Cachexia occurs in approximately half of hepatocellular carcinoma (HCC) patients as the disease progresses and is correlated with a poor prognosis. Therefore, early identification of HCC patients at risk of developing cachexia and their prognosis is crucial. This study investigated the functional liver imaging score (FLIS) derived from gadoxetic acid-enhanced magnetic resonance imaging (MRI) to identify cachexia in HCC patients and their prognosis.
Pretreatment clinical and MRI data from 339 HCC patients who underwent gadoxetic acid-enhanced MRI scans were retrospectively collected. Patient weights were recorded for 6 months following the MRI scan to diagnose cachexia. The FLIS was calculated as the sum of the enhancement quality score, the excretion quality score, and the portal vein sign quality score. A Cox proportional hazards model was used to determine the significant factors affecting overall survival (OS). Multivariable logistic regression was then conducted to identify variables predicting cachexia in HCC patients, which were subsequently used to predict OS.
Cox regression analysis revealed a significant association between cachexia and worse OS. Both FLIS (0–4 vs. 5–6 points) (OR, 9.20; 95% CI: 4.68–18.10; P<0.001) and α-fetoprotein >100 ng/mL (OR, 4.08; 95% CI: 2.13–7.83; P<0.001) emerged as significant predictors of cachexia in patients with HCC. Furthermore, FLIS (0–4 vs. 5–6 points) (HR, 1.73; 95% CI: 1.19–2.51; P=0.004) was significantly associated with OS. Patients in the FLIS 0–4 points group had shorter OS than those in the FLIS 5–6 points group [20 months (95% CI, 14.7–25.3) vs. 43 months (95% CI, 27.7–58.3); P=0.001].
Cachexia was associated with worse OS. The functional liver imaging score emerged as a significant predictor of cachexia in HCC patients and their prognosis.
After endoscopic resection of colorectal cancer with submucosal invasion (pT1 CRC), additional surgical treatment is recommended if deep submucosal invasion (DSI) is present. This study aimed to further elucidate the risk factors for lymph node metastasis (LNM) in patients with pT1 CRC, especially the effect of DSI on LNM.
Patients with pT1 CRC who underwent lymph node dissection were selected. The Chi-square test and multivariate logistic regression were used to analyze the relationship between clinicopathological characteristics and LNM. The submucosal invasion depth (SID) was measured via 4 methods and analyzed with 3 cut-off values.
Twenty-eight of the 239 patients presented with LNM (11.7%), and the independent risk factors for LNM included high histological grade (P=0.003), lymphovascular invasion (LVI) (P=0.004), intermediate to high budding (Bd 2/3) (P=0.008), and cancer gland rupture (CGR) (P=0.008). Moreover, the SID, width of submucosal invasion (WSI), and area of submucosal invasion (ASI) were not significantly different. When one, two, three or more risk factors were identified, the LNM rates were 1.1% (1/95), 12.5% (7/56), and 48.8% (20/41), respectively.
Indicators such as the SID, WSI, and ASI are not risk factors for LNM and are subjective in their measurement, which renders them relatively inconvenient to apply in clinical practice. In contrast, histological grade, LVI, tumor budding and CGR are relatively straightforward to identify and have been demonstrated to be statistically significant. It would be prudent to focus on these histological factors rather than subjective measurements.
This study aimed to investigate the reasons behind the lower survival rates in male lung cancer patients than in female lung cancer patients.
Through various techniques, such as Argonaute immunoprecipitation, luciferase assays, and ChIP, this study confirmed the positive effects of androgen receptor (AR) on lung cancer cell invasion across different in vitro cell lines and in vivo mouse models.
The findings suggest that AR enhanced the invasion of lung cancer cells by modifying EPHB2 signals at the protein expression level, which in turn required changes in miRNA-23a-3p. Restoring miRNA-23a-3p could counteract the intensified invasion of lung cancer cells mediated by AR.
This study revealed that AR may facilitate the lung cancer matastasis by modulating miRNA-23a-3p/EPHB2 signaling and that targeting this signaling pathway could provide new approaches to inhibit lung cancer metastasis.
The medical metaverse is a combination of medicine, computer science, information technology and other cutting-edge technologies. It redefines the method of information interaction about doctor-patient communication, medical education and research through the integration of medical data, knowledge and services in a virtual environment. Artificial intelligence (AI) is a discipline that uses computer technology to study and develop human intelligence. AI has infiltrated every aspect of medical metaverse and is deeply integrated with the technologies that build medical metaverse, such as large language models (LLMs), digital twins, blockchain and extended reality (including VR/AR/XR). AI has become an integral part of the medical metaverse building process. Moreover, AI also provides richer medical metaverse functions, including diagnosis, education, and consulting. This paper aims to introduce how AI supports the development of medical metaverse, including its specific application scenarios, shortcomings and future development. Our goal is to contribute to the advancement of more sophisticated and intelligent medical methods.
Sepsis is a secondary condition resulting from severe systemic infections. It is a significant contributor to mortality in critically ill patients with rapid onset and severe symptoms. Acupuncture is a traditional Chinese medical treatment. Recent clinical studies have demonstrated that acupuncture, as an important synergistic therapy, has promising therapeutic effects in the treatment of sepsis. This paper reviews the mechanisms of immunomodulation and target organ protection associated with acupuncture and synergistic drug acupuncture in the treatment of sepsis. It also integrates existing studies to elucidate the modulation of the immune system and the protective effect of acupuncture on target organs.
Myocardial ischemia-reperfusion (I/R) injury is associated with a significant reduction in the mitochondrial membrane potential (MMP, ΔΨm). Fluorescence-based assays are effective for labelling active mitochondria in living cells; their application in heart tissue, however, represents a challenge because of a low yield of viable cardiomyocytes after cardiac perfusion. This study aimed to examine a novel method for detecting the changes in the MMP of mouse heart tissue following I/R injury.
The I/R model was established, which was characterized by distinct ischemic area and apoptosis in heart tissue. The MMP was detected via a confocal microscope after the ascending aorta was clamped and the mitochondrial probe solution (containing Mito-Tracker Deep Red FM) was perfused from the apex via a peristaltic pump.
This method enabled the distribution of the probe solution throughout the cardiac tissue via the coronary circulation. Fluorescence detection revealed that the MMP was profoundly reduced in both ischemic area and border area following I/R when compared with that in the sham group. There was no obvious difference in the MMP of the remote area between the I/R group and the sham group.
This study presents a novel method for detecting the MMP in heart tissue, and this method will facilitate the evaluation of changes in the MMP in different regions following I/R.
To investigate whether cardiac mast cells (MCs) participate in pressure overload-induced myocardial hypertrophy through the regulation of transient receptor potential vanilloid 4 (TRPV4).
Pressure overload-induced myocardial hypertrophy was induced via abdominal aortic constriction (AAC). Myocardial hypertrophy was evaluated by measuring the heart weight index (HW/BW), lung weight index (LW/BW), ratio of heart weight to tibia length (HW/TL), ratio of lung weight to tibia length (LW/TL), and cross-sectional area of myocardial cells. qRT-PCR was used to detect the mRNA expression of TRPV4. Western blotting was used to detect the protein expression of TRPV4, mast cell tryptase, myosin heavy chain beta (β-MHC), calcineurin A (CnA), and nuclear factor of activated T-cell c3 (NFATc3). ELISA was used to measure the levels of brain natriuretic peptide (BNP) and histamine. Fluo4 AM was used to detect the calcium signal in H9c2 myocardial cells.
Compared with those of the sham rats, the myocardial mast cells, tryptase, HW/BW, LW/BW, HW/TL, and LW/TL, the cross-sectional area of the myocardial cells, and the expression of β-MHC, TRPV4, CnA, and NFATc3 in the myocardial tissue and the serum BNP of the AAC-treated rats increased significantly, whereas the MC stabilizer cromolyn sodium (CS) reversed these indicators. In H9c2 cardiomyocytes, treatment with histamine and the TRPV4 agonist GSK1016790A upregulated the expression of TRPV4, β-MHC, BNP, CnA and NFATc3 and increased calcium ion influx, whereas these effects were inhibited by the H2 receptor inhibitor famotidine and the TRPV4 inhibitor HC067047.
Cardiac MCs participate in pressure overload-induced myocardial hypertrophy through the upregulation of TRPV4 via its mediator histamine, and the Ca2+/CnA/NFATc3 signaling pathway is involved in this process.
Our research aims to evaluate the diagnostic accuracy of colposcopy-guided biopsy (CGB) in detecting high-grade cervical lesions and explore how human papilloma virus (HPV) integration status and other factors affect its performance.
A retrospective cohort analysis involving 550 patients was conducted to evaluate whether the HPV integration plays a role in identifying high-grade cervical lesions and cervical cancer. Logistic regression models and area under the curve (AUC) calculations were employed.
Our findings revealed that 53.5% of CGB/surgery pairs demonstrated congruent diagnoses, whereas 17.1% showed underestimation and 29.5% overestimation. Furthermore, multivariate logistic regression analysis identified several key predictors for cervical intraepithelial neoplasia (CIN)2+ and CIN3+ according to surgical pathology. Notably, a CGB confirming CIN2+ [odds ratio (OR)=6.0, 95% confidence interval (CI): 3.9–9.1, P<0.001], high-grade cytology (OR=2.6, 95% CI: 1.4–1.9, P=0.003), and HPV integration positivity (OR=2.2, 95% CI: 1.3–3.5, P<0.001) emerged as significant factors for CIN2+. Similarly, for CIN3+ identification, CGB confirming CIN2+ (OR=5.3, 95% CI: 3.4-8.3, P<0.001), high-grade cytology (OR=2.6, 95% CI: 1.5–4.7, P=0.001), and HPV integration positivity (OR=2.0, 95% CI: 1.3–3.1, P=0.003) were independent predictors.
Our study highlights the innovative role of HPV integration testing as a pivotal adjunct to CGB and cytology, offering a comprehensive approach that may enhance the diagnostic precision for high-grade cervical lesions, ultimately achieving more precise management strategies.
The trigger receptor expressed on myeloid cells-2 (TREM2) pathway in myeloid cells is a key disease-inducing immune signaling hub that is essential for detecting tissue damage and limiting its pathological spread. However, the role and potential mechanisms of TREM2 in wound repair remain unclear. The purpose of this study was to determine the role and mechanism of TREM2 in skin wound healing in mice.
Immunofluorescence staining was used to determine the expression and cellular localization of TREM2 and test the effects of TREM2 knockout on angiogenesis, glycolysis, and lactylation in skin tissue. Western blotting was used to analyze the expression of the Akt/mTOR/HIF-1α signaling pathway in the wounded skin tissues of wild-type (WT) and TREM2 knockout mice. A coimmunoprecipitation assay was used to determine whether HIF-1α, which mediates angiogenesis, is modified by lactylation.
The number of TREM2+ macrophages was increased, and TREM2+ macrophages mediated angiogenesis after skin injury. TREM2 promoted glycolysis and lactylation in macrophages during wound healing. Mechanistically, TREM2 promoted macrophage glycolysis and angiogenesis in wounded skin tissues by activating the Akt/mTOR/HIF-1α signaling pathway. HIF-1α colocalized with Klac to mediate lactylation in macrophages, and lactate could stabilize the expression of the HIF-1α protein through lactylation. Lactate treatment ameliorated the impaired angiogenesis and delayed wound healing in wounded skin in TREM2 knockout mice.
TREM2+ macrophage-mediated glycolysis can promote angiogenesis and wound healing. Our findings provide an effective strategy and target for promoting skin wound healing.
The objective of this study was to explore the therapeutic effects of kaempferol (Kae) on rheumatoid arthritis (RA) and to elucidate the underlying mechanisms.
The collagen-induced arthritis (CIA) model was established using collagen II to induce RA. Mice were treated with Kae at a dose of 25 or 50 mg/kg/day via gavage. Pathological changes in the ankle joint were analyzed. Enzyme-linked immunosorbent assay (ELISA) was employed to measure the levels of inflammatory factors. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to assess the expression of genes associated with the balance of regulatory T (Treg)/T helper 17 (Th17) cells. Flow cytometry was utilized to determine the Treg/Th17 ratio. Furthermore, these techniques were employed to evaluate the impact of miR-34a and Foxp3 dysregulation on cellular functions in RA under the influence of Kae. Dual luciferase reporter assay was conducted to analyze the binding of miR-34a to Foxp3.
Treatment with Kae led to a downregulation of receptor-related orphan receptor gamma t (RORγt) and IL-17 expression, and an upregulation of Foxp3, IL-10, and TGF-β expression in CIA mice. Kae intervention inhibited the production of proinflammatory cytokines and increased the production of anti-inflammatory cytokines. Furthermore, Kae treatment suppressed the expression of miR-34a, which was identified as a target of miR-34a. Finally, Kae regulated Treg/ Th17 balance-related genes and cellular inflammation through the miR-34a/Foxp3 axis.
The study demonstrated that Kae effectively ameliorates CIA in mice by modulating the Treg/Th17 balance and related genes via the miR-34a/Foxp3 axis. These findings suggest that Kae may serve as a promising therapeutic agent for the treatment of RA and for restoring immune homeostasis.