Primary sclerosing cholangitis (PSC) is an immune-mediated cholestatic liver disease. Its molecular etiology remains poorly defined, hindering the development of mechanism-based diagnostics and therapies. Therefore, this study aimed to identify key molecular drivers and causal biomarkers of PSC by integrating transcriptomics, machine learning, and genetic causal inference.

We deployed an integrated computational framework combining transcriptomics, network biology, machine learning, and genetic causal inference. Peripheral blood transcriptomes from PSC patients and controls were analyzed to identify disease-associated modules. Candidate genes were refined via protein-protein interaction networks and a multi-algorithm machine learning screen. Causal inference was performed using two-sample Mendelian randomization, integrating plasma protein quantitative trait loci with PSC genome-wide association study summary statistics.

Transcriptomic analysis revealed a PSC-associated module enriched in ribosome biogenesis and protein homeostasis pathways. A machine learning-optimized nine-gene signature (including PTMA, SUMO1, Shwachman-Bodian-Diamond syndrome (SBDS), RPL7, EIF1AX, ANP32A, PCNA, FAM98A, and MPHOSPH6) achieved high diagnostic accuracy (mean AUC = 0.908) and was consistently downregulated in PSC. This signature was linked to a remodeled immune microenvironment characterized by myeloid skewing and specific transcriptional-immune covariation patterns. Mendelian randomization identified SBDS as a putatively causal protective factor, where genetically instrumented higher plasma SBDS protein levels were robustly associated with a lower PSC risk (IVW OR = 0.525, 95% CI: 0.356–0.773, P = 0.001). Sensitivity analyses supported the validity of the Mendelian randomization assumptions.

Our study establishes disrupted ribosome homeostasis as a causal pathway in PSC and nominates plasma SBDS as a high-confidence diagnostic biomarker and therapeutic target. The integrative framework provides a generalizable strategy for discovering causal biomarkers in complex diseases.

Hepatocellular carcinoma (HCC) remains one of the most fatal cancers, primarily due to late diagnosis and the lack of effective early biomarkers. Recent advances in multi-omics and liquid biopsy technologies hold promise for improving early detection, prognostication, and monitoring of HCC. Understanding the immune landscape of HCC through genetic and epigenetic signatures is essential for identifying therapeutic targets and improving immunotherapy outcomes. This review aims to present current findings on immune-related biomarkers, multi-omics strategies, and biomarker validation in HCC. It also aims to evaluate the role of liquid biopsy and gene signatures in predicting treatment responses, with a specific focus on their applications in immunotherapy. The goal is to provide a comprehensive framework for integrating these emerging tools into clinical practice. The integration of multi-omics approaches has led to the identification of robust gene signatures that predict HCC prognosis and response to immune checkpoint inhibitors. Liquid biopsy technologies, including circulating tumor DNA, provide non-invasive alternatives for monitoring tumor evolution and therapeutic responses. Despite promising results, challenges remain in clinical validation, particularly in cross-platform reproducibility and the interpretation of complex multi-omics data. While genetic biomarkers are rapidly advancing, their clinical application in personalized medicine remains hindered by technical and ethical challenges, such as data privacy, informed consent, and method standardization. The integration of multi-omics data and liquid biopsies offers a promising path toward real-time, personalized treatment and the development of universal prognostic signatures for HCC. However, successful clinical adoption depends on cross-disciplinary collaboration to standardize data protocols and overcome challenges regarding accuracy, reproducibility, and patient privacy.

Chikungunya fever, caused by the Chikungunya virus (CHIKV), has re-emerged as a significant global health concern in recent decades. A notable event was the largest-ever local outbreak in China in 2025, marking a critical juncture in its epidemiology. Although conventional treatment remains predominantly supportive, the integration of traditional Chinese medicine (TCM) offers promising complementary strategies for alleviating both acute symptoms and chronic polyarthralgia. This narrative review aims to consolidate current knowledge on the etiology, pathogenesis, clinical manifestations, and management of Chikungunya fever, with a particular focus on the evidence-based application of TCM. By integrating molecular virology with clinical and epidemiological insights, this review offers a comprehensive perspective on the challenges posed by CHIKV and underscores the strategic imperatives essential for its future management. In conclusion, addressing the expanding threat of CHIKV necessitates a multi-pronged public health strategy that integrates standard clinical and preventive measures with evidence-based TCM therapies, highlighting the urgent need for rigorous clinical trials to globally validate these integrative treatments.

Synucleinopathies, including Parkinson’s disease (PD), dementia with Lewy bodies, and multiple system atrophy (MSA), are a group of neurodegenerative diseases characterized by the oligomerization of α-synuclein protein in neurons or glial cells. Various splicing isoforms of α-synuclein have been described, each with different aggregation properties. The α-synuclein gene (SNCA) has been identified as a highly significant genetic risk locus associated with various synucleinopathies across populations. This study aimed to assess the association of SNCA genetic variants with MSA and the levels of SNCA transcripts in peripheral blood mononuclear cells (PBMCs) from MSA and PD patients.

In this retrospective case–control study, 96 MSA patients, 1086 PD patients, and 485 healthy volunteers were included. PCR followed by restriction endonuclease analysis was used to detect four SNCA single-nucleotide polymorphisms (rs356219, rs3756063, rs11931074, and rs356168) in these individuals. In addition, RT-qPCR was performed to detect the levels of α-synuclein transcripts (SNCA mRNA isoforms -140, -126, and -112) in PBMCs of 24 MSA patients (including parkinsonian (MSA-P) and cerebellar (MSA-C) variants), 31 PD patients, and 32 healthy volunteers.

The frequency of the ‘T’ allele (of rs11931074) was significantly higher in MSA patients than in the healthy controls. The level of SNCA-140 mRNA was significantly decreased in MSA and PD patients compared with the controls, while the level of SNCA-112 mRNA was significantly increased in MSA-P patients than in PD patients and the controls. SNCA-112 mRNA/SNCA-140 mRNA and SNCA-112 mRNA/SNCA-126 mRNA ratios were significantly increased in MSA patients than in the controls.

The SNCA rs11931074 polymorphism is associated with MSA. There is a pronounced alteration in the expression of SNCA transcripts in PBMCs of MSA and PD patients.

Chronic hepatitis B (CHB) remains a major global public health challenge. Current therapies based on nucleos(t)ide analogues and interferon mainly achieve long-term viral suppression, whereas only a small proportion of patients attain a functional cure, defined as sustained hepatitis B surface antigen loss with hepatitis B virus (HBV) DNA below the limit of quantification for at least 24 weeks after treatment discontinuation, with or without anti-HBs seroconversion. Emerging evidence from the gut–liver axis indicates that gut microbiota–derived metabolites, particularly short-chain fatty acids (SCFAs) and bile acids (BAs), modulate the HBV life cycle and immune regulation in CHB, thereby offering therapeutic targets to overcome immune tolerance. This review summarizes the biological characteristics of SCFAs and BAs and their mechanistic roles across different stages of HBV infection, with emphasis on translational relevance. In vitro and animal studies suggest that butyrate and related SCFAs suppress HBV gene expression by inhibiting histone deacetylases and remodeling covalently closed circular DNA minichromatin. SCFAs may also enhance antiviral immunity, although they may reinforce immune tolerance in certain contexts. For BAs, the farnesoid X receptor, Takeda G protein–coupled receptor 5, and the HBV entry receptor sodium taurocholate cotransporting polypeptide form a key signaling hub with dual effects on viral replication and host responses. Early-phase studies suggest that farnesoid X receptor agonists, pegylated interferon-α, or nucleos(t)ide analogues are associated with hepatitis B surface antigen reductions, though larger trials are needed. This review proposes biomarker-guided stratification and multi-target combination strategies to improve functional cure rates in CHB.

Pancreatic cystic neoplasms (PCNs) are increasingly detected in clinical practice, yet substantial variability exists in imaging interpretation and reporting, which may affect clinical decision-making. This guideline was developed to standardize diagnostic imaging evaluation and reporting for PCNs. A multidisciplinary expert panel conducted literature search and critical appraisal of domestic and international evidence, identified key clinical questions, and formulated recommendations using the Grading of Recommendations Assessment, Development and Evaluation framework. A modified Delphi consensus process and external review were performed to ensure the robustness of the recommendations. A total of 21 key questions were addressed, covering essential aspects of imaging evaluation and reporting for PCNs, including the preferred imaging modality for suspected lesions; standardized measurement of cyst size and mural nodules and their clinical significance; definitions of cyst wall and septal thickening; optimal imaging approaches for assessing the relationship between cystic lesions and the main pancreatic duct; measurement and evaluation of main pancreatic duct diameter and dilation; imaging-based classification of intraductal papillary mucinous neoplasms and serous cystic neoplasms; assessment of ductal obstruction, calcification, hemorrhage, and pancreatitis-related changes; criteria for suspicious lymph nodes; differentiation of PCNs from pancreatic pseudocysts or retention cysts; and recommended imaging modalities and follow-up intervals. This guideline provides a structured and evidence-based framework for imaging evaluation and reporting of PCNs, which may improve the consistency and clarity of imaging reports and support clinical decision-making.

Early risk stratification of severe acute liver injury (SLI), a precursor to acute liver failure (ALF), is vital for timely intervention, but no universal prognostic assessment tool covers both conditions. This study aimed to develop a simplified prognostic model for early risk assessment in SLI/ALF patients.

A retrospective cohort study consecutively enrolled SLI patients (including those progressing to ALF) from July 1, 2020 to May 31, 2025. Baseline clinical and laboratory data on admission were collected, with 90-day transplant-free survival as the primary outcome. Independent prognostic factors were screened via Cox regression to build a simplified scoring model, whose performance was compared with the Model for End-Stage Liver Disease (MELD), King’s College Criteria (KCC), and the Acute Liver Failure Study Group Prognostic Index (ALFSG-PI).

Of 302 patients, 190 (62.9%) achieved 90-day transplant-free survival. Multivariate Cox regression identified international normalized ratio (hazard ratio [HR]: 1.118, 95% confidence interval [CI]: 1.050–1.191), platelet count (HR: 0.995, 95% CI: 0.993–0.998), and hepatic encephalopathy grade ≥ 2 (HR: 5.187, 95% CI: 3.403–7.907) as independent predictors, forming the HIP (derived from the above-mentioned three predictors) model. It showed good discrimination ((area under the receiver operating characteristic curve [AUC]): 0.82), outperforming MELD (AUC: 0.76, P = 0.019) and KCC (AUC: 0.72, P = 0.002), and performing comparably to ALFSG-PI (AUC: 0.80, P = 0.429). The model also performed robustly in ALF subgroups defined by the American College of Gastroenterology and the 2024 Chinese Medical Association guidelines (AUCs: 0.80 and 0.76, respectively) and achieved an AUC of 0.85 in the validation set.

The HIP model is a simple and effective tool for prognostic risk stratification in SLI/ALF patients, suitable for emergency and primary care to facilitate timely intervention.

Alpha-1 antitrypsin deficiency (AATD) is an autosomal codominant genetic disorder caused by mutations in the SERPINA1 gene. It results in reduced circulating levels of alpha-1 antitrypsin (AAT), a serine proteinase inhibitor (PI) primarily produced by hepatocytes. The most common deficient alleles are PI*S and PI*Z, with PI*ZZ homozygotes having the most severe deficiency and highest risk for lung and liver disease. While AATD is well established as a cause of early-onset emphysema and liver cirrhosis, emerging evidence suggests a potential association with the formation of arterial aneurysms. The pathophysiological rationale for this association centers on protease-antiprotease imbalance and potential extracellular matrix degradation of elastin in arterial vessel walls. Several studies have reported increased frequencies of AATD alleles in patients with abdominal aortic aneurysms and intracranial aneurysms compared to the general population, with some demonstrating statistically significant associations. Additionally, patients with the PI*ZZ genotype have been shown to have larger aortic diameters, greater aortic stiffness, and reduced distensibility compared to controls. However, the evidence is inconsistent, as several large studies have failed to demonstrate significant associations between AATD and aneurysm formation. Overall, current evidence suggests an association of AATD with the development of arterial aneurysms. However, it is also clear that the presence of AATD alone is not sufficient to increase the risk of developing new-onset arterial aneurysms.

Cannabinoid hyperemesis syndrome is an underrecognized cause of recurrent vomiting, weight loss, and abdominal pain in adolescents, often overlooked due to its nonspecific presentation and overlap with other gastrointestinal conditions. This case report highlights a 13-year-old female who presented with significant weight loss and postprandial bilious vomiting initially attributed to superior mesenteric artery syndrome. Persistent symptoms, despite surgical removal of an incidental ovarian dermoid cyst, prompted reevaluation after nondiagnostic imaging and lack of improvement. Further history two weeks later revealed daily cannabis use, confirmed by a positive urine toxicology screen for tetrahydrocannabinol. Following supportive care and cannabis cessation, her symptoms resolved. This case illustrates how incomplete social histories and incidental findings can delay the identification of cannabinoid hyperemesis syndrome and lead to unnecessary procedures. Early use of urine toxicology screening and validated substance use tools (CRAFFT, BSTAD, S2BI) in adolescents with persistent vomiting and abdominal pain can facilitate timely recognition, reduce hospital length of stay, and improve outcomes.