Metabolic-associated steatohepatitis (MASH) is an advanced and progressive liver disease that potentially causes cirrhosis and hepatocellular carcinoma. Exercise is a crucial and effective intervention for ameliorating metabolic dysfunction-associated steatotic liver disease. This study aimed to provide a comprehensive understanding of the underlying mechanisms of MASH, which benefit a broad spectrum of MASH patients, including those who have difficulty engaging in physical activity.

We established a mouse model of MASH and selectively knocked down L-type amino acid transporter 1 and alanine-serine-cysteine transporter 2. Mice were fed a high-fat high-cholesterol diet and subjected to either short- or long-term exercise regimens. We assessed the phosphorylation and activity of branched-chain alpha-keto acid dehydrogenase (BCKDH) as well as branched-chain amino acid (BCAA) content in skeletal muscle following exercise.

Short-term exercise significantly reduced hepatic steatosis and inflammation without causing notable changes in body weight. It also enhanced BCKDH activity in skeletal muscle and decreased hepatic BCAA accumulation. Muscle-specific overexpression of BCKDH further promoted BCAA catabolism and significantly attenuated hepatic steatosis and inflammation in high-fat high-cholesterol-fed mice. In contrast, muscle-specific L-type amino acid transporter 1 knockdown, which suppresses BCAA uptake, markedly abolished these beneficial effects. Interestingly, BCKDH overexpression in muscle increased glutamine levels in both the blood and liver. Hepatic alanine-serine-cysteine transporter 2 knockdown, which inhibited glutamine uptake, lessened the protective effect of exercise on MASH. Further in vitro study revealed that glutamine derived from myocytes improved redox homeostasis and inhibited lipid accumulation in hepatocytes.

Short-term exercise enhances BCAA catabolism in skeletal muscle and promotes glutamine production, which circulates to the liver to improve redox balance and alleviate MASH.

Acute hepatitis E (AHE) in the elderly can lead to severe complications including liver failure and mortality, yet the epidemiological landscape remains poorly characterized. This study aimed to assess the burden, trends, and health inequalities of AHE among the elderly over the past three decades, and to further predict its changes by 2030.

Data on AHE in the elderly were obtained from the Global Burden of Disease 2021. The burden of AHE was analyzed by trends, decomposition, cross-country inequalities, and predictive analysis.

In 2021, the global incidence and Disability-Adjusted Life Years (DALYs) for AHE among the elderly were recorded as 1,130,013.35 and 20,084.77, respectively. Although there were significant differences in the incidence and DALYs across countries, the number of incident cases increased from 1990 to 2021, with a slight rise in age-standardized rates, while the number and age-standardized rate of DALYs showed a declining trend. Decomposition analysis revealed that population growth and aging are the drivers of changes in incidence, while epidemiological changes somewhat offset the increases in DALYs driven by population growth. Low socio-demographic index countries bear a disproportionate burden of elderly AHE, although inequality gaps have narrowed over time. Notably, up to 2030, the number of incident cases and DALYs will continue increasing. The burden in elderly women was more pronounced than in men.

The burden of elderly AHE, as a major public health issue, remains substantial. While cross-country inequities have been alleviated over time, the pressure on lower socio-demographic index countries to control the disease remains high. AHE in elderly women requires further attention. This emphasizes the significant challenges faced in controlling and managing elderly AHE.

Immunoinflammatory skin diseases are characterized by an imbalance in immune homeostasis, and their chronic inflammatory processes involve a complex regulatory network of CD4+ T cell differentiation. With the widespread use of biologics (e.g., interleukin-17/interleukin-23 inhibitors) in psoriasis, atopic dermatitis, and other diseases, the adverse effects triggered by the phenomenon of CD4+ T cell-mediated immune drift have attracted significant attention, with the skin being the primary target as an immune organ. In this paper, we provide a review of the clinical features of the skin and the mechanisms of immune drift caused by different types of biologics, as well as the therapeutic modalities.

Brain metastases from ovarian cancer (BMFOC) are rare but associated with poor prognosis. This study aimed to evaluate the efficacy and safety of Gamma Knife stereotactic radiosurgery (GKSRS) in managing patients with BMFOC.

A retrospective analysis was conducted on 22 patients with BMFOC who were treated with GKSRS between January 2015 and May 2019. The median age at the start of treatment was 57.7 years (range, 46–72 years). A total of 70 brain metastases were treated, with each patient having between one and nine metastatic tumors. The mean tumor volume was 3.6 cm3 (range, 0.1–22.7 cm3). The mean peripheral dose was 16 Gy (range, 7–20 Gy), and the mean isodose curve was 54.6% (range, 45–80%).

At 12 months post-GKSRS, 68 metastatic tumors were assessed: 32 (47.1%) showed complete response, 20 (29.4%) had partial response, 14 (20.6%) remained stable, and two (2.9%) progressed, leading to a tumor control rate of 97.1%. No acute or chronic toxicity was observed.

GKSRS appears to be an effective and well-tolerated treatment for BMFOC, offering high tumor control rates and prolonged survival in selected patients.

Non-invasive vagus nerve stimulation (nVNS), including transcutaneous cervical (tcVNS) and auricular (taVNS) modalities, has garnered increasing attention as a neuromodulatory therapy for various neurological and psychiatric disorders. This narrative review synthesizes findings from over 80 studies, including randomized controlled trials, meta-analyses, and observational research published up to March 2024, evaluating nVNS in epilepsy, depression, stroke rehabilitation, headache, Parkinson’s disease, and Alzheimer’s disease. Evidence suggests that taVNS can reduce seizure frequency and improve quality of life in epilepsy. In major depressive disorder, nVNS demonstrates antidepressant effects comparable to pharmacotherapy, though the optimal stimulation parameters remain unclear. For post-stroke motor rehabilitation, both tcVNS and closed-loop stimulation systems enhance neuroplasticity and motor recovery. In Parkinson’s and Alzheimer’s diseases, preliminary findings indicate possible modulation of neuroinflammatory pathways and cognitive-motor functions, although recent meta-analyses report mixed efficacy. Challenges include methodological heterogeneity, protocol variability, and difficulties in designing effective sham controls, all of which limit the generalizability of current findings. Mechanistic differences between tcVNS and taVNS remain inadequately characterized. Overall, nVNS appears to be a safe and accessible therapeutic approach with broad clinical potential, particularly for treatment-resistant or underserved populations. However, future research must prioritize standardized protocols, robust clinical endpoints, and adequately powered trials to define efficacy and optimize treatment strategies. A greater focus on long-term outcomes, biomarker-guided personalization, and clinical significance over statistical findings will be critical in translating nVNS into routine practice.

Colorectal cancer (CRC) is a type of cancer that originates in the colon or rectum from precancerous polyps, which can evolve into cancerous growths over time. This review aimed to provide a comprehensive analysis of CRC, its subtypes, clinical manifestations, point-of-care diagnostic approaches, and management strategies. The clinical presentation of CRC often includes symptoms such as blood in stool, changes in bowel habits, abdominal discomfort, weight loss, fatigue, a feeling of incomplete bowel emptying, and anemia. The identification of these signs prompts healthcare professionals to initiate diagnostic measures without delay. Point-of-care diagnosis plays a pivotal role in the early detection of CRC, employing screening tests such as stool tests and colonoscopies. These diagnostic modalities enable healthcare professionals to identify precancerous polyps or early-stage tumors, facilitating timely intervention and significantly improving treatment outcomes. Adherence to screening guidelines is crucial for the prevention and early detection of CRC. Despite advancements in screening and treatment options, there remains a crucial need for more specific, minimally invasive screening methods with minimal side effects. By improving current detection methods, a better screening approach for CRC can be developed. Recent advancements, including single-cell sequencing, spatial transcriptomics, and artificial intelligence integration, hold great promise for enhancing early diagnosis and advancing personalized treatment strategies. Moreover, a healthy lifestyle, including a balanced diet, regular exercise, no tobacco use, and limited alcohol consumption, can significantly lower the risk of CRC. By emphasizing the importance of lifestyle modifications, early screening, and timely intervention, healthcare professionals can significantly reduce the burden of CRC and improve patient outcomes.

Lung metastasis is common in hepatocellular carcinoma (HCC) and is typically associated with a poor prognosis. In this report, we present a case of advanced HCC in a 46-year-old Chinese male with lung metastases. The patient received two cycles of sequential hepatic arterial infusion chemotherapy and transarterial embolization in combination with lenvatinib (a tyrosine kinase inhibitor) and tislelizumab (a programmed cell death protein 1 immune checkpoint inhibitor). After three months of treatment, the intrahepatic tumors showed a partial response, while the bilateral lung metastases exhibited a complete response. Concurrently, levels of alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II decreased to normal levels. Systemic treatment with lenvatinib and tislelizumab was continued for 10 months. This case underscores the potential of combination therapies for advanced HCC with lung metastases and provides a novel perspective on a therapeutic approach involving sequential hepatic arterial infusion chemotherapy and transarterial embolization with immune checkpoint and tyrosine kinase inhibitors.

Malignant mixed Müllerian tumor (MMMT) or carcinosarcoma of the female genital tract is a rare but highly aggressive malignancy.

We report a unique case of primary ovarian MMMT with poorly differentiated angiosarcoma as its homologous sarcomatous component in a 53-year-old woman with a known germline BRCA1 mutation who presented with a pelvic mass. She underwent staging cytoreduction surgery including total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and pelvic and para-aortic lymph node dissections. The removed right ovarian tumor formed a 2.5 cm nodular to cystic mass replacing the entire organ. Microscopic examination revealed two distinct tumor components: high-grade serous carcinoma and poorly differentiated angiosarcoma. The proliferating sarcomatous cells were diffusely positive for CD31 and Factor VIII, but were negative for 100, SOX10 and cytokeratin. Both the serous carcinoma and angiosarcoma components demonstrated aberrant strong and diffuse p53 nuclear positivity. KRAS mutation analysis revealed guanine-adenine-thymine point mutation at codon 12 in both tumor components. Metastatic tumor was found involving the contralateral left ovary with the cellular composition of pure angiosarcomatous component.

This is the first report of an ovarian MMMT with angiosarcoma as its homologous sarcoma component. The presence of aberrant p53 expression and identical KRAS mutation in both the serous carcinoma and angiosarcoma components supports the theory of malignant mesenchymal transition/metaplasia in the development of MMMT.

Histopathology is the gold standard in cancer diagnosis. However, attenuated total reflectance (ATR)-Fourier transform infrared (FTIR) spectroscopy has shown diagnostic potential in other settings. Therefore, this study aimed to investigate the sensitivity and specificity of the ATR-FTIR spectroscopy in evaluating breast lesions.

This study was conducted on formalin-fixed, paraffin-embedded biopsy blocks received at Ladoke Akintola University of Technology Teaching Hospital between 2022 and 2023. The blocks were categorized into 10 normal (from benign breast tissue), 15 benign, and 31 malignant samples. Tissue sections of 15 µm were obtained during block trimming and floated onto FTIR slides. An additional 4 µm tissue sections were stained with hematoxylin and eosin for tumor diagnosis and to identify suitable areas on the FTIR slide. Spectrometer readings were taken within the range of 4000–600 cm−1, 32 scans, and 16 cm−1 resolution, using the average of 10 preprocessed spectra per slide. Biomarkers were calculated by ratioing peak intensities for A1632/A1543, A1632/A2922, A1632/A1080, A1080/A1543, A1237/A1080, and A1043/A1543, which represent protein, diagnostic marker, cytoplasm-nucleus ratio, carcinogenesis marker, phosphate, and glycogen, respectively. The receiver operating characteristic curve was used to determine sensitivity, specificity, and the area under the curve (AUC).

The AUC analysis showed that cytoplasm-nucleus ratio values of 0.99 and 0.95 effectively distinguished normal from malignant tissue, and benign from malignant tissue, respectively (p < 0.0001). Additionally, protein marker (AUC = 0.73), diagnostic marker (AUC = 0.85), and cytoplasm-nucleus ratio marker (AUC = 0.94) were able to discriminate normal from benign tissue. Overall, the receiver operating characteristic analysis showed 100% sensitivity and specificity ranging from 54% to 87%. Glycogen (AUC = 1.00) exhibited 100% sensitivity in discriminating fibroadenoma from fibrocystic changes.

ATR-FTIR spectroscopy demonstrates high diagnostic accuracy in differentiating normal, benign, and malignant breast tissues using specific spectral biomarkers. Among these, the cytoplasm-nucleus ratio marker showed strong potential as a reliable spectral indicator for distinguishing various types of breast tumors. The cytoplasm-nucleus ratio marker demonstrated strong potential as a reliable spectral indicator for distinguishing various types of breast tumors.

Gut dysbiosis has been reported in severe liver diseases. However, information on the impact of hepatitis E virus infection on the gut microbiota, and the association between enteric microbiota disturbances and acute hepatitis E (AHE), is limited, particularly in elderly patients with AHE (AHE-elderly). Our objective was to characterize the AHE-specific microbiome in elderly patients and evaluate its association with clinical outcomes.

Fecal samples and clinical data were collected from 58 AHE-elderly patients (46 self-healing cases, 12 non-self-healing cases) and 30 elderly patients with healthy controls (hereinafter referred to as HCs-elderly). Gut microbiota composition was analyzed using 16S rRNA gene sequencing. Bioinformatic analyses, including alpha diversity and STAMP, were performed. The predictive potential of Bacteroides fragilis was assessed using statistical analysis and receiver operating characteristic curves.

Alpha diversity indices showed no significant differences in microbial diversity between the AHE-elderly and HCs-elderly groups, nor between self-healing and non-self-healing groups among AHE-elderly patients. Nevertheless, a trend toward altered species richness was observed. In the AHE-elderly group, the relative abundance of Firmicutes, Lactobacillales, and Bacilli increased significantly. Meanwhile, compared with the self-healing group, Bacteroidetes were more abundant in the non-self-healing group. At the species level, Bacteroides fragilis was the most abundant in the non-self-healing group, significantly contributing to the divergence in gut microbiota between the two groups.

The relative abundance of Bacteroidetes significantly distinguished AHE-elderly patients from healthy controls and could more accurately predict recovery outcomes in elderly AHE patients. These findings suggest new strategies for preventing and managing AHE recurrence in the elderly patients.