cancer treatment.

Recent studies have highlighted a link between amyotrophic lateral sclerosis (ALS) and gut microbiota. This prospective study aimed to evaluate the effects of electroacupuncture combined with Chinese herbal medicine on gut microbiota and metabolomics in ALS patients.

Ten ALS patients were randomly assigned to either a treatment group (electroacupuncture with Chinese herbal medicine, n = 6) or a control group (waiting treatment, n = 4). Healthy controls (age- and sex-matched, n = 10) were also included. Data were collected after 12 sessions of electroacupuncture and follow-ups at three and six months. ALS functional rating scale scores were documented pre- and post-treatment. Stool samples were collected at two time points (T0 and T4 weeks) and analyzed, and metabolomic profiles from urine samples were analyzed post-treatment. Heatmap correlation analysis was used to explore relationships between microbiota, metabolomics, and clinical outcomes.

Treatment with electroacupuncture reduced Eisenbergiella abundance in the treatment group. A significant positive correlation was found between Lachnospiraceae and ALS functional rating scale scores (P < 0.005 and P < 0.001, respectively). Differential expression of purine metabolism was observed in ALS patients (P = 0.0017).

Imbalances in the gut microbiome and metabolic disorders have been found among patients with ALS. These imbalances appear to be partially mitigated by treatment with electroacupuncture combined with Chinese herbal medicine. Our research suggests that Eisenbergiella might be a diagnostic biomarker and a potential therapeutic target for ALS.

Acetaminophen (APAP) is one of the most commonly used analgesic and antipyretic medications and is generally considered safe at therapeutic doses. However, overdose remains a leading cause of acute liver failure, primarily characterized by centrilobular (zone 3) hepatic necrosis, oxidative stress, mitochondrial dysfunction, and sterile inflammation. The hepatotoxic effects of APAP are localized to the centrilobular region, where cytochrome P450 2E1 is highly expressed. Cytochrome P450 2E1 catalyzes the conversion of APAP to a toxic metabolite, N-acetyl-p-benzoquinone imine. During overdose, the liver’s detoxification capacity is overwhelmed and excess N-acetyl-p-benzoquinone imine binds to cellular proteins, initiating oxidative stress and mitochondrial injury that culminate in hepatocyte death. A central component of APAP-induced hepatotoxicity is the activation of innate immune responses, particularly via inflammasome pathways. Inflammasomes are cytosolic multiprotein complexes that detect cellular damage and trigger inflammation. Among these, the NOD-, LRR-, and pyrin domain-containing 3 (NLRP3) inflammasome plays a significant role in APAP-induced liver injury. Upon activation, the NLRP3 inflammasome promotes autocatalytic cleavage of procaspase-1 into its active form, caspase-1, which subsequently processes the pro-inflammatory cytokines pro-interleukin-1β and pro-interleukin-18 into their mature forms. These cytokines recruit additional immune cells and amplify liver inflammation, exacerbating tissue injury. Thus, the NLRP3 inflammasome serves as a key mechanistic link between the initial toxic insult and the ensuing inflammatory response in APAP hepatotoxicity. This review aimed to explore the molecular mechanisms underlying APAP-induced liver injury, particularly inflammasome activation, and evaluate the current and emerging therapeutic strategies.