Epidemiological data on bacterial infections in cirrhosis in China remain limited. Therefore, we aimed to conduct a multicenter study to investigate the characteristics and outcomes of patients with cirrhosis and bacterial infections in China.

We retrospectively enrolled 1,438 hospitalized adult patients with cirrhosis and bacterial or fungal infections from 24 hospitals across China between January 2018 and September 2024. Data on demographics, clinical features, microbiology, treatment, and outcomes were collected.

A total of 1,783 infection episodes were recorded, including 1,668 first infections and 115 second infections. Most infections were community-acquired (86.6%). Pneumonia was the most common infection type (26.7%), followed by spontaneous bacterial peritonitis (19.5%) and spontaneous bacteremia (14.1%). Among 754 pathogens isolated from 620 patients, Klebsiella pneumoniae (20.1%) was nearly as common as Escherichia coli (21.7%). Multidrug-resistant (MDR) organisms accounted for 41.0% of all isolates, with extended-spectrum β-lactamase-producing Escherichia coli being the most prevalent MDR strain (8.9% of patients). Adherence to empirical antibiotic treatment guidelines from the European Association for the Study of the Liver was significantly lower in this cohort compared to the global study (21.5% vs. 61.2%, P < 0.001), accompanied by a lower clinical resolution rate (63.5% vs. 79.8%, P < 0.001).

The clinical and microbiological characteristics of bacterial infections in patients with cirrhosis in China differ substantially from those reported in other regions. These findings highlight the need for region-specific management and prevention strategies, particularly in light of the changing microbiological landscape, high MDR prevalence, and suboptimal antibiotic practices.

Hepatic biliary adenofibroma is an exceedingly rare biliary neoplasm that primarily affects adults. It typically presents as a solitary mass composed of low-grade microcystic and tubuloglandular bile duct structures, which are lined by low columnar to cuboidal non-mucin-producing biliary epithelium and supported by abundant fibrous stroma. Histologically, it resembles the Von Meyenburg complex but is much larger in size and often shows cytologic atypia. Although considered benign, emerging case studies and analyses suggest that biliary adenofibroma may serve as a precursor lesion to intrahepatic cholangiocarcinoma. However, its extreme rarity, coupled with an incompletely understood histogenesis, perpetuates diagnostic uncertainty and may lead to misclassification with other similar entities. This review consolidates the current understanding of the histopathological and molecular characteristics of biliary adenofibroma, highlights its differential diagnosis, explores its potential progression to cholangiocarcinoma, and discusses unresolved questions while proposing future research directions.

Philadelphia chromosome-positive (Ph+) B-lymphoblastic leukemia/lymphoma (B-ALL/LBL) is an aggressive hematologic malignancy driven by the BCR::ABL1 fusion. While many cases respond well to treatment, some patients exhibit persistent BCR::ABL1 expression after therapy, presenting significant diagnostic challenges.

We present the case of a seven-year-old girl diagnosed with Ph+ B-ALL. Despite low percentages or negative results for blasts post-treatment, molecular and cytogenetic studies persistently detected high levels of BCR::ABL1, suggesting a high disease burden at the genetic level. This discordance supported multilineage involvement and the potential for retrospective revision of the initial diagnosis to lymphoblast crisis of chronic myeloid leukemia (LBC-CML).

Classifying such cases as de novo Ph+ B-ALL with multilineage involvement or LBC-CML is challenging, as there is currently no consensus among experts. Further studies are necessary to clarify the distinction, given the different management strategies and treatment responses between these two conditions.

The diagnosis of hepatic precancerous lesions (HPC) and early hepatocellular carcinoma (HCC) has significant public health implications and holds the potential to reduce the global burden of HCC. This study aimed to identify molecular features and biomarkers associated with HPC progression and early HCC development.

RNA sequencing was used to identify differentially expressed genes in mouse HPC tissues and normal liver tissues. Cyclin E1 (CCNE1) expression in HPC tissues and HCC cells was assessed using immunohistochemistry, Western blotting, and real-time polymerase chain reaction. The effects of CCNE1 on HCC cell proliferation, migration, invasion, and apoptosis were evaluated using colony formation, wound healing, Transwell assays, and flow cytometry. The mechanism of CCNE1 was explored through Kyoto Encyclopedia of Genes and Genomes pathway analysis and gene set enrichment analysis and further validated through in vitro experiments. The interaction between CCNE1 and tumor-associated macrophages (TAMs) was investigated by co-culturing HCC cells with macrophages.

RNA sequencing and TCGA database analysis showed that CCNE1 expression was significantly elevated in mouse HPC tissues and human HCC samples and was associated with reduced survival rates. In vitro assays demonstrated that CCNE1 promoted HCC cell proliferation, migration, invasion, and survival by activating the PI3K/Akt signaling pathway. Additionally, CCNE1 induced TAM polarization toward the M2 phenotype by promoting the expression of CCL2 and CCL5 in HCC cells.

CCNE1 promotes HPC progression and HCC cell proliferation, migration, invasion, and survival by activating the PI3K/Akt signaling pathway. Furthermore, CCNE1 enhances the secretion of CCL2 and CCL5 by HCC cells, promoting TAM infiltration and M2 polarization, thereby contributing to tumor progression.

Since the adoption of novel prognostic scores, such as the iterative model for end-stage liver disease (MELD 3.0) and the gender-equity model for liver allocation (GEMA), their utility has markedly expanded to diverse clinical scenarios. However, data concerning their prognostic value in more generalized cirrhotic populations are scarce. In this study, we aimed to elucidate the MELD 3.0/GEMA-Na for long-term mortality risk stratification and refine their usage scope.

This study retrospectively reviewed 310 hospitalized patients with decompensated cirrhosis. Discrimination and stratification were compared between MELD 3.0/GEMA-Na and other scores. Validation was performed in another 120 subjects.

In the investigated cohort, the median MELD-Na, MELD 3.0, and GEMA-Na were 9 (7, 12), 12 (10, 17), and 12 (9, 17), respectively. Compared to their predecessors, both MELD 3.0 and GEMA-Na models exhibited consistently better discriminative ability, especially in relation to long-term mortality. This effect was more pronounced for GEMA-Na, which was the only score to present an area under the receiver operating characteristic curve greater than 0.8 up to two years (0.807). Statistical analysis indicated that a MELD 3.0 score of 18 and a GEMA-Na score of 20 were the most optimal cutoffs to rank the risk of death, both of which were independently associated with two-year all-cause transplant-free mortality (MELD 3.0: hazard ratio: 1.13, 95% confidence interval: 1.10, 1.17; GEMA-Na: hazard ratio: 1.12, 95% confidence interval: 1.10, 1.17, both P < 0.001). Similar findings were affirmed in the validation cohort.

MELD 3.0 is superior to other MELD-based scores for long-term prognostication in hospitalized patients with cirrhosis, while GEMA-Na demonstrated even better accuracy and performance.

Neglected tropical diseases (NTDs) encompass a range of infectious diseases prevalent in tropical and subtropical regions, often overlooked despite their substantial health impacts and high mortality rates. Current treatments for NTDs frequently cause severe side effects due to the pharmacokinetic properties of drugs, which can be harmful even at therapeutic doses. There is a pressing need for innovative diagnostic and therapeutic strategies to mitigate these side effects and improve diagnostic capabilities, as many NTDs lack adequate diagnostic tools. Nanotechnology presents a promising avenue to address these challenges. Nanomaterials possess unique characteristics that enable dual functionality in disease diagnosis and treatment. When conjugated with drugs, nanomaterials can enhance the efficacy of treatments for parasitic diseases while reducing the toxicity associated with conventional medications. Nanomaterial-drug conjugates also serve as efficient carriers, improving drug delivery systems for existing NTD treatments and minimizing adverse effects. This study explores recent advancements in conjugating nanomaterials with drugs for the treatment and diagnosis of NTDs. A comprehensive review of primary database sources reveals significant gaps in current research, underscoring the vast potential for developing novel therapeutic and diagnostic tools. These innovations could revolutionize the management of NTDs, ushering in more effective and safer treatment modalities in the future.

Paget’s disease of the esophagus is extremely rare, with few cases reported. In this report, we describe a case of recurrent esophageal Paget’s disease coexisting with small cell carcinoma. A 63-year-old man presented with the chief complaint of a rediscovered early esophageal cancer. Endoscopic examination revealed two separate superficial flat tumors in the upper and mid esophagus. Endoscopic submucosal dissection was performed, diagnosing diffuse Paget’s disease (5.5 × 3.5 cm) and a small focus on intramucosal squamous cell carcinoma, respectively. Paget’s cells were also found in the distal and right margins of the first specimen of endoscopic submucosal dissection. Immunohistochemical analysis showed that Paget’s disease diffusely expressed cytokeratin 7 (CK7), CK18, and mucin 6 (MUC6), and focally expressed CD56 and chromogranin A, but not CK5/6, p63, p40, MUC5AC, MUC2, or synaptophysin. A complete absence of p53 and Rb1 was observed in Paget’s disease. However, overexpression of p53 and retention of Rb1 were seen in squamous cell carcinoma. Approximately 27 months later, a prominent tumor was found at the same location as the previous Paget’s disease. Subsequently, radical surgery was performed, and the final pathological evaluation revealed esophageal small cell carcinoma coexisting with Paget’s disease. Moreover, both p53 and Rb1 were completely absent in both Paget’s disease and the small cell carcinoma. This suggests that esophageal Paget’s disease may dedifferentiate and develop into small cell carcinoma. In conclusion, esophageal Paget’s disease can co-occur with invasive carcinomas, including small cell carcinoma, and should be completely resected endoscopically, with close follow-up.

This study investigates the potential of methyl eugenol (ME), a compound found in the essential oils of various plants, to inhibit oxidative stress and its impact on diseases associated with this process. ME has been shown to possess antioxidant properties and antiproliferative activity in several cancers. It also demonstrates neuroprotective potential in conditions such as Alzheimer’s disease and ischemic brain injury. The mechanism of action involves the activation of the nuclear factor erythroid 2-related factor 2, which facilitates the transcription of antioxidant genes and modulation of pathways such as AMP-activated protein kinase/glycogen synthase kinase 3 beta, thereby reducing the production of reactive oxygen species and pro-inflammatory cytokines. However, research has identified potential toxicological risks associated with ME, including hepatotoxicity and changes in the gut microbiota. These findings highlight the need for caution when considering prolonged exposure to this compound.

The incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) has been escalating annually, positioning it as the leading cause of chronic liver disease worldwide. Ursolic acid has demonstrated promising therapeutic efficacy in managing MASLD, thereby justifying the need for an in-depth exploration of its pharmacological mechanisms. This study aimed to investigate elucidate the therapeutic mechanisms by which ursolic acid modulates estrogen conversion in the treatment of MASLD.

Building upon prior studies that have highlighted the potent anti-inflammatory effects of ursolic acid and its specific targeting of 17β-hydroxysteroid dehydrogenase 14 (HSD17B14), this investigation employed a western diet to induce MASLD in murine models with varying severities over different time intervals.

The protein expression of HSD17B14 initially increased, followed by a subsequent decrease. This trend was accompanied by corresponding changes in 17β-estradiol (E2) and estrone (E1) levels. Intervention with ursolic acid resulted in a reduction in HSD17B14 and E1 levels during the phase of high HSD17B14 expression, while simultaneously elevating E2 levels. In steatotic hepatocytes, E1 promoted cellular inflammation, whereas E2 exhibited anti-inflammatory effects. However, the alleviated effects of E2 were antagonized by HSD17B14. As expected, ursolic acid modulated HSD17B14, thereby mitigating the inflammatory response in steatotic hepatocytes.

HSD17B14, a crucial enzyme regulating the balance between E1 and E2, catalyzes the conversion of estrogen E2 into E1, thereby exacerbating tissue inflammation induced by metabolic stress. Ursolic acid, by modulating HSD17B14-mediated estrogen conversion, appears to ameliorate immune-related inflammation in MASLD.