Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Port-wine stains (PWS) are congenital vascular malformations mainly occurring on the face and neck. Currently, pulsed dye laser (PDL) is the gold standard for the treatment of PWS, but its complete clearance rate is less than 20%. In recent years, 755 nm alexandrite laser, Nd:YAG laser, intense pulsed light and photodynamic therapy have been applied to the treatment of PWS, and there has been new insights into the histopathological characteristics and pathogenesis of PWS. This article analyzes the current treatment status and disease features of PWS, with a view to providing a theoretical basis and new ideas for the treatment of PWS.

Objective:To investigate the clinical efficacy of 595-nm pulsed dye laser (PDL) in the treatment of port-wine stains (PWS) in infants and toddlers.Methods:A retrospective analysis was conducted based on clinical data from 155 infants and toddlers with PWS treated with 595-nm PDL at West China Hospital of Sichuan University from January 2013 to October 2023, and the efficacy was evaluated according to pre- and post-treatment photographs. The children were grouped according to gender, age, lesion color, lesion area, lesion sites, and number of treatment sessions, separately, and the differences were analyzed between different groups. Further analysis was conducted to determine factors affecting efficacy of PDL for PWS. Adverse reactions after treatment were recorded. The Mann-Whitney U test and Kruskal-Wallis H test were used to analyze unidirectional ordered R × C contingency table data, the Bonferroni approach was used for multiple comparisons, and multivariate ordered logistic regression analysis was performed for multifactorial analysis. Results:After the treatment with 595-nm PDL, 135 infants and toddlers with PWS showed good response, with an overall response rate of 87.1%. Univariate analysis indicated that the efficacy was associated with the lesion area ( P = 0.016) and the number of treatment sessions ( P < 0.001), but not with age ( P = 0.340), gender ( P = 0.164), lesion color ( P = 0.530), or lesion sites ( P = 0.077), and the smaller the lesion area, the more the treatment sessions, the better the therapeutic effect. Multivariate ordered logistic regression analysis further confirmed the correlations of efficacy with lesion area ( P = 0.010) and number of treatment sessions ( P < 0.001). Adverse reactions occurred in 5 (3.2%) cases of PWS, including 2 (1.3%) of hypopigmentation, 2 (1.3%) of hyperpigmentation, and 1 (0.6%) of scar formation. Conclusion:The 595-nm PDL was safe and effective for the treatment of PWS in infants and toddlers with few adverse reactions, making it a reliable therapeutic option.

Port-wine stains (PWS) are one of the common congenital vascular malformations in dermatology, clinically manifesting as pink or red irregular patches occurring on the skin or mucosa at birth or shortly thereafter, which are often not elevated above the skin surface. In a minority of patients, vascular malformations not only affect the skin, but also involve the eyes, brain, limbs and viscera. These patients are at risk for glaucoma, epilepsy, limb pain, and other clinical conditions. In general, these conditions are referred to as PWS-associated syndromes. These syndromes are rare diseases, can affect multiple systems and exhibit a variety of clinical manifestations, which pose challenges in their diagnosis and treatment. This review focuses on the clinical manifestations, diagnoses, pathogenesis and treatment of PWS-associated syndromes.

Port-wine stains (PWS) are vascular malformations characterized by dilated capillaries and postcapillary venules in the skin. Clinically, they mainly manifest as pink or red irregular patches, most of which may become thickened, darkened in color, or even develop into nodules over age, making treatment more challenging. The mechanisms underlying the development and progression of PWS are not very clear, and may be related to heredity, gene mutations, abnormal ratios of blood vessels to nerves, etc. This review summarizes research progress in the mechanisms underlying the development and progression of PWS, so as to provide a theoretical basis for their treatment.

Humans ; Stroke, Lacunar ; Mendelian Randomization Analysis ; Leukocytes ; Telomere/genetics* ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide

This paper introduces the concept, basic theory and interventions of reminiscence therapy, summarizes the application status of reminiscence therapy in elderly patients with mental disorders and puts forward the prospect, so as to provide reference for research in China.

Objective: To analyze the prognosis and risk factors of lung metastasis of patients with adenoid cystic carcinoma(ACC) of head and neck. Methods: A retrospective study was conducted. The data of 157 patients with ACC of head and neck treated in Beijing Tongren Hospital, Capital Medical University from January 2014 to October 2020 were collected, including 72 males and 85 females, with onset age between 14 and 72 years old. According to whether lung metastasis occurred, the patients were divided into lung metastasis group (88 cases) and non-pulmonary metastasis group (69 cases). Kaplan-Meier method was used to calculate the overall survival rate and progression-free survival rate using SPSS 26.0 software. Log-rank test was used to evaluate statistically relevant clinicopathological factors. Cox proportional risk model was used in multivariate analysis for the factors affecting the lung metastasis-free survival using R Studio 1.2.5042. Results: The 3-year and 5-year overall survival rates were 91.5% and 85.2%, respectively. The 3-year and 5-year progression-free survival rates were 57.7% and 34.3%, respectively. Univariate analysis showed that primary site, histological grade, high-grade transformation, Ki-67, T stage, and lymph node status were the risk factors for lung metastasis (χ²=11.78, 10.41, 4.06, 4.71, 5.37, 16.20, respectively, all P<0.05). Multivariate analysis showed independent risk factors for lung metastasis, including submandibular gland and sublingual gland (HR=3.53, 95%CI: 1.19-10.46, P<0.05), T3-4 stage (HR=3.09, 95%CI: 1.54-6.23, P<0.05), and Grade Ⅱ-Ⅲ grade (HR=2.47, 95%CI: 1.26-4.86,P<0.05). Conclusion: Distant metastasis, mainly pulmonary metastasis, affects the long-term prognosis of patients with ACC significantly. Primary site, T stage and histopathological grade can be used as the predictors for the risk of lung metastasis.
Adolescent ; Adult ; Aged ; Carcinoma, Adenoid Cystic ; Female ; Humans ; Lung/pathology* ; Lung Neoplasms/secondary* ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Risk Factors ; Young Adult

Near-infrared spectroscopy(NIRS) combined with band screening method and modeling algorithm can be used to achieve the rapid and non-destructive detection of the traditional Chinese medicine(TCM) production process. This paper focused on the ginkgo leaf macroporous resin purification process, which is the key technology of Yinshen Tongluo Capsules, in order to achieve the rapid determination of quercetin, kaempferol and isorhamnetin in effluent. The abnormal spectrum was eliminated by Mahalanobis distance algorithm, and the data set was divided by the sample set partitioning method based on joint X-Y distances(SPXY). The key information bands were selected by synergy interval partial least squares(siPLS); based on that, competitive adaptive reweighted sampling(CARS), successive projections algorithm(SPA) and Monte Carlo uninformative variable(MC-UVE) were used to select wavelengths to obtain less but more critical variable data. With selected key variables as input, the quantitative analysis model was established by genetic algorithm joint extreme learning machine(GA-ELM) algorithm. The performance of the model was compared with that of partial least squares regression(PLSR). The results showed that the combination with siPLS-CARS-GA-ELM could achieve the optimal model performance with the minimum number of variables. The calibration set correlation coefficient R_c and the validation set correlation coefficient R_p of quercetin, kaempferol and isorhamnetin were all above 0.98. The root mean square error of calibration(RMSEC), the root mean square error of prediction(RMSEP) and the relative standard errors of prediction(RSEP) were 0.030 0, 0.029 2 and 8.88%, 0.041 4, 0.034 8 and 8.46%, 0.029 3, 0.027 1 and 10.10%, respectively. Compared with the PLSR me-thod, the performance of the GA-ELM model was greatly improved, which proved that NIRS combined with GA-ELM method has a great potential for rapid determination of effective components of TCM.
Algorithms ; Ginkgo biloba ; Least-Squares Analysis ; Plant Leaves ; Spectroscopy, Near-Infrared